EA044317B1 - KITS AND METHODS FOR OBTAINING PATHOGEN-INACTIVATED PLATELET COMPOSITION - Google Patents

Description

This application claims priority to U.S. Provisional Patent Application Nos. 62/467,021, filed March 3, 2017, and 62/622,127, filed January 25, 2018, each of which is incorporated herein by reference in its entirety.

Field of technology

This description relates to improved methods, compositions and processing kits for producing pathogen-inactivated platelet compositions.

State of the art

Platelets are a blood component that plays a key role in hemostasis, clot stability and retraction, as well as vascular repair and host antimicrobial defense. Thrombocytopenia, or low levels of platelets in the blood, can result from a number of conditions that, depending on the severity, may require transfusion of donor platelets for therapeutic treatment. Platelet transfusions are also given prophylactically to reduce the risk of bleeding in patients with treatment-induced hypoproliferative thrombocytopenia, such as in patients receiving chemotherapy or stem cell transplantation (eg, hematopoietic progenitor cell transplantation).

A variety of methods are used to collect and store platelet products for clinical use. Whole blood donations are typically in the form of platelet concentrates (PCs) obtained using buffy coat or platelet rich plasma processing techniques, and such PCs can be pooled (e.g., 4-6 individual donors) to yield a sufficient platelet unit therapeutic dosage to meet unit dosage criteria defined by government, regulatory, institutional, or accrediting organization standards. Apheresis donation provides a means to obtain platelet units of sufficient therapeutic dosage from a single donor without the need for pooling, using automated cell separation systems that separate platelets from donated blood and return the remaining blood components to the donor during the donation procedure. Platelet products are typically suspended in plasma or a mixture of plasma and a synthetic storage medium (eg, platelet supplement solution) prior to storage.

Regulatory criteria define certain quality attributes of platelet products, as well as the maximum shelf life between production of platelet units and clinical infusion to patients. Requirements for various parameters may vary between countries, including, for example, minimum platelet quantities per unit (e.g. platelet unit, therapeutic dosage unit, platelets per container) and minimum pH levels during storage period (e.g. 5 days, 7 days) . The current US FDA requirement for pH is 95%, ensuring that 95% of components exhibit a pH at 22°C >6.2. In CE marked regions the pH requirement is pH >6.4, but statistical requirements may vary between countries. Maximum storage times typically range from a few days to 7 days and reflect not only platelet quality parameters but also the risk of transfusion-transmitted infection, which may increase over time when stored at room temperature. Bacterial contamination of platelet components is the second most common cause of transfusion-related mortality in the United States.

Options to reduce the risk of common transfusion infections from platelet components include testing for bacteria and the use of pathogen inactivation technologies. Photochemical treatment with psoralens (eg, amotosalen) and ultraviolet light (eg, UVA) is a means of pathogen inactivation against a wide range of pathogens, including bacteria, viruses, and parasites. The commercially available INTERCEPT™ Blood System (Cerus Corp.) for photochemical inactivation of pathogens in platelets consists of treatment kits containing the photoactive psoralen compound amotosalen and a separate ultraviolet light emitting device. The treatment kits also contain a compound adsorption device to reduce levels of residual amotosalen and free photoproducts in pathogen-inactivated platelet preparations after irradiation.

Although the current INTERCEPT™ System is highly effective in reducing the risk of transfusion infections from platelet components, modifications to the system may lead to further improvements in platelet quality and shelf life, particularly for processing large quantities and/or volumes of platelets, including large quantities and/or volumes of platelets suspended in plasma.

The essence of the invention

To address this and other needs, the methods, compositions and processing kits described herein are used, among other things, to maintain platelet quality during storage after pathogen inactivation, particularly when processing large quantities and/or volumes of platelets, including platelets prepared in plasma.

In one aspect, provided herein is a method for producing pathogen-inactivated

- 1044317 platelet composition, comprising: (a) mixing the platelet composition with a pathogen-inactivating compound (PIC); (b) photochemical inactivation of the platelet composition mixed with IPA; and (c) transferring the resulting mixture from step (b) under sterile conditions into a container containing a compound adsorption device (CAD) to obtain a pathogen-inactivated platelet composition; where at least one of (i) and (ii) is used: (i) the volume of the container containing the UAS is greater than 1.0 liters; and (ii) the surface area of the interior of the container containing the UAS is greater than about 750 cm ² . In some embodiments, the method also includes: (d) transferring the pathogen-inactivated platelet composition under sterile conditions from a container containing the UAS to one or more storage containers. In some embodiments, the one or more storage containers are one storage container. In some embodiments, the one or more storage containers are two storage containers. In some embodiments, the one or more storage containers are three storage containers. In some embodiments, the volume of the container containing the UAS is greater than 1.0 liters. In some embodiments, the volume of the container containing the UAS is greater than 1.1 liters. In some embodiments, the volume of the container containing the UAS is greater than about 1.2 liters. In some embodiments, the volume of the container containing the UAS is approximately 1.3 liters. In some embodiments, the volume of the container containing the UAS is approximately 1.5 liters. In some embodiments, the volume of the container containing the UAS is less than about 1.6 liters. In some embodiments, the volume of the container containing the UAS is from about 1.2 liters to about 1.6 liters. In some embodiments, the surface area of the interior of the container containing the UAS is greater than about 750 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS is greater than about 800 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS is greater than about 850 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS is approximately 900 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS is less than about 1100 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS is from about 850 cm ² to about 1100 cm ² . In some embodiments, the platelet composition contains at least about 6.0x1011 platelets. In some embodiments, the platelet composition contains at least about 7.0x1011 platelets. In some embodiments, the platelet composition contains at least about 8.0x1011 platelets. In some embodiments, the platelet composition contains at least about 11.0x1011 platelets. In some embodiments, the platelet composition contains less than about 12.0x1011 platelets. In some embodiments, the platelet composition contains from about 6.0x1011 to about 12.0x1011 platelets. In some embodiments, the platelet composition has a volume of at least about 350 ml. In some embodiments, the platelet composition has a volume of at least about 400 ml. In some embodiments, the platelet composition has a volume of at least about 450 ml. In some embodiments, the platelet composition has a volume of at least about 500 ml. In some embodiments, the platelet composition has a volume of at least about 600 ml. In some embodiments, the platelet composition has a volume of less than about 650 ml. In some embodiments, the platelet composition has a volume of from about 350 ml to about 650 ml. In some embodiments, the platelet composition comprises plasma. In some embodiments, the platelet composition does not contain an additional platelet solution. In some embodiments, the platelet composition contains an additional platelet solution. In some embodiments, the platelet composition will contain from about 53% to about 68% of the additional platelet solution. In some embodiments, the platelet composition comprises platelets suspended in a suspension medium consisting essentially of plasma. In some embodiments, the method includes, prior to step (a), collecting one or more platelet donations from one or more donors. In some embodiments, the platelet composition is prepared from apheresis. In some embodiments, the platelet composition is prepared from whole blood. In some embodiments, the platelet composition comprises a single platelet donation. In some embodiments, the platelet composition comprises two platelet donations. In some embodiments, the platelet composition contains three or more platelet donations. In some embodiments, the UAS contains at least about three grams of absorbent beads. In some embodiments, the UAS contains less than about seven grams of absorbent beads. In some embodiments, the UAS contains at least about seven grams of absorbent beads. In some embodiments, the method includes, prior to step (a), sterilely connecting a container containing the platelet composition to a container containing IPA. In some embodiments, the method further includes: after step (d), storing the pathogen-inactivated platelet composition in one or more storage containers for at least 5 days at room temperature. In some embodiments, storage lasts for at least 6 days at room temperature. In some embodiments, storage lasts for at least 7 days at room temperature. In some embodiments, storage lasts for up to 7 days at room temperature. IN

- 2 044317 in some embodiments, the pH (eg, pH ₂₂ ° _C ) of the pathogen-inactivated platelet composition after storage is >6.2. In some embodiments, the pH (eg, pH ₂₂ ° _C ) of the pathogen-inactivated platelet composition after storage is >6.4. In some embodiments, after step (c) and before step (d), the pathogen-inactivated platelet composition is stored in a container containing the UAS for about 4 to about 24 hours. In some embodiments, the pathogen-inactivated platelet composition is one or more pathogen-inactivated platelet units suitable for infusion. In some embodiments, the pathogen-inactivated platelet composition is a single pathogen-inactivated platelet unit suitable for infusion. In some embodiments, the pathogen-inactivated platelet composition is two pathogen-inactivated platelet units suitable for infusion. In some embodiments, the pathogen-inactivated platelet composition is three pathogen-inactivated platelet units suitable for infusion. In some embodiments, the pathogen-inactivated platelet unit suitable for infusion is a therapeutic dosage unit of pathogen-inactivated platelets. In some embodiments, the pathogen-inactivated platelet composition contains at least 2.0x1011 platelets. In some embodiments, the pathogen-inactivated platelet composition contains at least 2.4x1011 platelets. In some embodiments, the pathogen-inactivated platelet composition contains at least 3.0x1011 platelets.

In one aspect, provided herein is a pathogen-inactivated platelet composition prepared by a method in accordance with any of the above embodiments. In some embodiments, the pathogen-inactivated platelet composition is one or more pathogen-inactivated platelet units suitable for infusion. In some embodiments, the pathogen-inactivated platelet composition is a single pathogen-inactivated platelet unit suitable for infusion. In some embodiments, the pathogen-inactivated platelet composition is two pathogen-inactivated platelet units suitable for infusion. In some embodiments, there are three pathogen-inactivated platelet units suitable for infusion. In some embodiments, the pathogen-inactivated platelet unit suitable for infusion is a therapeutic dosage unit of pathogen-inactivated platelets. In some embodiments, the pathogen-inactivated platelet composition contains at least 2.0x1011 platelets. In some embodiments, the pathogen-inactivated platelet composition contains at least 2.4x1011 platelets. In some embodiments, the pathogen-inactivated platelet composition contains at least 3.0x1011 platelets.

In one aspect, provided herein is a method of infusing a platelet composition to a subject in need thereof, wherein the method comprises infusing the subject with a pathogen-inactivated platelet composition obtained by a method of any of the above embodiments, or a pathogen-inactivated platelet composition according to any of the above embodiments.

In one aspect, provided herein is a processing kit for producing a pathogen-inactivated platelet composition, comprising: (a) a first container that contains a pathogen-inactivating compound (PIC) and is suitable for combining the platelet composition with the PIC; (b) a second container connected to the first container, in which the platelet composition mixed with IPA can be photochemically inactivated; and (c) a third container containing a compound adsorption device (CAD), wherein the third container is connected to the second container so that the photochemically inactivated platelet composition can be transferred from the second container to the third container under sterile conditions; where at least one of (i) and (ii) applies: (i) the volume of the third container is greater than 1.0 L; and (ii) the surface area of the interior of the third container is greater than about 750 cm ² . In some embodiments, the treatment kit further comprises one or more fourth containers, wherein the one or more fourth containers are connected to a third container so that the photochemically inactivated platelet composition can be transferred from the third container to the one or more fourth containers under sterile conditions to produce a pathogen -inactivated platelet composition. In some embodiments, the treatment kit contains one fourth container. In some embodiments, the treatment kit contains two fourth containers. In some embodiments, the treatment kit contains three-fourths of the container. In some embodiments, the volume of the third container is greater than 1.0 liters. In some embodiments, the volume of the third container is greater than 1.1 liters. In some embodiments, the third container has a volume greater than about 1.2 liters. In some embodiments, the third container has a volume of approximately 1.3 liters. In some embodiments, the third container has a volume of approximately 1.5 liters. In some embodiments, the volume of the third container is less than 1.6 liters. In some embodiments, the volume of the third container is from about 1.2 L to about 1.6 L. In some embodiments, the surface area of the interior of the third container is greater than about 750 cm ² . In some embodiments, the surface area of the interior of the third container is greater than about 800 cm ² . In some embodiments, the surface area of the interior of the third container is greater than about 850 cm ² . In some embodiments, the surface area

- 3 044317 size of the inside of the container containing the UAS, approximately 900 cm ² . In some embodiments, the surface area of the interior of the third container is less than about 1100 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS is from about 850 cm ² to about 1100 cm ² . In some embodiments, the platelet composition contains at least about 6.0x1011 platelets. In some embodiments, the platelet composition contains at least about 7.0x1011 platelets. In some embodiments, the platelet composition contains at least about 8.0x1011 platelets. In some embodiments, the platelet composition contains at least about 11.0x1011 platelets. In some embodiments, the platelet composition contains less than about 12.0x1011 platelets. In some embodiments, the platelet composition contains from about 6.0x1011 to about 12.0x1011 platelets. In some embodiments, the platelet composition has a volume of at least about 350 ml. In some embodiments, the platelet composition has a volume of at least about 400 ml. In some embodiments, the platelet composition has a volume of at least about 450 ml. In some embodiments, the platelet composition has a volume of at least about 500 ml. In some embodiments, the platelet composition has a volume of at least about 600 ml. In some embodiments, the platelet composition has a volume of less than about 650 ml. In some embodiments, the platelet composition has a volume of from about 350 ml to about 650 ml. In some embodiments, the platelet composition comprises plasma. In some embodiments, the platelet composition does not contain an additional platelet solution. In some embodiments, the platelet composition contains an additional platelet solution. In some embodiments, the platelet composition contains from about 53% to about 68% additional platelet solution. In some embodiments, the platelet composition comprises platelets suspended in a suspension medium consisting essentially of plasma. In some embodiments, the platelet composition comprises one or more platelet donations from one or more donors. In some embodiments, the platelet composition is obtained from apheresis. In some embodiments, the platelet composition is derived from whole blood. In some embodiments, the platelet composition comprises a single platelet donation. In some embodiments, the platelet composition comprises two platelet donations. In some embodiments, the platelet composition contains three or more platelet donations. In some embodiments, the UAS contains at least about three grams of absorbent beads. In some embodiments, the UAS contains less than about seven grams of absorbent beads. In some embodiments, the UAS contains at least about seven grams of absorbent beads. In some embodiments, the first container is suitable for sterile connection with a container containing the platelet composition. In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 5 days at room temperature. In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 6 days at room temperature. In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 7 days at room temperature. In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for up to 7 days at room temperature. In some embodiments, the pH (eg, pH ₂₂ ° _C ) of the pathogen-inactivated platelet composition after storage is >6.2. In some embodiments, the pH (eg, pH ₂₂ ° _C ) of the pathogen-inactivated platelet composition after storage is >6.4. In some embodiments, the third container is suitable for storing the pathogen-inactivated platelet composition for about 4 to about 24 hours. In some embodiments, the pathogen-inactivated platelet composition is one or more pathogen-inactivated platelet units suitable for infusion. In some embodiments, the pathogen-inactivated platelet composition is a single pathogen-inactivated platelet unit suitable for infusion. In some embodiments, the pathogen-inactivated platelet composition is two pathogen-inactivated platelet units suitable for infusion. In some embodiments, there are three pathogen-inactivated platelet units suitable for infusion. In some embodiments, the pathogen-inactivated platelet unit suitable for infusion is a therapeutic dosage unit of pathogen-inactivated platelets. In some embodiments, the pathogen-inactivated platelet composition contains at least 2.0x1011 platelets. In some embodiments, the pathogen-inactivated platelet composition contains at least 2.4x1011 platelets. In some embodiments, the pathogen-inactivated platelet composition contains at least 3.0x1011 platelets.

In one aspect, the present invention provides a kit comprising a processing kit for producing a pathogen-inactivated platelet composition and instructions for use of a processing kit for producing a pathogen-inactivated platelet composition, wherein the kit for preparing

- 4 044317 container contains: (a) a first container that contains a pathogen-inactivating compound (PAC) and is suitable for combining a composition of platelets and PIA; (b) a second container connected to the first container, in which the platelet composition mixed with IPA can be photochemically inactivated; and (c) a third container containing a compound adsorption device (CAD), wherein the third container is connected to the second container so that the photochemically inactivated platelet composition can be transferred from the second container to the third container under sterile conditions; where at least one of (i) and (ii) applies: (i) the volume of the third container is greater than 1.0 L; and (ii) the surface area of the interior of the third container is greater than about 750 cm ² . In some embodiments, the treatment kit further comprises one or more fourth containers, wherein the one or more fourth containers are connected to a third container so that the photochemically inactivated platelet composition can be transferred from the third container to the one or more fourth containers under sterile conditions to produce a pathogen -inactivated platelet composition. In some embodiments, the treatment kit contains one fourth container. In some embodiments, the treatment kit contains two fourth containers. In some embodiments, the treatment kit contains three-fourths of the container. In some embodiments, the volume of the third container is greater than 1.0 liters. In some embodiments, the volume of the third container is greater than 1.1 liters. In some embodiments, the third container has a volume greater than about 1.2 liters. In some embodiments, the third container has a volume of approximately 1.3 liters. In some embodiments, the third container has a volume of approximately 1.5 liters. In some embodiments, the volume of the third container is less than 1.6 liters. In some embodiments, the volume of the third container is from about 1.2 L to about 1.6 L. In some embodiments, the surface area of the interior of the third container is greater than about 750 cm ² . In some embodiments, the surface area of the interior of the third container is greater than about 800 cm ² . In some embodiments, the surface area of the interior of the third container is greater than about 850 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS is approximately 900 cm ² . In some embodiments, the surface area of the interior of the third container is less than about 1100 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS is from about 850 cm ² to about 1100 cm ² . In some embodiments, the instructions indicate that the treatment kit is suitable for processing a platelet composition containing at least about 6, 0x1011 platelets. In some embodiments, the instructions state that the processing kit is suitable for processing a platelet composition containing at least about 7.0 x 1011 platelets. In some embodiments, the instructions state that the processing kit is suitable for processing a platelet composition containing at least about 8.0 x 1011 platelets. In some embodiments, the instructions state that the processing kit is suitable for processing a platelet composition containing at least about 11.0 x 1011 platelets. In some embodiments, the instructions state that the treatment kit is suitable for processing a platelet composition containing less than about 12.0 x 1011 platelets. In some embodiments, the instructions state that the treatment kit is suitable for processing a platelet composition containing from about 6.0x1011 to about 12.0x1011 platelets. In some embodiments, the instructions state that the treatment kit is suitable for treating a platelet composition having a volume of at least about 350 ml. In some embodiments, the instructions state that the treatment kit is suitable for treating a platelet composition having a volume of at least about 400 ml. In some embodiments, the instructions state that the treatment kit is suitable for treating a platelet composition having a volume of at least about 450 ml. In some embodiments, the instructions state that the treatment kit is suitable for treating a platelet composition having a volume of at least about 500 ml. In some embodiments, the instructions state that the treatment kit is suitable for treating a platelet composition having a volume of at least about 600 ml. In some embodiments, the instructions state that the processing kit is suitable for processing a platelet composition having a volume of less than about 650 ml. In some embodiments, the instructions state that the treatment kit is suitable for processing a platelet composition having a volume of from about 350 ml to about 650 ml. In some embodiments, the platelet composition comprises plasma. In some embodiments, the platelet composition does not contain an additional platelet solution. In some embodiments, the platelet composition contains an additional platelet solution. In some embodiments, the platelet composition contains from about 53% to about 68% additional platelet solution. In some embodiments, the platelet composition comprises platelets suspended in a suspension medium consisting essentially of plasma. In some embodiments, the platelet composition comprises one or more platelet donations from one or more donors. In some embodiments, the platelet composition is obtained from apheresis. In some embodiments, the platelet composition is derived from whole blood. In some embodiments, the platelet composition comprises a single platelet donation. In some embodiments, the platelet composition contains two platelet donations. In some embodiments, the composition

- 5 044317 platelets contains three or more platelet donations. In some embodiments, the UAS contains at least about three grams of absorbent beads. In some embodiments, the UAS contains less than about seven grams of absorbent beads. In some embodiments, the UAS contains at least about seven grams of absorbent beads. In some embodiments, the first container is suitable for sterile connection with a container containing the platelet composition. In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 5 days at room temperature. In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 6 days at room temperature. In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 7 days at room temperature. In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for up to 7 days at room temperature. In some embodiments, the instructions indicate that the treatment kit (eg, one or more quarter containers) is suitable for storing the pathogen-inactivated platelet composition for at least 5 days at room temperature. In some embodiments, the instructions indicate that the treatment kit (eg, one or more quarter containers) is suitable for storing the pathogen-inactivated platelet composition for at least 6 days at room temperature. In some embodiments, the instructions indicate that the treatment kit (eg, one or more quarter containers) is suitable for storing the pathogen-inactivated platelet composition for at least 7 days at room temperature. In some embodiments, the instructions indicate that the treatment kit (eg, one or more quarter containers) is suitable for storing the pathogen-inactivated platelet composition for up to 7 days at room temperature. In some embodiments, the pH (eg, pH ₂₂ ° _C ) of the pathogen-inactivated platelet composition after storage is >6.2. In some embodiments, the pH (eg, pH ₂₂ ° _C ) of the pathogen-inactivated platelet composition after storage is >6.4. In some embodiments, the third container is suitable for storing the pathogen-inactivated platelet composition for about 4 to about 24 hours.

It should be understood that one, some, or all of the properties of the various embodiments described herein may be combined to form other embodiments. These and other aspects will become apparent to one skilled in the art. These and other options are further described in the detailed description that follows.

Description of the figures

In fig. 1 shows a typical processing kit for use in producing a pathogen-inactivated platelet composition in accordance with some embodiments. The dotted components depict a single container of platelets (eg, donor platelets) sterilely connected to the processing kit. Abbreviations: IPA, pathogen-inactivating compound; UAS, compound adsorption device. The drawing is not to scale.

In fig. 2 shows a typical processing kit for use in producing a pathogen-inactivated platelet composition in accordance with some embodiments. The dotted components depict a single container of platelets (eg, donor platelets) sterilely connected to the processing kit. Abbreviations: IPA, pathogen-inactivating compound; UAS, compound adsorption device. The drawing is not to scale.

In fig. 3 shows a typical processing kit for use in producing a pathogen-inactivated platelet composition in accordance with some embodiments. The dotted components depict a single container of platelets (eg, donor platelets) sterilely connected to the processing kit. Abbreviations: IPA, pathogen-inactivating compound; UAS, compound adsorption device. The drawing is not to scale.

In fig. 4 shows a typical processing kit for use in producing a pathogen-inactivated platelet composition in accordance with some embodiments. The dotted components depict two platelet containers (eg, Donor Platelet 1, Donor Platelet 2) sterilely connected to each other (eg, for pooling) and to a processing kit. Abbreviations: IPA, pathogen-inactivating compound; UAS, compound adsorption device. The drawing is not to scale.

Detailed description

The term pathogen inactivation method means a method used to inactivate pathogens that may be present in a platelet preparation or other platelet composition, such as donor platelets, it being understood that the method does not necessarily completely inactivate all pathogens that may be present, but substantially reduces the number pathogens to significantly reduce the risk of transfusion-associated disease (eg, transfusion-transmitted infection, BTTI). Pathogen inactivation can be assessed by measuring the amount

- 6 044317 the presence of infectious pathogens (eg, viral particles, bacteria) in a certain volume before and after the pathogen inactivation method, and the level of inactivation is usually expressed as a logarithmic reduction in pathogen infectivity or a logarithmic reduction in titer. Methods for assessing the log reduction in titer and measuring it for pathogen inactivation are known in the art. When the inactivation method is tested for a variety of pathogens, the reduction in the specific active pathogen is at least about 1 log, at least about 2 log, at least about 3 log, at least about 4 log, or at least at least approximately 5 log reduction in titer. A variety of pathogen inactivation methods are known in the art and can be used in the methods of this invention, including, for example, commercially available pathogen inactivation methods such as the INTERCEPT™ Blood System (Cerus Corp). In certain embodiments, the method of inactivating a pathogen may include treatment with a pathogen-inactivating compound.

The term pathogen-inactivating compound means any suitable compound, such as a small organic compound, that can be used to inactivate a pathogen that may be present in a platelet-containing blood product. A photoactivated pathogen-inactivating compound is a suitable compound that requires a certain amount of light (eg, ultraviolet light) to sufficiently inactivate (eg, photochemically inactivate) the pathogen. Such compounds are preferred for inactivating pathogens in platelet products because they provide control of the inactivation process. Such photoactivated pathogen-inactivating compounds described herein include psoralens, isoalloxazines, alloxazines, phthalocyanines, phenothiazines and porphyrins, where these terms cover a general class of compounds, i.e. the basic compound and its suitable derivatives. For example, psoralens or psoralen generally describes the main compound psoralen and its derivatives (eg, amotosalen), isoalloxazins or isoalloxazine generally describes the main compound isoalloxazin and any derivatives thereof (eg, riboflavin), and so on. Such derivatives contain the basic structure of the compound, as well as additional substituents to the base. Descriptions of such compounds include any salts thereof.

The term amotosalen means the compound 3-(2-aminoethoxymethyl)-2,5,9-trimethylfuro[3,2g]chromen-7-one and any salts thereof. The compound may also be called 4'-(4-amino-2-oxa)butyl-4,5',8trimethylpsoralen. The compound may also be called 3-[(2-aminoethoxy)methyl]-2.5.9-trimethyl-7Hfuro[3,2-g][1]benzopyran-7-one. If platelet inactivation involves the addition of amotosalen HCl (HCl salt of amotosalen) to the platelet composition, removal of this compound from the platelet composition is not limited to removal of amotosalen HCl, since amotosalen may be present in solution as other salts or as a free base. As used in the methods described herein, removal of amotosalen means removal of the compound in any form, such as the free base or any salt, as measured in the studies described herein.

The term suitable for infusion refers to a platelet composition (eg, a pathogen-inactivated platelet composition) capable of being infused (eg, transfused) into a subject (eg, a human) as prescribed by a physician. In some embodiments, suitability refers to having sufficient biological activity for the intended use, i.e., for use where human platelet infusion is indicated, including, without limitation, prophylactic and therapeutic infusion such as, for example, treating thrombocytopenia or reducing the risk of bleeding. in patients susceptible to treatment-induced hypoproliferative thrombocytopenia. In some embodiments, suitability refers to having sufficient security. In some embodiments, suitability refers to meeting one or more standards (eg, having suitable characteristics, having a level of biological activity or function, having at least a minimum dose of platelets) established by an accrediting agency or regulatory body that governs the practice of infusion, such like AABB.

Pathogen-inactivated platelet compositions and methods.

In certain aspects of the present invention, pathogen-inactivated platelet compositions and related methods (eg, methods of production) are provided. A particular benefit, among others, provided by the improvements described herein is the ability to obtain pathogen-inactivated platelet compositions that retain favorable characteristics (particularly, suitable pH, but also including, but not limited to, any of dissolved hydrogen, carbon dioxide, glucose , lactate, ATP, LDH, p-selectin expression (e.g. CD62P), cellular morphology (e.g. morphology score), degree of shape change or SIF and hypotonic shock response or HSR) over a longer period and/or at levels similar to unprocessed (eg, non-pathogen inactivated) platelet compositions during storage after pathogen inactivation (eg, as described herein), as opposed to those produced by existing processing methods and kits. Such characteristics may be known in the art and measured by conventional methods, such as, for example, using assays known in the art. The discovery of this invention is that the conditions under which a platelet composition whose pathogens have been inactivated by photochemical treatment

- 7 044317 which are subjected to treatment with a compound adsorption device or UAS (eg, stored with UAS, incubated with UAS), can significantly improve the characteristics (for example, outlet pH) of the pathogen-inactivated platelet composition after storage, after the pathogen inactivation process. The improved characteristics are particularly useful for processing large quantities (eg, quantities) of platelets, including large quantities of platelets suspended in plasma at higher concentrations (eg, 100% plasma). The methods, compositions and treatment kits described herein provide pathogen-inactivated platelet compositions with improved pH even after pathogen inactivation and storage (eg, up to 7 days).

In some embodiments, methods in accordance with the present invention for producing a pathogen-inactivated platelet composition include: (a) mixing the platelet composition with a pathogen-inactivating compound (PIC); (b) photochemical inactivation of the platelet composition mixed with IPA; and transferring the resulting mixture from step (b) under sterile conditions into a container containing a compound adsorption device (CAD) to obtain a pathogen-inactivated platelet composition, wherein at least one of (i) and (ii) is used: (i) the volume of the container containing the UAS is greater than 1.0 L (for example, approximately 1.2 L or more); and (ii) the surface area of the interior of the container containing the UAS is greater than about 750 cm ² (eg, about 800 cm ² or greater). Also provided are pathogen-inactivated platelet compositions prepared by any of the methods in accordance with this invention.

In some embodiments, the volume of the container containing the UAS in accordance with this invention is greater than 1.0 liters (L), greater than about 1.1 L, greater than about 1.2 L, greater than about 1.3 L, greater than about 1.4 l, greater than approximately 1.5 l or greater than approximately 1.6 l. In some embodiments, the volume of the container containing the UAS in accordance with this invention is less than about any of the following volumes: 1.6 L, 1.5 L, 1.4 L, 1.3 L, or 1.2 L. In some embodiments, the volume of the container containing the UAS in accordance with this invention is greater than about any of the following volumes: 1.1 L, 1.2 L, 1.3 L, 1.4 L, or 1.5 L. That is, the volume of the container containing the UAS according to the present invention may be any volume within the range having an upper limit of 1.6 L, 1.5 L, 1.4 L, 1.3 L or 1.2 L, and independently selected lower limit of 1.1 L, 1.2 L, 1.3 L, 1.4 L or 1.5 L, where the upper limit is greater than the lower limit. In certain embodiments, the volume of the container containing the UAS in accordance with this invention is from about 1.1 L to about 1.6 L, from about 1.1 L to about 1.5 L, from about 1.1 L to about 1.4 L, from about 1.1 L to about 1.3 L, from about 1.1 L to about 1.2 L, from about 1.2 L to about 1.6 L, from about 1.2 L to about 1.5 L, from about 1.2 L to about 1.4 L, from about 1.2 L to about 1.3 L, from about 1.3 L to about 1.6 L, from about 1, 3 L to about 1.5 L, about 1.3 L to about 1.4 L, about 1.4 L to about 1.6 L, about 1.4 L to about 1.5 L, or about 1.5 L to approximately 1.6 L. In some embodiments, the volume of the container containing the UAS in accordance with this invention is about 1.1 L, about 1.2 L, about 1.3 L, about 1.4 L, about 1.5 L, or about 1.6 l.

In some embodiments, the surface area of the interior (e.g., internal surface area) of the container containing the UAS in accordance with this invention is greater than about 750 cm ² , greater than about 800 cm 2 , greater than about 850 ^{cm 2} , greater than about 900 cm ² , greater than greater than about 950 cm ² , greater than about 1000 cm ² , greater than about 1050 cm ² , greater than about 1100 cm ² , greater than about 1150 cm 2 , greater than about 1200 cm ^{2 or} greater than about 1300 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is less than about 1400 cm ² , less than about 1300 cm ² , less than about 1200 cm ² , less than about 1150 cm ² , less than about 1100 cm ² , less than about 1050 cm ² , less than about 1000 cm ² , less than about 950 cm ² , less than about 900 cm ² , less than about 850 cm ² or less than about 800 cm ² . That is, the surface area of the inside of the container containing the UAS according to the present invention may be a surface area in the range having an upper limit of 1400 cm ² , 1300 cm ² , 1200 cm ² , 1150 cm ² , 1100 cm ² , 1050 cm ² , 1000 cm ² , 950 cm ² , 900 cm ² , 850 cm ² or 800 cm ² and independently selected lower limit 750 cm ² , 800 cm ² , 850 cm ² , 900 cm ² , 950 cm ² , 1000 cm ² , 1050 cm ² , 1100 cm ² , 1150 cm ² , 1200 cm ² or 1300 cm ² , where the upper limit is greater than the lower limit. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is about 750 cm ² , about 800 cm ^{2 , about 850 cm 2 ,} about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , approximately 1100 cm ² , approximately 1150 cm ² or approximately 1200 cm ² . In certain embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is from about 750 cm ² to about 1400 cm ² , from about 750 cm ² to about 1300 cm ² , from about 750 cm ² to about 1200 cm ² , from about 750 cm ² to about 1150 cm ² , from about 750 cm ² to approx.

- 8 044317 especially 1100 cm ² , from about 750 cm ² to about 1050 cm ² , from about 750 cm ² to about 1000 cm ² , from about 750 cm ² to about 950 cm ² , from about 750 cm ² to about 900 cm ² , from about 750 cm ² to about 850 cm ² , from about 750 cm ² to about 800 cm ² , from about 800 cm ² to about 1400 cm ² , from about 800 cm ² to about 1300 cm ² , from about 800 cm ² to about 1200 cm ² , from about 800 cm ² to about 1150 cm ² , from about 800 cm ² to about 1100 cm ² , from about 800 cm ² to about 1050 cm ² , from about 800 cm ² to about 1000 cm ² , from about 800 cm ² to about 950 cm ² , from about 800 cm ² to about 900 cm ² , from about 800 cm ² to about 850 cm ² , from about 850 cm ² to about 1400 cm ² , from about 850 cm ² to about 1300 cm ² , from about 850 cm ² to about 1200 cm ² , from about 850 cm ² to about 1150 cm ² , from about 850 cm ² to about 1100 cm ² , from about 850 cm ² to about 1050 cm ² , from about 850 cm ² to about 1000 cm ² , from about 850 cm ² to about 950 cm ² , from about 850 cm ² to about 900 cm ² , from about 900 cm ² to about 1400 cm ² , from about 900 cm ² to about 1300 cm ² , from about 900 cm ² to about 1200 cm ² , from about 900 cm ² to about 1150 cm ² , from about 900 cm ² to about 1100 cm ² , from about 900 cm ² to about 1050 cm ² , from about 900 cm ² to about 1000 cm ² , from about 900 cm ² to about 950 cm ² , from about 950 cm ² to about 1400 cm ² , from about 950 cm ² to about 1300 cm ² , from about 950 cm ² to about 1200 cm ² , from about 950 cm ² to about 1150 cm ² , from about 950 cm ² to about 1100 cm ² , from about 950 cm ² to about 1050 cm ² , from about 950 cm ² to about 1000 cm ² , from about 1000 cm ² to about 1400 cm ² , from about 1000 cm ² to about 1300 cm ² , from about 1000 cm ² to about 1200 cm ² , from about 1000 cm ² to about 1150 cm ² , from about 1000 cm ² to about 1100 cm ² , from about 1000 cm ² to about 1050 cm ² , from about 1050 cm ² to about 1400 cm ² , from about 1050 cm ² to about 1300 cm ² , from about 1050 cm ² to about 1200 cm ² , from about 1050 cm ² to about 1150 cm ² , from about 1050 cm ² to about 1100 cm ² , from about 1100 cm ² to about 1400 cm ² , from about 1100 cm ² to about 1300 cm ² , from about 1100 cm ² to about 1200 cm ² , from about 1200 cm ² to about 1400 cm ² , from about 1200 cm ² to about 1300 cm ² , or from about 1300 cm ² to about 1400 cm ² .

In some embodiments, the volume of the container containing the UAS in accordance with the present invention is greater than 1.0 liters and the surface area of the interior (e.g., internal surface area) of the container containing the UAS is greater than about 750 cm ² greater than about 800 cm ² greater than about 850 cm ² , greater than about 900 cm ² , greater than about 950 cm ² , greater than about 1000 cm 2 , greater than about 1050 cm ² , greater than about 1100 cm ² , greater than about 1150 cm ² , greater than about 1200 cm ^{2 or} greater than about 1300 cm ² . In some embodiments, the volume of the container containing the UAS in accordance with the present invention is greater than about 1.1 liters and the surface area of the interior (e.g., internal surface area) of the container containing the UAS is greater than about 750 cm ² greater than about 800 cm ² greater greater than about 850 cm ² , greater than about 900 cm ² , greater than about 950 cm ² , greater than about 1000 cm ² , greater than about 1050 cm ² , greater than about 1100 cm ² , greater than about 1150 cm ² , greater than about 1200 cm ² or greater than about 1300 cm ² . In some embodiments, the volume of the container containing the UAS in accordance with the present invention is greater than about 1.2 liters and the surface area of the interior (e.g., internal surface area) of the container containing the UAS is greater than about 750 cm ² greater than about 800 cm ² greater greater than about 850 cm ² , greater than about 900 cm ² , greater than about 950 cm ² , greater than about 1000 cm ² , greater than about 1050 cm ² , greater than about 1100 cm ² , greater than about 1150 cm ² , greater than about 1200 cm ² or greater than about 1300 cm ² . In some embodiments, the volume of the container containing the UAS in accordance with the present invention is greater than about 1.3 liters, and the surface area of the interior (e.g., internal surface area) of the container containing the UAS is greater than about 750 cm ² , greater than about 800 cm ² , greater than about 850 cm ² , greater than about 900 cm ² , greater than about 950 cm ² , greater than about 1000 cm ² , greater than about 1050 cm ² , greater than about 1100 cm ² , greater than about 1150 cm ² , greater than about 1200 cm ² or greater than approximately 1300 cm ² . In some embodiments, the volume of the container containing the UAS in accordance with the present invention is greater than about 1.4 liters, and the surface area of the interior (e.g., internal surface area) of the container containing the UAS is greater than about 750 cm ² , greater than about 800 cm ² , greater than about 850 cm ² , greater than about 900 cm ² , greater than about 950 cm ² , greater than about 1000 cm ² , greater than about 1050 cm ² , greater than about 1100 cm ² , greater than about 1150 cm ² , greater than approximately

- 9 044317

1200 cm ² or more approximately 1300 cm ² . In some embodiments, the volume of the container containing the UAS in accordance with the present invention is greater than about 1.5 liters, and the surface area of the interior (e.g., internal surface area) of the container containing the UAS is greater than about 750 cm ² , greater than about 800 cm ² , greater than about 850 cm ² , greater than about 900 cm ² , greater than about 950 cm ² , greater than about 1000 cm ² , greater than about 1050 cm ² , greater than about 1100 cm ² , greater than about 1150 cm ² , greater than about 1200 cm 2 or greater than about 1300 cm ² . In some embodiments, the volume of the container containing the UAS in accordance with the present invention is greater than about 1.6 liters, and the surface area of the interior (e.g., internal surface area) of the container containing the UAS is greater than about 750 cm ² , greater than about 800 cm ² , greater than about 850 cm ² , greater than about 900 cm ² , greater than about 950 cm ² , greater than about 1000 cm ² , greater than about 1050 cm ² , greater than about 1100 cm ² , greater than about 1150 cm ² , greater than about 1200 cm ² or greater than approximately 1300 cm ² . In some embodiments, the volume of the container containing the UAS is less than about any of the following volumes (in L): 1.6, 1.5, 1.4, 1.3, or 1.2. In some embodiments, the volume of the container containing the UAS is about 1.1 L, about 1.2 L, about 1.3 L, about 1.4 L, about 1.5 L, or about 1.6 L. In some embodiments, the surface area of the container containing the UAS is less than about 1400 cm ² , less than about 1300 cm ² , less than about 1200 cm ² , less than about 1150 cm ² , less than about 1100 cm ² , less than about 1050 cm ² , less than about 1000 cm ² , less than about 950 cm ² , less than about 900 cm ² , less than about 850 cm ² or less than about 800 cm ² . In some embodiments, the surface area of the container containing the UAS is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , about 1100 cm ² , approximately 1150 cm ² or approximately 1200 cm ² .

In some embodiments, the volume of the container containing the UAS in accordance with this invention is from about 1.1 L to about 1.6 L, and the surface area of the container containing the UAS is from about 750 cm ² to about 1400 cm ² , from about 800 cm ² to about 1300 cm ² , from about 800 cm ² to about 1200 cm ² , from about 850 cm ² to about 1200 cm ² , from about 850 cm ² to about 1150 cm ² or from about 850 cm ² to about 1100 cm ² . In some embodiments, the volume of the container containing the UAS in accordance with this invention is from about 1.2 L to about 1.6 L, and the surface area of the container containing the UAS is from about 750 cm ² to about 1400 cm ² , from about 800 cm ² to about 1300 cm ² , from about 800 cm ² to about 1200 cm ² , from about 850 cm ² to about 1200 cm ² , from about 850 cm ² to about 1150 cm ² or from about 850 cm ² to about 1100 cm ^2. In some embodiments, the volume of the container containing the UAS in accordance with this invention is from about 1.2 L to about 1.5 L, and the surface area of the container containing the UAS is from about 750 cm ² to about 1400 cm ² , from about 800 cm ² to about 1300 cm ² , from about 800 cm ² to about 1200 cm ² , from about 850 cm ² to about 1200 cm ² , from about 850 cm ² to about 1150 cm ² or from about 850 cm ² to about 1100 cm ² . In some embodiments, the volume of the container containing the UAS in accordance with this invention is from about 1.2 L to about 1.4 L, and the surface area of the container containing the UAS is from about 750 cm ² to about 1400 cm ² , from about 800 cm ² to about 1300 cm ² , from about 800 cm ² to about 1200 cm ² , from about 850 cm ² to about 1200 cm ² , from about 850 cm ² to about 1150 cm ² or from about 850 cm ² to about 1100 cm ² . In some embodiments, the volume of the container containing the UAS in accordance with this invention is about 1.1 liters and the surface area of the container containing the UAS is from about 750 cm ² to about 820 cm ² (for example, about 750 cm ² , about 760 cm ² , approximately 770 cm ² , approximately 780 cm ² , approximately 790 cm ² , approximately 800 cm ² , approximately 810 cm ² , approximately 820 cm ² ). In some embodiments, the volume of the container containing the UAS in accordance with this invention is about 1.2 liters and the surface area of the container containing the UAS is from about 800 cm 2 to about 870 cm ² (for example, about 800 cm ² , about 810 cm ² , approximately 820 cm ² , approximately 830 cm ² , approximately 840 cm ² , approximately 850 cm ² , approximately 860 cm ² , approximately 870 cm ² ). In some embodiments, the volume of the container containing the UAS in accordance with this invention is about 1.3 liters and the surface area of the container containing the UAS is from about 850 cm ² to about 920 cm ² (for example, about 850 cm ² , about 860 cm ² , approximately 870 cm ² , approximately 880 cm ² , approximately 890 cm ² , approximately 900 cm ² , approximately 910 cm ² , approximately 920 cm ² ). In some embodiments, the volume of the container containing the UAS in accordance with the present invention is about 1.5 cm, the surface area of the container containing the UAS is from about 930 cm ² to about 1000 cm ² (for example, about 930 cm ² , about 940 cm ² , approx. 950 cm ² , approx. 960 cm ² , approx.

- 10 044317 = 970 cm ² , approximately 980 cm ² , approximately 990 cm ² , approximately 1000 cm ² ).

In some embodiments, the surface area of the interior of the container containing the UAS in accordance with the present invention is greater than the surface area of the interior of the container containing the UAS (for example, a third container) INTERCEPT™ Blood System (Cerus Corp.) Dual Storage Processing Set, Part Number INT2510. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is at least 3%, at least 5%, at least 10%, at least 15%, at least , 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, or at least 70% greater than the surface area of the interior of the container containing the INTERCEPT™ Blood System Dual Storage Processing Set, Part Number INT2510. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is less than 75%, less than 70%, less than 65%, less than 60%, less than 55%, less than 50%, less than 45%, less than 40%, less than 35%, less than 30%, less than 25%, less than 20%, less than 15%, or less than 10% greater than the surface area of the interior of the container containing the INTERCEPT™ Blood System Dual Storage Processing Set, Part Number INT2510. That is, the surface area of the interior of the container containing the UAS according to the present invention may be any surface area in the range having an upper limit of 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, or 10% greater than the surface area of the interior of the container containing the INTERCEPT™ Blood System Dual Storage Processing Set, Part Number INT2510, and an independently selected lower limit on 3%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65% or 70% greater than the surface area of the inner parts of the container containing the INTERCEPT™ Blood System Dual Storage Processing Set, Part Number INT2510, where the upper limit is greater than the lower limit. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is from about 5% to about 70%, from about 5% to about 65%, from about 5% to about 60%, from about 5% to about 55%, from about 5% to about 50%, from about 5% to about 45%, from about 5% to about 40%, from about 5% to about 35%, from about 5% to about 30%, from about 5% to about 25%, about 5% to about 20%, about 5% to about 15%, about 5% to about 10%, about 10% to about 70%, about 10% to about 65 %, from about 10% to about 60%, from about 10% to about 55%, from about 10% to about 50%, from about 10% to about 45%, from about 10% to about 40%, from about 10 % to about 35%, from about 10% to about 30%, from about 10% to about 25%, from about 10% to about 20%, from about 10% to about 15%, about 15% to about 70%, from about 15% to about 65%, from about 15% to about 60%, from about 15% to about 55%, from about 15% to about 50%, from about 15% to about 45%, from about 15% to about 40%, from about 15% to about 35%, from about 15% to about 30%, from about 15% to about 25%, from about 15% to about 20%, from about 20% to about 70%, from about 20% to about 65%, about 20% to about 60%, about 20% to about 55%, about 20% to about 50%, about 20% to about 45%, about 20% to about 40%, from about 20% to about 35%, from about 20% to about 30%, from about 20% to about 25%, from about 25% to about 70%, from about 25% to about 65%, from about 25% to about 60%, from about 25% to about 55%, from about 25% to about 50%, from about 25% to about 45%, from about 25% to about 40%, from about 25% to about 35 %, from about 25% to about 30%, from about 30% to about 70%, from about 30% to about 65%, from about 30% to about 60%, from about 30% to about 55%, from about 30 % to about 50%, from about 30% to about 45%, from about 30% to about 40%, from about 30% to about 35%, from about 35% to about 70%, from about 35% to about 65% , from about 35% to about 60%, from about 35% to about 55%, from about 35% to about 50%, from about 35% to about 45%, from about 35% to about 40%, from about 40% to about 70%, from about 40% to about 65%, from about 40% to about 60%, from about 40% to about 55%, from about 40% to about 50%, from about 40% to about 45%, from about 45% to about 70%, from about 45%

- 11 044317 to approximately 65%, from approximately 45% to approximately 60%, from approximately 45% to approximately 55%, from approximately 45% to approximately 50%, from approximately 50% to approximately 70%, from approximately 50% to approximately 60% or about 50% to about 70% greater than the surface area of the interior of the container containing the UAS, INTERCEPT™ Blood System Dual Storage Processing Set, Part Number INT2510.

The specified surface area of the interior of the container containing the UAS (eg, the third container) in accordance with the present invention may be an approximate surface area. For example, the interior surface of a container containing a UAS, where the container contains a hemocompatible pouch (eg, PVC pouch, EVA pouch, polyolefin pouch), may exhibit an amount of stretch and, therefore, an amount of surface area change relative to the container in an unstretched state. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention may comprise the specified surface area plus or minus a certain amount. For example, in some embodiments, the surface area of the interior of a container containing the UAS in accordance with this invention is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , approximately 1050 cm ² , approximately 1100 cm ² , approximately 1150 cm ² , approximately 1200 cm ² , approximately 1300 cm ² or approximately 1400 cm ² , each value ±5 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , approximately 1100 cm ² , approximately 1150 cm ² , approximately 1200 cm ² , approximately 1300 cm ² or approximately 1400 cm ² , each value ±10 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , approximately 1100 cm ² , approximately 1150 cm ² , approximately 1200 cm ² , approximately 1300 cm ² or approximately 1400 cm ² , each value ±15 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , approximately 1100 cm ² , approximately 1150 cm ² , approximately 1200 cm ² , approximately 1300 cm ² or approximately 1400 cm ² , each value ±20 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , approximately 1100 cm ² , approximately 1150 cm ² , approximately 1200 cm ² , approximately 1300 cm ² or approximately 1400 cm ² , each value ±25 cm ² . In some embodiments, the volume of the container containing the UAS in accordance with this invention is approximately 1.1 liters, and the surface area of the container containing the UAS is about 750 cm ² , about 760 cm ² , about 770 cm ² , about 780 cm ² , about 790 cm ² , about 800 cm ² , about 810 cm ² or about 820 cm ² (eg, ±5 cm ² , ±10 cm ² , ±15 cm ² , ±20 cm ² , ±25 cm ² ). In some embodiments, the volume of the container containing the UAS in accordance with this invention is approximately 1.2 liters, and the surface area of the container containing the UAS is about 800 cm ² , about 810 cm ² , about 820 cm ² , about 830 cm ² , about 840 cm ² , about 850 cm ² , about 860 cm ² or about 870 cm ² (eg, ±5 cm ² , ±10 cm ² , ±15 cm ² , ±20 cm ² , ±25 cm ² ). In some embodiments, the volume of the container containing the UAS in accordance with this invention is approximately 1.3 liters, and the surface area of the container containing the UAS is about 850 cm ² , about 860 cm ² , about 870 cm ² , about 880 cm ² , about 890 cm ² , about 900 cm ² , about 910 cm ² or about 920 cm ² (eg, ±5 cm ² , ±10 cm ² , ±15 cm ² , ±20 cm ² , ±25 cm ² ). In some embodiments, the volume of the container containing the UAS in accordance with this invention is approximately 1.5 liters, and the surface area of the container containing the UAS is about 930 cm ² , about 940 cm ² , about 950 cm ² , about 960 cm ² , about 970 cm ² , about 980 cm ² , about 990 cm ² or about 1000 cm ² (eg, ±5 cm ² , ±10 cm ² , ±15 cm ² , ±20 cm ² , ±25 cm ² ). In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is approximately 750 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is approximately 800 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is approximately 850 cm ² ±1%,

- 12 044317 ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is approximately 900 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is approximately 950 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is approximately 1000 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is approximately 1050 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is approximately 1100 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is approximately 1150 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention is approximately 1200 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the volume of the container containing the UAS in accordance with this invention is approximately 1.1 liters, and the surface area of the container containing the UAS is about 750 cm ² , about 760 cm ² , about 770 cm ² , about 780 cm ² . about 790 cm ² , about 800 cm ² , about 810 cm ² or about 820 cm ² (eg, ±1%, ±2%, ±3%, ±4% or ±5%). In some embodiments, the volume of the container containing the UAS in accordance with this invention is approximately 1.2 liters, and the surface area of the container containing the UAS is about 800 cm ² , about 810 cm ² , about 820 cm ² , about 830 cm ² . about 840 cm ² , about 850 cm ² , about 860 cm ² or about 870 cm ² (eg, ±1%, ±2%, ±3%, ±4% or ±5%). In some embodiments, the volume of the container containing the UAS in accordance with this invention is approximately 1.3 liters, and the surface area of the container containing the UAS is about 850 cm ² , about 860 cm ² , about 870 cm ² , about 880 cm ² . about 890 cm ² , about 900 cm ² , about 910 cm ² or about 920 cm ² (eg, ±1%, ±2%, ±3%, ±4% or ±5%). In some embodiments, the volume of the container containing the UAS in accordance with this invention is approximately 1.5 liters, and the surface area of the container containing the UAS is about 930 cm ² , about 940 cm ² , about 950 cm ² , about 960 cm ² , about 970 cm ² , about 980 cm ² , about 990 cm ² or about 1000 cm ² (eg, ±1%, ±2%, ±3%, ±4% or ±5%). In some embodiments, the surface area of the interior of a container containing the UAS in accordance with this invention may refer to the interior surface area of the container.

In some embodiments, the platelet composition of the present invention contains at least (e.g., more than) about 6.0 x 1011 platelets, at least about 6.5 x 1011 platelets, at least about 7.0 x 1011 platelets, at least at least about 7.5x1011 platelets, at least about 8.0x1011 platelets, at least about 8.5x1011 platelets, at least about 9.0x1011 platelets, at least about 9.5x10 platelets, at least at least about 10.0x1011 platelets, at least about 10.5x1011 platelets, at least about 11.0x1011 platelets, at least about 11.5x1011 platelets, or at least about 12.0x1011 platelets. In some embodiments, the platelet composition in accordance with this invention contains less than about any of the following platelet values: 12.0x1011, 11.5x1011, 11.0x1011, 10.5x1011, 10.0x1011, 9.5x1011, 9.0x1011, 8. 5x1011, 8.0x1011, 7.5x1011, 7.0x1011 or 6.5x1011. In some embodiments, the platelet composition in accordance with this invention contains more than about any of the following platelet values: 6.0x1011, 6.5x1011, 7.0x1011, 7.5x1011, 8.0x1011, 8.5x1011, 9.0x1011, 9. 5x1011, 10.0x1011, 10.5x1011, 11.0x1011 or 11.5x1011. That is, the platelet composition according to the present invention may contain any number of platelets within the range having an upper limit of 12.0x1011, 11.5x1011, 11.0x1011, 10.5x1011, 10.0x1011, 9.5x1011, 9.0x1011, 8 .5x1011, 8.0x1011, 7.5x1011, 7.0x1011 or 6.5x1011 and independently selected lower limit 6.0x1011, 6.5x1011, 7.0x1011, 7.5x1011, 8.0x1011, 8.5x1011 , 9.0x1011 , 9.5x1011, 10.0x1011, 10.5x1011, 11.0x1011, or 11.5x1011, where the upper limit is greater than the lower limit. In certain embodiments, the platelet composition in accordance with this invention contains from about 6.0x1011 to about 12.0x1011 platelets. In some embodiments, the platelet composition in accordance with this invention contains more than about 6.0x1011 to about 12.0x1011 platelets. In some embodiments, the platelet composition of this invention contains from about 6.5x1011 to about 12.0x1011 platelets. In some embodiments, the platelet composition according to

- 13 044317 of this invention contains from approximately 7.0 x 1011 to approximately 12.0 x 1011 platelets. In some embodiments, the platelet composition of this invention contains from about 7.5 x 1011 to about 12.0 x 1011 platelets. In some embodiments, the platelet composition in accordance with this invention contains from about 8.0x1011 to about 12.0x1011 platelets. In some embodiments, the platelet composition of this invention contains from about 8.5x1011 to about 12.0x1011 platelets. In some embodiments, the platelet composition of this invention contains from about 9.0 x 1011 to about 12.0 x 1011 platelets. In some embodiments, the platelet composition of this invention contains from about 6.0 x 1011 to about 11.0 x 1011 platelets. In some embodiments, the platelet composition of this invention contains from about 6.0x1011 to about 10.0x1011 platelets. In some embodiments, the platelet composition in accordance with this invention contains from about 6.0x1011 to about 9.0x1011 platelets. In some embodiments, the platelet composition of this invention contains from about 6.0x1011 to about 8.0x1011 platelets.

In some embodiments, the platelet composition in accordance with this invention has a volume of at least about 250 ml, at least about 300 ml, at least about 350 ml, at least about 400 ml, at least about 450 ml, at least about 500 ml, at least about 550 ml, at least about 600 ml, or at least about 650 ml. In some embodiments, the platelet composition in accordance with this invention has a volume of less than about 650 ml. In some embodiments, the platelet composition in accordance with this invention has a volume less than about any of the following volumes (in ml): 750, 700, 650, 600, 550, 500, 450, 400, 350, or 300. In some embodiments, the platelet composition in accordance with this invention has a volume greater than approximately any of the following volumes (in ml): 250, 300, 350, 400, 450, 500, 550, 600, 650 or 700. That is, the platelet composition in accordance with this invention may have any volume within a volume range having an upper limit of 750, 700, 650, 600, 550, 500, 450, 400, 350 or 300 ml, and an independently selected lower limit of 250, 300, 350, 400, 450, 500, 550, 600 , 650 or 700 ml, where the upper limit is greater than the lower limit. In certain embodiments, the platelet composition in accordance with this invention has a volume of from about 350 ml to about 650 ml. In certain embodiments, the platelet composition in accordance with this invention has a volume of from about 300 ml to about 650 ml. In certain embodiments, the platelet composition in accordance with this invention has a volume of from about 250 ml to about 650 ml. In certain embodiments, the platelet composition in accordance with this invention has a volume of from about 250 ml to about 450 ml. In certain embodiments, the platelet composition in accordance with this invention has a volume of from about 250 ml to about 400 ml. In certain embodiments, the platelet composition in accordance with this invention has a volume of from about 300 ml to about 450 ml.

In some embodiments, the platelet composition of the present invention comprises platelets suspended in a suspension medium. In some embodiments, the platelet composition of the present invention comprises plasma. In some embodiments, the platelet composition in accordance with this invention contains platelets suspended in 100% plasma. In some embodiments, the platelet composition of the present invention comprises platelets suspended in a suspension medium consisting essentially of plasma. In some embodiments, the platelet composition in accordance with this invention does not contain an additional platelet solution. In other embodiments, the platelet composition in accordance with this invention contains platelet additive solution (DRS). For example, in some embodiments, the platelet composition in accordance with this invention contains from about 53% to about 68% additional platelet solution. A variety of suitable platelet supplement solutions (eg, approved by one or more regulatory authorities) are known in the art. Non-limiting examples of platelet supplement solution include InterSol™ solution (Fenwal, a Fresenius Kabi Company; Lake Zurich, IL), T-PAS+™ solution (Terumo BCT, Inc., Lakewood, CO), PAS III M™ solution (Grifols™, Barcelona, Spain), SSP+™ solution (Macopharma, Tourcoing, France) and Composoi™ solution (Fresenius Kabi). In some embodiments, the platelet composition in accordance with this invention contains from about 32% to about 47% plasma.

In some embodiments, the methods also include transferring the pathogen-inactivated platelet composition under sterile conditions from a container containing the UAS to one or more storage containers (eg, as shown in FIGS. 1-4). For example, a pathogen-inactivated platelet composition can be transferred under sterile conditions from a container containing the UAS into one storage container (see, for example, Fig. 1 of a typical processing kit), two storage containers

- 14 044317 neniya (see, for example, Fig. 2 of a typical processing set) or three storage containers (see, for example, Figs. 3 and 4 of a typical processing kit). In some embodiments, a platelet composition in accordance with this invention can be prepared by collecting one or more platelet donations from one or more donors.

In some embodiments, a platelet composition in accordance with this invention can be prepared by pooling platelets from multiple (eg, two or more) donations. The term pooled platelet preparation refers to a platelet preparation containing platelets obtained from more than one donation, such as an apheresis platelet donation, and then pooled (eg, in a single container). In general, platelet donations are received from different donors. Platelets may be pooled at any stage after donation and prior to therapeutic use, including, but not limited to, pooling before or after any addition of an additive solution, before or after any storage period, and before or after any pathogen-inactivating treatment or method. Platelets can be pooled into any container suitable for platelet preparations and of sufficient size to accommodate the volume of platelets, for example, by sterilely connecting containers with two platelet preparations (eg, connecting tube) and transferring platelets from one container to another, or sterilely connecting containers with two platelet preparations with a third container (eg, connecting tube) and transferring the platelets to the third container.

In some embodiments, a platelet composition in accordance with this invention comprises one or more, two or more, or three or more platelet donations. In some embodiments, a pathogen-inactivated platelet composition in accordance with this invention refers to one or more pathogen-inactivated platelet units suitable for infusion (e.g., one pathogen-inactivated platelet unit suitable for infusion), two pathogen-inactivated platelet units suitable for infusion, or three pathogen-inactivated platelet units suitable for infusion (eg, three pathogen-inactivated platelet units suitable for infusion). In some embodiments, a pathogen-inactivated platelet unit suitable for infusion, such as described herein, refers to a therapeutic dosage unit of pathogen-inactivated platelets. The pathogen-inactivated platelet unit suitable for infusion (e.g., a pathogen-inactivated platelet therapeutic dosage unit) typically (e.g., each) contains a certain minimum number (e.g., at least a certain minimum amount) of platelets per unit to meet the therapeutic dosage requirements, where the criterion per unit or therapeutic dose is usually determined by the standards of a government, regulatory or accrediting organization (eg, industry). Non-limiting examples of such standards include, for example, those set by the FDA, EDQM, AABB, PMDA, TGA and SFDA. The specified minimum, for example, may vary from country to country. For example, in some embodiments, the pathogen-inactivated platelet composition (e.g., pathogen-inactivated platelet infusion unit, therapeutic dosage unit) contains from at least about 2.0x1011 platelets, to at least about 2.2x1011 platelets , from at least about 2.4x1011 platelets, to at least about 2.5x1011 platelets, from at least about 2.6x1011 platelets, to at least about 2.7x1011 platelets, from at least about 2.8x1011 platelets, to at least about 2.9x1011 platelets, or at least about 3.0x1011 platelets.

In some embodiments, the platelet composition in accordance with this invention can be obtained by apheresis. Apheresis generally refers to an automated blood collection device that uses centrifugal or filtration separation to automatically collect whole blood from a donor, separate the whole blood into blood components, collect specific components (such as platelets), and return the remaining whole blood and remaining uncollected components to the donor blood. Thrombpheresis is the collection of platelets using an automated blood cell separation device that produces a high yield of platelets (eg, platelet apheresis) from a single donor. Some automated blood cell separation devices are capable of collecting not only one unit of platelets, but also double and triple units of platelets. Apheresis collection devices are well known in the art, and several such devices 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.).

In some embodiments, the platelet composition in accordance with this invention can be obtained from donor whole blood. Collection of platelets from donor whole blood typically takes the form of platelet concentrates (PCs) obtained using processing methods such as buffy coat or platelet-rich plasma methods, and such PCs can be pooled to produce a platelet unit with a sufficient therapeutic dose for transfusion. In about

- 15 044317 shchem, CT scans from four to six individual donors with compatible blood types are combined to obtain one unit of platelets with a sufficient therapeutic dose for transfusion.

This disclosure may, in certain embodiments, refer in various ways to platelet compositions collected from a donor (e.g., platelet donations, platelet preparations), such as, for example, platelet donations or platelet preparations collected with or without further processing (e.g., leukofiltration) . Typically, references to platelet donations or platelet preparations collected from a donor are made prior to any stage of pooling or combining with additional platelets (eg, from another donor, such as a second donor or third donor) that may yield a pooled platelet preparation.

In some embodiments, the methods further include, prior to mixing the platelet composition with a pathogen-inactivating compound (PIC), sterile connecting a container containing a platelet composition in accordance with the present invention to a container containing a PIC in accordance with the present invention. For example, in some embodiments, the platelet composition container may be connected to the IPA container by sterile tubing. In some embodiments, the platelet composition is mixed with IPA before or during transfer of the platelet composition to a container for photochemical inactivation (ie, photochemical inactivation of the pathogen if present in the platelet composition). In some embodiments, the platelet composition flows through a container containing IPA into a separate container for photochemical inactivation. In other embodiments, each of the container containing the platelet composition and the container containing IPA may be sterilely coupled to a photochemical inactivation container. This may, for example, allow the platelet and IPA composition to flow into the photochemical inactivation container while mixing occurs (eg, prior to photoillumination of the photochemical inactivation container).

In some embodiments, the methods further include, after transferring the pathogen-inactivated platelet composition under sterile conditions from the container containing the UAS to one or more storage containers, storing the pathogen-inactivated platelet composition in the one or more storage containers. Storage of the pathogen-inactivated platelet composition in one or more storage containers can be carried out under any suitable conditions (eg, temperature, agitation, storage period). In some embodiments, after transferring the pathogen-inactivated platelet composition in accordance with the present invention from the UAS container to one or more storage containers, the pathogen-inactivated platelet composition is stored in one or more storage containers for at least 5 days at room temperature (for example, from about 20°C to about 25°C, for example, about ₂₂ ° _C ), at least 6 days at room temperature or at least 7 days at room temperature. In some embodiments, after transferring the pathogen-inactivated platelet composition in accordance with the present invention from the UAS container to one or more storage containers, the pathogen-inactivated platelet composition is stored in the one or more storage containers for about 5 days, about 6 days or approximately 7 days at room temperature (eg, as described above). In some embodiments, after transferring the pathogen-inactivated platelet composition in accordance with the present invention from the UAS container to one or more storage containers, the pathogen-inactivated platelet composition is stored in the one or more storage containers for up to 7 days at room temperature (eg as described above).

In some embodiments, the pH of the pathogen-inactivated platelet composition of the present invention after storage (e.g., as described above) is greater than or equal to 6.2, greater than or equal to 6.3, greater than or equal to 6.4, greater than or equal to 6. 5, greater than or equal to 6.6, greater than or equal to 6.7, greater than or equal to 6.8, greater than or equal to 6.9, or greater than or equal to 7.0. In some embodiments, the pH of the pathogen-inactivated platelet composition of this invention after storage is the pH at room temperature (eg, approximately 22°C, pH ₂₂ ° _C ). In some embodiments, the pH of a pathogen-inactivated platelet composition in accordance with this invention after storage refers to a measurement taken (eg, from a sample) from an individual pathogen-inactivated platelet composition (eg, each pathogen-inactivated platelet composition obtained). In other embodiments, the pH of a pathogen-inactivated platelet composition in accordance with this invention after storage is relative to the average based on measurements taken from a plurality (e.g., not all) pathogen-inactivated platelet compositions (e.g., random samples in sufficient quantity to obtain a statistically significant choice). For example, the pH of a plurality of pathogen-inactivated platelet compositions can be determined during a specific production period (eg, 1 month of production) and tested to obtain a measurement that is stored as representative for other units that are not tested. In some embodiments, each pathogen-inactivated platelet composition has a pH set forth herein. In some embodiments, at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% pathogen

- 16 044317 inactivated platelet compositions (eg, for a variety of pathogen-inactivated platelet compositions obtained during a specific period) have the pH presented here.

In some embodiments, after transferring the platelet composition in accordance with the present invention mixed with the IPA in accordance with the present invention into a container containing the SAS in accordance with the present invention and before transferring the platelet composition from the container with the SAS, the platelet composition may be stored in the container with the SAS for about 1 hour to about 36 hours. In some embodiments, the platelet composition may be stored in the UAS container for from about 1 hour to about 24 hours. In some embodiments, the platelet composition may be stored in the UAS container for a period of time less than about any of the following time periods (in hours): 36, 30, 24, 23, 22, 21, 20, 19, 18, 17, 16. 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2. In some embodiments, the platelet composition may be stored in the UAS container for a period of time greater than about any of the following periods time (in hours): 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 30. That is, the platelet composition can be stored in the UAS container for any period of time within the range of time periods having an upper limit of 36, 30, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3 or 2 hours, and an independently selected lower limit of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 30 hours, where the upper limit is greater than the lower limit. In some embodiments, the platelet composition may be stored in the UAS container for at least 1 hour and up to about 24 hours. In certain embodiments, the platelet composition may be stored in the UAS container for from about 4 hours to about 24 hours. In certain embodiments, the platelet composition may be stored in the UAS container for at least 6 hours and up to about 24 hours. In certain embodiments, the platelet composition may be stored in the UAS container for at least 12 hours and up to about 24 hours. In certain embodiments, the platelet composition can be stored in the UAS container for at least 6 hours and up to about 20 hours. In certain embodiments, the platelet composition may be stored in the UAS container for at least 6 hours and up to about 16 hours. In some embodiments, after transferring the platelet composition in accordance with the present invention mixed with the IPA in accordance with the present invention into a container containing the SAS in accordance with the present invention and before transferring the platelet composition from the container with the SAS, the platelet composition may be stored in the container with the SAS for approximately 1 hour, approximately 2 hours, approximately 3 hours, approximately 4 hours, approximately 5 hours, approximately 6 hours, approximately 7 hours, approximately 8 hours, approximately 9 hours, approximately 10 hours, approximately 11 hours, approximately 12 hours, approximately 13 hours, approximately 14 hours, approximately 15 hours, approximately 16 hours, approximately 17 hours, approximately 18 hours, approximately 19 hours, approximately 20 hours, approximately 21 hours, approximately 22 hours, approximately 23 hours or approximately 24 hours.

The platelet composition in accordance with this invention can be used in a variety of areas known in the art. In certain aspects, provided herein are methods of infusing a platelet composition in accordance with the present invention to a subject in need thereof. In some embodiments, the subject is a human. Any of the platelet compositions according to the present invention may be used in an infusion method.

Platelet processing and processing kits and kits.

Certain aspects of this description apply to processing kits. Treatment kits in accordance with this invention can be used, among other things, to obtain a pathogen-inactivated platelet composition, for example, as described here. Any of the typical components, such as bags and tubes described below, can be used in kits for processing in accordance with this invention.

In some embodiments, treatment kits are provided to produce a pathogen-inactivated platelet composition. In some embodiments, the treatment kits comprise (a) a first container that contains a pathogen inhibitory compound (PIC) and is suitable for combining a platelet composition with the PIC; (b) a second container connected to the first container, in which the platelet composition mixed with IPA can be photochemically inactivated; and (c) a third container containing a compound adsorption device (CAD), wherein the third container is connected to the second container so that the photochemically inactivated platelet composition can be transferred from the second container to the third container under sterile conditions; wherein at least one of (i) and (ii) applies: (i) the volume of the third container is greater than 1.0 L (eg, approximately 1.2 L or more); and (ii) the surface area of the interior of the third container is greater than about 750 cm ² (eg, about 800 cm ² or greater). In some embodiments, the third container in accordance with this invention is suitable for containing any of the platelet compositions described herein. In some embodiments, the first container in accordance with this invention is suitable for sterile connection with a container containing a platelet composition in accordance with

- 17 044317 with this invention.

In some embodiments, the volume of the third container in accordance with this invention is greater than 1.0 L, greater than about 1.1 L, greater than about 1.2 L, greater than about 1.3 L, greater than about 1.4 L, greater than about 1. 5 L or more approximately 1.6 L. In some embodiments, the volume of the third container in accordance with this invention is less than about any of the following volumes (in L): 1.6, 1.5, 1.4, 1.3, or 1.2. In some embodiments, the volume of the third container in accordance with this invention is greater than about any of the following volumes (in L): 1.1, 1.2, 1.3, 1.4, or 1.5. That is, the volume of the third container in accordance with the present invention may be any volume within the range having an upper limit of 1.6, 1.5, 1.4, 1.3 or 1.2, and an independently selected lower limit of 1.1 , 1.2, 1.3, 1.4 or 1.5 liters, where the upper limit is greater than the lower limit. In certain embodiments, the volume of the third container in accordance with this invention is from about 1.1 L to about 1.6 L, from about 1.2 L to about 1.6 L, from about 1.2 L to about 1.5 L or from about 1.2 L to about 1.4 L. In some embodiments, the volume of the third container in accordance with this invention is about 1.1 L, about 1.2 L, about 1.3 L, about 1.4 L, about 1.5 L, or about 1.6 L.

In some embodiments, the surface area of the interior (e.g., internal surface area) of the third container in accordance with the present invention is greater than about 750 cm ² , greater than about 800 cm ² , greater than about 850 cm ² , greater than about 900 cm ² , greater than about 950 cm ² , greater than about 1000 cm ² , greater than about 1050 cm ² , greater than about 1100 cm ² , greater than about 1150 cm ² , greater than about 1200 cm , or greater than about 1300 cm ² . In some embodiments, the surface area of the interior of the third container in accordance with the present invention is less than about 1400 cm ² , less than about 1300 cm ² , less than about 1200 cm ² , less than about 1150 cm ² , less than about 1100 cm ² , less than about 1050 cm ² , less than about 1000 cm ² , less than about 950 cm ² , less than about 900 cm ² , less than about 850 cm ² or less than about 800 cm ² . That is, the surface area of the inside of the third container according to the present invention may be a surface area in the range having an upper limit of 1400 cm ² , 1300 cm ² , 1200 cm ² , 1150 cm ² , 1100 cm ² , 1050 cm ² , 1000 cm ² , 950 cm ² , 900 cm ² , 850 cm ² or 800 cm ² , and independently selected lower limit 750 cm ² , 800 cm ² , 850 cm ² , 900 cm ² , 950 cm ² , 1000 cm ² , 1050 cm ² , 1100 cm ² , 1150 cm ² , 1200 cm ² or 1300 cm ² , where the upper limit is greater than the lower limit. In some embodiments, the surface area of the interior of the third container in accordance with the present invention is about 750 cm ² , about 800 cm ^{2 , about 850 cm 2} , about 900 cm ² , about 950 ^{cm 2 ,} about 1000 cm ² , about 1050 cm ² , approximately 1100 cm ² , approximately 1150 cm ² or approximately 1200 cm ² . In certain embodiments, the surface area of the interior of the third container in accordance with this invention is from about 750 cm ² to about 1400 cm ² , from about 800 cm ² to about 1300 cm ² , from about 800 cm ² to about 1200 cm ² , from about 850 cm ² to about 1200 cm ² , from about 850 cm ² to about 1150 cm ² , or from about 850 cm ² to about 1100 cm ² .

In some embodiments, the surface area of the interior of the third container in accordance with the present invention is greater than the surface area of the container containing the UAS (eg, third container) INTERCEPT™ Blood System (Cerus Corp.) Dual Storage Processing Set, Part Number INT2510. In some embodiments, the surface area of the interior of the third container in accordance with this invention is at least 3%, at least 5%, at least 10%, at least 15%, at least 20 %, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55% at least 60%, at least 65%, or at least 70% greater than the surface area of the container containing the UAS, INTERCEPT™ Blood System Dual Storage Processing Set, Part Number INT2510. In some embodiments, the surface area of the interior of the third container in accordance with the present invention is less than 75%, less than 70%, less than 65%, less than 60%, less than 55%, less than 50%, less than 45%, less than 40%, less than 35 %, less than 30%, less than 25%, less than 20%, less than 15%, or less than 10% more than the surface area of the container containing the UAS, INTERCEPT™ Blood System Dual Storage Processing Set, Part Number INT2510. That is, the surface area of the inside of the third container according to the present invention can be any surface area in the range having an upper limit of 75%, 70%, 65%, 60%, 55%, 50%, 45%, 40%, 35%, 30%, 25%, 20%, 15%, or 10% greater than the surface area of the container containing the UAS, INTERCEPT™ Blood System Dual Storage Processing Set, Part Number INT2510, and an independently selected lower limit of 3%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65% or 70% greater than the surface area of the container containing the INTERCEPT™ Blood System UAS Dual Storage Processing Set, Part Number INT2510, where the upper limit is greater than the lower limit.

- 18 044317

The said surface area of the interior of the third container in accordance with the present invention may be an approximate surface area. For example, the interior surface of a container containing a UAS, where the container contains a hemocompatible pouch (eg, PVC pouch, EVA pouch, polyolefin pouch), may exhibit an amount of stretch and, therefore, an amount of surface area change relative to the container in an unstretched state. In some embodiments, the surface area of the interior of the container containing the UAS in accordance with this invention may comprise the specified surface area plus or minus a certain amount. For example, in some embodiments, the surface area of the interior of the third container in accordance with this invention is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , approximately 1100 cm ² , approximately 1150 cm ² or approximately 1200 cm , each value ±5 cm ² . In some embodiments, the surface area of the interior of the third container in accordance with this invention is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , approximately 1100 cm, approximately 1150 cm ² or approximately 1200 cm ² , each value ±10 cm ² . In some embodiments, the surface area of the interior of the third container in accordance with this invention is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , approximately 1100 cm ² , approximately 1150 cm ² or approximately 1200 cm , each value ±15 cm ² . In some embodiments, the surface area of the interior of the third container in accordance with this invention is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , approximately 1100 cm, approximately 1150 cm ² or approximately 1200 cm ² , each value ±20 cm ² . For example, in some embodiments, the surface area of the interior of the third container in accordance with this invention is about 750 cm ² , about 800 cm ² , about 850 cm ² , about 900 cm ² , about 950 cm ² , about 1000 cm ² , about 1050 cm ² , approximately 1100 cm ² , approximately 1150 cm ² or approximately 1200 cm ² , each value ±25 cm ² . In some embodiments, the surface area of the interior of the third container in accordance with this invention is approximately 750 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the third container in accordance with this invention is approximately 800 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the third container in accordance with this invention is approximately 850 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the third container in accordance with this invention is approximately 900 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the third container in accordance with this invention is approximately 950 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the third container in accordance with this invention is approximately 1000 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the third container in accordance with this invention is approximately 1050 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the third container in accordance with this invention is approximately 1100 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the third container in accordance with this invention is approximately 1150 cm ² ±1%, ±2%, ±3%, ±4% or ±5%. In some embodiments, the surface area of the interior of the third container in accordance with this invention is approximately 1200 cm ² ±1%, ±2%, ±3%, ±4% or ±5%.

In some embodiments, the surface area of the interior of the third container in accordance with the present invention may refer to the interior surface area of the container.

In some embodiments, the third container is suitable for storing the platelet composition in accordance with this invention for from about 1 hour to about 36 hours. In some embodiments, the third container is suitable for storing the platelet composition in accordance with this invention for from about 1 hour to about 24 hours. In some embodiments, the third container is suitable for storing the platelet composition in accordance with the present invention for a period of time less than about any of the following time periods (in hours): 36, 30, 24, 23, 22, 21, 20, 19, 18. 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2. In some embodiments, the third container is suitable for storing the platelet composition in accordance with the present invention for a time period greater than approximately any of the following time periods (in hours): 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 30. That is, the third container may be suitable for storing the platelet composition in accordance with the present invention for any period of time in the time interval having an upper limit

- 19 044317 cases 36, 30, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3 or 2 hours, and independently selected lower limit 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 or 30 hours, where the upper limit is greater than the lower limit. In certain embodiments, the third container may be suitable for storing the platelet composition in accordance with this invention for from about 4 hours to about 24 hours. In certain embodiments, the third container is suitable for storing the platelet composition in accordance with this invention for from about 6 hours to about 24 hours. In certain embodiments, the third container is suitable for storing the platelet composition in accordance with this invention for from about 12 hours to about 24 hours. In certain embodiments, the third container is suitable for storing the platelet composition in accordance with this invention for from about 6 hours to about 20 hours. In certain embodiments, the third container is suitable for storing the platelet composition in accordance with this invention for from about 6 hours to about 16 hours. In certain embodiments, the third container is suitable for storing the platelet composition in accordance with this invention for about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, approximately 9 hours, approximately 10 hours, approximately 11 hours, approximately 12 hours, approximately 13 hours, approximately 14 hours, approximately 15 hours, approximately 16 hours, approximately 17 hours, approximately 18 hours, approximately 19 hours, approximately 20 hours, approximately 21 hours, approximately 22 hours, approximately 23 hours or approximately 24 hours.

In some embodiments, a treatment kit in accordance with the present invention further comprises one or more fourth containers, wherein the one or more fourth containers are connected to the third container so that the photochemically inactivated platelet composition can be transferred from the third container to the one or more fourth containers in under sterile conditions to obtain a pathogen-inactivated platelet composition. For example, a treatment kit in accordance with this invention may contain one, two or three quarter containers. Typical parameters (e.g., volume of the container, internal surface area, number of platelets in the platelet composition, volume of the platelet composition, constituents of the platelet composition, amount of platelet donation in the platelet composition, and mass (e.g., weight in grams) of the adsorbent beads in the UAS) of the container containing the UAS in accordance with this invention (for example, a third container) are given above. In some embodiments, the first container is suitable for sterile connection (eg, through a sterile tube) with a container containing the platelet composition. In some embodiments, one or more fourth containers in accordance with this invention are suitable for storing a platelet composition, for example, as described above. In some embodiments, a treatment kit in accordance with the present invention further comprises any of one or more releasable clamps, in-line filters, and sampling containers (eg, sampling bag, derivation bag). Non-limiting descriptions of typical processing kits are described below with reference to FIGS. 1-4.

In some embodiments, a treatment kit in accordance with this invention contains one or more fourth containers suitable for storing a pathogen-inactivated platelet composition in accordance with this invention. Storage of the pathogen-inactivated platelet composition in one or more fourth containers may occur under any suitable conditions (eg, temperature, agitation, storage period). In some embodiments, a treatment kit in accordance with this invention contains one or more quarter containers suitable for storing a platelet composition in accordance with this invention for at least 5 days at room temperature (for example, from about 20° C. to approximately 25°C, for example approximately 22°C), at least 6 days at room temperature or at least 7 days at room temperature. In some embodiments, a treatment kit in accordance with this invention contains one or more quarter containers suitable for storing a platelet composition in accordance with this invention for up to 7 days at room temperature.

A typical processing set 100 is shown in FIG. 1. In some embodiments, an optional package 102 containing donor platelets is sterilely connected to the kit 100. The treatment kit 100 includes a container 104 (e.g., a first container) that contains a pathogen inactivating compound (PAI, e.g., psoralen, amotosalen) and sterilely connected (e.g., sterilely docked) to an optional container (e.g., pouch) 102 and coupled to a container (e.g., pouch) 106 for processing the donor platelets IPA sterilely transferring the donor platelets and IPA to the container 106 for photochemical inactivation (e.g., a second container). Treatment kit 100 further includes a UAS container 110 (e.g., a UAS bag; or a third container in accordance with the present invention) connected to the second container 106 via sterile tubing 112, which allows the transfer of donor platelets after photochemical inactivation into the UAS

- 20 044317 container. The UAS container 110 contains a UAS (eg, a UAS plate) 108 that removes or reduces the concentration of a pathogen-inactivating compound. For example, UAS 108 may include adsorbent particles enclosed in a porous package and/or matrix, such as, for example, a plate, containing adsorbent particles and a suitable binding agent (e.g., as described herein) that bind and/or otherwise adsorb an inactivating pathogen compound. Treatment kit 100 further includes a fourth container 114 that is connected to UAS container 110 by sterile tubing 116.

A typical processing set 200 is shown in FIG. 2. In some embodiments, an optional package 202 containing donor platelets is sterilely coupled to the kit 200. The treatment kit 200 includes a container 204 (e.g., a first container) that contains a pathogen inactivating compound (PAI, e.g., psoralen, amotosalen) and sterilely connected (e.g., sterilely docked) to an optional container (e.g., pouch) 202 and coupled to a container (e.g., pouch) 206 for processing donor platelets IPA for sterile transfer of donor platelets and IPA to container 206 for processing donor platelets IPA and sterile transfer for donor platelets and IPA into photochemical inactivation container 206 (eg, second container). Treatment kit 200 further includes a UAS container 210 (e.g., a UAS bag; or a third container in accordance with the present invention) connected to the second container 206 via sterile tubing 212, which allows the transfer of donor platelets after photochemical inactivation into the UAS container. The UAS container 210 contains a UAS (eg, a UAS plate) 208 that removes or reduces the concentration of a pathogen-inactivating compound. For example, UAS 208 may include adsorbent particles enclosed in a porous package and/or matrix, such as, for example, a plate, containing adsorbent particles and a suitable binding agent (e.g., as described herein) that bind and/or otherwise adsorb an inactivating pathogen compound. Treatment kit 200 further includes fourth containers 214 and 216 that are connected to UAS container 210 by sterile tubing 218 and guide 220.

A typical processing set 300 is shown in FIG. 3. In some embodiments, an optional package 302 containing donor platelets is sterilely connected to the kit 300. Treatment kit 300 includes a container 304 (e.g., a first container) that contains a pathogen-inactivating compound (PAI, e.g., psoralen, amotosalen) and sterilely connected (e.g., sterilely docked) to an optional container (e.g., pouch) 302 and coupled to a container (e.g., pouch) 306 for processing donor platelets IPA for sterile transfer of donor platelets and IPA to container 306 for processing donor platelets IPA and sterile transfer for donor platelets and IPA into a photochemical inactivation container 306 (eg, a second container). Treatment kit 300 further includes a UAS container 310 (e.g., a UAS bag; or a third container in accordance with the present invention) connected to the second container 306 via sterile tubing 312, which allows the transfer of donor platelets after photochemical inactivation into the UAS container. The UAS container 310 contains two UASs (eg, UAS plates) 308a and 308b that remove or reduce the concentration of a pathogen-inactivating compound. For example, each of the UASs 308a and 308b may include adsorbent particles enclosed in a porous package and/or matrix, such as, for example, a plate, containing the adsorbent particles and a suitable binding agent (for example, as described herein) that bind and/or other manner adsorb the pathogen-inactivating compound. Processing kit 300 further includes fourth containers 314, 316 and 318 that are connected to UAS container 310 by sterile tubing 320 and guide 322. Advantageously, this processing kit allows for the production of large quantities and/or volumes of platelet composition.

A typical processing set 400 is shown in FIG. 4. In some embodiments, optional bags 402a and 402b, each containing donor platelets, are sterilely coupled (e.g., sterile docked) to kit 400 instead of sterile coupled to bag 402 containing donor platelets, container 404 is sterile coupled to two containers 402a, and 402b containing donor platelets (eg, first donor platelets, second donor platelets). 402a and 402b are sterilely connected to each other (eg, for pooling) by sterile tubing 403. Advantageously, this configuration produces a pooled platelet composition that can be subjected to pathogen inactivation and then separated into individual platelet units (eg, 414, 416 and 418). Treatment kit 400 includes a container 404 (e.g., a first container) that contains a pathogen-inactivating compound (PIC, e.g., psoralen, amotosalen) and is sterilely coupled to an optional container (e.g., a pouch) 402 (e.g., an additional container) and connected to a container (eg, bag) 406 for treating donor platelets with IPA to sterilely transfer the donor platelets and IPA to a container 406 for photochemical inactivation (eg, a second container). Treatment kit 400 further includes a UAS container 410 (e.g., a UAS bag; or a third container in accordance with the present invention) connected to the second container 406 by sterile tubing 412, which allows the transfer of donor platelets after photochemical inactivation into the UAS container. UAS container 410 with

- 21 044317 holds two UAS (eg, UAS plates) 408a and 408b, which provide removal or reduction in the concentration of a pathogen-inactivating compound. For example, each of the UASs 408a and 408b may include adsorbent particles enclosed in a porous package and/or matrix, such as, for example, a plate, containing the adsorbent particles and a suitable binding agent (for example, as described herein) that bind and/or other manner adsorb the pathogen-inactivating compound. Treatment kit 400 further includes fourth containers 414, 416, and 418 that are connected to UAS container 410 by sterile tubing 420 and guide 422.

Certain aspects of this description also apply to kits. For example, the specification provides a kit containing (a) a treatment kit in accordance with the present invention (e.g., the above treatment kit) and (b) instructions for using the treatment kit to produce a platelet composition (e.g., a pathogen-inactivated platelet composition , as described here). In some embodiments, the kit comprises a treatment kit for producing a pathogen-inactivated platelet composition and instructions for using the treatment kit for producing a pathogen-inactivated platelet composition, wherein the treatment kit includes: (a) a first container that contains a pathogen-inactivating compound (PIC) and suitable for combining platelet composition with IPA; (b) a second container connected to the first container, in which the platelet composition mixed with IPA can be photochemically inactivated; and (c) a third container containing a compound adsorption device (CAD), wherein the third container is connected to the second container so that the photochemically inactivated platelet composition can be transferred from the second container to the third container under sterile conditions; wherein at least one of (i) and (ii) applies: (i) the volume of the third container is greater than 1.0 L (eg, approximately 1.2 L or more); and (ii) the surface area of the interior of the third container is greater than about 750 cm ² (eg, about 800 cm ² or greater). In some embodiments, the treatment kit further comprises one or more fourth containers, wherein the one or more fourth containers are coupled to a third container such that the photochemically inactivated platelet composition can be transferred from the third container to the one or more fourth containers under sterile conditions to produce a pathogen -inactivated platelet composition. In some embodiments, the treatment kit contains one fourth container. In some embodiments, the treatment kit contains two fourth containers. In some embodiments, the treatment kit contains three-fourths of the container. In some embodiments, the first container is suitable for sterile connection with a container containing the platelet composition.

In some embodiments, the volume of the third container is greater than 1.0 liters. In some embodiments, the volume of the third container is greater than 1.1 liters. In some embodiments, the third container has a volume greater than about 1.2 liters. In some embodiments, the third container has a volume of approximately 1.3 liters. In some embodiments, the third container has a volume of approximately 1.5 liters. In some embodiments, the volume of the third container is less than about 1.6 liters. In some embodiments, the volume of the third container is from about 1.2 L to about 1.6 L. In some embodiments, the surface area of the interior of the third container is greater than about 750 cm ² . In some embodiments, the surface area of the interior of the third container is greater than about 800 cm ² . In some embodiments, the surface area of the interior of the third container is greater than about 850 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS is approximately 900 cm ² . In some embodiments, the surface area of the interior of the third container is less than about 1100 cm ² . In some embodiments, the surface area of the interior of the container containing the UAS is from about 850 cm ² to about 1100 cm ² . In some embodiments, the UAS contains at least about three grams of absorbent beads. In some embodiments, the UAS contains less than about seven grams of absorbent beads. In some embodiments, the UAS contains at least about seven grams of absorbent beads. In some embodiments, the UAS includes a single plate containing adsorbent beads. In some embodiments, the UAS comprises more than one (eg, two) plates containing absorbent beads.

In some embodiments, the instructions indicate that the processing kit is suitable for processing a platelet composition that contains at least about 6.0x1011 platelets, at least about 6.5x1011 platelets, at least about 7.0x1011 platelets at least about 7.5x1011 platelets, at least about 8.0x1011 platelets, at least about 8.5x1011 platelets, at least about 9.0x1011 platelets, at least about 9.5x1011 platelets at least about 10.0x1011 platelets, at least about 10.5x1011 platelets, at least about 11.0x1011 platelets, at least about 11.5x1011 platelets, or at least about 12.0x1011 platelets (eg, from about 6.0x1011 to about 12.0x1011 platelets). In some embodiments, the instructions indicate that the treatment kit is suitable for processing a platelet composition that contains less than about 12.0 x 1011 platelets. In some variants, the instructions indicate

- 22 044317 that the processing kit is suitable for processing a platelet composition having a volume of at least about 250 ml, at least about 300 ml, at least about 350 ml, at least about 400 ml, at least at least about 450 ml, at least about 500 ml, at least about 550 ml, at least about 600 ml, or at least about 650 ml (e.g., a volume of from about 350 ml to about 650 ml , volume from about 300 ml to about 650 ml or volume from about 250 ml to about 650 ml). In some embodiments, the instructions indicate that the processing kit is suitable for processing a platelet composition having a volume of less than about 650 ml.

In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 5 days at room temperature. In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 6 days at room temperature.

In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 7 days at room temperature. In some embodiments, the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for up to 7 days at room temperature. In some embodiments, the instructions indicate that the treatment kit (eg, one or more quarter containers) is suitable for storing the pathogen-inactivated platelet composition for at least 5 days at room temperature. In some embodiments, the instructions indicate that the treatment kit (eg, one or more quarter containers) is suitable for storing the pathogen-inactivated platelet composition for at least 6 days at room temperature. In some embodiments, the instructions indicate that the treatment kit (eg, one or more quarter containers) is suitable for storing the pathogen-inactivated platelet composition for at least 7 days at room temperature. In some embodiments, the instructions indicate that the treatment kit (eg, one or more quarter containers) is suitable for storing the pathogen-inactivated platelet composition for up to 7 days at room temperature. In some embodiments, the pH (eg, pH ₂₂ °C) of the pathogen-inactivated platelet composition after storage is >6.2. In some embodiments, the pH (eg, pH ₂₂ ° _C ) of the pathogen-inactivated platelet composition after storage is >6.4. In some embodiments, the third container is suitable for storing the pathogen-inactivated platelet composition for from about 4 to about 24 hours.

The platelet processing described in this invention may involve the use of a system of blood product containers or blood product bags that are well known in the art. In general, such systems may include more than one plastic container, typically plastic bags, where the bags are integrally connected to a plastic tube. Some of the containers described herein include those plastic bags that are known for storing and handling blood products (ie, hemocompatible plastic bags), including platelet products. Blood bags can typically be designed to contain different volumes of liquid, including, but not limited to, volumes from 50 ml to 2 liters, for example having a capacity of up to 350 ml, a 450 ml capacity, a 500 ml capacity, a 1 liter capacity, capacity up to 1.5 liters or capacity up to 2 liters. It is understood that when a container or bag is mentioned in the method, it includes any such plastic bags used for processing blood products. If such bags are called a pooling bag, a mixing bag, a removal bag, a drug bag, a storage bag, or a lighting bag, it is understood that these bags are typical blood product processing bags or similar bags in nature. Plastic bags suitable for use in accordance with this invention include, for example, bags containing PL2410, as well as other suitable plastics known in the art. Plastic bag materials include polyvinyl chloride, ethylene vinyl acetate, ethylene vinyl acetate mixed with other plastics, and the like.

As described herein, if a tube is described as connecting, for example, two packages, such as a pooling and/or a processing set, it is understood that the tubes may be connected at a certain point between them by another connection component between the two packages. For example, a disposal bag is connected to a drug bag by a tube, where the tube contains a filter between the two bags, i.e., the tube is divided by a filter so that liquid flows from one bag to the other through the tube and filter. In one example, the tubing connecting the disposal bag and the product bag may include a filter for removing loose particles from the liquid flowing from the disposal device into the product bag, i.e. the tube is divided or interrupted by a filter between packets. These filters are designed to remove any small particles that may come from the removal device, allowing platelets to pass through the filter. Tubes between the bags allow liquid to flow from one bag to another.

- 23 044317 another, this can be blocked to prevent flow until needed, for example to prevent part of the liquid processed in one bag from flowing into the next bag until needed for the next stage of the process. As such, an openable closure, such as a clip, stopper, valve or the like, is placed in or on a tube connecting the bags, where the clip, stopper, valve or the like can be selectively opened as needed, for example, to transfer liquid from one bag to another. another. In certain embodiments, the conduit between the bags includes a rupture closure, such as a rupture valve or a rupture connector, where rupture of the rupture closure allows the blood product solution to flow between the bags through the conduit. It is understood that the breakable closure is contained in the connection between the containers so that the sterility of the system is maintained. It is also understood that the tube containing the filter or closure includes options where the tube may be interrupted by the filter or closure, for example, the tube extends from one bag and is connected to the filter or closure (the inlet portion of the tube), and the tube extends from another portion of the filter or capping to another package (the exiting part of the tube). In this configuration, liquid flows from the first bag, through the inlet portion of the tube, through the filter or closure, and through the outlet portion of the tube and into the other package.

Different containers (eg bags) in a blood product bag system can be used at different stages of the process. For example, a pouch system used to inactivate a pathogen in a platelet preparation may include a container with a pathogen-inactivating compound inside, a pouch for receiving the platelet unit (e.g., platelet donation) and a pathogen-inactivating compound (e.g., an illumination pouch), a pouch for illuminating the platelet unit where the method of inactivating the pathogen involves illumination (e.g., a bag for illumination, and typically the same bag for obtaining a unit of platelets and a pathogen-inactivating compound), a bag containing one or more compositions for removing pathogen-inactivating compounds and/or by-products thereof (e.g. photoproducts) from the processed unit of platelets (eg, a named removal bag, compound adsorption device, UAS, UAS container) and one or more bags for containing the final platelet preparation, i.e. unit of pathogen-inactivated platelets (eg, therapeutic dosage unit) that has the concentration of the inactivating compound and/or its by-products reduced to below the desired concentration, which is ready for use or can be stored for future use (eg, a named drug pouch, pouch for storage). Each bag in the system is typically made from plastic material. For example, a container for containing a solution of a pathogen-inactivating compound can be made from a suitable plastic such as PL2411 (Baxter Healthcare) or other plastics such as polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate mixed with other plastics, and the like. This container may also be wrapped in a material that is impervious to light or waves that could activate the pathogen-inactivating compound (eg, a suitable plastic such as PL2420, Baxter Healthcare). A package for illuminating a photoactivated pathogen-inactivating compound requires a clear, durable thermoplastic material that is transparent to the selected wavelengths. Suitable plastics that are transparent to UVA wavelengths include polyvinyl chloride, polyolefins, ethylene vinyl acetate, ethylene vinyl acetate mixed 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 produce a disposal bag and a drug bag. Drug packages include, for example, packages derived from PL2410. Suitable pouch materials are discussed, for example, in KTT Publication No. WO 2003078023 and US Pat. No. 7,025,877, the disclosure of which is incorporated herein by reference as it relates to such pouch materials and related materials. In all cases, the materials used to prepare the processing kit must be sterilizable by known methods, such as steam or irradiation with gamma rays or electron beams, used to ensure the sterility of the processing kit. Although these are typical materials for making pouches, the methods described herein are applicable to processes using any suitable pouch material that would be readily available to one of ordinary skill in the art and can also be used with containers other than pouches. Bags used for illumination, removal and storage also allow gases such as oxygen and carbon dioxide to pass in and out of the blood bag so that platelets stored there have sufficient oxygen supply and carbon dioxide levels during processing and storage.

Pathogen inactivation.

Blood products, including platelet-containing blood products, may contain pathogens or may be contaminated with pathogens during processing. Thus, it is desirable to subject such blood products to a pathogen inactivation process to reduce the risk of transfusion-transmitted diseases. Various processes and methods have been evaluated to reduce the risk of transfusion-associated disease transmission in blood products containing platelets. In addition to screening and detection of pathogens and subsequent disposal of contaminated blood products, processes are available that include pathogen inactivation treatments (i.e., pathogen inactivation) that

- 24 044317 may be present. Ideally, this 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 preferred embodiments, pathogen inactivation methods require adding an amount of a pathogen-inactivating compound to the platelet preparation (eg, to treat the platelet preparation). For example, inactivating a pathogen may involve adding a small molecule compound that inactivates a variety of pathogens, where a preferred method involves adding a photosensitizer that, when activated by illumination using light of a suitable wavelength, inactivates a variety of pathogens that may be present. Two preferred methods involve adding amotosalen or riboflavin to platelets, followed by exposure to 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, isoalloxazines other than riboflavin, dyes such as phthalocyanines, phenothiazine dyes (eg, methylene blue, azure B, azure C, thionine, toluidine blue), porphyrin derivatives (eg, dihematoporphyrin ester, hematoporphyrin derivatives, benzoporphyrin derivatives, alkyl-substituted sapphirin) 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 KTT publications No. WO 2012071135; WO 2012018484; WO 2003090794; WO 2003049784; WO 1998018908; WO 1998030327; WO 1996008965; WO 1996039815; WO 1996039820; WO 1996040857; WO 1993000005; US Patent Application No. US 20050202395; and US Pat. Nos. 8,296,071 and 6,548,242, the disclosures of which are incorporated herein by reference to the extent that 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, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen. In some embodiments, the pathogen-inactivating compound is amotosalen. If addition of a compound to platelets is used to inactivate a pathogen, whether the method requires illumination or not, in some cases it is desirable to remove any residual pathogen-inactivating compound or byproduct thereof.

The methods for inactivating a pathogen and removing a pathogen-inactivating compound described herein apply to any platelet preparation, regardless of whether the preparation contains individual platelet donations (eg, apheresis-collected platelets) or pooled platelet preparations. These methods typically provide a platelet preparation that is either about 85-100% plasma or contains some platelet add-on solution, typically in the range of 50-95% platelet add-on solution, where the remaining volume is effectively plasma, i.e. plasma in an amount of 5-50%. It is understood that a solution of a pathogen-inactivating compound may be added during processing to inactivate pathogens, since the pathogen-inactivating compound is typically not combined in solid form but dissolved in solution (eg, amotosalen is an HCl salt dissolved in saline). Thus, in some cases, when a platelet preparation is designated as approximately 100% plasma, it is implied that no additional platelet supplement solution is added to the platelet unit. If such a platelet preparation in approximately 100% plasma is processed for pathogen inactivation, some volume of the pathogen inactivating compound solution will be included in the final product, as well as some volume of the anticoagulant used in collecting the blood to isolate the platelets. Although the plasma has been partially diluted with any amount of anticoagulant and the solution that is used to contain the pathogen-inactivating compound, the resulting platelet preparation containing the pathogen-inactivating compound may be said to contain about 100% plasma or may be said to contain about 85-100% plasma (typically less than about 5 -15% of the volume will consist of a solution delivering the pathogen-inactivating compound). Platelet preparations can also be prepared with some amount of platelet supplement solution, which can, for example, be added after platelet concentration, removing a portion of the plasma from the supernatant, and adding the desired amount of platelet supplement solution to the platelet preparation. Platelet supplement is added to obtain the desired proportion of platelet supplement solution. This platelet preparation is usually adjusted to a plasma content of approximately 5-50%, where the remaining solution is a platelet addition solution, i.e. 50-95% platelet supplement solution. If the amounts of plasma and platelet supplement solution are described, it is understood that for platelet preparations described as being approximately 100% plasma, some volume of the solution containing the pathogen-inactivating compound may be included in the platelet unit containing the pathogen-inactivating compound. Although the solution is partially diluted with any amount of solution that is used to contain the pathogen-inactivating compound, it should be understood that, for example, a platelet preparation designated as containing 35% plasma and 65% platelet supplement solution may refer to relative amounts of plasma and platelet supplement solution up to adding a solution containing an inactivating agent

- 25 044317 pathogen compound.

Some methods of platelet inactivation may require the use of a removal device, i.e. devices for reducing the concentration of a pathogen-inactivating compound, such as a small organic compound, such as a platelet-inactivating compound, and its by-products in a platelet preparation while sufficiently maintaining the desired biological activity of the platelets. In some embodiments, the removal device is referred to as a compound adsorption device (CAD) and may comprise a container (e.g., a CAD container, a CAD bag) containing one or more materials, such as, for example, adsorbent particles (e.g., adsorbent beads), and which is also suitable for containing a platelet preparation in which it is necessary to reduce the concentration of a pathogen-inactivating compound and its by-products. Such a removal device is typically intended to be used in a batch mode, that is, the device is in contact with the platelets and continuously contacts the removal device, such as by shaking, to allow substantially all of the platelet solution to come into contact with the removal device during the contact time period, such that leads to a decrease in the level of a pathogen-inactivating compound. Such batch devices entail the use of an adsorbent particle that binds a pathogen-inactivating compound, and can be used by either adding the adsorbent particles directly to a platelet container (e.g., a bag) after illumination, or by transferring the platelets into a bag containing the adsorbent particles followed by illumination. and the platelets are mixed for a certain period of time, while the platelet preparations are contacted with the removal device. Although loose adsorbent particles can be used as a removal device, such particles can be contained in a porous bag, such as a polyester or nylon porous bag, which allows the platelet solution to contact the adsorbent particles while retaining the particles within the bag. Alternatively, the adsorbent particles may be immobilized within a matrix, where the immobilized matrix may be contained directly in a blood bag used for periodic removal, or may also be contained within a porous bag. In some cases, the removal device contains porous adsorbent particles in an amount sufficient to reduce the pathogen-inactivating compound below a desired concentration, where the adsorbent particles have an affinity for the pathogen-inactivating compound, where it is understood that such adsorbent particles can be selected for best adsorption of the removed compound or compounds , with minimal impact on components that should not be removed or damaged by contact with adsorbent particles. A variety of adsorbent particles are known, including typically particles made from any natural or synthetic material capable of reacting with the compounds being removed, including particles made from natural materials such as activated carbon, silica, diatomaceous earth and cellulose, and synthetic materials such as 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. Detailed descriptions of such removal devices suitable for use in the methods described herein can be found in KTT Publication Nos. WO 1996040857, WO 1998030327, WO 1999034914 and WO 2003078023, the descriptions of which are incorporated herein by reference to the extent that they apply. such removal devices and adsorbent particles and other materials used to obtain such devices. Typical adsorbent particles include, but are not limited to, Amberlite (Rohm and Haas) XAD2, 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, XUS-43493 (also designated Optipore V493 (dry form) or Optipore L493 (hydrogenated 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. The material used to obtain the fixed matrix is contains 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 medium. While it is understood that the methods and devices described herein cover removal devices that are known in the art, such methods and devices can be exemplified using a commercially available platelet drug inactivating amotosalen removal device. Such a removal device contains Hypersol Macronet MN-200 adsorbent contained in a sintered matrix, where the sintered matrix contains PL2410 plastic as a binding agent. In one case, the removal device contains Hypersol Macronet MN200 adsorbent in a sintered matrix containing PL2410, wherein Hypersol Macronet MN-200 is in an amount of about 3-50 grams, about 3-40 grams, about 3-30 grams, about 3-20 grams , approximately 3-7 grams, approximately 7-15 grams, approximately 10-20 grams, approximately 5-50 grams, approximately 5-10 grams, approximately 10-15 grams,

- 26 044317 approximately 15-20 grams, approximately 20-25 grams, approximately 25-30 grams, approximately 30-35 grams, approximately 35-40 grams, approximately 40-45 grams or approximately 45-50 grams dry weight equivalent.

Because different resins may require different processing in use to make removal devices useful for the methods and devices described herein, comparisons of amounts of adsorbent resins described herein, unless otherwise noted, are comparisons of resin dry weight. For example, resins are dried to <5% water prior to treatment, and the dry weight equivalent of the adsorbent is used when comparing application amounts of resin. For example, Hypersol Macronet MN-200 is treated to stabilize the adsorbent, or what is commonly called adsorbent wetting, so that it can be used in direct contact with the platelet unit. Such a wetted sample may include, for example, about 50% glycerol or other suitable wetting agent. In some embodiments, the adsorbent resin is polystyrene divinyl benzene resin. In some embodiments, the polystyrene-divinylbenzene resin is Hypersol Macronet MN-200. In some embodiments, the adsorbent is contained in a sintered matrix, where the sintered matrix contains a PL2410 coupling agent. In some embodiments, Hypersol Macronet MN-200 adsorbent is contained in a sintered matrix to form a removal device.

In some embodiments, the compound adsorption device in accordance with this invention contains at least about 3 grams and less than about 50 grams, at least about 3 grams and less than about 40 grams, at least about 3 grams and less than about 30 grams, at least about 3 grams and less than about 20 grams dry weight equivalent of absorbent beads. In some embodiments, a compound adsorption device (CAD) in accordance with this invention contains at least about 3 grams of adsorbent beads. In some embodiments, the compound adsorption device in accordance with this invention contains less than about 7 grams of adsorbent beads. In some embodiments, a compound adsorption device in accordance with this invention contains at least about 7 grams of adsorbent beads. In some embodiments, the compound adsorption device of this invention contains at least about 3 grams and less than about 7 grams. In some embodiments, a compound adsorption device in accordance with this invention contains at least about 7 grams and less than about 15 grams of adsorbent beads. In some embodiments, the UAS includes a single plate containing adsorbent beads. In some embodiments, the UAS comprises more than one (eg, two) plates containing absorbent beads.

Platelet units.

Also provided herein are pathogen-inactivated platelet compositions (eg, platelet units) suitable for infusion (eg, infusion into a human), such as a platelet unit selected from a variety of platelet units obtained by any of the methods of the present invention. The platelet units (eg, each platelet unit) in the plurality of platelet units contain a therapeutic dose (eg, therapeutic dosage unit) of platelets suitable for infusion into a person (eg, a subject requiring platelet infusion). In some embodiments, the therapeutic dose contains a minimum amount (e.g., at least a minimum number) of platelets as determined by criteria (e.g., eligibility criteria) of a government agency, regulatory agency, institution, and/or accrediting organization (e.g., government agency, regulatory agency , institution and/or accrediting organization for donated blood products (eg, donated platelets)). In some embodiments, the platelet units are prepared in the country of the government agency, regulatory agency, agency, and/or accrediting organization that defines the platelet therapeutic dose criteria. In some embodiments, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98 %, at least about 99% or more of the platelet units in the plurality of platelet units contain a minimum number of platelets in a therapeutic dose. In some embodiments, each of the platelet units in the plurality of platelet units contains a minimum amount of platelets in a therapeutic dose. In some embodiments, the minimum platelet count in a therapeutic dose is 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 units in the plurality of platelet units comprise at least about 2.0 x 1011 platelets of at least

- 27 044317 at least approximately 2.2x1011 platelets, at least approximately 2.4x1011 platelets, at least approximately 2.5x1011 platelets, at least approximately 2.6x1011 platelets, at least approximately 2.7x1011 platelets at least about 2.8x1011 platelets, at least about 2.9x1011 platelets, or at least about 3.0x1011 or more platelets. In some embodiments, each of the platelet units in the plurality of platelet units 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 or more platelets. In some embodiments, at least about 75% of the platelet units in the plurality of platelet units contain 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 3.0 x 1011 or more platelets. In some embodiments, at least about 80% of the platelet units in the plurality of platelet units contain 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 3.0 x 1011 or more platelets. In some embodiments, at least about 85% of the platelet units in the plurality of platelet units contain 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 3.0 x 1011 or more platelets. In some embodiments, at least about 90% of the platelet units in the plurality of platelet units contain 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 3.0 x 1011 or more platelets. In some embodiments, at least about 95% of the platelet units in the plurality of platelet units contain 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 3.0 x 1011 or more platelets. In some embodiments, at least about 98% of the platelet units in the plurality of platelet units contain 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 3.0 x 1011 or more platelets. In some embodiments, at least about 99% of the platelet units in the plurality of platelet units contain 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 3.0 x 1011 or more platelets.

In another aspect, provided herein is a therapeutic platelet dosage unit suitable for infusion into a subject, wherein the therapeutic dosage unit comprises bullets

- 28 044317 pooled platelet compositions from two or more donors, and where the pooled platelet compositions are treated with a pathogen-inactivating compound. In some embodiments, the platelet compositions are treated with a pathogen-inactivating compound prior to pooling. In some embodiments, the platelet compositions are treated with a pathogen-inactivating compound after pooling. In some embodiments, the pathogen-inactivating compound is a photoactive pathogen-inactivating compound selected from the group consisting of psoralen, isoalloxazine, alloxazine, phthalocyanine, phenothiazine, porphyrin, and merocyanine 540. In some embodiments, the pathogen-inactivating compound is psoralen. In some embodiments, the pathogen-inactivating compound is amotosalen. In some embodiments, platelet compositions are obtained from donors with the same ABO blood type. In some embodiments, platelet compositions are taken from donors with the same ABO and Rh type. In some embodiments, the therapeutic platelet dosage unit 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, at least about 3.0x1011 or more platelets . In some embodiments, the therapeutic platelet dosage unit contains at least 2.4 x 1011 platelets. In some embodiments, the therapeutic platelet dosage unit contains at least 2.6x1011 platelets. In some embodiments, the therapeutic platelet dosage unit contains at least 3.0x1011 platelets. In some embodiments, the therapeutic platelet dosage unit contains a minimum amount (e.g., at least a minimum amount) of platelets determined by criteria (e.g., eligibility criteria) of a government agency, regulatory agency, agency, and/or accrediting organization (e.g., a government agency, regulatory body, institution and/or accrediting organization for donated blood products (e.g. donated platelets)). In some embodiments, the therapeutic platelet dosage units are prepared in the country of the government agency, regulatory agency, agency, and/or accrediting organization defining the criteria for the therapeutic platelet dosage unit.

Also provided herein is a method of infusing platelets to a subject (eg, a human) in need thereof, comprising infusing the subject with the above platelet unit or the above therapeutic platelet dosage unit.

It will also be appreciated by those skilled in the art that changes in the form and details of the implementations described herein may be made without departing from the scope of this description. In addition, although various advantages, aspects and objects have been described with reference to various embodiments, the scope of this description should not be limited by reference to such advantages, aspects and objects. Rather, the scope of this specification should be determined by reference to the appended claims.

The invention is further illustrated by the following examples, which should not be construed as limiting the scope and spirit of the invention to the specific procedures described herein.

Examples

Example 1: Preparation of pathogen-inactivated platelets in a double processing kit.

Platelets collected by apheresis in 100% plasma are subjected to pathogen-inactivating photochemical treatment with amotosalen and UVA using the INTERCEPT™ Blood System Dual Storage Kit (see, e.g., FIG. 2) according to the manufacturer's instructions (Cerus Corp.), except for sample collection for analyses. The incoming platelet components do not contain visible aggregates and have a volume of 327-420 ml and a platelet dose of 3.1-7.9 x 1011 platelets. The incoming platelet content is 919-1957χ10 ³ /mkl. The incoming platelet components are connected to the tubing of the processing kit using a sterile coupling device (SDU). Amotosalen is added to the component by passing incoming platelets into and through the amotosalen container and into the illumination container. Air is removed from the illumination container containing the platelet-amotosalen mixture, and the tubes connecting the amotosalen container to the illumination container are sealed and the amotosalen container and the original platelet container are separated. Platelet components with amotosalen are illuminated for 3.6-4.3 minutes with a dose of 3.90 J/cm UVA.

After illumination, the pathogen-inactivated platelets are transferred to a UAS container containing a 1.0 L container and a UAS plate, then the illumination container is detached and discarded, and the platelets in the UAS container are placed in an incubator at 22°C on a platelet-type agitator at speed rotation >60 rpm Processing of UAS with stirring lasts 22.8±0.6 hours. The sample taken to determine the concentration of amotosalen after UAS is 0.73 ± 0.34 μM. The UAS container is suspended and the platelets are transferred by gravity to the storage container(s), air is removed from the storage container(s), and the empty UAS container is detached and discarded. Platelet components with incoming platelet content >6.0x1011 platelets transferred

- 29 044317 fits in one storage container. Platelet components with an incoming platelet content of >6.1 x ¹¹ platelets are divided into equal parts (mass) into two storage containers. All pathogen-inactivated platelet components are stored under standard conditions with continuous gentle stirring at 22°C until the end of the seventh day after blood collection (day 7).

The pH and in-vitro characteristics of the processed apheresis platelet concentrates were assessed after 7 days using standard techniques. pH ₂ 2°C ^on day 7 is 7.1±0.3, while three of the 67 platelet components do not maintain pH 22°C ^6.4 on day 7. Additional parameters assessed include pO2 (mmHg)=134±19, pCO2 (mmHg)=28±7, HCO3=5.6±2.4, supernatant glucose (mg/dL) =188±67, normalized supernatant lactate (mmol/ ¹⁰⁶ platelets)=11.2±3.9, normalized total ATP (nmol/ ¹⁰⁸ platelets)=4.4±1.6, morphology=283±46 , SIF (%)=20.5±5.6 and RGS (%)=51±12.

Example 2: Preparation of PI-treated platelets in a double processing set with a modified VAC container.

In another study, a dual storage treatment kit (see Example 1) was used to evaluate the effect of a compound adsorption device (CAD) container on in vitro platelet quality in 100% plasma subjected to pathogen inactivation at high platelet counts. In addition to the commercially available dual storage treatment kit described above, which contains UAS in a 1.0 L UAS container, a modified dual storage treatment kit containing UAS in a larger 1.3 L UAS container (e.g., internal surface area greater than 800 cm ² ), also designed for research and used for comparison.

Apheresis platelets in 100% plasma are pooled and separated to produce mated pairs of approximately 8.1 x ¹¹ platelets in approximately 420 mL of 100% plasma, then treated to photochemically inactivate the pathogen with amotosalen and UVA as described (see, e.g., Example 1) with 1.0 l or 1.3 l UAS treatment kit. After pH ₂ 2°C treatment, pathogen-inactivated platelets are monitored for up to 7 days of storage.

Eight independent replicates were processed and tested. On day 7, six of eight platelet preparations processed using the double set with a 1.0 L UAS container had a pH ₂ 2°C below 6.4. Surprisingly, and conversely, results for platelet preparations processed with a double set with a 1.3 L UAS container showed a significant improvement in pH after 7 days, with eight of eight (100%) having a pH _{of 2} 2°c >6.4. High-input-dose, high-volume CT scans showed decreased pH with a modern, commercially available DC kit compared to a prototype DC kit with a large UAS container. These data suggest that UAS stage may significantly influence the final pH at day 7.

Another pooling and splitting study was performed using a dual storage treatment kit with UAS in a 1.3 L UAS container and a high dose of platelets. After pathogen inactivation as described, the treated platelets are stored at 22°C with a pH of 22°C ^and in vitro characteristics of the treated platelets measured during storage. On day 5, all units maintained pH22°C >6.4 (7.0±0.1). Some additional parameters assessed include pOg (mm Hg) = 71.5 ± 30.9, pCO (mm Hg) = 21.4 ± 1.1, HCOz' = 3.2 ± 1.1, supernatant glucose (mmol/L)=8.4±1.4, supernatant lactate (mmol/L platelets)=20.4±2.2, morphology=252.0±4.7, NIF (% )=27.0±3.1 and RGS (%)=47.7±10.3.

Another study was conducted to compare pathogen inactivation in platelets using a commercially available dual storage treatment kit containing UAS in a 1.0 L container with a dual storage treatment kit in accordance with the present invention containing UAS in a larger 1.3 L container. container. For this study, ABO-coupled platelets in 100% plasma are pooled and separated to yield units of approximately 7.1 x ¹⁰ -8.0 x ¹⁰ (eg mean 7.6 x 10 ^p ) platelets per 375-420 ml (eg mean 390 ml, 391 ml), which are treated to inactivate pathogens using two different treatment kits, and then kept under stirring at 22°C. Before treatment and again on days 5 and 7 after treatment, samples are removed and assessed using standard in vitro platelet quality/function assays. Data for some parameters are presented in the following table.______________________________

Day 1 entry Day 5 Day 7

-30044317

1.0 l 1.3 l 1.0 l 1.3 l pH ₂ 2°C 7.3±0.1 6.2±0.5 7.1±0.1 6.1±0.3 6.8±0.3 pCO ₂ (mm Hg) 57.5±10.3 12.6±6.7 22.2±2.9 9.2±7.6 20.3±1.7 pO ₂ (mm Hg) 36.6±19.7 136.9±50.1 74.3±9.4 158.7±44.4 91.3±16.3 Total ATP (mmol/10 ⁸ tb) 4.5±0.5 3.0±0.5 4.7±0.5 2.7±0.7 3.8±1.5 Morphology assessment (share 400) 265±13 203±58 267±11 170±55 228±46 RGS (%) 51.9±5.9 23.4±28.0 56.2±7.3 21.7±30.7 46.2±24.2 CD62P 22.4±5.8 71.0±32.4 28.0±6.3 77.0±23.1 57.0±22.7

The data shows a favorable outcome on days 5 and 7 of storage using treatment kits with a large UAS container compared to a commercially available 1.0 L UAS container. For platelets treated with treatment kits containing a larger 1.3 L UAS container, results showed higher pH, higher pCO2, lower pO2, higher ATP, higher morphology score, better hypotonic shock response (HSR), and lower CD62P.

Example 3: Preparation of PI treated platelets in a triple treatment kit.

The 1.3 L UAS container is also introduced into the INTERCEPT™ Triple Processing Kit (see, for example, FIGS. 3 and 4). The 1.3 l container contains two UAS plates, hermetically sealed in a porous bag. The study was conducted to evaluate the in vitro functions of pooled apheresis platelet donations suspended in 35% plasma and 65% DPT following treatment using the INTERCEPT™ platelet processing kit with three storage containers. Pooling of two apheresis platelets is used to deliver a high dose, high volume of approximately 10.2-1 1.8x1ο ¹¹ platelets in approximately 623-648 ml of 35% plasma/65% DRT-3, UAS incubation time is 14.2-15.0 hours, and amotosalen levels after UAS are <0.14 μM. Following pathogen inactivation, pH ₂₂ ° _C , and in vitro characteristics of the treated platelets are monitored for up to 7 days of storage. On day 7, all units maintained a pH of ₂₂ ° _with >6.4 (7.0±0.1). Some additional parameters assessed include pO ₂ (mm Hg) = 135 ± 8, pCO ₂ (mm Hg) = 11 ± 1, HCO ₃ - = 2 ± 1, supernatant glucose (mmol/l) =0.0±0.0, normalized supernatant lactate (mmol/ ¹⁰⁶ platelets)=9.1±1.0, total ATP (nmol/ ¹⁰⁸ platelets)=2.1±0.5, morphology = 246±10, SIF (%) =14.6±3.0 and RPP (%)=32.4±3.9.

All references, including publications, patent applications and patents cited herein, are incorporated herein by reference to the same extent as if each reference had been separately and specifically stated to be incorporated by reference and set forth herein in its entirety. its completeness.

The use of the terms a and an and the and similar references (especially in the context of the following claims) should be construed to cover both the singular and plural unless otherwise stated herein or the context clearly conflicts. The terms containing, having, including and containing are to be construed as open terms (i.e., meaning including but not limited to) unless otherwise noted. Wherever an open term is used to describe a characteristic or element, it is specifically intended that the closed term may be used in place of the open term without departing from the spirit and scope of the description. The listing of ranges of values herein is simply intended to serve as a concise means of individually referring to each individual value falling within that range unless otherwise noted herein, and each individual value is included in the description as if it were separately stated herein. All methods described herein may be performed in any suitable order, unless otherwise indicated herein or otherwise clearly inconsistent with the context. The use of any and all examples or exemplary language (eg, such as) presented herein is intended merely to better illuminate the description and does not constitute a limitation on the scope of the description unless otherwise stated. No term in the specification should be construed as indicating any element not claimed as essential to the practice of the methods, systems and compositions described herein.

Preferred embodiments are described here. Variations to these preferred embodiments may become apparent to those skilled in the art upon reading the foregoing description. It is expected that those skilled in the art will be able to use such variations depending on the situation and in the practical application of methods, systems and

- 31 044317 compositions described herein, otherwise than specifically described here. Accordingly, the methods, systems and compositions described herein include all modifications and equivalents of the subject matter set forth in the appended claims as permitted by applicable law. Moreover, any combination of the above-described elements in all their possible variations is covered by the description, unless otherwise indicated herein or otherwise clearly inconsistent with the context.

List of options:

Option 1. Method for obtaining a pathogen-inactivated platelet composition, including:

(a) mixing the platelet composition with a pathogen-inactivating compound (PAC);

(b) photochemical inactivation of the platelet composition mixed with IPA; and (c) transferring the resulting mixture from step (b) under sterile conditions into a container containing a compound adsorption device (CAD) to obtain a pathogen-inactivated platelet composition;

where at least one of (i) and (ii) applies:

(i) the volume of the container containing the UAS is greater than 1.0 liters; and (ii) the surface area of the interior of the container containing the UAS is greater than about 750 cm ² .

Option 2. Method according to option 1, additionally including:

(d) transferring the pathogen-inactivated platelet composition under sterile conditions from the container containing the UAS to one or more storage containers.

Option 3. The method as in Option 2, wherein the one or more storage containers are one storage container.

Option 4. The method as in Option 2, wherein the one or more storage containers are two storage containers.

Embodiment 5: The method as in Embodiment 2, wherein the one or more storage containers are three storage containers.

Option 6. Method according to any of options 1-5, where the volume of the container containing the UAS is more than 1.0 liters.

Option 7. The method according to any of options 1-6, where the volume of the container containing the UAS is greater than approximately 1.2 liters.

Option 8. The method according to any of options 1-7, where the volume of the container containing the UAS is approximately 1.3 liters.

Option 9. The method according to any of options 1-7, where the volume of the container containing the UAS is approximately 1.5 liters.

Option 10. The method of any one of options 1-7, wherein the volume of the container containing the UAS is from about 1.2 liters to about 1.6 liters.

Embodiment 11. The method of any one of embodiments 1-10, wherein the surface area of the interior of the container containing the UAS is greater than about 750 cm ² .

Embodiment 12. The method of any one of embodiments 1-11, wherein the surface area of the interior of the container containing the UAS is greater than about 850 cm ² .

Embodiment 13. The method of any one of embodiments 1-12, wherein the surface area of the interior of the container containing the UAS is approximately 900 cm ² .

Embodiment 14. The method of any one of embodiments 1-12, wherein the surface area of the interior of the container containing the UAS is from about 850 cm ² to about 1100 cm ² .

Embodiment 15. The method of any one of embodiments 1-14, wherein the platelet composition contains at least about 6.0x1011 platelets.

Embodiment 16. The method of any one of embodiments 1-14, wherein the platelet composition contains at least about 7.0x1011 platelets.

Embodiment 17. The method of any one of embodiments 1-14, wherein the platelet composition contains at least about 8.0x1011 platelets.

Embodiment 18. The method of any one of embodiments 1-14, wherein the platelet composition contains at least about 11.0x1011 platelets.

Embodiment 19. The method of any one of embodiments 1-14, wherein the platelet composition contains from about 6.0x1011 to about 12.0x1011 platelets.

Embodiment 20. The method of any one of embodiments 1-19, wherein the platelet composition has a volume of at least about 350 ml.

Embodiment 21. The method of any one of embodiments 1-19, wherein the platelet composition has a volume of at least about 400 ml.

Embodiment 22. The method of any one of embodiments 1-19, wherein the platelet composition has a volume of at least about 450 ml.

Embodiment 23. The method of any one of embodiments 1-19, wherein the platelet composition has a volume of at least about 500 ml.

- 32 044317

Embodiment 24. The method of any one of embodiments 1-19, wherein the platelet composition has a volume of at least about 600 ml.

Embodiment 25. The method of any one of embodiments 1-19, wherein the platelet composition has a volume of from about 350 ml to about 650 ml.

Embodiment 26. The method of any one of embodiments 1-25, wherein the platelet composition comprises plasma.

Embodiment 27. The method of embodiment 26, wherein the platelet composition does not contain an additional platelet solution.

Embodiment 28. The method of any one of embodiments 1-26, wherein the platelet composition comprises an additional platelet solution.

Embodiment 29. The method of embodiment 28, wherein the platelet composition contains from about 53% to about 68% platelet addition solution.

Embodiment 30. The method of any one of embodiments 1-27, wherein the platelet composition comprises platelets suspended in a suspension medium consisting essentially of plasma.

Embodiment 31. The method as in any one of embodiments 1-30, wherein the method comprises, prior to step (a), collecting one or more platelet donations from one or more donors.

Option 32. The method of any one of options 1-31, wherein the platelet composition is prepared from an apheresis donation.

Embodiment 33. The method of any one of embodiments 1-31, wherein the platelet composition is prepared from a whole blood donation.

Embodiment 34. The method of any one of embodiments 1-33, wherein the platelet composition comprises one platelet donation.

Embodiment 35. The method of any one of embodiments 1-33, wherein the platelet composition comprises two platelet donations.

Embodiment 36. The method of any one of embodiments 1-33, wherein the platelet composition comprises three or more platelet donations.

Embodiment 37. The method of any one of embodiments 1-36, wherein the UAS comprises at least about three grams of absorbent beads.

Embodiment 38. The method of embodiment 37, wherein the UAS contains less than about seven grams of absorbent beads.

Embodiment 39. The method of any one of embodiments 1-36, wherein the UAS comprises at least about seven grams of absorbent beads.

Embodiment 40. The method of any one of embodiments 1-39, wherein the method comprises, prior to step (a), sterilely combining a container containing the platelet composition with a container containing IPA.

Embodiment 41. The method of any one of embodiments 2-38, further comprising, after step (d), storing the pathogen-inactivated platelet composition in one or more storage containers for at least 5 days at room temperature.

Option 42. Method according to option 41, where storage is carried out for at least 6 days at room temperature.

Option 43. Method according to option 41, where storage is carried out for at least 7 days at room temperature.

Option 44. The method according to any one of options 41-43, where storage is carried out for up to 7 days at room temperature.

Embodiment 45. The method of any one of embodiments 41-44, wherein the pH of the pathogen-inactivated platelet composition after storage is >6.2.

Embodiment 46. The method of any one of embodiments 41-44, wherein the pH of the pathogen-inactivated platelet composition after storage is >6.4.

Embodiment 47. The method as in any one of embodiments 2-46, wherein after step (c) and before step (d), the pathogen-inactivated platelet composition is stored in a container containing the UAS for about 4 to about 24 hours.

Embodiment 48. The method of any one of embodiments 1-47, wherein the pathogen-inactivated platelet composition is one or more pathogen-inactivated platelet units suitable for infusion.

Embodiment 49. The method of any one of embodiments 1-47, wherein the pathogen-inactivated platelet composition is one pathogen-inactivated platelet unit suitable for infusion.

Embodiment 50. The method of any one of embodiments 1-47, wherein the pathogen-inactivated platelet composition is two or more pathogen-inactivated platelet units suitable for infusion.

Embodiment 51. The method of any one of embodiments 1-47, wherein the pathogen-inactivated platelet composition is three or more pathogen-inactivated platelet units suitable for infusion.

Option 52. The method of any one of embodiments 48-51, wherein the pathogen-inactivated unit is trom

- 33 044317 bocyte suitable for infusion is a therapeutic dosage unit of pathogen-inactivated platelets.

Embodiment 53. The method of any one of embodiments 1-52, wherein the pathogen-inactivated platelet composition contains at least 2.0x1011 platelets.

Embodiment 54. The method of any one of embodiments 1-52, wherein the pathogen-inactivated platelet composition contains at least 2.4x1011 platelets.

Embodiment 55. The method of any one of embodiments 1-52, wherein the pathogen-inactivated platelet composition contains at least 3.0x1011 platelets.

Embodiment 56 The pathogen-inactivated platelet composition is prepared by the method of any one of embodiments 1-55.

Embodiment 57. The pathogen-inactivated platelet composition of embodiment 56, wherein the pathogen-inactivated platelet composition is one or more pathogen-inactivated platelet units suitable for infusion.

Embodiment 58. The pathogen-inactivated platelet composition of embodiment 56, wherein the pathogen-inactivated platelet composition is one pathogen-inactivated platelet unit suitable for infusion.

Embodiment 59. The pathogen-inactivated platelet composition of embodiment 56, wherein the pathogen-inactivated platelet composition is two pathogen-inactivated platelet units suitable for infusion.

Embodiment 60. The pathogen-inactivated platelet composition of embodiment 56, wherein the pathogen-inactivated platelet composition is three pathogen-inactivated platelet units suitable for infusion.

Embodiment 61. The pathogen-inactivated platelet composition of any one of embodiments 57-60, wherein the pathogen-inactivated platelet unit suitable for infusion is a therapeutic dosage unit of pathogen-inactivated platelets.

Embodiment 62. The pathogen-inactivated platelet composition of any one of embodiments 56-61, wherein the pathogen-inactivated platelet composition contains at least 2.0x1011 platelets.

Embodiment 63. The pathogen-inactivated platelet composition of any one of embodiments 56-61, wherein the pathogen-inactivated platelet composition contains at least 2.4x1011 platelets.

Embodiment 64. The pathogen-inactivated platelet composition of any one of embodiments 56-61, wherein the pathogen-inactivated platelet composition contains at least 3.0x1011 platelets.

Embodiment 65. A method of infusing a platelet composition to a subject in need thereof, wherein the method comprises infusing the subject with a pathogen-inactivated platelet composition obtained by the method of any of embodiments 1-55, or a pathogen-inactivated platelet unit of any of embodiments 57-64.

Embodiment 66. A processing kit for producing a pathogen-inactivated platelet composition, comprising:

(a) a first container that contains a pathogen-inactivating compound (PIC) and is suitable for combining the platelet composition with the PIC;

(b) a second container connected to the first container, in which the platelet composition mixed with IPA can be photochemically inactivated; and (c) a third container containing a compound adsorption device (CAD), wherein the third container is connected to the second container so that the photochemically inactivated platelet composition can be transferred from the second container to the third container under sterile conditions;

where at least one of (i) and (ii) applies:

(i) the volume of the third container is greater than 1.0 liters; and (ii) the surface area of the interior of the third container is greater than about 750 cm ² .

Embodiment 67. The treatment kit of Embodiment 66, further comprising one or more fourth containers, wherein the one or more fourth containers are connected to the third container so that the photochemically inactivated platelet composition can be transferred from the third container to the one or more fourth containers under sterile conditions. to obtain a pathogen-inactivated platelet composition.

Option 68. Processing kit according to Option 67, containing one fourth container.

Option 69. Option 67 treatment kit containing two quarter containers.

Option 70. Option 67 processing kit containing three-quarters of the container.

Option 71. Set for processing according to any of options 66-70, where the volume of the third container is more than 1.0 liters.

Option 72. Set for processing according to any of options 66-71, where the volume of the third container

- 34 044317 more than approximately 1.2 l.

Option 73. Treatment kit according to any of options 66-71, where the volume of the third container is approximately 1.3 liters.

Option 74. Treatment kit according to any of options 66-71, where the volume of the third container is approximately 1.5 liters.

Embodiment 75: The treatment kit of any one of embodiments 66-71, wherein the third container has a volume of from about 1.2 L to about 1.6 L.

Embodiment 76: The treatment kit of any one of embodiments 66-75, wherein the surface area of the interior of the third container is greater than about 750 cm ² .

Embodiment 77: The treatment kit of any one of embodiments 66-75, wherein the surface area of the interior of the third container is greater than about 850 cm ² .

Embodiment 78: The treatment kit of any one of embodiments 66-77, wherein the surface area of the interior of the container containing the UAS is approximately 900 cm ² .

Embodiment 79. The treatment kit of any one of embodiments 66-77, wherein the surface area of the interior of the container containing the UAS is from about 850 cm ² to about 1100 cm ² .

Embodiment 80. The treatment kit of any one of embodiments 66-79, wherein the platelet composition contains at least about 6.0x1011 platelets.

Embodiment 81. The treatment kit of any one of embodiments 66-79, wherein the platelet composition contains at least about 7.0x1011 platelets.

Embodiment 82. The treatment kit of any one of embodiments 66-79, wherein the platelet composition contains at least about 8.0x1011 platelets.

Embodiment 83. The treatment kit of any one of embodiments 66-79, wherein the platelet composition contains at least about 11.0x1011 platelets.

Embodiment 84. The treatment kit of any one of embodiments 66-79, wherein the platelet composition contains from about 6.0x1011 to about 12.0x1011 platelets.

Embodiment 85. The treatment kit of any one of embodiments 66-84, wherein the platelet composition has a volume of at least about 350 mL.

Embodiment 86. The treatment kit of any one of embodiments 66-84, wherein the platelet composition has a volume of at least about 400 ml.

Embodiment 87. The treatment kit of any one of embodiments 66-84, wherein the platelet composition has a volume of at least about 450 ml.

Embodiment 88. The treatment kit of any one of embodiments 66-84, wherein the platelet composition has a volume of at least about 500 mL.

Embodiment 89. The treatment kit of any one of embodiments 66-84, wherein the platelet composition has a volume of at least about 600 ml.

Embodiment 90. The treatment kit of any one of embodiments 66-84, wherein the platelet composition has a volume of from about 350 ml to about 650 ml.

Embodiment 91. The treatment kit of any one of embodiments 66-90, wherein the platelet composition comprises plasma.

Embodiment 92: The treatment kit of Embodiment 91, wherein the platelet composition does not contain a platelet add-on solution.

Embodiment 93. The treatment kit of any one of embodiments 66-91, wherein the platelet composition comprises a platelet supplement solution.

Embodiment 94. The treatment kit of Embodiment 93, wherein the platelet composition contains from about 53% to about 68% platelet addition solution.

Embodiment 95. The treatment kit of any one of embodiments 66-92, wherein the platelet composition comprises platelets suspended in a suspension medium consisting essentially of plasma.

Embodiment 96. The treatment kit of any one of embodiments 66-95, wherein the platelet composition comprises one or more platelet donations from one or more donors.

Embodiment 97. The treatment kit of any one of embodiments 66-96, wherein the platelet composition is obtained from an apheresis donation.

Embodiment 98. The treatment kit of any one of embodiments 66-96, wherein the platelet composition is obtained from a whole blood donation.

Embodiment 99. The treatment kit of any one of embodiments 66-98, wherein the platelet composition comprises one platelet donation.

Option 100. The treatment kit of any one of embodiments 66-98, wherein the platelet composition comprises two platelet donations.

Embodiment 101. The treatment kit of any one of embodiments 66-98, wherein the platelet composition comprises three or more platelet donations.

Embodiment 102. The treatment kit of any one of embodiments 66-101, wherein the UAS contains at least about three grams of absorbent beads.

- 35 044317

Embodiment 103: The treatment kit of Embodiment 102, wherein the UAS contains less than about seven grams of absorbent beads.

Embodiment 104. The treatment kit of any one of embodiments 66-102, wherein the UAS contains at least about seven grams of absorbent beads.

Embodiment 105. The treatment kit of any one of embodiments 66-104, wherein the first container is suitable for sterile combination with a container containing the platelet composition.

Embodiment 106. The treatment kit of any one of embodiments 67-105, wherein the one or more quarter containers are suitable for storing the pathogen-inactivated platelet composition for at least 5 days at room temperature.

Embodiment 107. The treatment kit of embodiment 106, wherein the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 6 days at room temperature.

Embodiment 108. The treatment kit of embodiment 106, wherein the one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 7 days at room temperature.

Embodiment 109. The treatment kit of any one of embodiments 106-108, wherein the one or more quarter containers are suitable for storing the pathogen-inactivated platelet composition for up to 7 days at room temperature.

Option 110. The treatment kit of any one of embodiments 106-109, wherein the pH of the pathogen-inactivated platelet composition after storage is >6.2.

Option 111. The treatment kit of any one of embodiments 106-109, wherein the pH of the pathogen-inactivated platelet composition after storage is >6.4.

Embodiment 112. The treatment kit of any one of embodiments 66-111, wherein the third container is suitable for storing the pathogen-inactivated platelet composition for about 4 to about 24 hours.

Embodiment 113. The treatment kit of any one of embodiments 66-112, wherein the pathogen-inactivated platelet composition is one or more pathogen-inactivated platelet units suitable for infusion.

Embodiment 114. The treatment kit of any one of embodiments 66-112, wherein the pathogen-inactivated platelet composition is one pathogen-inactivated platelet unit suitable for infusion.

Embodiment 115. The treatment kit of any one of embodiments 66-112, wherein the pathogen-inactivated platelet composition is two pathogen-inactivated platelet units suitable for infusion.

Embodiment 116. The treatment kit of any one of embodiments 66-112, wherein the pathogen-inactivated platelet composition is three pathogen-inactivated platelet units suitable for infusion.

Embodiment 117. The treatment kit of any one of embodiments 113-116, wherein the pathogen-inactivated unit suitable for infusion is a therapeutic dosage unit of pathogen-inactivated platelets.

Embodiment 118. The treatment kit of any one of embodiments 66-117, wherein the pathogen-inactivated platelet composition contains at least 2.0x1011 platelets.

Embodiment 119. The treatment kit of any one of embodiments 66-117, wherein the pathogen-inactivated platelet composition contains at least 2.4x1011 platelets.

Embodiment 120. The treatment kit of any one of embodiments 66-117, wherein the pathogen-inactivated platelet composition contains at least 3.0x1011 platelets.

Claims (43)

1. A method for obtaining a pathogen-inactivated platelet composition, including: (a) mixing the platelet composition with a pathogen-inactivating compound (PIC), wherein the PIC is psoralen, and where the platelet composition has a volume of from 250 ml to 750 ml; (b) photochemical inactivation of the platelet composition mixed with IPA; and (c) transferring the resulting mixture from step (b) under sterile conditions into a container containing a compound adsorption device (CAD) to obtain a pathogen-inactivated platelet composition; where at least one of (i) and (ii) applies: (i) the volume of the container containing the UAS is from 1.2 l to 1.6 l; and (ii) the surface area of the interior of the container containing the UAS is from 800 cm ² to 1200 cm ² . 2. The method according to paragraph 1, additionally containing: (d) transferring the pathogen-inactivated platelet composition under sterile conditions from the container containing the UAS to one or more storage containers. 3. The method of claim 2, wherein the one or more storage containers are two storage containers. 4. The method of claim 2, wherein the one or more storage containers are three storage containers. 5. The method according to any one of claims 1-4, where the volume of the container containing the UAS is 1.3 liters. 6. The method according to any one of claims 1-5, where the surface area of the inside of the container containing the UAS is from 850 cm ² to 1100 cm ² . 7. The method according to any one of claims 1 to 6, wherein the platelet composition contains at least 6.0x1011 platelets or from 6.0x1011 to 12.0x1011 platelets. 8. The method according to any one of claims 1 to 7, wherein the platelet composition contains plasma and/or where the platelet composition contains an additional platelet solution. 9. The method according to any one of claims 1 to 8, where the method includes, prior to step (a), collecting one or more platelet donations from one or more donors. 10. The method according to any one of claims 1 to 9, wherein the platelet composition contains one platelet donation or where the platelet composition contains two platelet donations. 11. The method according to any one of claims 1 to 10, wherein the UAS contains at least three grams of absorbent beads, optionally wherein the UAS contains less than seven grams of absorbent beads. 12. The method according to any one of claims 1-10, where the UAS contains at least seven grams of absorbent beads. 13. The method according to any one of claims 2-12, further comprising, after step (d), storing the pathogen-inactivated platelet composition in one or more storage containers for at least 5 days at room temperature, optionally where storage is carried out for up to 7 days at room temperature. 14. The method of claim 13, wherein the pH of the pathogen-inactivated platelet composition after storage is >6.2, or wherein the pH of the pathogen-inactivated platelet composition after storage is >6.4. 15. The method according to any one of claims 2-14, where, after step (c) and before step (d), the pathogen-inactivated platelet composition is stored in a container containing the UAS for 4 to 24 hours. 16. The method according to any one of claims 1 to 15, wherein the pathogen-inactivated platelet composition comprises one or more pathogen-inactivated platelet units suitable for infusion, or two pathogen-inactivated platelet units suitable for infusion. 17. The method according to any one of claims 1 to 15, wherein the pathogen-inactivated platelet composition contains three pathogen-inactivated platelet units suitable for infusion. 18. The method according to any one of claims 16-17, wherein the pathogen-inactivated platelet unit suitable for infusion comprises a therapeutic dosage unit of pathogen-inactivated platelets. 19. The method according to any one of claims 16-18, wherein the pathogen-inactivated platelet unit suitable for infusion contains at least 2.0 x 1011 platelets. 20. A method for producing a pathogen-inactivated platelet composition, including: (a) mixing the platelet composition with a pathogen-inactivating compound (PIC), wherein the PIC is psoralen, and where the platelet composition has a volume of from 250 ml to 750 ml; (b) photochemical inactivation of the platelet composition mixed with IPA; and (c) transferring the resulting mixture from step (b) under sterile conditions into a container containing a compound adsorption device (CAD) to obtain a pathogen-inactivated platelet composition; wherein the UAS contains less than seven grams of adsorbent beads, and at least one of (i) and (ii) applies: - 37 044317 (i) the volume of the container containing the UAS is from 1.2 to 1.6 l; (ii) the surface area of the inside of the container containing the UAS is from 800 cm ² to 1200 cm ² ; and (d) transferring the pathogen-inactivated platelet composition under sterile conditions from a container containing the UAS to two storage containers, wherein the pathogen-inactivated platelet composition in each of said two storage containers contains a therapeutic dosage unit of pathogen-inactivated platelets suitable for infusions. 21. A method for obtaining a pathogen-inactivated platelet composition, including: (a) mixing the platelet composition with a pathogen-inactivating compound (PIC), wherein the PIC is psoralen, and where the platelet composition has a volume of from 250 ml to 750 ml; (b) photochemical inactivation of the platelet composition mixed with IPA; and (c) transferring the resulting mixture from step (b) under sterile conditions into a container containing a compound adsorption device (CAD) to obtain a pathogen-inactivated platelet composition; wherein the UAS contains at least seven grams of absorbent beads, and at least one of (i) and (ii) applies: (i) the volume of the container containing the UAS is from 1.2 to 1.6 liters; (ii) the surface area of the inside of the container containing the UAS is from 800 cm ² to 1200 cm ² ; and (d) transferring the pathogen-inactivated platelet composition under sterile conditions from the container containing the UAS to three storage containers, wherein the pathogen-inactivated platelet composition in each of said three storage containers contains a therapeutic dosage unit of pathogen-inactivated platelets suitable for infusions. 22. A method for preventing or treating a condition that requires platelet transfusion, wherein the method comprises infusing into a subject in need thereof a pathogen-inactivated platelet composition obtained by the method of any one of claims 1 to 21. 23. A kit for processing platelets to obtain a pathogen-inactivated platelet composition, containing: (a) a first container that contains a pathogen inactivating compound (PIC) and is suitable for combining a platelet composition with a PIA, where the PIA is psoralen, and where the platelet composition has a volume of from 250 ml to 750 ml; (b) a second container connected to the first container, in which the platelet composition mixed with IPA can be photochemically inactivated; and (c) a third container containing a compound adsorption device (CAD), wherein the third container is connected to the second container so that the photochemically inactivated platelet composition can be transferred from the second container to the third container under sterile conditions; where at least one of (i) and (ii) applies: (i) the volume of the third container is from 1.2 l to 1.6 l; and (ii) a surface area of the interior of the third container from 800 cm ² to 1200 cm ² . 24. The kit of claim 23, further comprising one or more additional containers, wherein the one or more additional containers are connected to a third container such that the photochemically inactivated platelet composition can be transferred from the third container to the one or more additional containers under sterile storage conditions pathogen-inactivated platelet composition. 25. The kit according to claim 24, containing two additional containers for storing the pathogen-inactivated platelet composition. 26. The kit according to claim 24, containing three additional containers for storing the pathogen-inactivated platelet composition. 27. The set according to any one of paragraphs 23-26, where the volume of the third container is 1.3 liters. 28. The set according to any one of claims 22 to 27, wherein the surface area of the inside of the third container is from 850 cm ² to 1100 cm ² . 29. The kit according to any one of claims 23-28, wherein the platelet composition contains at least 6.0x1011 platelets or from 6.0x1011 to 12.0x1011 platelets. 30. The kit according to any one of claims 23-29, wherein the platelet composition contains plasma and/or where the platelet composition contains an additional platelet solution. 31. The kit according to any one of claims 23-30, wherein the platelet composition comprises one or more platelet donations from one or more donors. 32. The kit according to any one of claims 23-31, wherein the platelet composition contains one platelet donation or where the platelet composition contains two platelet donations. 33. The set according to any one of paragraphs 23-32, where the UAS contains at least three grams of adsorbent - 38 044317 beads, optional, where the UAS contains less than seven grams of absorbent beads. 34. The kit according to any one of claims 23-32, where the UAS contains at least seven grams of absorbent beads. 35. The kit according to any one of claims 24-34, wherein one or more fourth containers are suitable for storing the pathogen-inactivated platelet composition for at least 5 days at room temperature, optionally wherein one or more fourth containers are suitable for storing pathogen-inactivated platelet composition for up to 7 days at room temperature. 36. The kit of claim 35, wherein the pH of the pathogen-inactivated platelet composition after storage is >6.2, or where the pH of the pathogen-inactivated platelet composition after storage is >6.4. 37. The kit according to any one of claims 23 to 36, wherein the third container is suitable for storing the pathogen-inactivated platelet composition for 4 to 24 hours. 38. The kit according to any one of claims 23 to 37, wherein the pathogen-inactivated platelet composition comprises one or more pathogen-inactivated platelet units suitable for infusion, or two pathogen-inactivated platelet units suitable for infusion. 39. The kit according to any one of claims 23-37, wherein the pathogen-inactivated platelet composition contains three pathogen-inactivated platelet units suitable for infusion. 40. The kit according to any one of claims 38-39, wherein the pathogen-inactivated platelet unit suitable for infusion comprises a therapeutic dosage unit of pathogen-inactivated platelets. 41. The kit according to any one of claims 38-40, wherein the pathogen-inactivated platelet unit suitable for infusion contains at least 2.0 x 1011 platelets or wherein the pathogen-inactivated platelet unit suitable for infusion contains at least , 2.4x1011 platelets, or wherein the pathogen-inactivated platelet unit suitable for infusion contains at least 3.0x1011 platelets. 42. A kit for processing platelets to obtain a pathogen-inactivated platelet composition, containing: (a) a first container that contains a pathogen inactivating compound (PIC) and is suitable for combining a platelet composition with a PIA, where the PIA is psoralen, and where the platelet composition has a volume of from 250 ml to 750 ml; (b) a second container connected to the first container, in which the platelet composition mixed with IPA can be photochemically inactivated; and (c) a third container containing a compound adsorption device (CAD), wherein the third container is connected to the second container so that the photochemically inactivated platelet composition can be transferred from the second container to the third container under sterile conditions, where the CAD contains less than seven grams of adsorbent beads , and, where at least one of ^{(i) and (ii)} applies: (i) the volume of the third container is from 1.2 l to 1.6 l; and (ii) a surface area of the interior of the third container from 800 cm ² to 1200 cm ² ; and (d) two fourth containers, where the fourth containers are connected to the third container so that the photochemically inactivated platelet composition can be transferred from the third container to the fourth container under sterile conditions to obtain a pathogen-inactivated platelet composition, and where the fourth containers are suitable for storing the pathogen -inactivated platelet composition for at least 5 days at room temperature. 43. A kit for processing platelets to obtain a pathogen-inactivated platelet composition, containing: (a) a first container that contains a pathogen inactivating compound (PIC) and is suitable for combining a platelet composition with a PIA, where the PIA is psoralen, and where the platelet composition has a volume of from 250 ml to 750 ml; (b) a second container connected to the first container, in which the platelet composition mixed with IPA can be photochemically inactivated; and (c) a third container containing a compound adsorption device (CAD), wherein the third container is connected to the second container so that the photochemically inactivated platelet composition can be transferred from the second container to the third container under sterile conditions, where the CAD contains less than seven grams of adsorbent beads , and, where at least one of (i) and (ii) applies: (i) the volume of the third container is from 1.2 l to 1.6 l; and (ii) a surface area of the interior of the third container from 800 cm ² to 1200 cm ² ; and (d) three fourth containers, wherein the fourth containers are connected to the third container so that the photochemically inactivated platelet composition can be transferred from the third container to the fourth container under sterile conditions to obtain a pathogen-inactivated platelet composition, and where the fourth containers are suitable for storing the pathogen -inactivated compo- - 39 044317 platelet position for at least 5 days at room temperature.