CA2651793C - Hiv fusion inhibitor peptides with improved biological properties - Google Patents
Hiv fusion inhibitor peptides with improved biological properties Download PDFInfo
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- CA2651793C CA2651793C CA2651793A CA2651793A CA2651793C CA 2651793 C CA2651793 C CA 2651793C CA 2651793 A CA2651793 A CA 2651793A CA 2651793 A CA2651793 A CA 2651793A CA 2651793 C CA2651793 C CA 2651793C
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- fusion inhibitor
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16022—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2740/00—Reverse transcribing RNA viruses
- C12N2740/00011—Details
- C12N2740/10011—Retroviridae
- C12N2740/16011—Human Immunodeficiency Virus, HIV
- C12N2740/16111—Human Immunodeficiency Virus, HIV concerning HIV env
- C12N2740/16122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/005—Assays involving biological materials from specific organisms or of a specific nature from viruses
- G01N2333/08—RNA viruses
- G01N2333/15—Retroviridae, e.g. bovine leukaemia virus, feline leukaemia virus, feline leukaemia virus, human T-cell leukaemia-lymphoma virus
- G01N2333/155—Lentiviridae, e.g. visna-maedi virus, equine infectious virus, FIV, SIV
- G01N2333/16—HIV-1, HIV-2
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/26—Infectious diseases, e.g. generalised sepsis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Virology (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
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| US76467406P | 2006-02-02 | 2006-02-02 | |
| US60/764,674 | 2006-02-02 | ||
| PCT/US2007/002990 WO2007097903A2 (en) | 2006-02-02 | 2007-02-02 | Hiv fusion inhibitor peptides with improved biological properties |
Publications (2)
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| CA2651793A1 CA2651793A1 (en) | 2007-08-30 |
| CA2651793C true CA2651793C (en) | 2015-07-07 |
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| EP (1) | EP1989220B1 (enExample) |
| JP (1) | JP4682251B2 (enExample) |
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| AU (1) | AU2007218025A1 (enExample) |
| CA (1) | CA2651793C (enExample) |
| CY (1) | CY1113115T1 (enExample) |
| DK (1) | DK1989220T3 (enExample) |
| ES (1) | ES2381631T3 (enExample) |
| NZ (1) | NZ570300A (enExample) |
| PT (1) | PT1989220E (enExample) |
| TW (1) | TWI341844B (enExample) |
| WO (1) | WO2007097903A2 (enExample) |
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| EP1989220B1 (en) | 2006-02-02 | 2011-12-14 | Trimeris, Inc. | Hiv fusion inhibitor peptides with improved biological properties |
| BRPI0817697A2 (pt) * | 2007-09-25 | 2015-04-07 | Trimeris Inc | Método de síntese de um peptídeo, conjunto de fragmentos de peptídeo, e, peptídeo |
| US8828931B2 (en) * | 2008-05-28 | 2014-09-09 | New York Blood Center, Inc. | Bifunctional molecules for inhibiting HIV entry |
| US7919101B2 (en) | 2008-08-13 | 2011-04-05 | New York Blood Center | Highly potent synergistic combinations of human immunodeficiency virus (HIV) fusion inhibitors |
| WO2010045613A1 (en) * | 2008-10-16 | 2010-04-22 | New York Blood Center | Immunoenhancer-linked oligomeric hiv vaccines |
| WO2010047826A2 (en) * | 2008-10-24 | 2010-04-29 | Trimeris, Inc. | Dosing regimens and dosage formulations of an antiviral peptide therapeutic |
| CA2751865A1 (en) * | 2009-02-09 | 2010-08-12 | New York Blood Center, Inc. | Trimeric hiv fusion inhibitors for treating or preventing hiv infection |
| CA2794632A1 (en) | 2010-05-03 | 2011-11-10 | New York Blood Center, Inc. | Bifunctional molecules for inactivating hiv and blocking hiv entry |
| RU2014129907A (ru) * | 2011-12-19 | 2016-02-10 | ЯНССЕН Ар ЭНД Ди АЙРЛЭНД | Ингибиторы слияния hiv с мембраной |
| US20150045291A1 (en) | 2012-04-04 | 2015-02-12 | Yeda Research And Development Co., Ltd. | Lipopeptide conjugates comprising sphingolipid and hiv gp41 derived peptides |
| CN103724404B (zh) * | 2013-12-08 | 2016-11-02 | 北京工业大学 | 抑制hiv病毒与宿主细胞融合的非对映体多肽及其用途 |
| GB201509782D0 (en) * | 2015-06-05 | 2015-07-22 | Isis Innovation | Methods and products for fusion protein synthesis |
| CN109320593A (zh) * | 2018-11-05 | 2019-02-12 | 中国人民解放军军事科学院军事医学研究院 | 抑制hiv感染的螺旋多肽及其用途 |
Family Cites Families (42)
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| JPS55154991A (en) | 1979-05-23 | 1980-12-02 | Hisamitsu Pharmaceut Co Inc | Beta-d-fructopyranoside derivative |
| IE52535B1 (en) | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
| US4530840A (en) | 1982-07-29 | 1985-07-23 | The Stolle Research And Development Corporation | Injectable, long-acting microparticle formulation for the delivery of anti-inflammatory agents |
| US5411951A (en) | 1984-10-04 | 1995-05-02 | Monsanto Company | Prolonged release of biologically active somatotropin |
| US4629783A (en) | 1985-04-29 | 1986-12-16 | Genetic Systems Corporation | Synthetic antigen for the detection of AIDS-related disease |
| US5234520A (en) | 1987-03-20 | 1993-08-10 | Morgan Adhesives Co. | Method of making an adhesive construction |
| CN1030256A (zh) * | 1987-06-29 | 1989-01-11 | 日清食品株式会社 | 检测和治疗人类免疫缺陷病毒的方法和物质 |
| US4938763B1 (en) | 1988-10-03 | 1995-07-04 | Atrix Lab Inc | Biodegradable in-situ forming implants and method of producing the same |
| US5462863A (en) | 1989-02-09 | 1995-10-31 | Development Center For Biotechnology | Isolation of Hepatitis B surface antigen from transformed yeast cells |
| US5776963A (en) | 1989-05-19 | 1998-07-07 | Hoechst Marion Roussel, Inc. | 3-(heteroaryl)-1- (2,3-dihydro-1h-isoindol-2-yl)alkyl!pyrrolidines and 3-(heteroaryl)-1- (2,3-dihydro-1h-indol-1-yl)alkyl!pyrrolidines and related compounds and their therapeutic untility |
| AU2791792A (en) | 1991-10-04 | 1993-05-03 | Robert H. Cornett | Approaching emergency vehicle warning system |
| ES2139017T3 (es) | 1992-07-20 | 2000-02-01 | Univ Duke | Compuestos que inhiben la replicacion del vih. |
| US5728553A (en) | 1992-09-23 | 1998-03-17 | Delta Biotechnology Limited | High purity albumin and method of producing |
| US5589167A (en) | 1993-02-23 | 1996-12-31 | Genentech, Inc. | Excipient stabilization of polypeptides treated with organic solvents |
| US6479055B1 (en) | 1993-06-07 | 2002-11-12 | Trimeris, Inc. | Methods for inhibition of membrane fusion-associated events, including respiratory syncytial virus transmission |
| US5464933A (en) | 1993-06-07 | 1995-11-07 | Duke University | Synthetic peptide inhibitors of HIV transmission |
| GB9404270D0 (en) | 1994-03-05 | 1994-04-20 | Delta Biotechnology Ltd | Yeast strains and modified albumins |
| US6004549A (en) | 1994-12-14 | 1999-12-21 | Schering Corporation | Crystalline protein controlled release compositions |
| US5747058A (en) | 1995-06-07 | 1998-05-05 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system |
| CA2224008C (en) | 1995-06-07 | 2009-08-18 | Trimeris, Inc. | The treatment of hiv and other viral infections using combinatorial therapy |
| US6413536B1 (en) | 1995-06-07 | 2002-07-02 | Southern Biosystems, Inc. | High viscosity liquid controlled delivery system and medical or surgical device |
| ZA965368B (en) | 1995-07-14 | 1997-01-14 | Novo Nordisk As | A pharmaceutical formulation |
| US20020064546A1 (en) | 1996-09-13 | 2002-05-30 | J. Milton Harris | Degradable poly(ethylene glycol) hydrogels with controlled half-life and precursors therefor |
| US6191107B1 (en) | 1997-09-26 | 2001-02-20 | Takeda Chemical Industries, Ltd. | Complex of human growth hormone and zinc |
| WO1999033489A1 (fr) | 1997-12-26 | 1999-07-08 | Yamanouchi Pharmaceutical Co., Ltd. | Compositions medicinales a liberation prolongee |
| JPH11209456A (ja) * | 1998-01-29 | 1999-08-03 | Hitachi Chem Co Ltd | 印刷配線板用難燃性エポキシ樹脂組成物及びこれを用いたプリプレグ、金属箔張り積層板 |
| US6281331B1 (en) | 1998-03-23 | 2001-08-28 | Trimeris, Inc. | Methods and compositions for peptide synthesis |
| US6656906B1 (en) | 1998-05-20 | 2003-12-02 | Trimeris, Inc. | Hybrid polypeptides with enhanced pharmacokinetic properties |
| US6258782B1 (en) | 1998-05-20 | 2001-07-10 | Trimeris, Inc. | Hybrid polypeptides with enhanced pharmacokinetic properties |
| US6143314A (en) | 1998-10-28 | 2000-11-07 | Atrix Laboratories, Inc. | Controlled release liquid delivery compositions with low initial drug burst |
| US6565874B1 (en) | 1998-10-28 | 2003-05-20 | Atrix Laboratories | Polymeric delivery formulations of leuprolide with improved efficacy |
| US7582301B1 (en) | 1999-05-17 | 2009-09-01 | Conjuchem Biotechnologies, Inc. | Long-lasting antiviral fusion inhibitor peptide conjugates comprising albumin and human immunodeficiency virus (HIV) peptides |
| US6541020B1 (en) | 1999-07-09 | 2003-04-01 | Trimeris, Inc. | Methods and compositions for administration of therapeutic reagents |
| WO2001078683A2 (en) | 2000-04-19 | 2001-10-25 | Genentech, Inc. | Sustained release formulations comprising growth hormone |
| ES2554106T3 (es) | 2001-06-21 | 2015-12-16 | Genentech, Inc. | Formulación de liberación sostenida |
| CN1100564C (zh) | 2001-08-29 | 2003-02-05 | 周根发 | 用于治疗hiv感染的药物、其组合物及其用途 |
| US7045552B2 (en) | 2002-09-27 | 2006-05-16 | Trimeris, Inc. | Pharmaceutical composition for improved administration of HIV gp41-derived peptides, and its use in therapy |
| BRPI0418304A (pt) | 2004-01-07 | 2007-05-02 | Trimeris Inc | peptìdeo sintético, uso do mesmo, composição farmacêutica, seqüência de nucleotìdeos, e, métodos para inibição da transmissão de hiv para uma célula, para inibição da fusão de hiv, e para tratamento de um indivìduo infectado com hiv |
| CN101132812A (zh) | 2004-03-15 | 2008-02-27 | 阿拉巴马耐科塔医药公司 | Hiv进入抑制剂的聚合物基组合物和结合物 |
| CA2556032A1 (en) * | 2004-03-15 | 2005-09-29 | Trimeris, Inc. | Site-specific chemical modification of hiv gp41-derived peptides |
| EP1989220B1 (en) | 2006-02-02 | 2011-12-14 | Trimeris, Inc. | Hiv fusion inhibitor peptides with improved biological properties |
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2007
- 2007-02-02 EP EP07749903A patent/EP1989220B1/en active Active
- 2007-02-02 US US11/701,910 patent/US7456251B2/en active Active
- 2007-02-02 JP JP2008553389A patent/JP4682251B2/ja not_active Expired - Fee Related
- 2007-02-02 AR ARP070100450A patent/AR059300A1/es active IP Right Grant
- 2007-02-02 WO PCT/US2007/002990 patent/WO2007097903A2/en not_active Ceased
- 2007-02-02 TW TW096104190A patent/TWI341844B/zh not_active IP Right Cessation
- 2007-02-02 CN CN200780011992.6A patent/CN101415723B/zh not_active Expired - Fee Related
- 2007-02-02 ES ES07749903T patent/ES2381631T3/es active Active
- 2007-02-02 PT PT07749903T patent/PT1989220E/pt unknown
- 2007-02-02 DK DK07749903.6T patent/DK1989220T3/da active
- 2007-02-02 NZ NZ570300A patent/NZ570300A/en not_active IP Right Cessation
- 2007-02-02 AU AU2007218025A patent/AU2007218025A1/en not_active Abandoned
- 2007-02-02 CA CA2651793A patent/CA2651793C/en not_active Expired - Fee Related
- 2007-02-02 AT AT07749903T patent/ATE537183T1/de active
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2008
- 2008-10-20 US US12/254,259 patent/US8034899B2/en active Active
-
2011
- 2011-08-31 US US13/222,766 patent/US20120040891A1/en not_active Abandoned
-
2012
- 2012-03-14 CY CY20121100268T patent/CY1113115T1/el unknown
-
2017
- 2017-05-02 AR ARP170101125A patent/AR108277A2/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2007097903A3 (en) | 2008-05-22 |
| TWI341844B (en) | 2011-05-11 |
| JP2009525051A (ja) | 2009-07-09 |
| US7456251B2 (en) | 2008-11-25 |
| CY1113115T1 (el) | 2016-04-13 |
| DK1989220T3 (da) | 2012-04-02 |
| TW200806687A (en) | 2008-02-01 |
| ATE537183T1 (de) | 2011-12-15 |
| JP4682251B2 (ja) | 2011-05-11 |
| EP1989220A4 (en) | 2009-05-06 |
| PT1989220E (pt) | 2012-03-23 |
| CN101415723A (zh) | 2009-04-22 |
| EP1989220A2 (en) | 2008-11-12 |
| WO2007097903A2 (en) | 2007-08-30 |
| US20090105143A1 (en) | 2009-04-23 |
| EP1989220B1 (en) | 2011-12-14 |
| NZ570300A (en) | 2011-08-26 |
| AR059300A1 (es) | 2008-03-26 |
| CN101415723B (zh) | 2014-06-25 |
| US20120040891A1 (en) | 2012-02-16 |
| ES2381631T3 (es) | 2012-05-30 |
| CA2651793A1 (en) | 2007-08-30 |
| US20070179278A1 (en) | 2007-08-02 |
| US8034899B2 (en) | 2011-10-11 |
| AU2007218025A1 (en) | 2007-08-30 |
| AR108277A2 (es) | 2018-08-01 |
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