EA042974B1 - COMPOSITIONS AND METHODS FOR INACTIVATION OF PLATELET PATHOGENIC MICROORGANISMS - Google Patents

Description

Cross-reference to related applications

This application claims priority under U.S. Provisional Application No. 62/616,338 filed January 11, 2018, U.S. Provisional Application No. 62/586,739 filed November 15, 2017, and U.S. Provisional Application No. 62/561157, filed September 20, 2017, the disclosures of each of which are hereby incorporated by reference in their entirety.

The technical field to which the invention belongs

The invention provides methods and kits for preparing platelet compositions suitable for infusion. In some aspects, the disclosure provides improved methods and kits for pathogen inactivation of a platelet preparation, including a platelet preparation by apheresis.

Prior Art

The collection and processing of blood components play an important role in public health throughout the world, with millions of units of donated blood components collected from blood banks each year. Although some units of whole blood are taken from donors and used directly for transfusion, most donated blood is usually separated into blood components (erythrocytes, platelets and plasma) for more specific therapeutic applications. Separation can take place either after the collection of donated whole blood or at the site of collection if a suitable separation device system is used, such as an apheresis collection device. The individual blood components are then used for various medical needs and to treat conditions based on therapeutic need.

Platelets play a key role in hemostasis, clot stability and retraction, as well as vascular repair and host antimicrobial defense. A variety of methods are used to collect and store blood platelet preparations for clinical use. The collection of platelets from donated whole blood usually takes place in the form of platelet concentrates (PC) obtained using processing methods such as buffy coat or platelet-rich plasma. Platelets are also obtained from apheresis harvesting, which uses an automated device that separates donor platelets from the donated blood and returns the rest of the blood components (eg, red blood cells and plasma) to the donor during the donation process.

To minimize the risk of infection in a patient receiving a blood product, it is important to ensure that blood products such as platelets are free of pathogens. Testing for the presence of a blood pathogen is limited by the pathogens tested and the sensitivity of the assay. As an alternative to, or in addition to, pathogen testing, methods are known in the art to inactivate pathogens using compound-based (e.g., chemical, photochemical) inactivation methods (e.g., as disclosed in Schlenke et al., TransfUs Med Hemother, 2014, 41, 309-325 and Prowse, Vox Sanguinis, 2013, 104, 183-199). Such inactivation methods may require specific guard interval ranges for administered platelet volumes and platelet counts to achieve the desired compound concentration to inactivate pathogens. For example, the concentration required to achieve a certain level of pathogen inactivation can be used to determine the minimum concentration, and the concentration at which a treatment can affect the function of the processed blood product can be used to determine the maximum concentration. Donated blood volumes and platelet counts can vary significantly from donor to donor or donation to donation, and an improved level of processing flexibility remains desirable to maximize the use of pathogen inactivation systems for donating blood components. This document describes methods, kits and compositions for achieving increased flexibility and improved processing performance.

All references cited in this document, including patent applications and publications, are incorporated by reference in their entirety.

The essence of the invention

In one aspect, a method for preparing a platelet composition (eg, a pathogen inactivated platelet composition) is provided, comprising: (a) providing a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing the solution of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, a method for preparing a platelet composition (eg, a pathogen inactivated platelet composition) is provided, comprising (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing the solution of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition.

In some embodiments, providing in the first container a solution containing

- 1 042974 th PAS and PIC, includes the first combination of a solution of PAS and a solution of PIC to obtain a solution containing PAS and PIC. In some embodiments, the method includes, prior to step (a), combining the PAS solution and the PIC solution to form a solution containing PAS and PIC. In some embodiments, the PAS solution is taken from a PAS container (eg, a PAS storage container). In some embodiments, the PIC solution is taken from a PIC container (eg, a PIC storage container). In some embodiments, the PAS solution and the PIC solution are combined in the first container of step (a). In some embodiments, the first container in step (a) is a PAS container. In some embodiments, the first container in step (a) is a PIC container. In some embodiments, the PAS solution and the PIC solution are combined less than 24 hours (eg, within 24 hours) prior to mixing in step (b). In some embodiments, the mixing in step (b) takes place in the first container. In some embodiments, the mixing in step (b) takes place in a second container. In some embodiments, mixing occurs in two or more second containers. In some embodiments, the platelet preparation is obtained by apheresis. In some embodiments, the method further comprises, prior to step (b), connecting the first container to the apheresis device. In some embodiments, the PAS container is connected to an apheresis device. In some embodiments, the PIC container is connected to an apheresis device. In some embodiments, the implementation of the second container is connected to the apheresis device. In some embodiments, two or more second containers are connected to an apheresis device. In some embodiments, the platelet preparation is prepared from one or more whole blood portion(s) by the buffy coat method or by the platelet-rich plasma (PRP) method. In some embodiments, the method further comprises, after step (c), transferring the platelet composition to a third container. In some embodiments, the method further comprises, after step (c), transferring the platelet composition to two or more third containers. In some embodiments, the third container contains a compound adsorption device (CAD). In some embodiments, the third container is suitable for storing the platelet composition. In some embodiments, the method further comprises transferring the platelet composition from the third container to one or more fourth containers. In some embodiments, one or more of the fourth containers is/are suitable for storing the platelet composition.

In some embodiments, the implementation of the solution of step (a) has a volume between about 100 ml and about 1000 ml. In some embodiments, the implementation of the solution of step (a) contains PIC at a concentration of from about to about 1500 μm. In some embodiments, the implementation of the solution of step (a) contains PIC in a concentration of from about to about 235 μm. In some embodiments, the solution of step (a) contains PIC at a concentration of from about 225 µM to about 235 µM. In some embodiments, the PIC is psoralen. In some embodiments, the PIC is amotosalen. In some embodiments, the platelet preparation contains plasma, wherein the plasma contains approximately 3247% by volume of the mixture of step (b), with the platelet supplement solution (eg, PIC platelet supplement solution) containing the remainder. In some embodiments, the plasma PAS ratio by volume in the mixture of step (b) is approximately 65:35. In some embodiments, the total volume of the mixture of step (b) is from about 100 ml to about 1000 ml. In some embodiments, the mixture of step (b) contains PIC at a concentration sufficient to inactivate the pathogen, if present, by at least 1 order of magnitude. In some embodiments, the mixture of step (b) contains PIC at a concentration sufficient to inactivate the pathogen, if present, by at least 3 orders of magnitude. In some embodiments, the mixture of step (b) contains PIC at a concentration sufficient to inactivate the pathogen, if present, by at least 4 orders of magnitude. In some embodiments, the mixture of step (b) contains PIC at a concentration of from about 5 μM to about 500 μM. In some embodiments, the mixture of step (b) contains PIC at a concentration of from about 15 μM to about 150 μM. In some embodiments, the mixture of step (b) contains PIC at a concentration of from about 15 μM to about 30 μM. In some embodiments, the mixture of step (b) contains PIC at a concentration of from about 30 μM to about 150 μM. In some embodiments, the mixture of step (b) contains PIC at a concentration of from about 30 μM to about 90 μM. In some embodiments, the implementation of the mixture of stage (b) contains PIC at a concentration of approximately 75 μm. In some embodiments, the mixture of step (b) contains PIC at a concentration of from about 145 μM to about 155 μM. In some embodiments, the PAS contains one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate. In some embodiments, the method further comprises prior to step (c) incubating the mixture of step (b) for a period of 30 minutes to 24 hours. In some embodiments, the platelet composition contains at least 2x1011 platelets.

In some embodiments, the method is sufficient to inactivate a pathogen

- 2 042974 microorganisms by at least 1 order, and the platelet composition after step (c) is suitable for infusion to the subject without additional processing to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 4 orders of magnitude, and wherein the platelet composition after step (c) is suitable for infusion into the subject without further treatment to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude, and wherein the platelet composition after step (c) is suitable for infusion into a subject without transferring the platelet composition to a container containing a compound adsorption device (CAD). In some embodiments, the method is sufficient to inactivate the pathogen by at least 4 orders of magnitude, and wherein the platelet composition after step (c) is suitable for infusion into a subject without transferring the platelet composition to a container containing a compound adsorption device (CAD). In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude, and wherein the platelet composition after step (c) contains a PIC of 5 μM or less. In some embodiments, the method is sufficient to inactivate the pathogen by at least 4 orders of magnitude, and wherein the platelet composition after step (c) contains a PIC of 5 μM or less. In some embodiments, the method is sufficient to inactivate the pathogen by at least 4 orders of magnitude, and wherein the platelet composition after step (c) contains 2 μM or less (eg, less than 2 μM) PIC. In some embodiments, the method is sufficient to inactivate the hepatitis E virus by at least 4 orders of magnitude. In some embodiments, a platelet composition suitable for infusion into a subject contains about 5 μM or less of PIC. In some embodiments, a platelet composition suitable for infusion into a subject contains about 2 μM or less (eg, less than 2 μM) PIC. In some embodiments, the concentration of PIC in the mixture of step (b) is at least 10 μM. In some embodiments, the concentration of PIC in the mixture of step (b) is at least 30 μM.

In yet another aspect, there is provided a kit for preparing a platelet composition comprising (a) a first container containing a solution containing a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC), and (b) a second container suitable for holding a platelet preparation in mixtures with a solution containing PAS and PIC, while the first container is not connected to the second container.

In some embodiments, the first container is suitable for mixing a platelet preparation with a solution containing PAS and PIC. In some embodiments, the second container is suitable for mixing the platelet preparation with the solution containing PAS and PIC. In some embodiments, the second container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the first container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the second container contains a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the kit further comprises a third container. In some embodiments, the third container contains a compound adsorption device (CAD) and the third container is connected to the second container. In some embodiments, the kit further comprises at least one storage container, wherein the at least one storage container is suitable for storing the platelet composition, and wherein the at least one storage container is connected to a second container or a third container, wherein availability. In some embodiments, the kit does not contain a compound adsorption device (CAD).

In some embodiments, the solution containing PAS and PIC has a volume between about 100 ml and about 1000 ml. In some embodiments, the implementation of the PIC is at a concentration of from about 15 μm to about 1500 μm. In some embodiments, the implementation of the PIC is at a concentration of from about 225 μm to about 235 μm. In some embodiments, the PIC is psoralen. In some embodiments, the PIC is amotosalen.

In some embodiments, the first container, the second container, or both the first container and the second container are suitable for connection to an apheresis device or to a container containing a platelet preparation.

In yet another aspect, there is provided a platelet composition preparation kit comprising: (a) a first container containing a platelet supplemental solution (PAS); (b) a second container containing a pathogen inactivating compound (PIC); and (c) a third container suitable for containing the platelet preparation in admixture with PAS and PIC, wherein neither of the first and second

- 3 042974 horn of containers is not connected to the third container. In some embodiments, the platelet composition preparation kit is a kit comprising (a) a first container containing platelet supplemental solution (PAS); (b) a second container containing a pathogen inactivating compound (PIC); and (c) a third container suitable for holding the platelet preparation in admixture with PAS and PIC, wherein the first and second containers are communicable to each other, and neither of the first and second containers is connected to the third container. In some embodiments, the platelet composition preparation kit is a kit comprising (a) a first container containing platelet supplemental solution (PAS); (b) a second container containing a pathogen inactivating compound (PIC); and (c) a third container suitable for containing the platelet preparation in admixture with PAS and PIC, wherein the first and second containers are connected to each other, and neither of the first and second containers is connected to the third container. In some embodiments, the first and second containers are connected to each other by a sealed but openable flow path (eg, frangible element, frangible connector).

In some embodiments, the implementation of the second container is suitable for combining PAS with PIC. In some embodiments, the second container is suitable for mixing the platelet preparation with PAS and PIC. In some embodiments, the first container is suitable for combining PAS with PIC. In some embodiments, the first container is suitable for mixing the platelet preparation with PAS and PIC. In some embodiments, the third container is suitable for mixing the platelet preparation with PAS and PIC. In some embodiments, the third container is suitable for exposing the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the second container is suitable for exposing the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the first container is suitable for exposing the platelet preparation in admixture with PAS and PIC to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the third container contains a compound adsorption device (CAD). In some embodiments, the third container is suitable for storing the platelet composition. In some embodiments, the kit further comprises a fourth container. In some embodiments, the fourth container contains a compound adsorption device (CAD) and the fourth container is connected to the third container. In some embodiments, the kit further comprises at least one storage container, wherein the at least one storage container is suitable for storing the platelet composition, and wherein the at least one storage container is connected to a third container or a fourth container, wherein availability. In some embodiments, the PIC is psoralen. In some embodiments, the PIC is amotosalen. In some embodiments, the first container, the second container, or both the first container and the second container are suitable for connection to an apheresis device or to a container containing a platelet preparation. In some embodiments, the third container is suitable for connection to an apheresis device or to a container containing a platelet preparation. In some embodiments, the kit does not contain a compound adsorption device (CAD).

These and other aspects and advantages of the present disclosure will become apparent from the following detailed description and the appended claims. It is to be understood that one, some or all of the features of the various embodiments described herein may be combined to form other embodiments of the present disclosure.

Brief description of the drawings

In FIG. 1A shows an exemplary kit for preparing a platelet composition. The dotted lines show alternative sites for adding the platelet preparation.

In FIG. 1B shows an exemplary kit for preparing a platelet composition. The dotted lines show alternative sites for adding the platelet preparation.

In FIG. 1C shows an exemplary platelet composition preparation kit. The dotted lines show alternative sites for adding the platelet preparation.

In FIG. 1D shows an exemplary kit for preparing a platelet composition. The dotted lines show alternative sites for adding the platelet preparation.

In FIG. 1E shows an exemplary platelet composition preparation kit. The dotted line shows the site of addition of the platelet preparation.

In FIG. 2A shows exemplary kits for preparing a platelet composition. The dotted lines show alternative sites for adding the platelet preparation.

In FIG. 2B is an exemplary kit for preparing a platelet composition. The dotted lines show alternative sites for adding the platelet preparation.

In FIG. 2C shows an exemplary platelet composition preparation kit. The dotted lines show alternative sites for adding the platelet preparation.

- 4 042974

In FIG. 2D shows an exemplary platelet composition preparation kit. The dotted lines show alternative sites for adding the platelet preparation.

In FIG. 2E shows an exemplary platelet composition preparation kit. The dotted line shows the place where the platelet preparation was added.

In FIG. 3 shows a container containing a solution containing a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC) connected to an exemplary apheresis device.

Detailed description of the invention

The invention provides, in some aspects, improved methods, kits, and compositions for inactivating pathogens in a platelet preparation, including a platelet preparation by apheresis, to provide an infusionable platelet composition.

The methods, kits and compositions disclosed herein relate to administering a dose of a pathogen inactivating compound (PIC), such as a photochemical compound such as amotosalen, to a platelet preparation at a fixed concentration of PIC to inactivate pathogens.

For example, the disclosure provides pre-mixing PIC with platelet supplement (PAS) at the desired (e.g., standardized) concentration and then dosing the PIC/PAS solution into the platelet preparation, thus providing, for example, (i) improved processing flexibility and control, (ii) improved pathogen inactivation, including, for example, providing reduced amounts of PIC used to inactivate pathogens, (iii) reduced processing steps, such as not requiring additional processing by a compound adsorption device (CAD) to remove residual PIC or its photoproducts prior to administration to the patient and/or (iv) improved platelet quality. Addition of premixed PIC/PAS solution in standard volumes that are multiples of single, double and triple volume, i.e. 1x, 2x, and 3x can help optimize both the collection, e.g., by combining with apheresis platelet collection, and processing processes so that all therapeutic doses of pathogen-inactivated platelets, e.g., at 65/35 PAS/plasma, are identical independently. whether they come from a single, double, or triple volume of donated blood and can always be treated with the same concentration of PIC.

With the improved methods, kits, and compositions disclosed herein, a number of benefits can be obtained, such as increased standardization of processing conditions that provide pathogen inactivation at more constant PIC concentrations, eliminating some of the restrictive guard intervals for platelet volume and/or input given platelet concentrations, providing greater flexibility in the processing options available for pathogen inactivation of platelet preparations and/or reducing the amounts of PIC required to inactivate pathogens. The opening can thus allow for much greater fluctuation in the processed volumes of donated blood. This, in turn, can also allow for reduced variation in subsequent processing steps (eg, compound adsorption device (CAD) treatment) and ultimately less variation in the residual PIC in the final platelet preparation (eg, platelet composition).

In addition, the use of premixed PIC/PAS may allow the PIC component to be separately obtained and/or supplied from other components of disposable treatment kits or as uncombined components supplied with treatment kits (e.g., as kits), greatly simplifying by this and reducing the cost of products for disposable kits associated with production processes. For example, the methods, kits, and compositions disclosed herein may include treatment kits with separate/unrelated wet side components (e.g., PIC and PAS) and dry side components (e.g., lighting, CAD, and/or storage containers). ), thus simplifying the manufacture and risks of their sterilization.

In addition, the methods, kits, and compositions disclosed herein may provide improved (e.g., increased) pathogen inactivation, e.g., in multiple types or species of inactivated pathogens, and/or the degree of pathogen inactivation of a single type or species of pathogen, and/or inactivation of pathogens by reduced concentrations of PIC, for example by pre-incubation of PIC with a platelet preparation.

Definitions

A platelet preparation in the context of the present invention means a composition containing platelets that has not been subjected to a pathogen inactivation process. In some embodiments, the platelet preparation is donated blood with platelets. In some embodiments, the platelet preparation is obtained from donated blood after apheresis. In some embodiments, the platelet preparation is obtained from donated whole blood (eg, buffy coat method, platelet-rich plasma (PRP) method). In some embodiments, the platelet preparation is obtained from more than one donor. In some embodiments, the platelet preparation contains plasma.

Pathogen inactivation process in the context of the present invention means a process useful for inactivating possibly present pathogens in a platelet preparation such as donated blood with platelets, it being understood that the process does not necessarily completely inactivate all pathogens that may be present, but significantly reduces the number pathogens, significantly reducing the risk of transfusion-related illness. Pathogen inactivation can be analyzed, for example, by measuring the number of infectious pathogens (e.g., viruses or bacteria) in a certain volume, and the level of inactivation is usually displayed by decreasing the degree of infectivity of the pathogen or decreasing the order of the number in the titer. Methods are known in the art for analyzing and measuring order reduction in titer to inactivate pathogens. Methods for assaying titer reduction and measuring it for pathogen inactivation are described, for example, in US Pat. Therefore, for any given pathogen, known amounts can be added to a platelet unit being tested (e.g., a platelet preparation) to assess how much inactivation is due to the process, where typically the pathogen inactivation process results in a decrease in the order of magnitude in titer of at least about 1 or to decrease the order of the number in the title by about 2, about 3, about 4, or at least about 5 or more. While the methods described herein are applicable to any pathogen inactivation process, the pathogen inactivation process needs to be capable of inactivating a plurality of pathogens with an order of magnitude decrease in titer of at least 1, including a pathogen selected from the group consisting of HIV-1, HBV, HCV, HTLV-1, HTLV-2, West Nile virus, hepatitis E virus, Escherichia coli, Klebsiella pneumoniae, Yersinia enterocolitica, Staphylococcus epidermidis, Staphylococcus aureus, Treponema pallidum, Borrelia burgdorferi, Plasmodium falciparum, Trypanosoma cruzi and Babesia microti. In some embodiments, the pathogen inactivation process may include treatment with a pathogen inactivating compound (PIC).

Pathogen inactivating compound or PIC in the context of the present invention means any suitable compound, such as a small organic compound, which can be used to inactivate a pathogen and which may be present in a blood product containing platelets. A photoactivated pathogen-inactivating compound is a suitable compound that requires a certain level of light to sufficiently inactivate (eg, photochemically inactivate) a pathogen. Such compounds are useful for the inactivation of pathogens in platelet preparations or other blood products, as they provide regulation of the inactivation process. Such photoactivated pathogen inactivating compounds described herein include psoralens, isoalloxazins, alloxazins, phthalocyanines, phenothiazines, and porphyrins, it being understood that these terms encompass the general class of compounds, i. the basic compound and its suitable derivatives. For example, psoralens or psoralen usually describes the basic compound psoralen and any derivative thereof (eg amotosalen), isoalloxazines or isoalloxazin usually describes the basic compound isoalloxazin and any derivative thereof (eg riboflavin), and so on. Such derivatives contain the structure of the main compound, as well as additional substituents to the base. Descriptions of such compounds include any of their salts.

The term amotosalen within the scope of the invention means the compound 3-(2-aminoethoxymethyl)-2,5,9trimethylfuro[3,2-G]chromen-7-one and any salts thereof. The amotosalen compound may also be referred to as 3[(2-aminoethoxy)methyl]-2,5,9-trimethyl-7H-furo[3,2-G][1]benzopyran-7-one-hydrochloride. The amotosalen compound may also be referred to as 4'-(4-amino-2-oxa)butyl-4,5',8-trimethyl psoralen. When inactivation of blood products, such as a platelet preparation, involves the addition of amotosalen HCl (the HCl salt of amotosalen) to the blood product, the removal of this compound from the blood product is not limited to the removal of amotosalen HCl, since amotosalen may be present in solution as other salts or as free grounds.

The composition of platelets in the context of the present invention means a composition with inactivated pathogens containing platelets.

With inactivated pathogens, the present invention describes a blood product (eg, a platelet composition) that is subjected to a pathogen inactivation process (eg, using the methods described herein) to inactivate possibly present pathogens. It is understood that the pathogen inactivation process does not necessarily completely inactivate all pathogens,

- 6 042974 which may be present, but significantly reduces the number of one or more pathogens, significantly reducing the risk of transfusion-related illness.

The term suitable for infusion refers to any blood product (e.g., platelet composition, pathogen inactivated platelet composition) that can be used for infusion (e.g., transfusion) into a subject (e.g., human patient) according to medical judgment. In some embodiments, suitability refers to having sufficient biological activity for its intended use, ie. for use when transfusion of human coagulation factors is indicated, including, without limitation, management of bleeding associated with fibrinogen deficiency, treatment of factor XIII deficiency, treatment of factor VIII deficiency, treatment of von Willebrand disease, maintenance of hemostasis, treatment of disseminated intravascular coagulation (DIC) or bleeding large volume and/or obtaining fibrin glue. In some embodiments, suitability refers to having sufficient safety, such as when a drug is subjected to a treatment that improves drug safety (e.g., pathogen inactivation) and/or demonstrates satisfactory performance with respect to one or more safety-related measurements (such as viral or bacterial titer). ). Photochemical inactivation of pathogens in blood product units using amotosalen and ultraviolet A, as described herein, is well known to produce a blood product (eg, platelet composition) that is suitable for human infusion. In some embodiments, suitability refers to meeting one or more standards (e.g., level of biological activity or biological component, safety criteria, and the like) set by an accrediting agency or regulatory body that governs the practice of infusion, such as AABB. In some embodiments, the suitability of a platelet composition subjected to pathogen inactivation (e.g., photochemical pathogen inactivation with amotosalen/ultraviolet A) refers to a platelet composition with a PIC concentration (e.g., residual PIC) below a certain level after the pathogen inactivation process.

The term sterile or sterile within the scope of the present invention refers to maintaining the sterility of the system, for example by connecting two bags from a blood treatment kit, or refers to a means by which contamination is not introduced into the process. For example, as used in the methods described herein, a block source of a blood product such as a platelet preparation (e.g., in a suitable container) containing a tubing for connection to a treatment kit or a container for a pathogen inactivating compound containing a similar tubing, can be joined under sterile conditions using methods known in the art, for example, using a sterile connecting device that acts to fuse or weld the tubing together to provide a sterile flow path between two containers. Similarly, when the methods described herein describe the sealing of such tubes, the sealing is carried out under sterile conditions, for example, using a tube welding machine.

Methods for preparing a platelet composition

The present disclosure provides, in some aspects, methods for preparing a platelet composition (e.g., a pathogen-inactivated platelet composition) comprising: (a) providing (e.g., in a first container) a solution containing a platelet supplemental solution (PAS) and a pathogen-inactivating compound ( PIC); (b) mixing the solution of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition.

Methods for preparing a platelet composition (e.g., pathogen inactivated platelet composition) disclosed herein include (a) providing a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC), wherein the solution containing PAS and The PIC is of sufficient volume to produce any number of platelet compositions (eg, a single or therapeutic dose of platelets). In some embodiments, the first container of step (a) contains a sufficient volume of a solution containing a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC) to produce a single platelet composition (e.g., a single therapeutic dose of platelets). In some embodiments, the first container of step (a) contains a sufficient volume of a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC) to produce two or more (e.g., three) platelet compositions. In some embodiments, the first container of step (a) contains a sufficient volume of a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC) to obtain a platelet composition from a single platelet donor. In some embodiments, the first container of step (a)

- 7 042974 contains a sufficient volume of a solution containing platelet additive solution (PAS) and a pathogen inactivating compound (PIC) to obtain platelet compositions from two or more platelet donors.

In some embodiments, a method is provided, including: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing in the first container the solution of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, the first container is made from a material substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (b) is exposed to light in the first container . In some embodiments, the solution containing PAS and PIC is combined with the platelet preparation when mixed in step (b) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (c). In some embodiments, the first container contains a compound adsorption device (CAD). In some embodiments, the first container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to a container containing the CAD. In some embodiments, the CAD-containing container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided, including: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing in the second container the solution of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, the second container is made from a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (b) is exposed to light in the second container . In some embodiments, the solution containing PAS and PIC is combined with the platelet preparation when mixed in step (b) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (c). In some embodiments, the second container contains a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to a container containing the CAD. In some embodiments, the CAD-containing container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided, including: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container to the apheresis device; (c) mixing in the first container the solution of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, the first container is sterile connected to the apheresis device. In some embodiments, the implementation of the first container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the first container is made from a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the first container. . In some embodiments, the solution containing PAS and PIC is combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the first container contains a compound adsorption device (CAD). In some embodiments, the first container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition to a container containing the CAD. In some embodiments, the CAD-containing container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (e.g., sterile) the platelet composition into at least one (e.g., 1, 2, or 3) container suitable for storage.

- 8 042974 platelet compositions.

In some embodiments, a method is provided, including: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container to the apheresis device; (c) mixing in the second container the solution of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, the first container is sterile connected to the apheresis device. In some embodiments, the implementation of the first container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the second container. . In some embodiments, the solution containing PAS and PIC is combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the second container contains a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition to a container containing the CAD. In some embodiments, the CAD-containing container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition into at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided, including: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container and the second container with the apheresis device; (c) mixing in the second container the solution of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, the first and/or second container is sterile connected to the apheresis device. In some embodiments, the implementation of the first and/or second container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the second container. . In some embodiments, the solution containing PAS and PIC is combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the second container contains a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition to a container containing the CAD. In some embodiments, the CAD-containing container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition into at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided comprising: (a) combining (eg, mixing) in a first container a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing in the first container the mixture of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, the first container is made from a material substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (b) is exposed to light in the first container . In some embodiments, the PAS solution and the PIC solution combined in step (a) are combined with the platelet preparation when mixed in step (b) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (c). In some embodiments, the first container contains a compound adsorption device (CAD). In some embodiments, the first container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to a container containing the CAD. In some embodiments, the CAD-containing container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition into at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided comprising: (a) combining (eg, mixing) in a first container a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing, in a second container, the mixture of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, the second container is made from a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (b) is exposed to light in the second container . In some embodiments, the PAS solution and the PIC solution combined in step (a) are combined with the platelet preparation when mixed in step (b) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (c). In some embodiments, the second container contains a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to a container containing the CAD. In some embodiments, the CAD-containing container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided comprising: (a) combining (eg, mixing) in a first container a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container to the apheresis device; (c) mixing in the first container the mixture of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, the first container is sterile connected to the apheresis device. In some embodiments, the implementation of the first container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the first container is made from a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the first container. . In some embodiments, the PAS solution and PIC solution combined in step (a) are combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the first container contains a compound adsorption device (CAD). In some embodiments, the first container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition to a container containing the CAD. In some embodiments, the CAD-containing container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition into at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided comprising: (a) combining (eg, mixing) in a first container a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container to the apheresis device; (c) mixing in the second container the mixture of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, the first container is sterile connected to the apheresis device. In some embodiments, the implementation of the first container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the second container. . In some embodiments, the PAS solution and PIC solution combined in step (a) are combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the second container contains a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition to a container containing the CAD. In some embodiments, the container containing the CAD is suitable for storing the composition.

- 10 042974 platelets. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition to at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided comprising: (a) combining (eg, mixing) in a first container a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container and the second container with the apheresis device; (c) mixing in the second container the mixture of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition. In some embodiments, the first and/or second container is sterile connected to the apheresis device. In some embodiments, the implementation of the first and/or second container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the second container. . In some embodiments, the PAS solution and PIC solution combined in step (a) are combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the second container contains a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition to a container containing the CAD. In some embodiments, the container containing the CAD is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition to at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided, comprising: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing in the first container the solution of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen microorganism by at least 4 orders of magnitude) and wherein the platelet composition after step (c) is suitable for infusion into a subject without further processing, including without exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen by at least 4 orders of magnitude) and wherein the platelet composition after step (c) contains less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution containing PAS and PIC is combined with the platelet preparation when mixed in step (b) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (c). In some embodiments, the first container is made of a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (b) is exposed to light in the first container. . In some embodiments, the first container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided, including: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing in the second container the solution of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen microorganism by at least 4 orders of magnitude) and wherein the platelet composition after step (c) is suitable for infusion into a subject without further processing, including exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen by at least 4 orders of magnitude) and wherein the platelet composition after step (c) contains less than 5 μM PIC (e.g., less than 2 μM PIC). In some

- 11 042974 embodiments, the solution containing PAS and PIC is combined with the platelet preparation when mixed in step (b) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (c). In some embodiments, the second container is made from a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (b) is exposed to light in the second container . In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided, including: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container to the apheresis device; (c) mixing in the first container the solution of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen microorganism by at least 4 orders of magnitude) and wherein the platelet composition after step (d) is suitable for infusion into a subject without further processing, including exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen by at least 4 orders of magnitude) and wherein the platelet composition after step (d) contains less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution containing PAS and PIC is combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the first container is sterile connected to the apheresis device. In some embodiments, the implementation of the first container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the first container is made from a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the first container. . In some embodiments, the first container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition into at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided, including: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container to the apheresis device; (c) mixing in the second container the solution of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen microorganism by at least 4 orders of magnitude) and wherein the platelet composition after step (d) is suitable for infusion into a subject without further processing, including exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen by at least 4 orders of magnitude) and wherein the platelet composition after step (d) contains less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution containing PAS and PIC is combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the first container is sterile connected to the apheresis device. In some embodiments, the implementation of the first container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the second container. . In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition into at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

- 12 042974

In some embodiments, a method is provided, including: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container and the second container with the apheresis device; (c) mixing in the second container the solution of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen microorganism by at least 4 orders of magnitude) and wherein the platelet composition after step (d) is suitable for infusion into a subject without further processing, including exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen by at least 4 orders of magnitude) and wherein the platelet composition after step (d) contains less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the solution containing PAS and PIC is combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the first and/or second container is sterile connected to the apheresis device. In some embodiments, the implementation of the first and/or second container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the second container. . In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition into at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided comprising: (a) combining (eg, mixing) in a first container a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing in the first container the mixture of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen microorganism by at least 4 orders of magnitude) and wherein the platelet composition after step (c) is suitable for infusion into a subject without further processing, including exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen by at least 4 orders of magnitude) and wherein the platelet composition after step (c) contains less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the PAS solution and the PIC solution combined in step (a) are combined with the platelet preparation when mixed in step (b) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (c). In some embodiments, the first container is made from a material substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (b) is exposed to light in the first container . In some embodiments, the first container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided comprising: (a) combining (eg, mixing) in a first container a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing, in a second container, the mixture of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen microorganism by at least 4 orders of magnitude) and wherein the platelet composition after step (c) is suitable for infusion into a subject without further processing, including exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen by at least 4 orders of magnitude) and wherein the platelet composition after step (c) contains less than 5 μM PIC (e.g., less than 2 μM PIC). In some

- 13 042974 embodiments, the PAS solution and the PIC solution combined in step (a) are combined with the platelet preparation when mixed in step (b) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (c) . In some embodiments, the second container is made from a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (b) is exposed to light in the second container . In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (c), transferring (eg, sterile) the platelet composition to at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided comprising: (a) combining (eg, mixing) in a first container a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container to the apheresis device; (c) mixing in the first container the mixture of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen microorganism by at least 4 orders of magnitude) and wherein the platelet composition after step (d) is suitable for infusion into a subject without further processing, including exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen by at least 4 orders of magnitude) and wherein the platelet composition after step (d) contains less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the PAS solution and PIC solution combined in step (a) are combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the first container is sterile connected to the apheresis device. In some embodiments, the implementation of the first container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the first container is made from a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the first container. . In some embodiments, the first container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition into at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In some embodiments, a method is provided comprising: (a) combining (eg, mixing) in a first container a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container to the apheresis device; (c) mixing in the second container the mixture of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen microorganism by at least 4 orders of magnitude) and wherein the platelet composition after step (d) is suitable for infusion into a subject without further processing, including exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen by at least 4 orders of magnitude) and wherein the platelet composition after step (d) contains less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the PAS solution and PIC solution combined in step (a) are combined with the platelet preparation when mixed in step (b) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the first container is sterile connected to the apheresis device. In some embodiments, the implementation of the first container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the second container. . In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition into at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

- 14 042974

In some embodiments, a method is provided comprising: (a) combining (eg, mixing) in a first container a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) connecting the first container and the second container with the apheresis device; (c) mixing in the second container the mixture of step (a) with the platelet preparation; and (d) exposing the mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen microorganism by at least 4 orders of magnitude) and wherein the platelet composition after step (d) is suitable for infusion into a subject without further processing, including exposure to a compound adsorption device (CAD), to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude (e.g., inactivate the pathogen by at least 4 orders of magnitude) and wherein the platelet composition after step (d) contains less than 5 μM PIC (e.g., less than 2 μM PIC). In some embodiments, the PAS solution and PIC solution combined in step (a) are combined with the platelet preparation when mixed in step (c) and incubated for a period of 30 minutes to 24 hours before exposing the mixture to light in step (d). In some embodiments, the first and/or second container is sterile connected to the apheresis device. In some embodiments, the implementation of the first and/or second container is connected to the passage or channel for the flow of fluid of the apheresis device. In some embodiments, the second container is made of a material that is substantially translucent to light in the photochemical inactivation wavelength range (e.g., about 200 nm to about 400 nm, ultraviolet A), and the mixture of step (c) is exposed to light in the second container. . In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the method further comprises, after step (d), transferring (eg, sterile) the platelet composition into at least one (eg, 1, 2, or 3) container suitable for storing the platelet composition.

In any or all of the above embodiments, providing a solution containing PAS and PIC in a first container comprises first combining a solution of PAS and a solution of PIC to form a solution containing PAS and PIC. In any or all of the above embodiments, the method comprises, prior to step (a), combining the PAS solution and the PIC solution to form a solution containing PAS and PIC. In some embodiments, the PAS solution is taken from a PAS container (eg, a PAS storage container). In some embodiments, the PIC solution is taken from a PIC container (eg, a PIC storage container). In some embodiments, the PAS solution and the PIC solution are combined in the first container of step (a). In some embodiments, the first container in step (a) is a PAS container. In some embodiments, the PAS solution and the PIC solution are combined less than 24 hours (eg, within 24 hours) prior to mixing step (b). In some embodiments, the first container in step (a) is a PIC container. In some embodiments, the PAS container is connected to an apheresis device. In some embodiments, the PIC container is connected to an apheresis device.

In any or all of the above embodiments, the container containing the mixture of Platelet Supplemental Solution (PAS), Pathogen Inactivating Compound (PIC), and Platelet Preparation can be detached (e.g., sterile detached) from the apheresis device prior to exposing the mixture to light sufficient for photochemical inactivation. pathogenic microorganism, if present.

The present disclosure provides, in some aspects, methods for preparing a platelet composition suitable for infusion into a patient from a platelet preparation. In some embodiments of any of the methods, kits, and compositions described herein, one or more platelet preparations are processed by the methods disclosed herein, thereby obtaining one or more platelet compositions. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude, and wherein the platelet composition after step (c) is suitable for infusion into the subject without further treatment to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude, and wherein the platelet composition after step (c) contains a PIC of 5 μM or less. In some embodiments, the concentration of PIC in the mixture of step (b) is at least 10 μM.

Platelet preparations

In some embodiments, the platelet preparation is derived from one or more, e.g., at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least at least 8, at least 9, or at least 10 apheresis-derived portions of donor platelets. In some embodiments, the platelet preparation is prepared from one or more, eg, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 apheresis-derived portions of donor platelets. In some embodiments

- 15 042974 platelet preparation is obtained from one or more, for example at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9 or at least 10 whole blood-derived (eg, PRP, buffy coat) portions of donor platelets. In some embodiments, the platelet preparation is prepared from one or more, e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 whole blood (e.g., PRP, buffy coat) portions of donor platelets.

Platelets collected by apheresis

In some embodiments of any of the methods, kits, and compositions described herein, a platelet preparation is obtained by apheresis.

Apheresis techniques generally refer to methods of using an automated blood collection device (such as an apheresis device) that uses separation by centrifugation or filtration to automatically obtain whole blood from a donor, separate whole blood into blood components, collect certain components (such as platelets), and returning to the donor some or all of the remaining whole blood and/or remaining uncollected blood components. Thrombopheresis is the collection of platelets using such an automated blood cell separation device that results in a high yield of platelets (eg platelets from apheresis) from a single donor. In some embodiments, the desired amount of plasma is stored with the collected platelets. Some apheresis devices allow methods for collecting not only single platelet units, but also double and triple platelet units. The apheresis device may also comprise an anticoagulant container from which the anticoagulant is dispensed into the flow channel and mixed with incoming whole blood. An anticoagulant is needed because of the tendency of blood to clot and stick to the walls of plastic surfaces with which it comes into contact. Exemplary anticoagulants are well known in the art and may include, but are not limited to, citrate phosphate dextrose (CPD) anticoagulant solution, double dextrose phosphate citrate (CP2D) anticoagulant solution, adenine phosphate dextrose (CPDA) citrate anticoagulant solution (e.g., CPDA-1), acidic citrate dextrose (ACD) (eg, ACD-A) and sodium citrate anticoagulant solution 4% w/v. Apheresis collection devices are well known in the art, some of which are commercially available including, for example, the Amicus® System (Fenwal, Inc.), the Trima Accel® System (Terumo BCT), and the MCS®+9000 Mobile System (Haemonetics, Inc.). Inc.).

Donor platelet portions resulting from apheresis are based on specific donor parameters such as, for example, gender, physical size (e.g., weight), hemoglobin level, platelet count on donation day, pre-donation history, and donation frequency, in part to ensure collection only a safe platelet count. Any or all of these parameters can be entered into the computer system and/or collection device for the purpose of apheresis. Based on these parameters, apheresis portions of donor platelets are typically harvested from an individual donor by volume to produce one, two, or three platelet units (e.g., therapeutic dose units) each containing a specified minimum amount (e.g., at least a specified minimum number) of platelets per unit corresponding to the requirement for a therapeutic dose, and such criteria for a single or therapeutic dose are usually determined by the standards (for example, industry) of governmental, regulatory or accrediting organizations. Non-limiting examples of such standards include, for example, those set forth by the FDA, EDQM, AABB, PMDA, TGA, and SFDA. The specified minimum, for example, may vary from country to country. Typically, the platelet count can be determined for each unit of the platelet preparation, for example, based on the pre-donation platelet count and collected volume information, or alternatively by testing the units after collection. In some embodiments, each unit of platelet preparation will contain a minimum number of platelets; however, determining the number of platelets for each unit may not be an absolute requirement, and some platelet units in a plurality of platelet units may have less than the specified number.

Whole blood collection and platelet processing

In some embodiments of any of the methods, kits, and compositions described herein, a platelet preparation is prepared from one or more whole blood portion(s) by the buffy coat method or by the platelet-rich plasma (PRP) method.

In some embodiments, the platelet preparation is prepared from one or more whole blood unit(s) by the buffy coat method.

In some embodiments, the platelet preparation is obtained from one or more whole blood portion(s) by the platelet-rich plasma (PRP) method.

Whole blood for use in a platelet preparation as described in this document,

- 16 042974 can be collected using a number of methods known in this field. One of the most common blood collection techniques is the manual collection of whole blood from donors. As is generally understood and within the scope of the present invention, manual collection refers to a collection method where the flow of whole blood from a donor into a collection container is provided without the use of external pumps or similar devices. In this it differs from so-called automated methods, where blood is taken from a donor and further processed with an instrument that typically contains a processing or separation device and pumps to move the blood or blood components into and out of the device.

Taking blood from a donor typically involves inserting a vein access device, such as a needle, into the donor's arm (more specifically, into the donor's vein) and drawing blood from the donor through the needle. A venipuncture needle is usually attached to one end of a plastic tube that provides a passageway for blood. The other end of the plastic tube terminates in one or more pre-attached plastic blood containers or bags for blood collection. The needle, tubing, and containers make up the blood collection kit, which is pre-sterilized and discarded after one use. The sterile blood collection container usually serves as the primary container for the initial separation of blood components (eg, separation of plasma from red blood cells and platelets).

The blood collection container and plastic tubing may also contain a volume of liquid anticoagulant, while a separate anticoagulant container can be provided by automated technique from which the anticoagulant is dispensed into the flow channel and mixed with incoming whole blood. An anticoagulant is needed because of the tendency of blood to clot and stick to the walls of the plastic surfaces inside. Exemplary anticoagulants are well known in the art and may include, but are not limited to, citrate phosphate dextrose (CPD) anticoagulant solution, citrate phosphate double dextrose (CP2D) anticoagulant solution, citrate phosphate dextrose (CPDA) anticoagulant solution (e.g., CPDA1), acid citrate dextrose (ACD) (eg, ACD-A), and 4% w/v sodium citrate anticoagulant solution.

Blood can be identified or characterized with respect to one or more parameters such as, for example, hematocrit. Such identification or characterization is usually carried out before or shortly after blood collection, but before further processing of the collected whole blood, for example, according to the methods presented herein. In addition, during or close to collection and prior to transfusion, tests may be performed on the patient to determine the type of blood and the presence of pathogens such as virus, bacteria and/or other foreign substances in the donated blood. This testing usually requires obtaining a sample of donated blood. Typically, the collection of a blood sample can be performed before, during or after blood donation, but without compromising the sterility of the system and/or the collected blood product. For example, samples can typically be obtained by finger prick, heel prick, or venipuncture. In the case where blood for hemoglobin testing is collected with a capillary rod, a disposable sterile lancet can be used. Another well-known technique is to simply draw or collect blood remaining in the flow channel of the collection device after blood donation. This involves removing the needle from the donor, inserting the needle into a sealed tube or sampling tube, and allowing blood to drain from the flow channel into the tube. Another alternative is to clamp the flow channel near the collection container and divert the blood that is taken from the donor into a collection (sample) tube or tube. This method can use a disposable set with a particular type of tubing, which has a pre-attached sampling site in the main flow channel. Blood at or near the sampling site may be obtained by piercing the sampling site with a separately provided needle or other piercing device and attaching a sampling tube thereto. To minimize the risk that incoming blood will be exposed to the environment, the sample is usually taken after the blood donation is completed. Alternatively, some collection bags or collection kits include diversion bags to separate a portion (eg, the first 20 ml) of the collected blood. Another example of a blood sampling system is described in US Pat. No. 5,167,656, incorporated herein by reference in its entirety, which describes blood collection kits with an enlarged sampling portion enclosed in a flow channel. Blood for sampling is collected from the enlarged portion by clamping the flow channel near the collection container and allowing blood to fill the enlarged portion of the tube.

Buffy coat techniques are known in the art. Buffy coat methods involve separating blood components from unclotting blood samples by centrifugation to obtain a plasma containing layer, a red blood cell containing layer, and a platelet and white blood cell containing layer (i.e., buffy coat). After centrifugation, the buffy coat can be isolated from other blood components to obtain a platelet preparation.

Platelet-rich plasma (PRP) techniques are known in the art. PRP methods involve separating blood components from unclotting blood samples by centrifugation to obtain a layer containing erythrocytes and a layer containing plasma and platelets. After centrifugation, the plasma layer and platelets can be isolated from other blood components (and optionally further centrifuged to concentrate platelets) to obtain a platelet preparation.

Pathogen Inactivating Compound (PIC)

In some embodiments of any of the methods, kits, and compositions provided herein, pathogen inactivation requires the addition of an amount of a pathogen-inactivating compound (eg, to a platelet preparation). For example, pathogen inactivation may involve the addition of a small molecule compound that inactivates a variety of pathogens, a specific method comprising the addition of a photosensitizer that, when activated by illumination using appropriate wavelength light, will inactivate a variety of pathogens that may be present. Two commercially available methods involve adding amotosalen or riboflavin to platelets followed by UV light illumination. Other methods include lighting with other photoactive compounds, including non-amotosalen derivatives of psoralen, non-riboflavin isoalloxazins, alloxazins, dyes such as phthalocyanines, phenothiazine dyes (e.g., methylene blue, azure B, azure C, thionine, toluidine blue) , porphyrin derivatives (e.g. dihematoporphyrin ester, hematoporphyrin derivatives, benzoporphyrin derivatives, alkyl-substituted sapphirine) and merocyanine 540 (Prodouz et al. Blood Cells 1992, 18(1): 101-14; Sofer, Gail, BioPharm, August 2002). In some embodiments, the pathogen inactivating compound provides for photoactive pathogen inactivation. In some embodiments, the pathogen inactivating compound (PIC) is psoralen. In some embodiments, the pathogen inactivating compound (PIC) is amotosalen. In some embodiments, the pathogen inactivating compound (PIC) is selected from the group consisting of isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, merocyanine 540, and salts or free bases thereof.

Platelet Supplemental Solution (PAS)

Additional platelet solutions are known in the art, for example, as described in Alhumaidan et al. and Ringwald et al. (Alhumaidan, H. and Sweeney, J. J. Clin. Apheresis, 27: 93-98 (2012); Ringwald et al., Transfusion Medicine Reviews, 20: 158-64 (2006)), which are incorporated herein by reference in their entirety. In some embodiments of any of the methods, kits, and compositions provided herein, the platelet supplemental solution (PAS) contains one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate. In some embodiments of any of the methods, kits, and compositions provided herein, the platelet supplemental solution (PAS) is a PAS approved by a regulatory body or accrediting body generally accepted in the art.

In some embodiments of any of the methods, kits, and compositions provided herein, the platelet supplemental solution (PAS) contains one or more of sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, sodium phosphate, sodium gluconate, glucose and sodium bicarbonate.

In some embodiments, the PAS contains chloride, citrate, phosphate, and potassium. In some embodiments, the implementation of the PAS contains chloride, citrate and acetate. In some embodiments, the PAS contains chloride, citrate, phosphate, and acetate. In some embodiments, the PAS contains chloride, citrate, acetate, magnesium, potassium, and gluconate. In some embodiments, the PAS contains chloride, citrate, phosphate, acetate, magnesium, and potassium. In some embodiments, the PAS contains chloride, acetate, magnesium, potassium, and gluconate. In some embodiments, the PAS contains chloride, citrate, phosphate, acetate, magnesium, potassium, and glucose.

In some embodiments, the PAS contains sodium chloride, sodium acetate, potassium chloride, magnesium chloride, and sodium gluconate. In some embodiments, the PAS contains sodium chloride, sodium acetate, and sodium citrate. In some embodiments, the implementation of the PAS contains sodium chloride, sodium acetate, sodium citrate and sodium phosphate. In some embodiments, the PAS contains sodium chloride, sodium citrate, sodium phosphate, and potassium chloride. In some embodiments, the PAS contains sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, and sodium phosphate. In some embodiments, the PAS contains sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, and sodium gluconate. In some embodiments, the PAS contains sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, sodium phosphate, glucose, and sodium bicarbonate. In some embodiments, the PAS contains sodium chloride, sodium acetate, sodium citrate, potassium chloride, magnesium chloride, glucose, and sodium bicarbonate.

In some embodiments, the PAS is PAS-I. In some embodiments, the PAS is a PlasmaLyte. In some embodiments, the PAS is Pas-II. In some embodiments, PAS is T-Sol. In some embodiments, the PAS is PAS-III. In some embodiments, the PAS is Intersol. In some embodiments, the PAS is PASIIIM SSP. In some embodiments, the PAS is ComposolPAS-G. In some embodiments, PAS is M-Sol. In some embodiments, the PAS is an Isoplate. In some embodiments, the PAS is PAS-A. In some embodiments, the PAS is PAS-B. In some embodiments, the PAS is PAS-C. In some embodiments, the PAS is PAS-D. In some embodiments, the PAS is PAS-E. In some embodiments, the PAS is PAS-F. In some embodiments, the PAS is PAS-G.

PAS and PIC solution

Typically, the solution containing PAS and PIC may be of any volume sufficient for use in any of the methods, kits, and compositions described herein. In some embodiments of any of the methods, kits, and compositions described herein, the solution containing PAS and PIC has a volume between about 100 ml and about 1000 ml. In some embodiments, the solution containing PAS and PIC has a volume between about 200 ml and about 900 ml, between about 300 ml and about 800 ml, between about 400 ml and about 700 ml, or between about 500 ml and about 600 ml. In some embodiments, the solution containing PAS and PIC has a volume of about 100 ml, about 200 ml, about 300 ml, about 400 ml, about 500 ml, about 600 ml, about 700 ml, about 800 ml, about 900 ml, or about 1000 ml. In some embodiments, the solution containing PAS and PIC has a volume of less than about 1000 ml, less than about 800 ml, less than about 600 ml, less than about 500 ml, less than about 400 ml, less than about 300 ml, or less than about 200 ml. In some embodiments, the solution containing PAS and PIC has a volume of greater than about 800 ml, greater than about 700 ml, greater than about 600 ml, greater than about 500 ml, greater than about 400 ml, greater than about 300 ml, more than about 200 ml or more than about 100 ml. In some embodiments, the solution containing PAS and PIC has a volume between about 1000 ml and about 5000 ml.

Generally, the concentration of PIC in a solution containing PAS and PIC may be any suitable concentration of PIC that provides the final desired concentration of PIC when the solution containing PAS and PIC is mixed with a platelet preparation for use in any of the methods, kits, and compositions described. in this document, such as, for example, considering the volumes to be combined when mixing a solution containing PAS and PIC and a platelet preparation. In some embodiments, the concentration of PIC in the solution containing PAS and PIC is from about 25 µM to about 1200 µM, from about 50 µM to about 1000 µM, from about 50 µM to about 750 µM, from about 50 µM to about 500 µM , from about 75 µM to about 500 µM, from about 100 µM to about 400 µM, from about 150 µM to about 350 µM, from about 200 µM to about 300 µM, or from about 225 µM to about 250 µM. In some embodiments, the concentration of PIC in the solution containing PAS and PIC is about 25 µM, about 50 µM, about 75 µM, about 100 µM, about 125 µM, about 150 µM, about 175 µM, about 200 µM, about 250 µM approximately 275 μM, approximately 300 μM, approximately 325 μM, approximately 350 μM, approximately 375 μM, approximately 400 μM, approximately 450 μM, approximately 500 μM, approximately 550 μM, approximately 600 μM, approximately 650 μM, approximately 700 μM, approximately 750 µM, about 800 µM, about 850 µM, about 900 µM, about 1000 µM, about 1100 µM, about 1200 µM, about 1300 µM, about 1400 µM, or about 1500 µM. In some embodiments, the concentration of PIC in a solution containing PAS and PIC is from about 225 μM to about 235 μM. In some embodiments, the concentration of PIC in a solution containing PAS and PIC is about 225 µM, about 226 µM, about 227 µM, about 228 µM, about 229 µM, about 230 µM, about 231 µM, about 232 µM, about 233 µM , approximately 234 μM or approximately 235 μM.

In some embodiments, a solution containing PAS and PIC is obtained by combining a solution of PAS and a solution of PIC to form a solution containing PAS and PIC. In some embodiments, the method includes, prior to step (a), combining the PAS solution and the PIC solution to form a solution containing PAS and PIC. In some embodiments, the PAS solution is taken from a PAS container (eg, a PAS storage container). In some embodiments,

- 19 042974 The PIC solution is taken from the PIC container (eg PIC storage container). In some embodiments, the PAS solution and the PIC solution are combined in less than (e.g., within) about 6 months, less than about 4 months, less than about 3 months, less than about 2 months, less than about 1 month. less than about 3 weeks, less than about 2 weeks, less than about 1 week, less than about 5 days, less than about 4 days, less than about 3 days, less than about 48 hours, less than about 36 hours, less than about 24 hours, less than about 18 hours, less than about 12 hours, less than about 8 hours, less than about 6 hours, less than about 4 hours, less than about 2 hours or less than about 1 hour before mixing the solution containing PAS and PIC with the platelet preparation. In some embodiments, the PAS solution and the PIC solution are combined from about 5 minutes to about 72 hours, from about 5 minutes to about 48 hours, from about 5 minutes to about 36 hours, from about 5 minutes to about 24 hours, from about 5 minutes to about 18 hours, from about 5 minutes to about 12 hours, from about 5 minutes to about 8 hours, from about 5 minutes to about 6 hours, from about 5 minutes to about 4 hours, from about 5 minutes to about 2 hours or from about 5 minutes to about 1 hour before mixing the solution containing PAS and PIC with the platelet preparation.

Mixture of PAS, PIC and platelet preparation

In some embodiments of any of the methods, kits, and compositions described herein, the volume of the mixture of PAS, PIC, and platelet preparation is from about 100 ml to about 1000 ml. In some embodiments, the volume of the mixture of PAS, PIC, and platelet preparation is from about 200 ml to about 800 ml, from about 200 ml to about 775 ml, from about 250 ml to about 775 ml, from about 225 ml to about 525 ml, from about 500 ml to about 775 ml, from about 200 ml to about 300 ml, from about 300 ml to about 400 ml, from about 400 ml to about 500 ml, from about 500 ml to about 600 ml, from about 600 ml to about 700 ml or from about 700 ml to about 800 ml. In some embodiments, the volume of the mixture of PAS, PIC, and platelet preparation is about 255 ml, 510 ml, or about 765 ml. In some embodiments, the mixture of PAS, PIC, and platelet preparation, wherein the platelet preparation contains plasma, has a PAS to plasma ratio of approximately 65:35.

In some embodiments, the total volume of the mixture of PAS, PIC, and platelet preparation, wherein the platelet preparation contains plasma, contains plasma from about 32% to about 47% by volume. In some embodiments, the total volume of the mixture of PAS, PIC, and platelet preparation, wherein the platelet preparation contains plasma, contains PAS from about 53% to about 63% by volume. In some embodiments, the plasma contains approximately 32-47% by volume of a mixture of PAS, PIC, and platelet preparation, with the platelet supplement solution (e.g., platelet supplement with PIC) containing the remainder (i.e., 53-68% PAS, with % plasma + % PAS=100). Plasma volume may also include, for example, any volume that is not PAS (eg, PAS with PIC), such as, for example, any volume associated with platelets and/or any volume associated with the anticoagulant used during treatment. In some embodiments, the platelet preparation contains plasma about 32%, about 33%, about 34%, about 35%, about 36%, about 37%, about 38%, about 39%, about 40%, about 41%, about 42 %, approximately 43%, approximately 44%, approximately 45%, approximately 46% or approximately 47% by volume of the mixture of PAS, PIC and platelet preparation. In some embodiments, the ratio of PAS to plasma by volume in the mixture of PAS, PIC, and platelet preparation is about 68:32, about 67:33, about 66:34, about 65:35, about 64:36, about 63:37, about 62:38, approximately 61:39, approximately 60:40, approximately 59:41, approximately 58:42, approximately 57:43, approximately 56:44, approximately 55:45, approximately 54:46, or approximately 53:47.

Inactivation of pathogenic microorganisms

In some embodiments of any of the methods, kits, and compositions described herein, the mixture of PAS, PIC, and platelet preparation contains PIC at a concentration sufficient to result in at least about 1 order of magnitude inactivation of the pathogen, if present. In some embodiments, the mixture of PAS, PIC, and platelet preparation contains PIC at a concentration sufficient to inactivate the pathogen by at least about 1 order of magnitude, if present, after exposing the mixture to light, sufficient to photochemically inactivate the pathogen. In some embodiments, the PIC concentration is sufficient to inactivate the pathogen when present by at least about 1 order of magnitude, at least about

- 20 042974 positively 2 orders of magnitude, at least about 3 orders of magnitude, at least about 4 orders of magnitude, at least about 5 orders of magnitude, at least about 6 orders of magnitude, or at least about 7 orders of magnitude, at least at least about 8 orders of magnitude, at least about 9 orders of magnitude, or at least about 10 orders of magnitude (eg, after exposing the mixture to light sufficient to photochemically inactivate the pathogen).

In some embodiments of any of the methods, kits, and compositions described herein, the mixture of PAS, PIC, and platelet preparation contains PIC at a concentration of from about 5 μM to about 500 μM. In some embodiments, the mixture contains PIC at a concentration of less than about 150 μM. In some embodiments, the mixture contains PIC at a concentration of from about 15 µM to about 400 µM, from about 25 µM to about 300 µM, from about 50 µM to about 250 µM, from about 75 µM to about 225 µM, from about 100 µM to about 200 µM, about 125 µM to about 175 µM, about 25 µM to about 250 µM, about 25 µM to about 200 µM, about 25 µM to about 150 µM, from about 25 µM to about 100 µM, from about 25 µM to about 50 µM, about 25 µM to about 35 µM, about 30 µM to about 150 µM, about 30 µM to about 90 µM, about 50 µM to about 150 µM, about 50 µM to about 100 µM, about 50 µM to about 75 µM, about 75 µM to about 150 µM, about 75 µM to about 100 µM, about 10 µM to about 400 µM, about 10 µM to about 250 µM, from about 10 µM to about 200 µM, about 10 µM to about 150 µM, about 10 µM to about 100 µM, about 10 µM to about 50 µM, about 10 µM to about 25 µM, about 15 µM to about 250 µM, about 15 µM to about 200 µM, about 15 µM to about 150 µM, about 15 µM to about 90 µM, about 15 µM to about 50 µM, about 15 µM to about 30 µM, or about 15 µM to about 25 µM. In some embodiments, the mixture contains PIC at a concentration of from about 145 µM to about 155 µM. In some embodiments, the mixture contains PIC at a concentration of about 145 µM, about 146 µM, about 147 µM, about 148 µM, about 149 µM, about 150 µM, about 151 µM, about 152 µM, about 153 µM, about 154 µM, or about 155 µM. In some embodiments, the mixture contains PIC at a concentration of about 10 µM, about 15 µM, about 20 µM, about 25 µM, about 30 µM, about 35 µM, about 40 µM, about 45 µM, about 50 µM, about 55 µM, about 60 µM, about 65 µM, about 70 µM, about 75 µM, about 80 µM, about 85 µM, about 90 µM, about 95 µM, about 100 µM, about 110 µM, about 120 µM, about 130 µM, or about 140 µM .

In some embodiments of any of the methods, kits, and compositions provided herein, the mixture of PAS, PIC, and platelet preparation, the platelet preparation contains from about 2.0x1011 platelets to about 14.0x1011 platelets. In some embodiments, the mixture contains at least about 2.0x1011 platelets, at least about 3.0x1011 platelets, at least about 4.0x1011 platelets, at least about 5.0x1011 platelets, at least about 6.0x1011 platelets , at least about 7.0x1011 platelets, at least about 8.0x1011 platelets, at least about 9.0x1011 platelets, at least about 10.0x1011 platelets, at least about 11.0x1011 platelets, or at least about 12.0x1011 platelets. In some embodiments, the platelet preparation contains at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about 2.5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 platelets.

In some embodiments, the method for preparing the platelet composition further comprises incubating the mixture of PAS, PIC, and platelet preparation for a period of from about 30 minutes to about 24 hours, wherein the incubation is performed before exposing the mixture to light sufficient to photochemically inactivate the pathogen, if present. Incubation before exposing the mixture to light may be referred to as pre-incubation. In some variants

- 21 042974 the incubation of the mixture of PAS, PIC and platelet preparation before exposing the mixture to light sufficient to photochemically inactivate the pathogen, if present, is carried out for a period of less than about 24 hours, less than about 22 hours, less than about 20 hours, less than about 18 hours, less than about 16 hours, less than about 14 hours, less than about 12 hours, less than about 10 hours, less than about 8 hours, less than about 6 hours, less than about 5 hours, less than about 4 hours, less than about 3 hours, less than about 2 hours, or less than about 1 hour. spend over a period of more than about 22 hours, more than about 20 hours, more than about 18 hours, more than about 16 hours, more than about 14 hours, more than about 12 hours, more than about 10 hours, more than about 8 more than about 6 hours, more than about 5 hours, more than about 4 hours, more than about 3 hours, more than about 2 hours, more than about 1 hour, or more than about 30 minutes. In some embodiments, the incubation of the mixture of PAS, PIC, and platelet preparation prior to exposing the mixture to light sufficient to photochemically inactivate the pathogen, if present, is for a period of about 2 hours, about 4 hours, about 6 hours, about 8 hours, about 10 h, approximately 12 h, approximately 14 h, approximately 16 h, approximately 18 h, approximately 20 h, approximately 22 h, or approximately 24 h. exposing the mixture to light sufficient to photochemically inactivate the pathogen may result in improved pathogen inactivation. In some embodiments, such pre-incubation may result in an increase in the degree of inactivation of a pathogen present in a platelet preparation compared to the degree of inactivation of that pathogen (i.e., the same pathogen) resulting from the same method for producing a platelet composition. but without the pre-incubation step. An increase in the degree of pathogen inactivation may be an increase in pathogen inactivation by at least 1 order, at least 2 orders, at least 3 orders, at least 4 orders, at least 5 orders, at least 6 orders of magnitude, at least 7 orders of magnitude, at least 8 orders of magnitude, at least 9 orders of magnitude, or at least 10 orders of magnitude. In some embodiments, the pre-incubation may result in an increase in the number of pathogens that can be inactivated in the presence of platelets in the preparation (for example, by at least 1, 2, 3, 4, or 5 orders of magnitude) compared to the number of pathogens that can be inactivated. in the presence of platelets in the preparation as a result of the same method for obtaining the platelet composition, but without the pre-incubation step. In some embodiments, improvement in the inactivation of the pathogens described herein is demonstrated against one or more bacteria or viruses (eg, enveloped virus, non-enveloped virus) or parasites.

In some embodiments of any of the methods, kits, and compositions described herein, the wavelength of light to which the mixture of PAS, PIC, and platelet preparation is exposed is between about 200 nm and about 400 nm. In some embodiments, the wavelength of the light is within the ultraviolet A spectrum (eg, approximately 315-400 nm). In some embodiments, the light duration is between about 1 second and about 30 minutes. In some embodiments, the light intensity is between about 1 and about 30 mW/cm ² . In some embodiments, the light dose is between about 1 J/cm ² and about 20 J/cm ² .

In some embodiments of any of the methods described herein, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude, and the platelet composition after exposing the mixture of platelet preparation and solution containing PAS and PIC to light (e.g., the mixture of step (b)) is suitable for infusion into a subject without further treatment to remove residual PIC or its photoproducts. In some embodiments, the method is sufficient to inactivate the pathogen by at least 2 orders of magnitude, at least 3 orders of magnitude, or at least 4 orders of magnitude or more, and the platelet composition after exposing the mixture of platelet preparation and solution containing PAS and PIC (eg, the mixture of step (b)), is suitable for infusion into the subject without further processing to remove residual PIC or its photoproducts. In some embodiments, a platelet composition suitable for infusion into a subject contains about 5 µM or less, about 4 µM or less, about 3 µM or less, about 2 µM or less, about 1 µM or less, or about 0.5 µM or less pic. In some embodiments, a platelet composition suitable for infusion into a subject contains less than about

5 µM, less than about 4 µM, less than about 3 µM, less than about 2 µM, less than about 1 µM, or less than about 0.5 µM or less PIC. In some embodiments of any of the methods described herein, the method is sufficient to inactivate the pathogen by at least 1 order of magnitude, and the platelet composition after step (c) (e.g., after exposing the mixture of platelet preparation and PAS solution to light) and PIC) contains approximately 5 μM or less of PIC. In some embodiments, the method is sufficient to inactivate the pathogen by at least 2 orders of magnitude, at least 3 orders of magnitude, or at least 4 orders of magnitude or more, and the platelet composition after step (c) (e.g., after exposing the mixture to light a platelet preparation and a solution containing PAS and PIC) contains about 4 µM or less, about 3 µM or less, about 2 µM or less, about 1 µM or less, or about 0.5 µM or less PIC. In some embodiments, the platelet composition after step (c) (for example, after exposing the mixture of platelet preparation and solution containing PAS and PIC to light) contains less than 5 μM, less than 4 μM, less than 3 μM, less than 2 μM, less than 1 μM or less than 0.5 μM PIC. For example, in some embodiments, the method is sufficient to inactivate the pathogen by at least 4 orders of magnitude, and the platelet composition after step (c) (for example, after exposing the mixture of platelet preparation and solution containing PAS and PIC to light) contains approximately 4 μM or less, about 3 µM or less, about 2 µM or less, about 1 µM or less, or about 0.5 µM or less (e.g., less than 5 µM, less than 4 µM, less than 3 µM, less than 2 µM , less than 1 μM, less than 0.5 μM) PIC. In some embodiments, the concentration of PIC in the mixture of step (b) is at least 10 μM, at least 15 μM, at least 20 μM, at least 25 μM, at least 30 μM, at least 40 μM, according to at least 50 µM, at least 60 µM, at least 70 µM, at least 80 µM, at least 90 µM, at least 100 µM, at least 110 µM, at least 120 µM, at least 130 μM, at least 140 μM, or at least 150 μM.

In some embodiments, a method for preparing a platelet composition comprises incubating a mixture of a platelet preparation and a solution containing PAS and PIC for a period of about 30 minutes to about 24 hours prior to exposing the mixture to light, wherein: (a) the method is sufficient to inactivate the pathogen a microorganism, if present, at least 1 order of magnitude, at least 2 orders of magnitude, at least 3 orders of magnitude, at least 4 orders of magnitude, or at least 5 orders of magnitude or more; (b) the concentration of PIC in the mixture of PAS, PIC and platelet preparation is from about 15 μM to about 150 μM and (c) the composition of platelets after light exposure of the mixture of platelet preparation and solution containing PAS and PIC contains less than 5 μM, than 4 μM, less than 3 μM, less than 2 μM, less than 1 μM, or less than 0.5 μM PIC.

Platelet quality

The invention also provides platelet compositions with improved platelet quality suitable for infusion (eg, infusion into a human subject after inactivation of pathogens), wherein the platelet compositions are prepared by any of the methods disclosed herein. For example, platelet compositions prepared by any of the methods disclosed herein retain the preferred characteristics (in particular, suitable pH, but also including and without limitation any of dissolved oxygen, carbon dioxide, glucose, lactate, ATP, LDH, p- selectin (eg, CD62P), cell morphology (eg, morphology scores), degree of reshaping or ESC and hypotonic shock response or HSR) for a longer duration and/or at a level closer to untreated (eg, with non-inactivated pathogens). microorganisms) to platelet compositions during storage after exposure to pathogen inactivation (eg, as described herein) than existing methods and processing kits provide. Such characteristics of platelet compositions may be those known in the art and are usually measured, for example, using assays known in the art.

In some embodiments, platelet compositions prepared by any of the methods disclosed herein maintain a pH, even after exposure to pathogen inactivation and storage (e.g., up to 7 days), closer to the pH of untreated (e.g., pathogen-inactivated). microorganisms) a platelet composition or a platelet composition that has not been stored after pathogen inactivation. In some embodiments, the pH of a platelet composition prepared by any of the methods disclosed herein is >6.2, wherein the platelet composition is stored after platelet inactivation at room temperature for at least about 1 day, e.g., for at least approximately any of 2, 3, 4, 5, 6 and 7 days. In some embodiments, the pH of a platelet composition prepared by any of the methods disclosed herein is >6.4 when

In this case, the platelet composition was stored after platelet inactivation at room temperature for at least about 1 day, for example, for at least about any of 2, 3, 4, 5, 6, and 7 days.

Platelet Units

The invention also provides a composition of platelets suitable for infusion (eg, infusion into a human subject), for example, a composition of platelets obtained by any of the methods disclosed herein, containing a minimum number of platelets.

In some embodiments of any of the methods, kits, and compositions provided herein, the platelet composition comprises at least about 2.0x1011 platelets, at least about 3.0x1011 platelets, at least about 4.0x1011 platelets, at least about 5.0x1011 platelets, at least about 6.0x1011 platelets, at least about 7.0x1011 platelets, at least about 8.0x1011 platelets, at least about 9.0x1011 platelets, at least about 10.0x1011 platelets , at least about 11.0x1011 platelets, or at least about 12.0x1011 platelets. In some embodiments, the platelet composition comprises at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011 platelets, at least about 2.5x1011 platelets, at least about 2.6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 platelets.

In some embodiments, the platelet composition comprises a therapeutic dose (eg, a therapeutic dose unit) of platelets suitable for infusion into a human subject (eg, a subject in need of platelet infusion). In some embodiments, the therapeutic dose contains a minimum number (e.g., at least a minimum number) of platelets, which is determined by the criteria (e.g., acceptance criteria) of a government agency, regulatory body, institution, and/or accrediting organization (e.g., government agency, regulatory body, institution and/or accrediting organization for donated blood products (e.g. donated platelets)). In some embodiments, the regulatory agency is the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), the Australian Medical Devices Administration (TGA), the China Food and Drug Administration (CFDA). ) or the Department of Health, Labor and Welfare (MHLW). In some embodiments, the accrediting organization is AABB or the European Authority for the Quality of Medicines and Health Care (EDQM). In some embodiments, the platelet composition is produced in the country of a government agency, regulatory body, institution, and/or accrediting organization that defines criteria for a therapeutic dose of platelets. In some embodiments, a platelet therapeutic dose unit contains at least about 2.0x1011 platelets, at least about 2.2x1011 platelets, at least about 2.4x1011, at least about 2.5x1011 platelets, at least about 2, 6x1011 platelets, at least about 2.7x1011 platelets, at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 platelets. In some embodiments, the platelet therapeutic dose unit contains at least about 2.4x1011 platelets. In some embodiments, a platelet therapeutic dose unit contains at least about 2.6 x 1011 platelets. In some embodiments, a platelet therapeutic dose unit contains at least about 3.0 x 1011 platelets.

In some embodiments, the platelet composition comprises platelets from a plurality of platelet compositions or platelet preparations. In some embodiments, the platelet composition comprises pooled apheresis-derived platelets from two or more donors, and wherein the pooled apheresis-derived platelets are processed by any of the methods disclosed herein. In some embodiments, the platelet composition comprises pooled whole blood-derived platelets (e.g., buffy coat platelets, PRP platelets) from two or more donors, and wherein the pooled whole-blood-derived platelets are processed by any of the methods disclosed herein. In some embodiments, a plurality of platelet compositions or platelet preparations are processed according to the methods disclosed herein prior to pooling. In some embodiments, a plurality of platelet compositions or platelet preparations are processed according to the methods disclosed herein after pooling. IN

- 24 042974 In some embodiments, the platelet composition contains platelets from donors with the same ABO blood type. In some embodiments, the platelet composition contains platelets of the same ABO and Rh type.

Storage

In some embodiments of any of the methods, kits, and compositions described herein, the platelet composition can be stored for at least 1, at least 2, at least 3, at least 4, at least 5, at least at least 6 or at least 7 days, eg on a plate mixer (eg 60 cycles per minute, model LPR-3, Melco, Glendale, CA, USA) in a temperature controlled room, eg at 22±2°C. In some embodiments, the platelet composition can be stored for up to 5, up to 6, or up to 7 days, e.g., on a plate mixer (e.g., 60 cycles per minute, model LPR-3, Melco, Glendale, CA, USA) in a controlled storage room. temperature, for example, at 22±2°C.

Platelet processing

Processing of platelets as described in this disclosure may involve the use of a blood product container or blood product bag systems, which are well known in the art. In general, such systems may comprise more than one plastic container, typically plastic bags, the bags being integrally connected with plastic tubes. Some of the containers described herein include those plastic bags known for the storage and handling of blood products, including platelet products. Blood bags can typically be configured to contain various volumes of fluid including, but not limited to, volumes ranging from 50 ml to 2 L, e.g. capacity up to 1.5 l or capacity up to 2 l. It will be understood that when the method refers to a bag, it includes any such plastic bags used for handling blood products. When such bags are referred to as a pooling bag, a mixing bag, a disposal bag, a product bag, a storage bag, or a lighting bag, it is understood that these bags are or are similar in nature to conventional blood handling bags. . Suitable plastic bags for use in accordance with the present disclosure include, for example, bags containing PL2410, as well as other suitable plastics known in the art. Plastic bag materials include polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate mixed with other plastics, and the like.

Within the scope of the present invention, when the tube is described as connecting, for example, two packages, for example for pooling, and/or a set for processing, it should be understood that the tube can be connected at some point between them using another component of the connection between the two packages. For example, a disposal bag connected to a product bag by a tubing includes a configuration where the tubing contains a filter between the two bags, i.e. the tube is separated by a filter such that fluid flows from one bag to another through the tube and the filter. In one example, the tubing connecting the disposal bag and the product bag may include a filter to remove any particulate matter from the fluid flowing from the disposal device into the product bag, i. tubing split or interrupted by filter between packets. Such filters are designed to remove any small particles that may exit the removal device while allowing platelets to pass through the filter. The tubing between the bags allows fluid to flow from one bag to another, which can be blocked to prevent leakage until needed, for example, as part of the processing, fluid can be prevented from flowing from one bag into the next bag until needed for the next step in progress. In this regard, the tube connecting the packages or on it contains an openable closure, such as a clip, plug, valve, and the like, and the clip, plug, valve, and the like, if necessary, can be selectively opened, for example, to transfer fluid from one package. Next. In some embodiments, the tubing between the packets includes a breakable closure, such as a breakable valve, wherein breaking the breakable seal allows the blood product solution to flow between the packets through the tube. It is understood that the breakable closure is within the connection between the containers so that the sterility of the system is maintained. It is also understood that there is a tube containing a filter or a breakable closure, and the tube can be interrupted by a filter or closure, for example, the tube extends from one package and is connected to the filter or closure (the inlet part of the tube), and the tube continues from another part of the filter or closure to another package (outlet tube). In this configuration, fluid flows from the first bag, through the inlet of the tube, through the filter or closure, and through the outlet of the tube, and into the other bag.

Different containers (eg, bags) within a blood product handling system can be used for different steps in the process. For example, the pouch system to be used for pathogen inactivation of a platelet preparation may comprise one or more containers with a pathogen inactivating compound (PIC) contained within,

- 25 042974 container with platelet supplement solution (PAS) contained inside, container with PIC and PAS contained inside, container for obtaining a platelet preparation (for example, donated blood with platelets) and PIC and PAS (for example, a bag for lighting), a bag to remove compounds to inactivate pathogens and/or their by-products from a processed unit of platelets (e.g., called a disposal bag, a compound adsorption device, CAD) and one or more bags to contain the final composition of platelets, for example, a unit of platelets with inactivated pathogens (e.g., units of therapeutic dose) that has a concentration of the inactivating compound and/or their by-products reduced below the desired concentration that is ready for use, or can be stored for later use (e.g., called product bag, storage bag) . Each bag in the system is usually made from a plastic material. For example, the container for containing the solution of the pathogen inactivating compound can be made from a suitable plastic such as PL2411 (Baxter Healthcare) or other plastic such as polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate mixed with other plastics, and the like. This container is also wrapped in a material that is transparent to light at a wavelength that will activate a photoactive pathogen inactivating compound (eg, a suitable plastic such as PL2420, Baxter Healthcare). The illumination package for the photoactivated pathogen inactivating compound requires a transparent, strong thermoplastic material that is translucent to light of a selected wavelength. Suitable plastics that are translucent to UVA light include polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate blended with other plastics, or other mixtures of thermoplastic polymers. Such suitable plastics include PL2410 (Baxter Healthcare) and PL732 (Baxter Healthcare). Similar materials can be used to obtain an uninstall package and a product package. Product packages include, for example, packages derived from PL2410. Suitable bag materials are discussed, for example, in PCT Publication Number WO 2003078023, and US Pat. No. 7,025,877, the disclosures of which are incorporated herein by reference as they pertain to such bag materials and related materials. In all cases, the materials used in the preparation of the processing kit should be sterilized using known methods, such as steam and gamma or electron beam radiation used to ensure the sterility of the processing kit. While these are illustrative materials for making pouches, the methods, kits, and compositions described herein are applicable to processes using any suitable pouches material that will be readily available to one of skill in the art and can also be used with non-pouch containers. The bags used for illumination, removal and storage are also configured to allow gases such as oxygen and carbon dioxide to pass into and out of the blood bag so that the platelets therein have adequate levels of oxygen and carbon dioxide supply during processing and storage.

Certain aspects of this disclosure relate to processing kits. The processing kits of the present disclosure may find use, inter alia, in preparing a variety of platelet compositions (eg, platelet units) suitable for infusion, eg, as described herein. Any of the exemplary components such as the bags and tubes described above may find use in processing kits according to the present disclosure.

Inactivation of pathogenic microorganisms

Blood products, including blood products containing platelets, may contain pathogens or may be contaminated with pathogens during processing. Therefore, it is necessary to subject such blood products to a process of pathogen inactivation in order to reduce the risk of transfusion-transmitted diseases. Various processes and methods for reducing the risk associated with transfusion transmission of disease in platelet-containing blood products were evaluated. In addition to pathogen screening and detection and subsequent disposal of contaminated blood products, processes are available that include pathogen inactivation treatments (ie, pathogen inactivation) that may be present. Ideally, such a process results in the inactivation of a wide range of pathogens such as viruses, bacteria and parasites that may be present in the blood product. In some embodiments, methods for inactivating pathogens require adding an amount of a pathogen inactivating compound to a platelet preparation (eg, when processing a platelet preparation). For example, pathogen inactivation may involve the addition of a small molecule compound that inactivates a variety of pathogens, a specific method comprising the addition of a photosensitizer that, when activated by illumination using appropriate wavelength light, will inactivate a variety of pathogens that may be present. Two commercially available methods include adding amotosalen or riboflavin to platelets with

- 26 042974 subsequent illumination with UV light. Other methods include illumination with UV light without the addition of a photosensitizer, as well as illumination with other photoactive compounds, including psoralen derivatives other than amotosalen, isoalloxazins other than riboflavin, alloxazins, dyes such as phthalocyanines, phenothiazine dyes (eg, methylene blue, azure B , azure C, thionine, toluidine blue), porphyrin derivatives (e.g. dihematoporphyrin ester, hematoporphyrin derivatives, benzoporphyrin derivatives, alkyl-substituted sapphirine) and merocyanine 540 (Prodouz et al. Blood cells 1992, 18(1): 101-14; Sofer, Gail, BioPharm, August 2002). Other pathogen inactivation systems include, for example, those described in PCT publication number WO 2012071135; W02012018484; W02003090794; W02003049784; WO 1998018908; WO 1998030327; WO 1996008965; WO 1996039815; WO 1996039820; WO 1996040857; WO 1993000005; US patent application number US 20050202395; and US Pat. Nos. 8,296,071 and 6,548,242, the disclosures of which are incorporated herein by reference as they relate to the inactivation of pathogens in blood products. In some embodiments, the pathogen inactivating compound is a photoactive pathogen inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazin, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen inactivating compound is psoralen. In some embodiments, the pathogen-inactivating compound is amotosalen. When the addition of a compound to platelets is used to inactivate pathogens, whether the method requires illumination or not, in some cases it is necessary to remove any residual pathogen inactivating compound or its by-product (eg, photoproduct).

Methods for inactivating pathogens and removing a pathogen inactivating compound of the present invention are applicable to any platelet preparation, whether platelet preparations contain single portions of donor platelets (e.g., collected by platelet apheresis) or pooled platelet preparations.

Some pathogen inactivation methods disclosed herein may not require the use of a removal device (i.e., a device for reducing the concentration of a pathogen-inactivating compound, such as a small organic compound, and their by-products in a platelet preparation) while maintaining the same time is essentially the required biological activity of platelets.

Some pathogen inactivation methods may require the use of a removal device (i.e., a device for reducing the concentration of a pathogen-inactivating compound, such as a small organic compound, and their by-products in a platelet preparation) while maintaining substantially the necessary biological platelet activity. In some embodiments, the removal device is referred to as a compound adsorption device (CAD) and may comprise a container (e.g., CAD container, CAD bag) containing one or more materials, such as, for example, adsorbent particles, and which is also suitable for containing a platelet preparation, in which the concentration of the pathogen-inactivating compound and its by-products should be reduced. Such a removal device is generally intended to be used in batch mode, i. e. the device is in contact with the platelets and continues to be in contact with the remover, eg, with shaking, allowing substantially complete contact of the platelet solution with the remover during contact, resulting in lower levels of the pathogen-inactivating compound. Such batch devices cause the use of adsorbent particles that bind the pathogen inactivating compound and which can be used either by adding the adsorbent particles directly to the platelet container (e.g. bag) after illumination, or by transferring the platelets to the bag containing the adsorbent particles after illumination, and then the platelets are shaken for a specified period of time, with the platelet preparations in contact with the removal device. While loose adsorbent particles can be used as the removal device, such particles can be contained within a mesh bag, such as a polyester or nylon mesh bag, which allows the platelet solution to be in contact with the adsorbent particles while the particles are inside the bag. Alternatively, the adsorbent particles may be immobilized within a matrix, wherein the immobilization matrix may be directly in the blood bag used for intermittent removal, or similarly may be contained within a mesh bag. In some cases, the disposal device contains porous adsorbent particles in an amount sufficient to reduce the pathogen inactivating compound below the desired concentration, while the adsorbent particles have an affinity for the pathogen inactivating compound, and it is understood that such adsorbent particles can be selected for the best adsorption of the subject to be removed. compounds or compounds with minimal effect on components that do not need to be removed or damaged by contact with adsorbent particles. A variety of adsorbent particles are known, including in general particles derived from any natural or synthetic material capable of interacting with the compounds to be removed, including solid particles derived from natural materials such as activated carbon, silica, diatomaceous earth and cellulose, and such synthetic materials. like hydrophobic resins, hydrophilic resins or ion exchange resins. Such synthetic resins include, for example, carbonaceous materials, polystyrene, polyacrylic, polyacrylic ether, cation exchange resin, and polystyrene-divinylbenzene. A detailed description of such removal devices suitable for use in the methods of the present invention can be found in PCT Publication Numbers WO 1996040857, WO 1998030327, WO 1999034914 and WO 2003078023, the disclosures of which are incorporated herein by reference in connection with a discussion of such removal devices and adsorbent particles and other materials used to make such devices. Exemplary absorbent particles include, but are not limited to, Amberlite (Rohm and Haas) XAD-2, XAD-4, XAD-7, XAD-16, XAD-18, XAD-1180, XAD-1600, XAD-2000, XAD-2010 ; Amberchrom (Toso Haas) CG-71m, CG-71c, CG-161m, CG161c; Diaion Sepabeads (Mitsubishi Chemicals) HP20, SP206, SP207, SP850, HP2MG, HP20SS, SP20MS; Dowex (Dow Chemical) XUS-40285, XUS-40323, XUS43493 (also called Optipore V493 (dry form) or Optipore L493 (hydrated form)), Optipore V503, Optipore SD-2; Hypersol Macronet (Purolite) MN-100 MN-102 MN-150 MN-152 MN-170 MN-200 MN-202 MN-250 MN-252 MN-270 MN-300 MN -400, MN-500, MN-502, Purosorb (Purolite) PAD 350, PAD 400, PAD 428, PAD 500, PAD 550, PAD 600, PAD 700, PAD 900 and PAD 950 Material used to form the matrix for immobilization , includes a low melting polymer such as nylon, polyester, polyethylene, polyamide, polyolefin, polyvinyl alcohol, ethylene vinyl acetate or polysulfone. In one example, the adsorbent particles immobilized in the matrix are in the form of a sintered material. While it is understood that the methods, kits, and compositions described herein may encompass removal devices known in the art, such methods and devices can be exemplified using a commercially available platelet preparation inactivating amotosalen removal device. Such a removal device comprises a Hypersol Macronet MN-200 adsorbent contained within a sintered matrix, the sintered matrix containing PL2410 plastic as a binder. In one case, the removal device contains in a sintered matrix an adsorbent Hypersol Macronet MN-200 containing PL2410, while Hypersol Macronet MN-200 is in an amount equivalent to a dry weight of about 5-50 g, about 5-10 g, about 10-15 g, about 15-20 g, about 20-25 g, about 25-30 g, about 30-35 g, about 35-40 g, about 40-45 g, or about 45-50 g.

Since different resins may require different processing when used to obtain a removal device useful in the methods, kits and compositions of the present invention, comparison of the amounts of adsorbent resins described herein, unless otherwise indicated, is a dry weight comparison of the resin. . For example, resins are dried to <5% water content before treatment, and the equivalent dry weight of the adsorbent is used to compare amounts of resin in use. For example, Hypersol Macronet MN-200 is treated to stabilize the adsorbent, or what is commonly referred to as wetting the adsorbent, so that it can be used directly in contact with a platelet unit. Such a wetted sample may contain, for example, about 50% glycerol or other suitable wetting agent. In some embodiments, the adsorbent resin is a polystyrene-divinylbenzene resin. In some embodiments, the polystyrene-divinylbenzene resin is Hypersol Macronet MN-200. In some embodiments, the implementation of the adsorbent is inside the sintered matrix, while the sintered matrix contains a binder PL2410. In some embodiments, Hypersol Macronet MN-200 adsorbent is within a sintered matrix to provide a removal device.

In some embodiments of any of the methods, kits, and compositions described herein, one or more components (e.g., container, CAD, PIC) can be obtained from a commercially available pathogen inactivation system, such as, for example, the INTERCEPT® Blood System (Cerus ), or he may be essentially like her. The INTERCEPT® Blood System is well known in the art as a pathogen inactivation system that has become widespread in European blood centers and has received FDA approval in the USA. For a more detailed description of the INTERCEPT® Blood System and related methods and compositions for inactivating pathogens, see, for example, US Pat. 2593, 6004741, 6004742, 6017691, 6194139, 6218100, 6503699, 6544727, 6951713, 7037642 and 7611831; and PCT publication number WO 1995000141, WO 1996014739, WO 1997 021346, WO 1998030327, WO 1999034914 and WO 1999034915, the disclosures of each of which are incorporated herein by reference , as they relate to the inactivation of pathogenic microorganisms in blood products.

- 28 042974

Platelet Composition Kits

The invention provides, in certain aspects, kits, such as processing kits, for preparing a platelet composition according to any of the methods disclosed herein.

In some embodiments, the kit is a disposable treatment kit.

In some embodiments, the kit comprises (a) a first container containing a solution containing a platelet supplement (PAS) and a pathogen inactivating compound (PIC), and (b) instructions for use in preparing the platelet composition.

The platelet composition preparation kits (e.g., pathogen inactivated platelet compositions) disclosed herein contain a solution containing a platelet additive solution (PAS) and a pathogen inactivating compound (PIC), wherein the solution containing PAS and PIC has sufficient volume to produce any number of platelet compositions (eg, a single or therapeutic dose of platelets). In some embodiments, the kit comprises two or more first containers, wherein each of the two or more first containers contains a different volume of solution containing a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC), and wherein one of the two or more the first containers can be selected for use based on the amount or volume of platelet compositions to be prepared. In some embodiments, the kit contains three first containers, with one first container containing a sufficient volume of a solution containing a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC) to produce one platelet composition (e.g., a single therapeutic dose of platelets), the other first container contains a sufficient volume of a solution containing a platelet additive solution (PAS) and a pathogen inactivating compound (PIC) to obtain two platelet compositions, and another first container contains a sufficient volume of a solution containing a platelet additive solution (PAS) and a pathogen inactivating compound. microorganisms compound (PIC), to obtain three compositions of platelets. When using this kit in any of the methods presented herein, one of the first three containers may be selected for use based on the number of platelet compositions to be prepared.

In some embodiments, the platelet composition preparation kit comprises: (a) a first container containing a solution containing a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC), and (b) a second container suitable for holding a platelet preparation in the mixture. with a solution containing PAS and PIC, while the first container is not connected to the second container. In some embodiments, the first container is suitable for mixing a platelet preparation with a solution containing PAS and PIC. In some embodiments, the first container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the first container is made from a material substantially translucent to light in the photochemical inactivation wavelength range (eg, about 200 nm to about 400 nm, ultraviolet A). In some embodiments, the second container contains a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the first container is configured to be integrally connected to the second container (eg, with a flexible plastic tube). In some embodiments, the implementation of the first container is made with the possibility of sterile connection with the second container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the first container to the second container. In some embodiments, the platelet composition kit further comprises at least one (e.g., 1, 2, or 3) storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one the storage container is connected to the second container. In some embodiments, at least one storage container is integrally connected to the second container (eg, with a flexible plastic tube). In some embodiments, at least one storage container is sealed but has a flow channel that opens into the second container. In some embodiments, at least one storage container is sterile connected to the second container. In some embodiments, the first container is suitable for connection to an apheresis device or to a container containing a platelet preparation.

In some embodiments, the platelet composition preparation kit comprises: (a) a first container containing a solution containing a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC), and (b) a second container suitable for holding a platelet preparation in the mixture. with a solution containing PAS and PIC, while the first container is not connected to the second container. In some embodiments, the first container is suitable for mixing a platelet preparation with a solution containing PAS and PIC. In some embodiments, the second container is suitable for mixing the platelet preparation with the solution containing PAS and PIC. In some embodiments, the second container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the second container is made from a material substantially translucent to light in the photochemical inactivation wavelength range (eg, about 200 nm to about 400 nm, ultraviolet A). In some embodiments, the second container contains a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the first container is configured to be integrally connected to the second container (eg, with a flexible plastic tube). In some embodiments, the implementation of the first container is made with the possibility of sterile connection with the second container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the first container to the second container. In some embodiments, the platelet composition kit further comprises at least one (e.g., 1, 2, or 3) storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one the storage container is connected to the second container. In some embodiments, at least one storage container is integrally connected to the second container (eg, with a flexible plastic tube). In some embodiments, at least one storage container is sealed but has a flow channel that opens into the second container. In some embodiments, at least one storage container is sterile connected to the second container. In some embodiments, the first container is suitable for connection to an apheresis device or to a container containing a platelet preparation.

In some embodiments, the platelet composition preparation kit comprises: (a) a first container containing a solution containing a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC), and (b) a second container suitable for holding a platelet preparation in the mixture. with a solution containing PAS and PIC, while the first container is not connected to the second container. In some embodiments, the first container is suitable for mixing a platelet preparation with a solution containing PAS and PIC. In some embodiments, the second container is suitable for mixing the platelet preparation with the solution containing PAS and PIC. In some embodiments, the second container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the second container is made from a material substantially translucent to light in the photochemical inactivation wavelength range (eg, about 200 nm to about 400 nm, ultraviolet A). In some embodiments, the first container is configured to be integrally connected to the second container (eg, with a flexible plastic tube). In some embodiments, the implementation of the first container is made with the possibility of sterile connection with the second container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the first container to the second container. In some embodiments, the platelet composition kit further comprises a third container, wherein the third container contains a compound adsorption device (CAD), and wherein the third container is connected to the second container. In some embodiments, the third container is integrally connected to the second container (eg, with a flexible plastic tube). In some embodiments, the third container is sealed but has a flow channel that opens into the second container. In some embodiments, the implementation of the third container is sterile connected with the second container. In some embodiments, the third container is suitable for storing the platelet composition. In some embodiments, the platelet composition kit further comprises at least one (e.g., 1, 2, or 3) storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one the storage container is connected to the third container. In some embodiments, at least one storage container is integrally connected to the third container (eg, with a flexible plastic tube). In some embodiments, at least one storage container is sealed but has a flow channel that opens into a third container. In some embodiments, at least one storage container is sterile connected to the third container. In some embodiments, the first container is suitable for connection to an apheresis device or to a container containing a platelet preparation.

- 30 042974

In some embodiments, the platelet composition preparation kit comprises: (a) a first container containing a solution containing a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC), and (b) a second container suitable for holding a platelet preparation in the mixture. with a solution containing PAS and PIC, while the first container is not connected to the second container. In some embodiments, the second container is suitable for mixing the platelet preparation with the solution containing PAS and PIC. In some embodiments, the second container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the second container is made from a material substantially translucent to light in the photochemical inactivation wavelength range (eg, about 200 nm to about 400 nm, ultraviolet A). In some embodiments, the second container contains a compound adsorption device (CAD). In some embodiments, the second container is suitable for storing the platelet composition. In some embodiments, the first container is configured to be integrally connected to the second container (eg, with a flexible plastic tube). In some embodiments, the implementation of the first container is made with the possibility of sterile connection with the second container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the first container to the second container. In some embodiments, the platelet composition kit further comprises at least one (e.g., 1, 2, or 3) storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one the storage container is connected to the second container. In some embodiments, at least one storage container is integrally connected to the second container (eg, with a flexible plastic tube). In some embodiments, at least one storage container is sealed but has a flow channel that opens into the second container. In some embodiments, at least one storage container is sterile connected to the second container. In some embodiments, the second container is suitable for connection to an apheresis device or to a container containing a platelet preparation.

In some embodiments, the platelet composition preparation kit comprises: (a) a first container containing a solution containing a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC), and (b) a second container suitable for holding a platelet preparation in the mixture. with a solution containing PAS and PIC, while the first container is not connected to the second container. In some embodiments, the second container is suitable for mixing the platelet preparation with the solution containing PAS and PIC. In some embodiments, the second container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the second container is made from a material substantially translucent to light in the photochemical inactivation wavelength range (eg, about 200 nm to about 400 nm, ultraviolet A). In some embodiments, the first container is configured to be integrally connected to the second container (eg, with a flexible plastic tube). In some embodiments, the implementation of the first container is made with the possibility of sterile connection with the second container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the first container to the second container. In some embodiments, the platelet composition kit further comprises a third container, wherein the third container contains a compound adsorption device (CAD), and wherein the third container is connected to the second container. In some embodiments, the third container is integrally connected to the second container (eg, with a flexible plastic tube). In some embodiments, the third container is sealed but has a flow channel that opens into the second container. In some embodiments, the implementation of the third container is sterile connected with the second container. In some embodiments, the third container is suitable for storing the platelet composition. In some embodiments, the platelet composition kit further comprises at least one (e.g., 1, 2, or 3) storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one the storage container is connected to the third container. In some embodiments, at least one storage container is integrally connected to the third container (eg, with a flexible plastic tube). In some embodiments, at least one storage container is sealed but has a flow channel that opens into a third container. In some embodiments, at least one storage container is sterile connected to the third container. In some embodiments, the second container is suitable for connection to an apheresis device or to a container containing a platelet preparation.

In some embodiments, the platelet formulation kit comprises (a) a first container containing a platelet supplement solution (PAS), (b) a second container containing a pathogen inactivating compound (PIC), and (c) a third container suitable for containing the drug. platelets in a mixture with PAS and PIC, while the first and second containers are connected to each other, and while none of the first and second containers is connected to the third container. In some embodiments, the first container and the second container are configured to have a sealed but openable flow channel between them. In some embodiments, the implementation of the first container is made with the possibility of connection in the form of a third container (for example, using a flexible plastic tube). In some embodiments, the implementation of the first container is made with the possibility of sterile connection with the third container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the first container to the third container. In some embodiments, the implementation of the second container is made with the possibility of connection in the form of a third container (for example, using a flexible plastic tube). In some embodiments, the implementation of the second container is made with the possibility of sterile connection with the third container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the second container to the third container. In some embodiments, the first container is suitable for combining PAS with PIC. In some embodiments, the implementation of the second container is suitable for combining PAS with PIC. Any one or more of the first, second and third containers may be suitable for mixing the platelet preparation with the solution containing PAS and PIC. In some embodiments, the first container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the second container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the third container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. Any one or more of the first, second, and third containers can be made from a material substantially translucent to light in the photochemical inactivation wavelength range (eg, about 200 nm to about 400 nm, ultraviolet A). In some embodiments, the third container contains a compound adsorption device (CAD). In some embodiments, the third container is suitable for storing the platelet composition. In some embodiments, the platelet composition kit further comprises at least one (e.g., 1, 2, or 3) storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one the storage container is connected to the third container. In some embodiments, at least one storage container is integrally connected to the third container (eg, with a flexible plastic tube). In some embodiments, at least one storage container is sealed but has a flow channel that opens into a third container. In some embodiments, at least one storage container is sterile connected to the third container. Any one or more of the first, second and third containers may be suitable for connection to the apheresis device or to the container containing the platelet preparation.

In some embodiments, the platelet formulation kit comprises (a) a first container containing a platelet supplement solution (PAS), (b) a second container containing a pathogen inactivating compound (PIC), and (c) a third container suitable for containing the drug. platelets in a mixture with PAS and PIC, while the first and second containers are connected to each other, and while none of the first and second containers is connected to the third container. In some embodiments, the first container and the second container are configured to have a sealed but openable flow channel between them. In some embodiments, the implementation of the first container is made with the possibility of connection in the form of a third container (for example, using a flexible plastic tube). In some embodiments, the implementation of the first container is made with the possibility of sterile connection with the third container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the first container to the third container. In some embodiments, the implementation of the second container is made with the possibility of connection in the form of a third container (for example, using a flexible plastic tube). In some embodiments, the implementation of the second container is made with the possibility of sterile connection with the third container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the second container to the third container. In some embodiments, the first container is suitable for combining PAS with PIC. In some embodiments, the implementation of the second container is suitable for combining PAS with PIC. Any one or more of the first, second and third containers may be suitable for mixing the platelet preparation with the solution containing PAS and PIC. In some embodiments, the first container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the second container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the third container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. Any one or more of the first, second, and third containers can be made from a material substantially translucent to light in the photochemical inactivation wavelength range (eg, about 200 nm to about 400 nm, ultraviolet A). In some embodiments, the platelet composition kit further comprises a fourth container, wherein the fourth container contains a compound adsorption device (CAD). In some embodiments, the fourth container is configured to be integrally connected to the third container (eg, with a flexible plastic tube). In some embodiments, the fourth container is configured to have a flow channel that opens into the third container. In some embodiments, the implementation of the fourth container is made with the possibility of sterile connection with the third container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the fourth container to the third container. In some embodiments, the fourth container is suitable for storing the platelet composition. In some embodiments, the platelet composition kit further comprises at least one (e.g., 1, 2, or 3) storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one the storage container is connected to the fourth container. In some embodiments, at least one storage container is integrally connected to the fourth container (eg, with a flexible plastic tube). In some embodiments, at least one storage container is sealed but has a flow channel that opens into the fourth container. In some embodiments, the platelet composition kit further comprises at least one (e.g., 1, 2, or 3) storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one the storage container is connected to the fourth container. Any one or more of the first, second and third containers may be suitable for connection to the apheresis device or to the container containing the platelet preparation.

In some embodiments, the platelet formulation kit comprises (a) a first container containing a platelet supplement solution (PAS), (b) a second container containing a pathogen inactivating compound (PIC), and (c) a third container suitable for containing the drug. platelets mixed with PAS and PIC, with none of the first and second containers connected to the third container. In some embodiments, the implementation of the first container and the second container are made with the possibility of connection (eg, sterile connection) with each other. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the first container to the second container. In some embodiments, the implementation of the first container is made with the possibility of connection in the form of a third container (for example, using a flexible plastic tube). In some embodiments, the implementation of the first container is made with the possibility of sterile connection with the third container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the first container to the third container. In some embodiments, the implementation of the second container is made with the possibility of connection in the form of a third container (for example, using a flexible plastic tube). In some embodiments, the implementation of the second container is made with the possibility of sterile connection with the third container. In some embodiments, the kit further comprises one or more components (eg, tubing, flexible plastic tubing) for connecting the second container to the third container. In some embodiments, the first container is suitable for combining PAS with PIC. In some embodiments, the implementation of the second container is suitable for combining PAS with PIC. Any one or more of the first, second and third containers may be suitable for mixing the platelet preparation with the solution containing PAS and PIC. In some embodiments, the first container is suitable

- 33 042974 for exposing a platelet preparation mixed with a solution containing PAS and PIC to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the second container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In some embodiments, the third container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. Any one or more of the first, second, and third containers can be made from a material substantially translucent to light in the photochemical inactivation wavelength range (eg, about 200 nm to about 400 nm, UVA spectrum). In some embodiments, the third container contains a compound adsorption device (CAD). In some embodiments, the third container is suitable for storing the platelet composition. In some embodiments, the platelet composition kit further comprises at least one (e.g., 1, 2, or 3) storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one the storage container is connected to the third container. In some embodiments, at least one storage container is integrally connected to the third container (eg, with a flexible plastic tube). In some embodiments, at least one storage container is sealed but has a flow channel that opens into a third container. In some embodiments, at least one storage container is sterile connected to the third container. Any one or more of the first, second and third containers may be suitable for connection to the apheresis device or to the container containing the platelet preparation.

In some embodiments of any of the kits described herein, the PAS and PIC solution has a volume between about 10 ml and about 1000 ml. In some embodiments, the PAS and PIC solution has a volume between about 200 ml and about 900 ml, between about 300 ml and about 800 ml, between about 400 ml and about 700 ml, or between about 500 ml and about 600 ml. In some embodiments, the PAS and PIC solution has a volume of about 100 ml, about 200 ml, about 300 ml, about 400 ml, about 500 ml, about 600 ml, about 700 ml, about 800 ml, about 900 ml, or about 1000 ml. In some embodiments, the PAS and PIC solution has a volume of less than about 1000 ml, less than about 800 ml, less than about 600 ml, less than about 500 ml, less than about 400 ml, less than about 300 ml, less than about 200 ml. ml, less than about 100 ml, or less than about 50 ml. In some embodiments, the PAS and PIC solution has a volume of greater than about 800 ml, greater than about 600 ml, greater than about 500 ml, greater than about 400 ml, greater than about 300 ml, greater than about 200 ml, greater than about 100 ml, greater than about 50 ml, or greater than about 10 ml.

In some embodiments of any of the kits described herein, the concentration of PIC in the PAS and PIC solution is from about 25 µM to about 1200 µM, from about 50 µM to about 1000 µM, from about 50 µM to about 750 µM, from about 50 µM to about 500 µM, about 75 µM to about 500 µM, about 100 µM to about 400 µM, about 150 µM to about 350 µM, about 200 µM to about 300 µM, or about 225 µM to about 250 µM. In some embodiments, the PIC concentration is about 25 µM, about 50 µM, about 75 µM, about 100 µM, about 125 µM, about 150 µM, about 175 µM, about 200 µM, about 250 µM, about 275 µM, about 300 µM, approximately 325 μM, approximately 350 μM, approximately 375 μM, approximately 400 μM, approximately 450 μM, approximately 500 μM, approximately 550 μM, approximately 600 μM, approximately 650 μM, approximately 700 μM, approximately 750 μM, approximately 800 μM, approximately 850 μM, approximately 900 μM, approximately 1000 μM, approximately 1100 μM, approximately 1200 μM, approximately 1300 μM, approximately 1400 μM, or approximately 1500 μM. In some embodiments, the PIC concentration is from about 225 µM to about 235 µM. In some embodiments, the PIC concentration is about 225 µM, about 226 µM, about 227 µM, about 228 µM, about 229 µM, about 230 µM, about 231 µM, about 232 µM, about 233 µM, about 234 µM, or about 235 µM .

In some embodiments of any of the kits described herein, the PIC is psoralen. In some embodiments of any of the kits described herein, the PIC is amotosalen. In some embodiments, any

- 34 042974 of the kits described herein, PIC is selected from the group consisting of isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, merocyanine 540 and their salts or free bases.

Non-limiting examples of kits for preparing a platelet composition according to the methods disclosed herein are shown in FIG. 1A-1E and 2A-2E.

The exemplary set 100 shown in FIG. 1A contains: (a) a first container 105 containing a solution containing platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC), and (b) a second container 110 (e.g., a platelet container), wherein the first container 105 not connected to the second container 110. The dotted lines 115, 120 indicate that the platelet preparation can be added to the first container 105 containing the solution containing PAS and PIC, or the platelet preparation can be added to the second container 110. The first container 105 shown in FIG. 1A is suitable for mixing a platelet preparation with a solution containing PAS and PIC, and optionally suitable for exposing the platelet preparation mixed with a solution containing PAS and PIC to light sufficient to photochemically inactivate the pathogen, if present. The second container 110 shown in FIG. 1A is suitable for mixing a platelet preparation with a solution containing PAS and PIC, and suitable for containing a platelet preparation mixed with a solution containing PAS and PIC. In addition, the second container 110 is suitable for one or more of: exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present; compound adsorption device content (CAD); and storage of the platelet composition. In some embodiments, the exemplary set shown in FIG. 1A does not contain CAD.

In FIG. 1B shows an alternative configuration for an exemplary kit 101 according to the disclosure. This configuration optionally further includes a third container 125 connected (eg, via a sterile tube 135) to a second container 110, the third container 125 containing a compound adsorption device (CAD) 130. As shown in FIG. 1B, the second container 110 is suitable for exposing a platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In addition, the third container 125 is optionally suitable for storing the platelet composition.

In FIG. 1C shows yet another alternative configuration for an exemplary set 102 according to the disclosure. This configuration optionally further includes a fourth container 140 that is suitable for storing the platelet composition, wherein the third container 125 containing a compound adsorption device (CAD) 130 is connected (for example, via a sterile tube 145) to the fourth container 140.

Another alternative configuration for the exemplary set 103 according to the disclosure is shown in FIG. 1D. This configuration optionally further includes at least one storage container 140, 150, 155, wherein at least one storage container 140, 150, 155 is suitable for storing the platelet composition, and wherein at least one container 140, 150, 155 for storage is connected (for example, through a sterile tube 146) with the third container 125 containing the device 130 adsorption compound (CAD).

Another alternative configuration for the exemplary set 104 according to the disclosure is shown in FIG. 1E. As shown in FIG. 1E, the first container 105 is suitable for mixing a platelet preparation with a solution containing PAS and PIC, and in addition for exposing the platelet preparation mixed with a solution containing PAS and PIC to light sufficient to photochemically inactivate a pathogen, if present, and the second container 110 includes a compound adsorption device (CAD) 130 . This configuration further includes a third container 125 connected (eg, via a sterile tube 135) to a second container 110, the third container 125 being optionally suitable for storing the platelet composition.

The exemplary arrays 200, 201 shown in FIG. 2A contain: (a) a first container 215, 225 containing platelet supplemental solution (PAS); (b) a second container 205, 235 containing a pathogen inactivating compound (PIC); and (c) a third container 220, 240 (e.g., a platelet container) suitable for containing the platelet preparation in admixture with PAS and PIC, wherein the first and second containers are connected to each other (e.g., a sealed but openable flow channel 210, 230) and neither of the first and second containers is connected to the third container. The dotted lines 250, 251, 252, 253, 254, 255 indicate that the platelet preparation may be added to the first container containing PAS, the platelet preparation may be added to the second container containing PIC, or the platelet preparation may be added to the third container. The first container shown in FIG. 2A (left side of page 200), suitable for combining PAS with PIC, and additional admixture of the platelet preparation. Alternatively, the second container shown in FIG. 2A (right side of page 201), suitable for combining PAS with PIC, and additional mixing of the platelet preparation, and optionally suitable for exposing the platelet preparation mixed with a solution containing PAS and PIC to light sufficient to photochemically inactivate the pathogen. , in the presence of. In addition, in each configuration 200 or 201, the third container 220, 240 is suitable for one or more of: exposing the platelet preparation, mixed with the solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present; compound adsorption device content (CAD); and storage of the platelet composition. In some embodiments, the exemplary kits shown in FIG. 2A do not contain CAD.

An alternative configuration 202 for an exemplary set according to the disclosure is shown in FIG. 2B. This configuration optionally further includes a fourth container 265 connected (eg, via a sterile tube 270) to a third container 220, the fourth container 265 containing a compound adsorption device (CAD) 265 . As shown in FIG. 2B, the third container 220 is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen, if present. In addition, the fourth container 260 is optionally suitable for storing the platelet composition.

Another alternative configuration 203 for an exemplary set according to the disclosure is shown in FIG. 2C. This configuration optionally further includes a fifth container 275 that is suitable for storing the platelet composition, wherein the fourth container 260 containing a compound adsorption device (CAD) 265 is connected (for example, via a sterile tube 280) to the fifth container 275.

Another alternative configuration 204 for an exemplary set according to the disclosure is shown in FIG. 2D. This configuration optionally further includes at least one storage container 275, 285, 290, wherein at least one storage container 275, 285, 290 is suitable for storing the platelet composition, and wherein at least one container 275, 285, 290 for storage is connected (for example, through a sterile tube 281) with the fourth container 260 containing the device 265 adsorption compound (CAD).

Another alternative configuration 206 for an exemplary set according to the disclosure is shown in FIG. 2E. As shown in FIG. 2E, the first container 205 is suitable for combining PAS with PIC and additional admixture of the platelet preparation. The third container 220 contains a compound adsorption device (CAD) 265 . This configuration further includes a fourth container 260 connected (eg, via a sterile tube 270) to a third container 220, the fourth container 260 being optionally suitable for storing the platelet composition.

As disclosed herein, a platelet preparation can be obtained by apheresis. As shown in FIG. 3, the apheresis device can be connected to any kit disclosed herein as a source of platelet preparation (eg, platelets taken from a donor with an apheresis device), with a non-limiting example of a connection site in the apheresis device being shown. The kits disclosed herein can be used with any apheresis device, including those disclosed in US Pat. No. 5,868,696. For example, as shown in FIG. 1A-1E, the apheresis device can be connected to: a first container containing a solution containing PAS and PIC; and/or a second container. In other illustrative embodiments, which are shown in FIG. 2A-2E, the apheresis device may be connected to one or more of: a first container containing PAS; a second container containing the PIC; and a third container.

Compositions

In some aspects, the disclosure provides compositions comprising a platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC), wherein the composition does not contain platelets.

In some embodiments of a composition containing PAS and PIC, wherein the composition does not contain platelets, the PAS contains one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate.

In some embodiments of a composition containing PAS and PIC, wherein the composition does not contain platelets, the PIC is psoralen. In some embodiments of a composition containing PAS and PIC, wherein the composition does not contain platelets, the PIC is amotosalen. In some embodiments of a composition comprising PAS and PIC, wherein the composition does not contain platelets, the PIC is selected from the group consisting of isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, merocyanine 540, and salts or free bases thereof.

In some embodiments of a composition containing PAS and PIC, wherein the composition does not contain platelets, the solution containing PAS and PIC has a volume between about 100 ml and about 1000 ml. In some embodiments, the solution containing PAS and PIC has a volume between about 200 ml and about 900 ml, between about 300 ml and about 800 ml, between about 400 ml and about 700 ml, or between about 500 ml and about 600 ml. In some embodiments, the solution containing PAS and PIC has a volume of about 100 ml, about 200 ml, about 300 ml, about 400 ml, about 500 ml, about 600 ml, about 700 ml, about

- 36 042974

800 ml, approximately 900 ml or approximately 1000 ml. In some embodiments, the solution containing PAS and PIC has a volume of less than about 1000 ml, less than about 800 ml, less than about 600 ml, less than about 500 ml, less than about 400 ml, less than about 300 ml, or less than about 200 ml. In some embodiments, the solution containing PAS and PIC has a volume of greater than about 800 ml, greater than about 700 ml, greater than about 600 ml, greater than about 500 ml, greater than about 400 ml, greater than about 300 ml, more than about 200 ml or more than about 100 ml. In some embodiments, the solution containing PAS and PIC has a volume between about 1000 ml and about 5000 ml.

In some embodiments of a composition containing PAS and PIC, wherein the composition does not contain platelets, the concentration of PIC in the solution containing PAS and PIC is from about 25 µM to about 1200 µM, from about 50 µM to about 1000 µM, from about 50 µM to about 750 µM, about 50 µM to about 500 µM, about 75 µM to about 500 µM, about 100 µM to about 400 µM, about 150 µM to about 350 µM, about 200 µM to about 300 µM or from about 225 µM to about 250 µM. In some embodiments, the concentration of PIC in the solution containing PAS and PIC is about 25 µM, about 50 µM, about 75 µM, about 100 µM, about 125 µM, about 150 µM, about 175 µM, about 200 µM, about 250 µM approximately 275 μM, approximately 300 μM, approximately 325 μM, approximately 350 μM, approximately 375 μM, approximately 400 μM, approximately 450 μM, approximately 500 μM, approximately 550 μM, approximately 600 μM, approximately 650 μM, approximately 700 μM, approximately 750 µM, about 800 µM, about 850 µM, about 900 µM, about 1000 µM, about 1100 µM, about 1200 µM, about 1300 µM, about 1400 µM, or about 1500 µM. In some embodiments, the concentration of PIC in a solution containing PAS and PIC is from about 225 μM to about 235 μM. In some embodiments, the concentration of PIC in a solution containing PAS and PIC is about 225 µM, about 226 µM, about 227 µM, about 228 µM, about 229 µM, about 230 µM, about 231 µM, about 232 µM, about 233 µM , approximately 234 μM or approximately 235 μM.

In some embodiments, the implementation of the composition containing PAS and PIC, while the composition does not contain platelets, is a stock solution.

In some embodiments, a composition comprising a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC), wherein the composition does not contain platelets, is sterile.

The present disclosure, in some aspects, also provides platelet compositions prepared by any of the methods described herein.

The disclosed examples and embodiments disclosed herein further describe methods, kits, and compositions for preparing a platelet composition suitable for infusion into a patient. The illustrated components and steps are provided to explain the exemplary embodiments shown, and it is to be expected that current technological development will change the way in which specific functions are performed. These examples are provided herein by way of illustration and not limitation. In addition, the boundaries of the functional building blocks have been arbitrarily defined herein for convenience of description. Alternative boundaries can be defined provided that the specified functions and their interrelationships are performed properly. Alternatives (including equivalents, extensions, variations, deviations, etc. from what is described herein) will be understood by those skilled in the relevant art(s) based on the ideas presented herein. Such alternatives fall within the scope and spirit of the disclosed embodiments.

Containing, having, enclosing, and including, and other similar forms used herein, are intended to have an equivalent and unrestricted meaning in that the element or elements following any one of these words do not mean an exhaustive list of such element or elements, or do not imply limitation only the listed element or elements. For example, an article containing components A, B, and C may consist of (i.e., contain only) components A, B, and C, or may contain not only components A, B, and C, but also one or more other components. It is understood that contains and its grammatical equivalents include consisting of or essentially consisting of.

When presenting a range of value, it should be understood that the disclosure covers every intermediate value, up to a tenth of a unit lower bound, unless the context clearly requires otherwise, between the upper and lower limits of that range and any other specified or intermediate value in that range. specified range, subject to any specifically excluded limit within the specified range. When a specified range contains one or both of the limits, the disclosure also includes ranges with each or both of those included limits excluded.

A reference to an approximate value or parameter in this case includes (and describes) variations that refer to that value or parameter as such. For example, a description referring to approximately X includes a description of X.

Within the scope of the present invention and in the appended claims, unless the context clearly dictates otherwise, the singular forms include references to the plural, and those skilled in the art will appreciate that changes to the form and details of the embodiments described herein may be obtain without going beyond the scope of this disclosure. In addition, while various advantages, aspects, and purposes have been described with reference to various embodiments, the scope of this disclosure should not be limited by reference to such advantages, aspects, and purposes. Instead, the scope of this disclosure should be defined with reference to the appended claims.

The disclosure is further illustrated by the following examples, which should not be construed as limiting the disclosure to the scope or spirit of the specific methods described therein.

Examples

Example 1 Stability of Amotosalen in Platelet Supplemental Solution.

Initial studies evaluated the stability of the pathogen-inactivating compound amotosalen (S-59) that was combined with platelet supplemental solution (PAS). A 230 μM solution of psoralen compound S-59 (Irsch et al. Transfus Med Hemother, 38: 19-31 (2011)) was prepared in a commercially available PAS InterSol® solution (Fenwal Inc.) and stored at room temperature under ambient light conditions. HPLC analysis was performed on the samples at the times listed in Table 1. 1 on both S-59 and photo products. The results shown in table. 1 demonstrate the stability of S-59 in PAS InterSol over a 78 hour period under ambient light with <6% loss of S-59 in 78 hours. S-59 data are shown as concentration (µM) as well as peak area (UV S -59) for relative comparison with any photoproducts detected by HPLC (Table 1). Photoproducts in the form of peak D and peak E were also observed after 22 and 72 h, respectively, as well as the decomposition product of technological impurities 4'-HMT, with the shown values of the peak area (Table 1)

Table 1. Analysis of HPLC S-59 and photoproducts

Sample S-59 µM UV S-59 UV Peak D UV Peak E UV 4'-HMT THAT 237.49 3700.439 nd nd 4.924 5 h 230.62 3593.309 nd nd 5.624 6 h 229.50 3575.825 nd nd 5.090 22 h 223.71 3485.467 8.419 nd 5.125 30 h 226.56 3529.854 11.179 nd 5.334 47 h 223.76 3486.293 18,500 nd 4.954 56 h 220.82 3440.455 21.304 nd 4.742 72 h 226.88 3534.894 27.171 4.344 4.839 78 h 223.69 3485.093 28.960 4.623 4.793

Additional studies evaluated the stability of S-59 (amotosalen) pathogen inactivating compound combined with platelet supplemental solution (PAS) but protected from ambient light exposure. A 230 μM S-59 solution was prepared in a commercially available PAS InterSol® solution (Fenwal Inc.) and stored at room temperature protected from ambient light. HPLC analysis was performed on the samples at the times listed in Table 1. 2 on both S-59 and photo products. The results shown in table. 2 demonstrate the stability of S-59 in PAS InterSol over a 77 hour period when shielded from ambient light with no loss of S-59 after 77 hours as shown in both concentration (μM) and peak area (UV). Photoproducts in the form of peak D and peak E were not detected after 77 hours, while the decomposition product of technological impurities 4'-HMT was observed with the shown values of the peak area (Table 2)

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Table 2. Analysis of HPLC S-59 and photoproducts

Sample S-59 µM UV S-59 UV 4 -HMT THAT 228.82 3393.0647 3.8849 5.5 h 232.74 3451.6489 3.7162 21.5 h 231.93 3439.4907 4.3525 28.5 h 230.72 3421.447 3.8628 45.5 h 229.22 3399.0142 4.4036 53 h 230.72 3421.4934 4.0582 44 h 230.96 3425.1028 4.0199 77 h 232.41 3446.6414 4.4268

Example 2 Stability of amotosalen in 65% PAS with 35% plasma and platelets.

An additional study evaluated the stability and photo-switching of amotosalen (S-59) in PAS supplemented with plasma and also containing platelets. S-59 was added at a concentration of 150 μM to a suspended platelet preparation of 65% PAS InterSol® and 35% plasma, and the mixture was stored in a platelet incubator during the study. Samples were removed for HPLC analysis at times of 0, 5, 21, 29, and 48 h and then the mixture was treated with ~3J ultraviolet A after 55 h, with after UVA the sample was also analyzed by HPLC for both S-59 and photographic products. The results shown in table. 3 demonstrate the stability of S-59 in a PAS/plasma/platelet mixture with no loss of S-59 prior to UVA treatment at 55 h as shown in both concentration (μM) and peak area (UV). Photoproducts in the form of peak D and peak E were not detected (Table 3). UVA treatment of the samples after 55 hours showed that S-59 photo-switching was effective after S-59 incubation in PAS/plasma, with only 15.3% remaining in the UVA samples (Table 3).

Table 3 HPLC analysis of S-59 and photo products.

Sample S-59 µM UV S-59 THAT 148.12 1752.513 5h 149.30 1738.331 21 h 147.81 1739.214 29 h 148.04 1725.882 48 h 148.06 1750.513 55 hours after UVA 22.71 274.897

Example 3 Stability of Amotosalen in PAS/Plasma with Platelets and Bacteria.

Another study evaluated the stability and photo-switching of amotosalen (S-59) in PAS with plasma and platelets after 24 hours in the presence of bacteria. Two units of platelets with matching ABO in 100% plasma were pooled, divided into two units and PAS InterSol® (eg 65/35) was added. S-59 was added to the test unit at a concentration of 150 μM, but not initially to the control unit. A logarithmic growth culture of K. pneumoniae (order of cfu/mL ~8) was added to target units of ~60 cfu/unit and the units were incubated in a platelet mixer at 22° C. for approximately 24 h. At the end of incubation, S- 59 was also added to the control unit at the same concentration, and both control and test units were exposed to UVA. Samples were taken before and after UVA illumination to analyze the bacterial titer of both units and for HPLC. After illumination, both units were subjected to a CAD treatment step to remove residual amotosalen and photoproducts and stored in a platelet mixer for 7 days to confirm the absence of bacterial growth.

As shown in Table. 4, the concentration of S-59 was stable over the 24 h incubation period with effective photo-switching after 24 h UVA treatment of both control and test units. Thus, the presence of K. pneumoniae did not adversely affect the stability or photo-switching of S-59.

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Table 4. S-59 concentration during the 24 h period and after UVA treatment

Wed (S-59 µM) Repeat 1 (S-59 µM) Repeat 2 (S-59 µM) Temporary places Control Test Control Test Control Test THAT 0 152 0 149 0 155 T_24 h 149 153 144 149 153 157 Post-UFA 40 26 43 27 37 24 % switching S-59 27 17 thirty 18 24 15

Photochemical inactivation of K. pneumoniae was also measured after UVA treatment, with titration results (order of cfu/ml) shown in the following table. A high level of inactivation was observed for both control and test units, indicating no negative effect of K. pneumoniae on photochemical inactivation of S-59 after 24 hours of storage in PAS/plasma and platelets (Table 5).

_________________ Table 5. Inactivation of K.pneumoniae__________________

Repeat 1 Repeat 2 Unit W Control Test Control Test Title 0 hour 69-73 cfu/unit 86-101 cfu/unit Title 24 hour 6.6 6.5 5.6 5.4 Title After UVA <-0.7 <-0.7 <-0.7 <-0.7 Decrease order of magnitude >7.3 >7.3 >6.3 >6.2

Example 4 Inactivation of calicivirus with amotosalen in PAS/plasma.

It has previously been shown that caliciviruses such as feline calicivirus (FCV), which has been used as a model for hepatitis E virus, are very resistant to photochemical inactivation by amotosalen (S-59) with a reduction in log ₁₀ in titer of only about 1.7- 2.4 (Irsch et al. Transfus Med Hemother, 38: 19-31 (2011)). Based on the results of Examples 1 and 2 showing that amotosalen is stable in PAS and PAS/Plasma, an additional study was conducted in which the level of inactivation of FCV calicivirus by S-59 after prolonged incubation in PAS/plasma was evaluated. In this study, platelets in PAS/plasma (65%/35%) were pooled to approximately 1320 ml, with a total of approximately 16x1011 platelets, and a 1:100 dilution stock solution of calicivirus FCV was added. A sample was taken from the FCV-supplemented platelet pool to determine the initial titer. The FCV-supplemented platelets were then divided into 5 units, approximately 260 ml each, approximately 3.2 x 1011 platelets per unit. Each unit was dosed with S-59 at a concentration of approximately 150 μM, which concentration is used commercially in the INTERCEPT® Blood System for pathogen inactivation treatment. After addition of S-59, platelet units were incubated for 0, 2, 4, 8, or 24 h. ~3 J/cm ² to complete the photochemical processing for all tested samples. After UVA treatment, control and test samples were assessed for FCV inactivation using a standard viral plaque assay. As shown in Table. 6, incubation of S-59/PAS/Plasma for 2 or more hours prior to UVA exposure resulted in a significant increase in FCV inactivation below the detection limit compared to the time 0 sample (no pre-incubation prior to UVA treatment). The data support the additional benefit of the present disclosure by allowing platelets to be harvested in a premixed pathogen inactivating compound and supplemental solution (eg, S-59/PAS) and preincubated before the next UV exposure step in the photochemical process (Table 6).

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Table 6. FCV inactivation

Titer (Order of PFU/mL)

Exponent

* Inactivated to the limit of detection.

In table. 7 shows a recalculation of the above inactivation data normalized to the FCV pool titer.

Table 7. Normalized FCV inactivation

Titer (Order of PFU/mL)

Exponent

*

Conducted an additional study to assess the level of inactivation of FCV with a decrease in the number of S-59 after prolonged incubation (eg, pre-incubation) in PAS/plasma. In this study, a stock solution of FCV was added to platelets in PAS/plasma (65%/35%) at a dilution of 1:100. FCV-supplemented platelets were then divided into 16 individual test units. Each unit was dosed with S-59 at a concentration of approximately 150, 90, 30, or 15 μM. Following the addition of S-59 in one of the four dose groups, units of platelets in each dose group were incubated for 0, 4, 8, or 24 hours before illumination. A control sample was taken from each unit for virus titer determination and HPLC analysis of S-59 concentration prior to UVA treatment followed by UVA at ~3 J/cm ² for photochemical processing of test samples. After UVA treatment, control and test samples were assessed for FCV inactivation using a standard viral plaque assay. In table. 8 shows the FCV titers (order of PFU/mL) for each sample, and Table. 9 shows the degree of inactivation for each sample.

Table 8. FCV titers

Control 150 µM 90 µM 30 µM 15 µM 0h 5.84 4.33 4.90 4.91 5.65 4h 5.74 <0.22 <0.22 2.00 4.49 8h 5.86 < -0.48 < -0.48 < 1.22 2.22 24 hours 5.80 < -0.48 < -0.30 < -0.22 0.52

Table 9. FCV inactivation

150 µM 90 µM 30 µM 15 µM 0h 1.51 0.94 0.93 0.19

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4h 5.62 5.62 3.84 1.35 8h 5.84 5.84 4.62 3.62 24 hours 5.84 5.84 5.62 5.32

A pool of control titers at 0 h was used to calculate all degrees of inactivation (5.84 number/mL).

As these data show, pre-incubation of FCV-containing platelets in S59/PAS/Plasma prior to UVA illumination resulted in high levels of FCV inactivation even with low input concentrations of the pathogen-inactivating compound S-59. In particular, pre-incubation for 4, 8 or 24 hours in the case of S-59 concentrations of both 150 μM and 90 μM, for 8 or 24 hours in the case of S-59 concentrations of 30 μM, or for 24 hours in the case of concentrations of S-59 15 μm resulted in FCV inactivation by more than 4 orders of magnitude. Also, pre-incubation for 4 hours in the case of S-59 concentration of 30 μM resulted in FCV inactivation by almost 4 orders of magnitude, and pre-incubation for 8 hours in the case of S-59 concentration of 15 μM resulted in FCV inactivation by more than 3.5 order. HPLC analysis was also performed to determine the amount (eg, concentration) of S-59 remaining in the samples after UVA illumination and photoswitching (Table 10).

Table 10 S-59 concentration after UVA

Input value S-59 S-59 concentration (µM) after UVA 0h 4h 8 h 24 hours 150 µM 29 33 22 19 90 µM 14 10 AND 9 30 µM 5 2 2 3 15 µM 3 2 2 2

As shown in Table. 10, post-treatment residual S-59 concentrations decreased for all pre-incubation S-59 dose groups, including levels of less than 5 μM (eg, 2 μM). These data show that, based on the methods presented herein, pathogen inactivation treatment conditions can be obtained that result in high levels of inactivation (e.g., score >4) as well as effective S-59 photoswitching with residual concentrations of S -59 only 2 µM

Example 5 Pathogen Inactivated Platelets Obtained with Premixed Amotosalen/PAS.

Platelets with inactivated pathogens are obtained using kits and methods according to the present disclosure. More specifically, in one example, to obtain a single unit of 3.9x1011 platelets, approximately 89.2 ml of donated plasma (e.g., including any anticoagulant) is taken from a donor and transferred via a sterile connected tube to a container containing a solution of approximately 165.8 ml of PAS InterSol ® containing amotosalen at a concentration of approximately 231 μm (see, for example, Fig. 1C, 2C). The platelet/amotosalen/PAS/plasma mixture container at a concentration (e.g., total) of approximately 150 μM diluted amotosalen is then sterilely connected to the remaining dry side of the processing kit (see, e.g., FIGS. 1C, 2C) and the mixture is gravity-fed into lighting container. After UVA exposure of approximately 3 J/ ^cm2 using a commercially available INTERCEPT® Blood System illumination device (Cerus Corp.), the photochemically treated platelets are transferred to a CAD container to remove residual amotosalen and photoproducts, and then transferred to a single storage container. In yet another example, pathogen-inactivated platelets are prepared in a similar manner, but with 50% reduced concentrations of amotosalen (e.g., producing a mixture of platelets and amotosalen/PAS/plasma with a concentration (e.g., final) of diluted amotosalen of approximately 75 μM).

Example 6 Pathogen Inactivated Platelets Obtained with Premixed Amotosalen/PAS.

Pathogen-inactivated platelets are prepared using the kits and methods of the present disclosure, with amotosalen/PAS container(s) connected directly to an Amicus® apheresis device (Fenwal Inc.). More specifically, in one example, to obtain two platelet units (e.g., doubles), a 500 ml container of PAS InterSol® solution with amotosalen added to a concentration of approximately 231 μM (see, for example, Fig. 1C) is sterilely connected to the apheresis device, as shown in FIG. 3. Approximately 7.6x1ο ¹¹ platelets are taken from the donor by apheresis in a volume of approximately 178.5 ml of donor plasma (for example,

- 42 042974 including any anticoagulant), and approximately 331.5 ml of the PAS InterSol® solution containing amotosalen is automatically added by the device to obtain a mixture of platelets and amotosalen/PAS/plasma with a concentration (for example, final) of the diluted amotosalen of approximately 150 μM. The platelet mixture is then transferred to two Amicus® device collection bags, with platelets distributed approximately evenly between the two bags. Next, the two bags are detached from the apheresis device and each separately connected by sterile connection to the remaining dry side of two separate processing kits (see, for example, Fig. 1C) and the mixture is gravity-fed into the illumination container. After UVA exposure of approximately 3 J/ ^cm2 using a commercially available INTERCEPT® Blood System illumination device (Cerus Corp.), the photochemically treated platelets are transferred to a CAD container to remove residual amotosalen and photoproducts, and then each is transferred to a single storage container, receiving two units of platelets with inactivated pathogens. Alternatively, the collection bags removed from the apheresis device can be combined into a single illumination container by sterile bonding to the remaining dry side of the processing kit (see, for example, Figure 1D) but with two final storage bags, and processed, as described above, receiving two units of platelets with inactivated pathogens. In yet another example, pathogen-inactivated platelets are prepared in a similar manner, but with 50% reduced concentrations of amotosalen (e.g., producing a mixture of platelets and amotosalen/PAS/plasma with a concentration (e.g., final) of diluted amotosalen of approximately 75 μM).

Illustrative Embodiments

Embodiment 1. A method for producing a platelet composition, comprising:

(a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC);

(b) mixing the solution of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition.

Embodiment 2. The method according to Embodiment 1, wherein the mixing in step (b) takes place in the first container.

Embodiment 3. The method according to Embodiment 1, wherein the mixing in step (b) takes place in a second container.

Embodiment 4. The method according to Embodiment 1 or Embodiment 2, wherein the exposure of the mixture to light in step (c) takes place in the first container.

Embodiment 5. The method according to any one of Embodiments 1-3 wherein the exposure of the mixture to light in step (c) takes place in the second container.

Embodiment 6. The method according to any one of Embodiments 1-5, wherein the platelet preparation is obtained by apheresis.

Embodiment 7. The method according to Embodiment 6, wherein the method further comprises, before step (b), connecting the first container to the apheresis device.

Embodiment 8. The method according to Embodiment 6 or Embodiment 7, wherein the second container is connected to the apheresis device.

Embodiment 9. The method according to any one of Embodiments 1-5, wherein the platelet preparation is obtained from one or more whole blood portion(s) by buffy coat method or platelet-rich plasma (PRP) method.

Embodiment 10. The method according to any one of Embodiments 1-9 further comprising, after step (c): (d) transferring the platelet composition to a third container.

Embodiment 11. The method according to Embodiment 10, wherein the third container contains a compound adsorption device (CAD).

Embodiment 12. The method according to Embodiment 10 or Embodiment 11 wherein the third container is suitable for storing the platelet composition.

Embodiment 13. The method according to any one of embodiments 1-12, wherein the solution of step (a) contains PIC at a concentration of from about 15 µM to about 1500 µM.

Embodiment 14. The method according to any one of Embodiments 1-13, wherein the PIC is psoralen.

Embodiment 15. The method according to Embodiment 14, wherein the PIC is amotosalen.

Embodiment 16. The method according to any one of embodiments 1-15, wherein the platelet preparation contains plasma, wherein the plasma contains approximately 32-47% by volume of the mixture of step (b), with platelet supplemental solution making up the remainder.

Embodiment 17. The method of Embodiment 16 wherein the ratio

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PAS and plasma by volume in the mixture of step (b) is approximately 65:35.

Embodiment 18. The method according to any one of Embodiments 1-17, wherein the mixture of step (b) contains PIC at a concentration sufficient to result in pathogen inactivation, if present, by at least 1 order of magnitude.

Embodiment 19. The method according to any one of embodiments 1-18, wherein the mixture of step (b) contains PIC at a concentration sufficient to result in pathogen inactivation, if present, by at least 4 orders of magnitude.

Embodiment 20. The method of any one of Embodiments 1-19, wherein the mixture of step (b) contains PIC at a concentration of from about 5 µM to about 500 µM.

Embodiment 21. The method of Embodiment 20, wherein the mixture of step (b) contains PIC at a concentration of about 145 µM to about 155 µM.

Embodiment 22. The method of Embodiment 20, wherein the mixture of step (b) contains PIC at a concentration of about 30 µM to about 90 µM.

Embodiment 23. The method according to any one of Embodiments 1-22, wherein the PAS contains one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate.

Embodiment 24. The method according to any one of Embodiments 1-23, further comprising, before step (c): (b1) incubating the mixture of step (b) for a period of 30 minutes to 24 hours.

Embodiment 25. The method according to any one of Embodiments 1-24, wherein the platelet composition contains at least 2x1011 platelets.

Embodiment 26. The method according to any one of Embodiments 1-25, wherein the method is sufficient to inactivate the pathogen, if present, by at least 1 order of magnitude, and wherein the platelet composition after step (c) is suitable for infusion into a subject without further processing to remove residual PIC or its photoproducts.

Embodiment 27. The method according to any one of Embodiments 1-26, wherein the method is sufficient to inactivate the pathogen, if present, by at least 1 order of magnitude, and wherein the platelet composition after step (c) is suitable for infusion into a subject without transferring the platelet composition to a container containing a compound adsorption device (CAD).

Embodiment 28. The method according to any one of Embodiments 1-27, wherein the method is sufficient to inactivate the pathogen, if present by at least 1 order of magnitude, and wherein the platelet composition after step (c) contains a PIC of 5 μM or less.

Embodiment 29. The method according to any one of Embodiments 1-28, wherein the method is sufficient to inactivate the pathogen, if present by at least 4 orders of magnitude, wherein the platelet composition after step (c) contains a PIC of 2 μM or less , and the concentration of PIC in the mixture of platelet preparation and solution containing PAS and PIC is from about 15 μm to about 150 μm.

Embodiment 30. A method for preparing a platelet composition, comprising:

(a) providing a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC);

(b) mixing the solution of step (a) with the platelet preparation;

(c) incubating the mixture of the platelet preparation and the solution containing PAS and PIC for a period of from about 30 minutes to about 24 hours; and (d) exposing the incubated mixture of step (c) to light sufficient to photochemically inactivate the pathogen, if present, thereby obtaining a platelet composition, wherein:

(i) the method is sufficient to inactivate the pathogen, if present, by at least 1 order of magnitude;

(ii) the concentration of PIC in the mixture of platelet preparation and solution containing PAS and PIC is from about 15 μM to about 150 μM; and (iii) the composition of platelets after exposing the mixture of platelet preparation and solution containing PAS and PIC to light contains less than 5 μM PIC.

Embodiment 31. A platelet composition preparation kit comprising:

(a) a first container containing a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC), and (b) a second container suitable for containing a platelet preparation in admixture with a solution containing PAS and PIC, wherein the first the container is not connected to the second container.

Embodiment 32 A kit according to Embodiment 31 wherein the first container is suitable for mixing a platelet preparation with a solution containing PAS and PIC.

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Embodiment 33. A kit according to Embodiment 31 or Embodiment 32, wherein the second container is suitable for mixing a platelet preparation with a solution containing PAS and PIC.

Embodiment 34. A kit according to any one of Embodiments 31-33, wherein the second container is suitable for exposing the platelet preparation to light in admixture with a solution containing PAS and PIC sufficient to photochemically inactivate the pathogen, if present.

Embodiment 35. A kit according to any one of Embodiments 31-34, wherein the first container is suitable for exposing the platelet preparation to light in admixture with a solution containing PAS and PIC sufficient to photochemically inactivate the pathogen, if present.

Embodiment 36. A kit according to any one of Embodiments 31-35, wherein the second container contains a compound adsorption device (CAD).

Embodiment 37 A kit according to any one of Embodiments 31-36 wherein the second container is suitable for holding the platelet composition.

Embodiment 38. A kit according to any one of Embodiments 31-37, further comprising a third container, wherein the third container contains a compound adsorption device (CAD), and wherein the third container is connected to the second container.

Embodiment 39. A kit according to any one of Embodiments 31-38, further comprising at least one storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one storage container connected to the second container or to the third container, if any.

Embodiment 40. A kit according to any one of Embodiments 31-39, wherein the solution containing PAS and PIC has a volume between about 100 ml and about 1000 ml.

Embodiment 41. A kit according to any one of Embodiments 31-40 wherein PIC is at a concentration of from about 15 µM to about 1500 µM.

Embodiment 42 A kit according to any one of Embodiments 31-41, wherein PIC is psoralen.

Embodiment 43 A kit according to Embodiment 42 wherein the PIC is amotosalen.

Embodiment 44. A kit according to any one of Embodiments 31-43, wherein the first container, the second container, or both the first container and the second container are suitable for connection to an apheresis device or a container containing a platelet preparation.

Embodiment 45. A platelet composition preparation kit comprising:

(a) a first container containing platelet supplement solution (PAS);

(b) a second container containing a pathogen inactivating compound (PIC); and (c) a third container suitable for holding the platelet preparation in admixture with PAS and PIC, wherein the first and second containers are connected to each other and neither of the first and second containers is connected to the third container.

Embodiment 46. A kit according to Embodiment 45, wherein the second container is suitable for combining PAS with PIC.

Embodiment 47. A kit according to Embodiment 45, wherein the first container is suitable for combining PAS with PIC.

Embodiment 48 A kit according to any one of Embodiments 45-47 wherein the second container is suitable for mixing the platelet preparation with PAS and PIC.

Embodiment 49 A kit according to any one of Embodiments 45-47 wherein the first container is suitable for mixing the platelet preparation with PAS and PIC.

Embodiment 50 A kit according to any one of Embodiments 45-47 wherein the third container is suitable for mixing the platelet preparation with PAS and PIC.

Embodiment 51. A kit according to any one of embodiments 45-50, wherein the third container is suitable for exposing the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate the pathogen, if present.

Embodiment 52. A kit according to any one of embodiments 45-50, wherein the second container is suitable for exposing the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate the pathogen, if present.

Embodiment 53. A kit according to any one of embodiments 45-50, wherein the first container is suitable for exposing the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate the pathogen, if present.

Embodiment 54. A kit according to any one of Embodiments 45-53, with

- 45 042974 This third container contains a compound adsorption device (CAD).

Embodiment 55. A kit according to any one of Embodiments 45-54, wherein the third container is suitable for storing the platelet composition.

Embodiment 56. A kit according to any one of embodiments 45-55, further comprising a fourth container, wherein the fourth container contains a compound adsorption device (CAD), and wherein the fourth container is connected to the third container.

Embodiment 57. A kit according to any one of Embodiments 45-56, further comprising at least one storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one storage container connected to a third container or a fourth container, if any.

Embodiment 58 A kit according to any one of Embodiments 45-57 wherein the PIC is psoralen.

Embodiment 59 A kit according to Embodiment 58 wherein the PIC is amotosalen.

Embodiment 60. A kit according to any one of Embodiments 45-59, wherein the first container, the second container, or both the first container and the second container are suitable for connection to an apheresis device or a container containing a platelet preparation.

Embodiment 61. A composition comprising a pathogen inactivating compound (PIC) and a platelet supplement solution (PAS), wherein the composition does not contain platelets.

Embodiment 62. The composition of Embodiment 61 wherein the PIC concentration is from about 15 µM to about 1500 µM.

Embodiment 63 The composition of Embodiment 61 or Embodiment 62, wherein the PIC is psoralen.

Embodiment 64 The composition of Embodiment 63 wherein the PIC is amotosalen.

Embodiment 65 A composition according to any one of Embodiments 6164, wherein the PAS contains one or more of chloride, acetate, citrate, potassium, magnesium, phosphate, gluconate, glucose, and bicarbonate.

Embodiment 66. A composition according to any one of embodiments 6165, wherein the composition is sterile.

Embodiment 67 A platelet composition obtained by the method of any one of Embodiments 1-30.

Claims (54)

1. A method for producing a platelet composition, including: (a) providing in a first container a solution containing a platelet supplement solution (PAS) and a pathogen inactivating compound (PIC); (b) mixing the solution of step (a) with the platelet preparation; and (c) exposing the mixture of step (b) to light sufficient to photochemically inactivate the pathogen, where the wavelength of the light is from about 200 nm to about 400 nm, thereby obtaining a platelet composition. 2. Method according to claim 1, wherein the mixing in step (b) takes place in the first container. 3. Method according to claim 1, wherein the mixing in step (b) takes place in a second container. 4. Method according to claim 1 or 2, wherein the exposure of the mixture to light in step (c) takes place in the first container. 5. Method according to any one of claims 1 to 3, wherein the exposure of the mixture to light in step (c) takes place in the second container. 6. The method according to any one of claims 1 to 5, wherein the platelet preparation is obtained by apheresis. 7. The method of claim 6, wherein the method further comprises, prior to step (b), connecting the first container to the apheresis device and/or wherein the second container is connected to the apheresis device. 8. The method according to any one of claims 1 to 5, wherein the platelet preparation is obtained from one or more portion(s) of whole blood by the buffy coat method or by the platelet-rich plasma (PRP) method. 9. The method according to any one of claims 1 to 8, further comprising after step (c): (d) transferring the platelet composition to a third container. 10. The method of claim 9, wherein the third container contains a compound adsorption device (CAD) and/or wherein the third container is suitable for storing the platelet composition. 11. The method according to any one of claims 1 to 10, wherein the solution of step (a) contains PIC at a concentration of 15 to 1500 μM. - 46 042974 12. The method according to any one of claims 1 to 11, wherein the PIC is psoralen. 13. The method of claim 12 wherein the PIC is amotosalen. 14. The method according to any one of claims 1-13, wherein the platelet preparation contains plasma, wherein the plasma contains approximately 32-47% by volume of the mixture of step (b), with additional platelet solution making up the remainder of the volume. 15. The method of claim 14 wherein the ratio of PAS to plasma by volume in the mixture of step (b) is approximately 65:35. 16. The method according to any one of claims 1 to 15, wherein the mixture of step (b) contains PIC at a concentration sufficient to result in at least 1 order of magnitude or at least 4 orders of magnitude inactivation of the pathogen. 17. The method according to any one of claims 1 to 16, wherein the mixture of step (b) contains PIC at a concentration of 5 to 500 μM. 18. The method of claim 17, wherein the mixture of step (b) contains PIC at a concentration of 145 to 155 µM. 19. The method of claim 17, wherein the mixture of step (b) contains PIC at a concentration of 30 to 90 µM. 20. The method according to any one of claims 1 to 19, further comprising before step (c): (b1) incubating the mixture of step (b) for a period of 30 minutes to 24 hours. 21. The method according to any one of claims 1 to 20, wherein the platelet composition contains at least 2x1011 platelets. 22. A method according to any one of claims 1 to 21, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude and wherein the platelet composition after step (c) is suitable for infusion into a subject without additional treatment to remove residual PIC or its photoproducts and/or without transferring the platelet composition to a container containing a compound adsorption device (CAD). 23. The method according to any one of claims 1 to 22, wherein the method is sufficient to inactivate the pathogen by at least 1 order of magnitude, and wherein the platelet composition after step (c) contains a PIC of 5 μM or less and/or, while the method is sufficient to inactivate the pathogen by at least 4 orders of magnitude, wherein the platelet composition after step (c) contains a PIC of 2 μM or less, and the concentration of PIC in the mixture of the platelet preparation and the solution containing PAS and PIC is from approximately 15 µM to about 150 µM. 24. The method of obtaining a composition of platelets, including: (a) providing a solution containing an additional solution of platelets (PAS) and a connection for inactivation of pathogenic microorganisms (PIC); (b) mixing the solution of step (a) with the platelet preparation; (c) incubating the mixture of the platelet preparation and the solution containing PAS and PIC for a period of from about 30 minutes to about 24 hours; and (d) exposing the incubated mixture of step (c) to light sufficient to photochemically inactivate the pathogen, wherein the wavelength of the light is from about 200 nm to about 400 nm, thereby obtaining a platelet composition, wherein: (i) the method is sufficient to inactivate the pathogen by at least 1 order of magnitude; (ii) the concentration of PIC in the mixture of platelet preparation and solution containing PAS and PIC is from about 15 μM to about 150 μM; and (iii) the composition of platelets after exposing the mixture of platelet preparation and solution containing PAS and PIC to light contains less than 5 μM PIC. 25. The method of any one of claims 1-24, wherein the wavelength of the light is from about 315 nm to about 400 nm. 26. A kit for obtaining a platelet composition in accordance with the method according to any one of claims 125, containing: (a) a first container containing a solution containing platelet supplemental solution (PAS) and a pathogen inactivating compound (PIC); and (b) a second container suitable for containing the platelet preparation in admixture with the solution containing PAS and PIC, wherein the first container is not connected to the second container. 27. The kit of claim 26, wherein the first container is suitable for mixing the platelet preparation with the solution containing PAS and PIC. 28. The kit according to claim 26 or claim 27, wherein the second container is suitable for mixing the platelet preparation with the solution containing PAS and PIC. 29. A kit according to any one of claims 26-28, wherein the second container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen. 30. A kit according to any one of claims 26-29, wherein the first container is suitable for exposing the platelet preparation, mixed with a solution containing PAS and PIC, to light sufficient to photochemically inactivate the pathogen. 31. A kit according to any one of claims 26-30, wherein the second container contains a compound adsorption device (CAD). - 47 042974 32. The kit of claim 31, wherein the second container is suitable for storing the platelet composition. 33. A kit according to any one of claims 26-32, further comprising a third container, wherein the third container contains a compound adsorption device (CAD) and wherein the third container is connected to the second container. 34. The kit according to any one of claims 26-33, further comprising at least one storage container, wherein at least one storage container is suitable for storing the platelet composition, and at least one storage container is connected to the second container or with a third container. 35. A kit according to any one of claims 26-34, wherein the solution containing PAS and PIC has a volume between 100 and 1000 ml. 36. The kit according to claim 35, wherein the PIC is at a concentration of 15 to 1500 µM. 37. A kit according to any one of claims 26-36, wherein PIC is psoralen. 38. The kit of claim 37 wherein PIC is amotosalen. 39. A kit according to any one of claims 26-38, wherein the first container, the second container, or both the first container and the second container are suitable for connection to an apheresis device or a container containing a platelet preparation. 40. A kit for obtaining a platelet composition in accordance with the method according to any one of claims 125, containing: (a) a first container containing platelet supplement solution (PAS); (b) a second container containing a pathogen inactivating compound (PIC); and (c) a third container suitable for containing the platelet preparation in admixture with PAS and PIC, wherein the first and second containers are connected to each other and neither of the first and second containers is connected to the third container. 41. The kit according to claim 40, wherein the second container is suitable for combining PAS with PIC. 42. The kit according to claim 40, wherein the first container is suitable for combining PAS with PIC. 43. A kit according to any one of claims 40-42, wherein the second container is suitable for mixing the platelet preparation with PAS and PIC. 44. A kit according to any one of claims 40-42, wherein the first container is suitable for mixing the platelet preparation with PAS and PIC. 45. A kit according to any one of claims 40-42, wherein the third container is suitable for mixing the platelet preparation with PAS and PIC. 46. A kit according to any one of claims 40 to 45, wherein the third container is suitable for exposing the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate the pathogen. 47. A kit according to any one of claims 40 to 45, wherein the second container is suitable for exposing the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate the pathogen. 48. A kit according to any one of claims 40 to 45, wherein the first container is suitable for exposing the platelet preparation mixed with PAS and PIC to light sufficient to photochemically inactivate the pathogen. 49. A kit according to any one of claims 40-48, wherein the third container contains a compound adsorption device (CAD) and/or the third container is suitable for storing the platelet composition. 50. A kit according to any one of claims 40-49, further comprising a fourth container, wherein the fourth container contains a compound adsorption device (CAD) and wherein the fourth container is connected to the third container. 51. A kit according to any one of claims 40 to 50, further comprising at least one storage container, wherein at least one storage container is suitable for storing the platelet composition, and wherein at least one storage container is connected to a third container or with a fourth container. 52. A kit according to any one of claims 40-51, wherein PIC is psoralen. 53. The kit according to claim 52, wherein PIC is amotosalen. 54. A kit according to any one of claims 40-53, wherein the first container, the second container, or both the first container and the second container are suitable for connection to an apheresis device or a container containing a platelet preparation.