CA2067653C - Modified complement system regulator - Google Patents
Modified complement system regulator Download PDFInfo
- Publication number
- CA2067653C CA2067653C CA002067653A CA2067653A CA2067653C CA 2067653 C CA2067653 C CA 2067653C CA 002067653 A CA002067653 A CA 002067653A CA 2067653 A CA2067653 A CA 2067653A CA 2067653 C CA2067653 C CA 2067653C
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- Prior art keywords
- protein
- amino acid
- amino acids
- analog
- complement
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/027—New or modified breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07K14/472—Complement proteins, e.g. anaphylatoxin, C3a, C5a
-
- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Toxicology (AREA)
- General Chemical & Material Sciences (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Environmental Sciences (AREA)
- Immunology (AREA)
- Biotechnology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Cell Biology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US69551491A | 1991-05-03 | 1991-05-03 | |
| US695,514 | 1991-05-03 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2067653A1 CA2067653A1 (en) | 1992-11-04 |
| CA2067653C true CA2067653C (en) | 2001-02-13 |
Family
ID=24793320
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002067653A Expired - Fee Related CA2067653C (en) | 1991-05-03 | 1992-04-30 | Modified complement system regulator |
Country Status (5)
| Country | Link |
|---|---|
| US (6) | US6897290B1 (online.php) |
| EP (2) | EP1413587A2 (online.php) |
| JP (1) | JP2793431B2 (online.php) |
| AU (1) | AU657751B2 (online.php) |
| CA (1) | CA2067653C (online.php) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6482404B1 (en) | 1989-10-12 | 2002-11-19 | David James White | Transplantation of tissue comprising a DNA sequence encoding a homologous complement restriction factor |
| EP1413587A2 (en) | 1991-05-03 | 2004-04-28 | Washington University | Modified complement system regulator |
| US5976540A (en) * | 1993-05-17 | 1999-11-02 | T Cell Sciences, Inc. | Compositions comprising complement related proteins and carbohydrates, and methods for producing and using said compositions |
| SG52383A1 (en) | 1993-05-17 | 1998-09-28 | T Cell Sciences Inc | Compositions comprising complement related proteins and carbohydrates and methods for producing and using said compositions |
| US5856300A (en) * | 1994-05-12 | 1999-01-05 | T Cell Sciences, Inc. | Compositions comprising complement related proteins and carbohydrates, and methods for producing and using said compositions |
| US5679546A (en) * | 1993-09-24 | 1997-10-21 | Cytomed, Inc. | Chimeric proteins which block complement activation |
| CA2171953C (en) * | 1993-09-24 | 2003-02-04 | John P. Atkinson | Modified truncated complement system regulators |
| EP1493446A1 (en) * | 1993-09-24 | 2005-01-05 | Washington University | Modified truncated complement system regulators |
| US5866402A (en) * | 1995-05-05 | 1999-02-02 | Chiron Corporation | Chimeric MCP and DAF proteins with cell surface localizing domain |
| GB9604518D0 (en) * | 1996-03-02 | 1996-05-01 | Smithkline Beecham Plc | Novel compounds |
| GB9624731D0 (en) * | 1996-11-28 | 1997-01-15 | Univ Leicester | Complement inhibitor |
| GB9704519D0 (en) | 1997-03-05 | 1997-04-23 | Smithkline Beecham Plc | Compounds |
| US6221621B1 (en) | 1997-03-06 | 2001-04-24 | Bard Diagnostic Sciences, Inc. | Methods of screening for colorectal cancers in which a complement Factor I or related protein is associated |
| JP2001515589A (ja) * | 1997-03-06 | 2001-09-18 | バイオン ダイアグノスティック サイエンシーズ，インコーポレイテッド | 補体レギュレーターまたはレセプタータンパク質を使用するスクリーニングおよび処置 |
| WO2000061752A2 (en) * | 1999-04-09 | 2000-10-19 | Washington University | Modified complement system regulators |
| EP1185283B1 (en) * | 1999-05-25 | 2005-09-07 | King Faisal Specialist Hospital And Research Centre | Novel therapeutic use of viral inflammation modulatory protein in blocking xenograft rejection |
| US20090054330A1 (en) * | 1999-05-25 | 2009-02-26 | Kotwal Girish J | Novel Therapeutic Use of Viral Inflammation Modulatory Protein in Blocking Xenograft Rejection |
| US6820011B2 (en) | 2001-04-11 | 2004-11-16 | The Regents Of The University Of Colorado | Three-dimensional structure of complement receptor type 2 and uses thereof |
| CN1511041A (zh) * | 2001-05-17 | 2004-07-07 | ������ҩ������˾ | 利用抑制cd21的药剂治疗抗体介导的病变的方法 |
| CN100594037C (zh) | 2002-11-15 | 2010-03-17 | Musc研究发展基金会 | 通过补体受体2定向的补体调节剂 |
| DE10343620A1 (de) * | 2003-09-20 | 2005-04-28 | Leibrock Maschinenfabrik Im Un | Verfahren und Vorrichtung zum Erfassen der zum Rauen bestimmten Seitenbereiche von auf Leisten aufgebrachten Schuhschäften |
| US8124097B2 (en) * | 2004-01-21 | 2012-02-28 | Case Western Reserve University | Hybrid and chimeric polypeptides that regulate activation of complement |
| DK1713503T3 (da) * | 2004-02-10 | 2013-11-04 | Univ Colorado Regents | Hæmning af faktor b, den alternative komplemenpathway og dertil relaterede fremgangsmåde |
| US7947267B2 (en) * | 2004-10-08 | 2011-05-24 | Potentia Pharmaceuticals, Inc. | Viral complement control proteins for eye disorders |
| US8043609B2 (en) | 2004-10-08 | 2011-10-25 | Potentia Pharmaceuticals, Inc. | Viral complement control proteins for eye disorders |
| US8911733B2 (en) * | 2005-05-26 | 2014-12-16 | Musc Foundation For Research Development | Inhibition of the alternative complement pathway for treatment of traumatic brain injury, spinal cord injury and related conditions |
| US20070004625A1 (en) * | 2005-06-30 | 2007-01-04 | Li Liang-Man | Use of complement inhibitory proteins to treat spinal cord injury |
| EP1738763A1 (en) * | 2005-06-30 | 2007-01-03 | AVANT Immunotherapeutics, Inc. | Use of complement inhibitory proteins to treat spinal cord injury |
| CA2625206C (en) | 2005-10-08 | 2021-12-07 | Potentia Pharmaceuticals, Inc. | Compstatin and analogs thereof for eye disorders |
| US8168584B2 (en) | 2005-10-08 | 2012-05-01 | Potentia Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration by compstatin and analogs thereof |
| PT2044111E (pt) | 2006-06-21 | 2014-11-12 | Univ Colorado Regents | Abordagem seletiva do fator h do complemento para o tratamento de doenças |
| WO2008008986A2 (en) | 2006-07-13 | 2008-01-17 | University Of Iowa Research Foundation | Methods and reagents for treatment and diagnosis of vascular disorders and age-related macular degeneration |
| CA2680344A1 (en) | 2007-03-14 | 2008-11-20 | Woodruff Emlen | Humaneered anti-factor b antibody |
| US20110092446A1 (en) * | 2007-07-20 | 2011-04-21 | Cedric Francois | Compositions and methods for treatment of trauma |
| WO2009121065A2 (en) * | 2008-03-28 | 2009-10-01 | Apellis Ag | Modulation and repletion/enhancement of the complement system for treatment of trauma |
| RS20120461A1 (sr) | 2009-07-02 | 2013-06-28 | Musc Foundation For Research Development | Metode za stimulaciju regeneracije jetre |
| EP2496259B1 (en) | 2009-11-05 | 2017-02-22 | Alexion Pharmaceuticals, Inc. | Treatment of paroxysmal nocturnal hemoglobinuria |
| JP5986990B2 (ja) | 2010-05-14 | 2016-09-06 | ザ リージェンツ オブ ザ ユニヴァーシティ オブ コロラド，ア ボディ コーポレート | 改善された補体レセプター２（ｃｒ２）ターゲティング基 |
| US9421240B2 (en) | 2010-06-22 | 2016-08-23 | Apellis Pharmaceuticals, Inc. | Compstatin analogs for treatment of neuropathic pain |
| MX2012014975A (es) | 2010-06-22 | 2013-03-12 | Univ Colorado Regents | Anticuerpos al fragmento c3d de componente 3 de complemento. |
| WO2012031273A2 (en) | 2010-09-03 | 2012-03-08 | Stem Centrx, Inc. | Novel modulators and methods of use |
| US20120148542A1 (en) | 2010-12-10 | 2012-06-14 | Lifeline Scientific, Inc. | Machine perfusion with complement inhibitors |
| CA2835627C (en) | 2011-05-11 | 2023-01-10 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and uses thereof |
| EP2723361B1 (en) | 2011-06-22 | 2019-10-30 | Apellis Pharmaceuticals, Inc. | Methods of treating chronic disorders with complement inhibitors |
| EP2557089A2 (en) * | 2011-07-15 | 2013-02-13 | Fundació Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) | Compositions and methods for immunomodulation |
| US9803005B2 (en) | 2012-05-24 | 2017-10-31 | Alexion Pharmaceuticals, Inc. | Humaneered anti-factor B antibody |
| US10413620B2 (en) | 2012-08-17 | 2019-09-17 | The Regents Of The University Of Colorado, A Body Corporate | Light-emitting versions of the monoclonal antibody to C3D (MAB 3D29) for imaging |
| JP2015535212A (ja) | 2012-08-17 | 2015-12-10 | ザ・リージエンツ・オブ・ザ・ユニバーシテイ・オブ・コロラド、ア・ボデイー・コーポレイト | 補体活性化を検出するための組成物および方法 |
| EP3929206A1 (en) | 2012-11-15 | 2021-12-29 | Apellis Pharmaceuticals, Inc. | Long-acting compstatin analogs and related compositions and methods |
| US10308687B2 (en) | 2013-03-15 | 2019-06-04 | Apellis Pharmaceuticals, Inc. | Cell-penetrating compstatin analogs and uses thereof |
| US20160168237A1 (en) | 2014-12-12 | 2016-06-16 | Alexion Pharmaceuticals, Inc. | Method for treating a complement mediated disorder caused by an infectious agent in a patient |
| WO2017044811A1 (en) | 2015-09-11 | 2017-03-16 | Bruce Andrien | Recombinant glycosylated eculizumab and eculizumab variants |
| CA3287719A1 (en) | 2015-10-07 | 2026-03-02 | Apellis Pharmaceuticals, Inc. | Use of long-acting compstatin analog for treating a complement-mediated disorder |
| EP3359566A1 (en) | 2015-10-07 | 2018-08-15 | Alexion Pharmaceuticals, Inc. | A method for treating age-related macular degeneration in a patient |
| KR102566634B1 (ko) | 2016-06-28 | 2023-08-14 | 우니베르시테트 울름 | 보체 억제제 및 그의 용도 |
| ES2888904T3 (es) | 2016-10-19 | 2022-01-10 | Alexion Pharma Inc | Un método de cuantificación de C5a sin unir en una muestra |
| EP3529618B1 (en) | 2016-10-19 | 2020-12-02 | Alexion Pharmaceuticals, Inc. | A method of quantitating unbound c5 in a sample |
| CN116059313A (zh) | 2017-04-07 | 2023-05-05 | 阿佩利斯制药有限公司 | 给药方案以及相关组合物和方法 |
| KR20240167712A (ko) | 2017-12-15 | 2024-11-27 | 아펠리스 파마슈티컬스 인코포레이티드 | 투여 요법 및 관련 조성물 및 방법 |
| WO2020232319A1 (en) | 2019-05-15 | 2020-11-19 | Insideoutbio, Inc. | Modular therapeutics for the treatment of inflammatory diseases and cancer |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5212071A (en) | 1988-04-01 | 1993-05-18 | The Johns Hopkins University | Nucleic acids encoding a human C3b/C4b receptor (CR1) |
| US5109113A (en) * | 1986-05-02 | 1992-04-28 | Genentech, Inc. | Membrane anchor fusion polypeptides |
| JPH0742235B2 (ja) * | 1985-11-08 | 1995-05-10 | 三共株式会社 | 自己免疫性疾病の予防・治療剤 |
| US4935233A (en) * | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
| US5256642A (en) * | 1988-04-01 | 1993-10-26 | The Johns Hopkins University | Compositions of soluble complement receptor 1 (CR1) and a thrombolytic agent, and the methods of use thereof |
| IL89790A (en) | 1988-04-01 | 2002-05-23 | Johns Hopking University | Nucleic acid sequences that encode and cells that produce cr1 protein and methods of production and purification |
| JP2750220B2 (ja) * | 1989-07-21 | 1998-05-13 | ワシントン ユニバーシティ | 組換え産生したヒト細胞膜補助因子タンパク（ｍｃｐ） |
| AU655182B2 (en) * | 1990-05-11 | 1994-12-08 | Austin Research Institute, The | CD46 variants |
| EP0537171B1 (en) * | 1990-05-11 | 2002-09-18 | The Austin Research Institute | CD46 isoforms |
| EP1413587A2 (en) * | 1991-05-03 | 2004-04-28 | Washington University | Modified complement system regulator |
| JPH05271288A (ja) | 1992-02-21 | 1993-10-19 | Mochida Pharmaceut Co Ltd | 新規な薬理学的特性を有する蛋白質 |
-
1992
- 1992-04-28 EP EP20030024658 patent/EP1413587A2/en not_active Withdrawn
- 1992-04-28 EP EP92303826A patent/EP0512733A2/en not_active Ceased
- 1992-04-29 AU AU15902/92A patent/AU657751B2/en not_active Ceased
- 1992-04-30 CA CA002067653A patent/CA2067653C/en not_active Expired - Fee Related
- 1992-05-06 JP JP4113457A patent/JP2793431B2/ja not_active Expired - Fee Related
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1993
- 1993-09-24 US US08/126,505 patent/US6897290B1/en not_active Expired - Fee Related
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1994
- 1994-03-18 US US08/210,266 patent/US5545619A/en not_active Expired - Lifetime
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1995
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1996
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1999
- 1999-12-02 US US09/453,835 patent/US6521450B1/en not_active Expired - Lifetime
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2004
- 2004-11-23 US US10/997,454 patent/US20080119400A1/en not_active Abandoned
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| CA2067653A1 (en) | 1992-11-04 |
| EP0512733A3 (online.php) | 1994-08-03 |
| US6521450B1 (en) | 2003-02-18 |
| JPH0616696A (ja) | 1994-01-25 |
| US6897290B1 (en) | 2005-05-24 |
| EP1413587A2 (en) | 2004-04-28 |
| JP2793431B2 (ja) | 1998-09-03 |
| AU657751B2 (en) | 1995-03-23 |
| EP0512733A2 (en) | 1992-11-11 |
| AU1590292A (en) | 1992-11-05 |
| US5545619A (en) | 1996-08-13 |
| US6010873A (en) | 2000-01-04 |
| US5719127A (en) | 1998-02-17 |
| US20080119400A1 (en) | 2008-05-22 |
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