US20030108558A1 - Use of proteins as agents against autoimmune diseases - Google Patents
Use of proteins as agents against autoimmune diseases Download PDFInfo
- Publication number
- US20030108558A1 US20030108558A1 US10/232,712 US23271202A US2003108558A1 US 20030108558 A1 US20030108558 A1 US 20030108558A1 US 23271202 A US23271202 A US 23271202A US 2003108558 A1 US2003108558 A1 US 2003108558A1
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- Prior art keywords
- treatment
- ala
- val
- proteins
- pathology
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- RWOGENDAOGMHLX-DCAQKATOSA-N Val-Lys-Ala Chemical compound C[C@@H](C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)N RWOGENDAOGMHLX-DCAQKATOSA-N 0.000 description 1
- AOILQMZPNLUXCM-AVGNSLFASA-N Val-Val-Lys Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(O)=O)CCCCN AOILQMZPNLUXCM-AVGNSLFASA-N 0.000 description 1
- 108010047495 alanylglycine Proteins 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000000879 anti-atherosclerotic effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
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- 230000002917 arthritic effect Effects 0.000 description 1
- 108010069205 aspartyl-phenylalanine Proteins 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4702—Regulators; Modulating activity
- C07K14/4703—Inhibitors; Suppressors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/827—Proteins from mammals or birds
- Y10S530/843—Digestive system
- Y10S530/846—Liver
Definitions
- the present invention relates to the use of proteins extractable from animal organs, particularly from livers of mammals, for the preparation of medicaments active against autoimmune diseases, in particular activity against atherosclerosis, arthritis, multiple sclerosis, and diabetes.
- WO 92/10197 disclosed protein fractions extractable with perchloric acid from organs of mammals, and their use as anticancer agents. Within these fractions, three main components could be identified, having molecular weights 50, 14 and 10 KDa on gel electrophoresis. The purified extract containing these three components will be referred to as UK 101 in the following.
- the sequence of the 14 KDa protein component, which is the main, if not the only, responsible for the described activities, is reported in the Table hereinbelow and in WO 96/02567, and it has turned out to be related to that described by other authors (Levy-Pavatier, Eur. Biochem. 1903, 212 (3) 665-73) which have assumed that the novel identified sequences belong to the family of the proteins known as chaperoning, to which the HSPs themselves-belong.
- the invention relates preferably to the use of the purified proteins UK 101 and UK 114 for the preparation of medicaments for the prevention and the treatment of autoimmune diseases such as atherosclerosis following organ transplants, arthritis, multiple sclerosis, diabetes.
- the invention comprises the use of proteins showing a high homology degree to UK 114 , of at least 80%, preferably of at least 90%.
- the experimental model of transplant atherosclerosis consists in the venous by-passes at the level of arteries in the rat. After a short time, the formation of atherosclerotic plaques at the level of the host vase, as it happens in the human pathology, has been observed.
- the pre-treatment (7 days before) with UK 101 or UK 114 has significantly prevented the development of the pathology in a high percent of cases, compared with what observed in the animals non pre-treated before the transplant.
- UK 101 and UK 114 are capable of modifying the progress of or of preventing pathological conditions such as arthritis and rheumatoid arthritis.
- EAE allergic encephalomyelitis
- UK 101 and UK 114 are believed to be able of changing the progress of or preventing pathological conditions such as multiple sclerosis.
- UK 101 and UK 114 are believed to be capable of changing the course of diabetes or of preventing it.
- the proteins of the invention can be administered using suitable formulations, mainly injectable.
- the pattern of the administration (doses, frequency of administration, etc.) will be determined according to the circumstances, depending on factors such as conditions of the patient, phase of the disease, etc., but usually a daily dosage ranging from 1 to 100 mg will be suitable.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Physical Education & Sports Medicine (AREA)
- Transplantation (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
Abstract
The use of proteins extracted with perchloric acid from animal organs, for the preparation of medicaments active against autoimmune diseases, in particular with activity against atheroscelerosis, arthritis, multiple sclerosis, and diabetes.
Description
- This is a divisional of copending application Ser. No. 09/269,019, filed on Apr. 6, 1999, which was in turn a 35 USC 371 U.S. national stage application of international application number PCT/EP97/05079, filed on Sep. 17, 1997.
- The present invention relates to the use of proteins extractable from animal organs, particularly from livers of mammals, for the preparation of medicaments active against autoimmune diseases, in particular activity against atherosclerosis, arthritis, multiple sclerosis, and diabetes.
- The administration of complete Freund's adjuvant has proved to be capable of inducing an experimental arthritis very similar to rheumatoid arthritis in rats. On the other hand, the administration of adjuvant to rabbits induces no arthritic pathology, but atherosclerosis. The studies carried out have evidenced that, in both lesions, immunoreactivity to an endogenous factor, which has been identified as the Heat Shock Protein 60 (HSP60), is present. Subsequent searches have confirmed these observations, proving that the administration of complete Freund's adjuvant can be replaced by the administration of HSP60, resulting in the same pathologies. Afterwards, pre-treatment of rat with adjuvant, HSP60 or fragments thereof has proved to prevent the onset of arthritis, with a still obscure mechanism, whereas the administration subsequent to the adjuvant worsens the progress of the disease.
- More recently, pre-treatment with adjuvant has been found to also prevent other experimental pathologies which can be defined, generally speaking, as autoimmune disease, such as diabetes or experimental allergic encephalomyelitis (EAE). Finally, HSP60 has been found to have structural analogies to a high number of autoantigens, therefore it is assumed to be related to pathologies more widely than what up to now observed.
- WO 92/10197 disclosed protein fractions extractable with perchloric acid from organs of mammals, and their use as anticancer agents. Within these fractions, three main components could be identified, having molecular weights 50, 14 and 10 KDa on gel electrophoresis. The purified extract containing these three components will be referred to as UK 101 in the following. The sequence of the 14 KDa protein component, which is the main, if not the only, responsible for the described activities, is reported in the Table hereinbelow and in WO 96/02567, and it has turned out to be related to that described by other authors (Levy-Pavatier, Eur. Biochem. 1903, 212 (3) 665-73) which have assumed that the novel identified sequences belong to the family of the proteins known as chaperoning, to which the HSPs themselves-belong.
- The proteins described in WO 92/10197 and those of WO 96/02567 (in the following referred to as UK 114) show anyhow properties never observed for chaperonins or analogous proteins. More specifically, it has been found that said proteins can be used in the prevention and in the treatment of autoimmune diseases, in particular atherosclerotic conditions, such as the atherosclerosis induced by organ transplants, arthritis, multiple sclerosis, and diabetes.
- The invention relates preferably to the use of the purified proteins UK 101 and UK 114 for the preparation of medicaments for the prevention and the treatment of autoimmune diseases such as atherosclerosis following organ transplants, arthritis, multiple sclerosis, diabetes.
- Moreover the invention comprises the use of proteins showing a high homology degree to UK 114, of at least 80%, preferably of at least 90%.
- It has been ascertained that nowadays the more frequent cause of failure of organ transplants in time is no more the rejection, but the formation of atherosclerotic plaques at the contact point between the vases of the transplanted organ and those of the host. This pathology is worsened by the usual immunosuppressors such as cyclosporin, whereas the use of AZT, which is however very toxic, appears to be useful.
- The activity of the proteins UK 101 and UK 114 has been evidenced using both a conventional atherosclerosis model, which is that of the rabbit pre-treated with complete Freund's adjuvant, and a transplant atherosclerosis model. In the first case, the subcutaneous treatment with adjuvant induces within 21 days the formation of atherosclerotic plaques at the iliac bifurcation and at the aortic arch. The pretreatment (7 days before) with UK 101 or UK 114 has significantly prevented the development of the pathology in a high percent of cases compared with the treatment with the only adjuvant, which has lead to the development of the disease in all of the animals.
- On the other hand, the experimental model of transplant atherosclerosis consists in the venous by-passes at the level of arteries in the rat. After a short time, the formation of atherosclerotic plaques at the level of the host vase, as it happens in the human pathology, has been observed. The pre-treatment (7 days before) with UK 101 or UK 114 has significantly prevented the development of the pathology in a high percent of cases, compared with what observed in the animals non pre-treated before the transplant.
- This activity has been evidenced using a conventional arthritis model, which is the adjuvant-induced arthritis. In this model, Lewis rats are injected at the tail base with complete Freund's adjuvant: within 7 days, a pathology at the rear leg appears, characterized by swelling and joints alterations. The pathology reaches its peaks from the 14th to the 21st day, then decreasing until the leg returns to normal conditions. The pre-treatment (7 days before) with UK 101 or UK 114 has significantly prevented the development of the pathology in a high percent of cases compared with treatment with the only adjuvant, which has lead to the development of the pathology in 100% of the animals. The treatment with UK 101 or UK 114 after the administration of adjuvant has worsened the progress of the pathology.
- Therefore, it is considered that UK 101 and UK 114 are capable of modifying the progress of or of preventing pathological conditions such as arthritis and rheumatoid arthritis.
- This has been evidenced using a conventional multiple sclerosis model: the experimental allergic encephalomyelitis (EAE). The pathology is induced injecting subcutaneously Lewis rats with a Guinea-pig spinal cord homogenate together with complete Freund's adjuvant. The pathology appears as a progressive paralysis starting from the rear limbs, which begins at about the 12th day, reaches a maximum at about the 21st day and undergoes remission at about the 30th day from the administration of the immunogen. The pre-treatment (7 days before) with UK 101 or UK 114 has significantly prevented the development of the pathology in a high percent of cases and a less serious pathology has appeared, compared with treatment with the only marrow homogenate and adjuvant, which has lead to the development of the pathology in 100% of the animals.
- Therefore UK 101 and UK 114 are believed to be able of changing the progress of or preventing pathological conditions such as multiple sclerosis.
- This has been evidenced using a conventional diabetes model, represented by the BB rat which spontaneously develops diabetes around the 45th day of life. The animals have been treated at the 30th day of life with UK 101 or UK 114 and the development of the pathology has been observed, compared with untreated control animals. The pre-treatment has been found to decrease the incidence and the severity of the pathology in the experimental model. Some patients affected with tumors at different sites and also suffering from diabetes have been treated with UK 101 in the course of a compassionate treatment with the substance. All of the patients treated, independently of the effect on the tumor pathology, have shown a remission of the diabetic pathology going so far as to quit the insulin therapy.
- Therefore UK 101 and UK 114 are believed to be capable of changing the course of diabetes or of preventing it.
- The antidiabetic activity has in fact been confirmed, although up to now in a limited number of cases, also in vivo in patients suffering from diabetes.
- The proteins of the invention can be administered using suitable formulations, mainly injectable.
- The pattern of the administration (doses, frequency of administration, etc.) will be determined according to the circumstances, depending on factors such as conditions of the patient, phase of the disease, etc., but usually a daily dosage ranging from 1 to 100 mg will be suitable.
TABLE Met Ser Glu Asn Ser Glu Glu Pro Val Gly Glu Ala 1 5 10 Lys Ala Pro Ala Ala Ile Gly Pro Tyr Ser Gln Ala 15 20 Val Leu Val Asp Arg Thr Ile Tyr Tie Ser Gly Gln 25 30 35 Leu Gly Met Asp Pro Ala Ser Gly Gln Leu Val Pro 40 45 Gly Gly Val Val Glu Glu Ala Lys Gln Ala Leu Thr 50 55 60 Asn Ile Gly Glu Ile Leu Lys Ala Ala Gly Cys Asp 65 70 Phe Thr Asn Val Val Lys Ala Thr Val Leu Leu Ala 75 80 Asp Ile Asn Asp Phe Ser Ala Val Asn Asp Val Tyr 85 90 95 Lys Gln Tyr Phe Gln Ser Ser Phe Pro Ala Arg Ala 100 105 Ala Tyr Gln Val Ala Ala Leu Pro Lys Gly Gly Arg 110 115 120 Val Glu Ile Glu Ala Ile Ala Val Gln Gly Pro Leu 125 130 Thr Thr Ala Ser Val 135 -
-
1 1 1 137 PRT Unknown Protein extracted with perchloric acid from mammalian liver 1 Met Ser Glu Asn Ser Glu Glu Pro Val Gly Glu Ala Lys Ala Pro Ala 1 5 10 15 Ala Ile Gly Pro Tyr Ser Gln Ala Val Leu Val Asp Arg Thr Ile Tyr 20 25 30 Ile Ser Gly Gln Leu Gly Met Asp Pro Ala Ser Gly Gln Leu Val Pro 35 40 45 Gly Gly Val Val Glu Glu Ala Lys Gln Ala Leu Thr Asn Ile Gly Glu 50 55 60 Ile Leu Lys Ala Ala Gly Cys Asp Phe Thr Asn Val Val Lys Ala Thr 65 70 75 80 Val Leu Leu Ala Asp Ile Asn Asp Phe Ser Ala Val Asn Asp Val Tyr 85 90 95 Lys Gln Tyr Phe Gln Ser Ser Phe Pro Ala Arg Ala Ala Tyr Gln Val 100 105 110 Ala Ala Leu Pro Lys Gly Gly Arg Val Glu Ile Glu Ala Ile Ala Val 115 120 125 Gln Gly Pro Leu Thr Thr Ala Ser Val 130 135
Claims (7)
1. A method of treatment for autoimmune diseases, comprising administering to an animal in need of such treatment a treatment effective amount of proteins extracted with perchloric acid from mammal liver.
2. The method according to claim 1 , wherein the treatment is for atherosclerosis following a transplant.
3. The method of treatment for atherosclerosis of claim 2 , comprising administering to an animal in need of such treatment a treatment-effective amount of the protein of SEQ ID NO:1.
4. The method according to claim 1 , wherein the treatment is for arthritis.
5. The method of treatment for arthritis of claim 4 , comprising administering to an animal in need of such treatment a treatment-effective amount of the protein of SEQ ID NO:1.
6. The method according to claim 1 , wherein the treatment is for multiple sclerosis.
7. The method of treatment for multiple sclerosis of claim 6 , comprising administering to an animal in need of such treatment a treatment-effective amount of the protein of SEQ ID NO:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/232,712 US20030108558A1 (en) | 1996-09-18 | 2002-09-03 | Use of proteins as agents against autoimmune diseases |
Applications Claiming Priority (10)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI961919 IT1284553B1 (en) | 1996-09-18 | 1996-09-18 | Using proteins from mammalian liver as agents against auto-immune disease - by preparing medicaments useful to prevent and treat atherosclerosis following transplants, arthritis, multiple sclerosis or diabetes |
| ITMI961920 IT1284554B1 (en) | 1996-09-18 | 1996-09-18 | Using proteins from mammalian liver as agents against auto-immune disease - by preparing medicaments useful to prevent and treat atherosclerosis following transplants, arthritis, multiple sclerosis or diabetes |
| ITMI96A001919 | 1996-09-18 | ||
| ITMI96A001920 | 1996-09-18 | ||
| ITMI96A001922 | 1996-09-18 | ||
| ITMI96A001921 | 1996-09-18 | ||
| ITMI961922 IT1284556B1 (en) | 1996-09-18 | 1996-09-18 | Using proteins from mammalian liver as agents against auto-immune disease - by preparing medicaments useful to prevent and treat atherosclerosis following transplants, arthritis, multiple sclerosis or diabetes |
| ITMI961921 IT1284555B1 (en) | 1996-09-18 | 1996-09-18 | Using proteins from mammalian liver as agents against auto-immune disease - by preparing medicaments useful to prevent and treat atherosclerosis following transplants, arthritis, multiple sclerosis or diabetes |
| US09/269,019 US6468536B1 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as anti-diabetes agents |
| US10/232,712 US20030108558A1 (en) | 1996-09-18 | 2002-09-03 | Use of proteins as agents against autoimmune diseases |
Related Parent Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US09/269,019 Division US6468536B1 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as anti-diabetes agents |
| PCT/EP1997/005079 Division WO1998011909A1 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as agents against autoimmune diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20030108558A1 true US20030108558A1 (en) | 2003-06-12 |
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| US09/269,019 Expired - Fee Related US6468536B1 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as anti-diabetes agents |
| US10/232,712 Abandoned US20030108558A1 (en) | 1996-09-18 | 2002-09-03 | Use of proteins as agents against autoimmune diseases |
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| Application Number | Title | Priority Date | Filing Date |
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| US09/269,019 Expired - Fee Related US6468536B1 (en) | 1996-09-18 | 1997-09-17 | Use of proteins as anti-diabetes agents |
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| US (2) | US6468536B1 (en) |
| EP (1) | EP0928197B1 (en) |
| JP (1) | JP2001501925A (en) |
| KR (1) | KR20000036207A (en) |
| CN (1) | CN1151838C (en) |
| AR (1) | AR009952A1 (en) |
| AT (1) | ATE233569T1 (en) |
| AU (1) | AU723669B2 (en) |
| BR (1) | BR9711499A (en) |
| CA (1) | CA2266346A1 (en) |
| CZ (1) | CZ293926B6 (en) |
| DE (1) | DE69719525T2 (en) |
| DK (1) | DK0928197T3 (en) |
| ES (1) | ES2192669T3 (en) |
| IL (1) | IL129024A0 (en) |
| NO (1) | NO991175D0 (en) |
| NZ (1) | NZ334714A (en) |
| PL (1) | PL188746B1 (en) |
| PT (1) | PT928197E (en) |
| RU (1) | RU2196606C2 (en) |
| TR (1) | TR199900596T2 (en) |
| WO (1) | WO1998011909A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030162705A1 (en) * | 2000-06-08 | 2003-08-28 | Albert Panerai | Method of treatment of amyotrophic lateral sclerosis with a protein extractable from mammalian organs |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7112655B1 (en) | 1997-02-27 | 2006-09-26 | Japan Tobacco, Inc. | JTT-1 protein and methods of inhibiting lymphocyte activation |
| JP3521382B2 (en) | 1997-02-27 | 2004-04-19 | 日本たばこ産業株式会社 | Cell surface molecules that mediate cell-cell adhesion and signal transduction |
| IT1290828B1 (en) * | 1997-03-25 | 1998-12-11 | Zetesis Spa | USE OF EXTRACTABLE PROTEINS FROM ANIMAL ORGANS FOR THE PREPARATION OF MEDICATIONS FOR THE TREATMENT OF PATHOLOGICAL CONDITIONS |
| JP4210454B2 (en) | 2001-03-27 | 2009-01-21 | 日本たばこ産業株式会社 | Inflammatory bowel disease treatment |
| JP3871503B2 (en) | 1999-08-30 | 2007-01-24 | 日本たばこ産業株式会社 | Immune disease treatment |
| JP3597140B2 (en) | 2000-05-18 | 2004-12-02 | 日本たばこ産業株式会社 | Human monoclonal antibody against costimulatory molecule AILIM and pharmaceutical use thereof |
| JP4212278B2 (en) | 2001-03-01 | 2009-01-21 | 日本たばこ産業株式会社 | Graft rejection inhibitor |
| ITMI20010762A1 (en) * | 2001-04-10 | 2002-10-10 | Zetesis Spa | USE OF UK114 PROTEIN OR ITS FRAGMENTS FOR THE TREATMENT AND PREVENTION OF ENDOTOXIC SHOCK |
| ITMI20010761A1 (en) * | 2001-04-10 | 2002-10-10 | Zetesis Spa | USE OF UK114 PROTEIN FOR THE TREATMENT AND PREVENTION OF ACTIVE CHRONIC HEPATITIS |
| ATE548047T1 (en) * | 2004-01-16 | 2012-03-15 | Cbio Ltd | CHAPERONIN-10 MODULATION OF GREAT RECEPTOR-INDUCABLE CYTOKINE AND CHEMOKINE SECRETION |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4024247A (en) * | 1971-12-27 | 1977-05-17 | Palolab Pharmaceuticals Corporation | Composition and method of using a protein mixture derived from liver |
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| IT1244879B (en) * | 1990-12-11 | 1994-09-12 | Alberto Bartorelli | EXTRACTS FROM ANIMAL TISSUES, USEFUL IN THERAPY AND DIAGNOSTICS. |
| FR2688227A1 (en) | 1992-03-04 | 1993-09-10 | Inst Nat Sante Rech Med | PROTEINS FORMING COMPLEXES WITH CHAPERONES AND THEIR LIGANDS, THEIR FRAGMENTS, THEIR PRODUCTION AND THEIR BIOLOGICAL APPLICATIONS. |
| IT1270618B (en) * | 1994-07-14 | 1997-05-07 | Zetesis Spa | PROTEIN WITH ANTI-TUMOR ACTIVITY |
| IL115744A (en) * | 1994-10-27 | 2000-07-16 | Akzo Nobel Nv | Peptides comprising a subsequence of human cartilage glycoprotein - 39 |
-
1997
- 1997-09-17 TR TR1999/00596T patent/TR199900596T2/en unknown
- 1997-09-17 BR BR9711499A patent/BR9711499A/en not_active IP Right Cessation
- 1997-09-17 DE DE69719525T patent/DE69719525T2/en not_active Expired - Fee Related
- 1997-09-17 ES ES97910295T patent/ES2192669T3/en not_active Expired - Lifetime
- 1997-09-17 RU RU99107658/14A patent/RU2196606C2/en not_active IP Right Cessation
- 1997-09-17 AU AU47747/97A patent/AU723669B2/en not_active Ceased
- 1997-09-17 NZ NZ334714A patent/NZ334714A/en unknown
- 1997-09-17 CA CA002266346A patent/CA2266346A1/en not_active Abandoned
- 1997-09-17 US US09/269,019 patent/US6468536B1/en not_active Expired - Fee Related
- 1997-09-17 AT AT97910295T patent/ATE233569T1/en not_active IP Right Cessation
- 1997-09-17 PT PT97910295T patent/PT928197E/en unknown
- 1997-09-17 CZ CZ1999915A patent/CZ293926B6/en not_active IP Right Cessation
- 1997-09-17 CN CNB971980128A patent/CN1151838C/en not_active Expired - Fee Related
- 1997-09-17 JP JP10514285A patent/JP2001501925A/en not_active Ceased
- 1997-09-17 DK DK97910295T patent/DK0928197T3/en active
- 1997-09-17 KR KR1019997002267A patent/KR20000036207A/en not_active Ceased
- 1997-09-17 EP EP97910295A patent/EP0928197B1/en not_active Expired - Lifetime
- 1997-09-17 IL IL12902497A patent/IL129024A0/en unknown
- 1997-09-17 WO PCT/EP1997/005079 patent/WO1998011909A1/en not_active Application Discontinuation
- 1997-09-17 AR ARP970104244A patent/AR009952A1/en unknown
-
1999
- 1999-03-10 NO NO991175A patent/NO991175D0/en not_active Application Discontinuation
- 1999-03-17 PL PL97332282A patent/PL188746B1/en not_active IP Right Cessation
-
2002
- 2002-09-03 US US10/232,712 patent/US20030108558A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4024247A (en) * | 1971-12-27 | 1977-05-17 | Palolab Pharmaceuticals Corporation | Composition and method of using a protein mixture derived from liver |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030162705A1 (en) * | 2000-06-08 | 2003-08-28 | Albert Panerai | Method of treatment of amyotrophic lateral sclerosis with a protein extractable from mammalian organs |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2196606C2 (en) | 2003-01-20 |
| IL129024A0 (en) | 2000-02-17 |
| PT928197E (en) | 2003-06-30 |
| BR9711499A (en) | 1999-08-24 |
| ES2192669T3 (en) | 2003-10-16 |
| EP0928197A1 (en) | 1999-07-14 |
| CN1151838C (en) | 2004-06-02 |
| ATE233569T1 (en) | 2003-03-15 |
| PL332282A1 (en) | 1999-08-30 |
| TR199900596T2 (en) | 1999-06-21 |
| CZ91599A3 (en) | 1999-08-11 |
| JP2001501925A (en) | 2001-02-13 |
| NO991175L (en) | 1999-03-10 |
| EP0928197B1 (en) | 2003-03-05 |
| AU4774797A (en) | 1998-04-14 |
| DK0928197T3 (en) | 2003-06-23 |
| US6468536B1 (en) | 2002-10-22 |
| DE69719525D1 (en) | 2003-04-10 |
| AR009952A1 (en) | 2000-05-17 |
| KR20000036207A (en) | 2000-06-26 |
| AU723669B2 (en) | 2000-08-31 |
| DE69719525T2 (en) | 2003-10-02 |
| CA2266346A1 (en) | 1998-03-26 |
| PL188746B1 (en) | 2005-04-29 |
| NO991175D0 (en) | 1999-03-10 |
| CZ293926B6 (en) | 2004-08-18 |
| NZ334714A (en) | 2000-08-25 |
| CN1230892A (en) | 1999-10-06 |
| WO1998011909A1 (en) | 1998-03-26 |
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Legal Events
| Date | Code | Title | Description |
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| STCB | Information on status: application discontinuation |
Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION |