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)
- Zoology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Environmental Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Cardiology (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 (Sortimente) |
| EP (2) | EP0512733A2 (Sortimente) |
| JP (1) | JP2793431B2 (Sortimente) |
| AU (1) | AU657751B2 (Sortimente) |
| CA (1) | CA2067653C (Sortimente) |
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 |
| EP0512733A2 (en) * | 1991-05-03 | 1992-11-11 | Washington University | Modified complement system regulator |
| 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 |
| PT730608E (pt) | 1993-05-17 | 2002-09-30 | Avant Immunotherapeutics Inc | Composicoes compreendendo hidratos de carbono e proeinas relacionadas pelo complemento e metodos para produzir e utilizar as referidas composicoes |
| 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 |
| US5679546A (en) * | 1993-09-24 | 1997-10-21 | Cytomed, Inc. | Chimeric proteins which block complement activation |
| EP1493446A1 (en) * | 1993-09-24 | 2005-01-05 | Washington University | Modified truncated complement system regulators |
| ATE265221T1 (de) * | 1993-09-24 | 2004-05-15 | Univ Washington | Modifizierte, verkürzte regulatoren des komplementsystems |
| 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 |
| WO1998039659A1 (en) * | 1997-03-06 | 1998-09-11 | Bion Diagnostic Sciences, Inc. | Screening and treatment using complement regulator or receptor proteins |
| 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 |
| AU4452100A (en) * | 1999-04-09 | 2000-11-14 | Washington University | Modified complement system regulators |
| US20090054330A1 (en) * | 1999-05-25 | 2009-02-26 | Kotwal Girish J | Novel Therapeutic Use of Viral Inflammation Modulatory Protein in Blocking Xenograft Rejection |
| HK1045456B (en) * | 1999-05-25 | 2006-09-08 | King Faisal Specialist Hospital & Research Centre | 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 |
| JP2004529945A (ja) * | 2001-05-17 | 2004-09-30 | ラ ホヤ ファーマシューティカル カンパニー | Ｃｄ２１を阻害する薬剤を使用して抗体媒介性病理を処置する方法 |
| CA2505601C (en) * | 2002-11-15 | 2014-10-28 | Musc Foundation For Research Development | Complement receptor 2 targeted complement modulators |
| 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 |
| JP5137053B2 (ja) * | 2004-02-10 | 2013-02-06 | ザ リージェンツ オブ ザ ユニバーシティ オブ コロラド，ア ボディー コーポレイト | 抗ｂ因子抗体もしくはその抗原結合性フラグメント、それを含む組成物、抗原結合性ポリペプチド、および治療薬 |
| US8043609B2 (en) | 2004-10-08 | 2011-10-25 | Potentia Pharmaceuticals, Inc. | Viral complement control proteins for eye disorders |
| WO2006042252A2 (en) * | 2004-10-08 | 2006-04-20 | Potentia Pharmeceuticals, Inc. | Viral complement control proteins for eye disorders |
| JP5707024B2 (ja) * | 2005-05-26 | 2015-04-22 | ザ リージェンツ オブ ザ ユニバーシティ オブ コロラド，ア ボディー コーポレイトＴＨＥ ＲＥＧＥＮＴＳ ＯＦ ＴＨＥ ＵＮＩＶＥＲＳＩＴＹ ＯＦ ＣＯＬＯＲＡＤＯ，ａ ｂｏｄｙ ｃｏｒｐｏｒａｔｅ | 外傷性脳損傷、脊髄損傷および関連状態を治療するために補体副経路を阻害する作用剤 |
| 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 |
| DK1951279T3 (en) | 2005-10-08 | 2017-07-31 | Apellis Pharmaceuticals Inc | COMPSTATIN AND ANALOGUES THEREOF FOR EYE DISEASES |
| US8168584B2 (en) | 2005-10-08 | 2012-05-01 | Potentia Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration by compstatin and analogs thereof |
| PL2044111T3 (pl) | 2006-06-21 | 2015-02-27 | Musc Found For Res Dev | Celowanie czynnika H dopełniacza do leczenia chorób |
| EP2479284B1 (en) | 2006-07-13 | 2017-09-20 | University of Iowa Research Foundation | Methods and reagents for treatment and diagnosis of vascular disorders and age-related macular degeneration |
| BRPI0808227A2 (pt) * | 2007-03-14 | 2014-07-08 | Taligen Therapeutics Inc | Anticorpo humanizado anti-fator b |
| US20110092446A1 (en) * | 2007-07-20 | 2011-04-21 | Cedric Francois | Compositions and methods for treatment of trauma |
| EP2278987A4 (en) * | 2008-03-28 | 2012-08-22 | Apellis Ag | MODULATION AND REPLY / IMPROVEMENT OF THE COMPLEMENTARY SYSTEM IN THE TREATMENT OF TRAUMATISM |
| WO2011003098A1 (en) | 2009-07-02 | 2011-01-06 | Musc Foundation For Research Development | Methods of stimulating liver regeneration |
| NZ600393A (en) | 2009-11-05 | 2014-08-29 | Alexion Cambridge Corp | Treatment of paroxysmal nocturnal hemoglobinuria, hemolytic anemias and disease states involving intravascular and extravascular hemolysis |
| KR20130080443A (ko) | 2010-05-14 | 2013-07-12 | 더 리젠츠 오브 더 유니버시티 오브 콜로라도, 어 바디 코포레이트 | 개선된 보체 수용체 ２(ｃｒ２) 표적 그룹들 |
| MX2012014975A (es) | 2010-06-22 | 2013-03-12 | Univ Colorado Regents | Anticuerpos al fragmento c3d de componente 3 de complemento. |
| WO2011163394A2 (en) | 2010-06-22 | 2011-12-29 | Apellis Pharmaceuticals, Inc. | Compstatin analogs for treatment of neuropathic pain |
| AU2011295715B9 (en) | 2010-09-03 | 2017-02-23 | Abbvie Stemcentrx Llc | Novel modulators and methods of use |
| WO2012078968A2 (en) | 2010-12-10 | 2012-06-14 | Lifeline Scientific, Inc. | Machine perfusion with complement inhibitors |
| US10125171B2 (en) | 2011-05-11 | 2018-11-13 | Apellis Pharmaceuticals, Inc. | Cell-reactive, long-acting, or targeted compstatin analogs and uses thereof |
| BR112013033272A2 (pt) | 2011-06-22 | 2020-11-10 | Apellis Pharmaceuticals, Inc. | composição farmaceutica compreendendo um inibidor do complemento e um agente anti-th17, e usos dos mesmos |
| EP2557089A2 (en) * | 2011-07-15 | 2013-02-13 | Fundació Institut d'Investigació Biomèdica de Bellvitge (IDIBELL) | Compositions and methods for immunomodulation |
| WO2013177035A2 (en) | 2012-05-24 | 2013-11-28 | Alexion Pharmaceuticals, Inc. | Humaneered anti-factor b antibody |
| WO2014028865A1 (en) | 2012-08-17 | 2014-02-20 | The Regents Of The University Of Colorado, A Body Corporate | Compositions and methods for detecting complement activation |
| 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 |
| ES2879430T3 (es) | 2012-11-15 | 2021-11-22 | Apellis Pharmaceuticals Inc | Análogos de compstatina de acción prolongada y composiciones y métodos relacionados |
| WO2014152391A1 (en) | 2013-03-15 | 2014-09-25 | 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 |
| EP3328885A1 (en) | 2015-09-11 | 2018-06-06 | Bruce Andrien | Recombinant glycosylated eculizumab and eculizumab variants |
| FI3359555T3 (fi) | 2015-10-07 | 2024-03-20 | Apellis Pharmaceuticals Inc | Annostusohjeet |
| US11203634B2 (en) | 2015-10-07 | 2021-12-21 | Alexion Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration in a patient comprising administering an anti-C5a antibody |
| MX2019000059A (es) * | 2016-06-28 | 2020-09-07 | Univ Ulm | Inhibidores de complementos y usos de los mismos. |
| US11828683B2 (en) | 2016-10-19 | 2023-11-28 | Alexion Pharmaceuticals, Inc. | Method of quantitating unbound C5a in a sample |
| WO2018075758A1 (en) | 2016-10-19 | 2018-04-26 | Alexion Pharmaceuticals, Inc. | A method of quantitating unbound c5 in a sample |
| JP2020516607A (ja) | 2017-04-07 | 2020-06-11 | アペリス・ファーマシューティカルズ・インコーポレイテッドＡｐｅｌｌｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | 投与レジメンならびに関連組成物および方法 |
| WO2019118938A1 (en) | 2017-12-15 | 2019-06-20 | Apellis Pharmaceuticals, Inc. | Dosing regimens and related compositions and methods |
| 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 |
| EP0483247A4 (en) * | 1989-07-21 | 1992-12-09 | Washington University | Recombinantly produced human membrane cofactor protein (mcp) |
| WO1991018097A1 (en) * | 1990-05-11 | 1991-11-28 | University Of Melbourne | Cd46 variants |
| AU655182B2 (en) * | 1990-05-11 | 1994-12-08 | Austin Research Institute, The | CD46 variants |
| EP0512733A2 (en) * | 1991-05-03 | 1992-11-11 | 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 EP92303826A patent/EP0512733A2/en not_active Ceased
- 1992-04-28 EP EP20030024658 patent/EP1413587A2/en not_active Withdrawn
- 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
-
1994
- 1994-03-18 US US08/210,266 patent/US5545619A/en not_active Expired - Lifetime
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1995
- 1995-06-07 US US08/477,860 patent/US6010873A/en not_active Expired - Fee Related
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1996
- 1996-07-30 US US08/688,675 patent/US5719127A/en not_active Expired - Fee Related
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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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| JPH0616696A (ja) | 1994-01-25 |
| US20080119400A1 (en) | 2008-05-22 |
| EP0512733A3 (Sortimente) | 1994-08-03 |
| US5719127A (en) | 1998-02-17 |
| US6521450B1 (en) | 2003-02-18 |
| US6010873A (en) | 2000-01-04 |
| EP0512733A2 (en) | 1992-11-11 |
| JP2793431B2 (ja) | 1998-09-03 |
| CA2067653A1 (en) | 1992-11-04 |
| US6897290B1 (en) | 2005-05-24 |
| EP1413587A2 (en) | 2004-04-28 |
| AU1590292A (en) | 1992-11-05 |
| US5545619A (en) | 1996-08-13 |
| AU657751B2 (en) | 1995-03-23 |
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