CA2308116C - Low-toxicity human interferon-alpha analog - Google Patents
Low-toxicity human interferon-alpha analog Download PDFInfo
- Publication number
- CA2308116C CA2308116C CA2308116A CA2308116A CA2308116C CA 2308116 C CA2308116 C CA 2308116C CA 2308116 A CA2308116 A CA 2308116A CA 2308116 A CA2308116 A CA 2308116A CA 2308116 C CA2308116 C CA 2308116C
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- Prior art keywords
- leu
- ifn
- analog
- alpha
- glu
- Prior art date
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US08/954,395 | 1997-10-20 | ||
| US08/954,395 US6204022B1 (en) | 1996-04-12 | 1997-10-20 | Low-toxicity human interferon-alpha analogs |
| PCT/US1998/021936 WO1999020653A1 (en) | 1997-10-20 | 1998-10-20 | Low-toxicity human interferon-alpha analog |
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| CA2308116A1 CA2308116A1 (en) | 1999-04-29 |
| CA2308116C true CA2308116C (en) | 2010-12-14 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA2308116A Expired - Fee Related CA2308116C (en) | 1997-10-20 | 1998-10-20 | Low-toxicity human interferon-alpha analog |
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|---|---|
| US (1) | US6204022B1 (enExample) |
| EP (1) | EP1025124B1 (enExample) |
| JP (2) | JP2001520238A (enExample) |
| KR (2) | KR100861007B1 (enExample) |
| CN (1) | CN1240717C (enExample) |
| AT (1) | ATE402957T1 (enExample) |
| AU (1) | AU744774B2 (enExample) |
| CA (1) | CA2308116C (enExample) |
| DE (1) | DE69839812D1 (enExample) |
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| ES (1) | ES2310931T3 (enExample) |
| TW (1) | TW593336B (enExample) |
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| US6833256B1 (en) * | 1999-06-22 | 2004-12-21 | University Of Maryland | Interferon tau mutants and methods for making them |
| WO2001016178A1 (en) * | 1999-08-27 | 2001-03-08 | University Of Florida | MATERIALS AND METHODS FOR INHIBITION OF IgE PRODUCTION |
| AU2001266557A1 (en) * | 2000-04-12 | 2001-10-23 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| WO2002036072A2 (en) * | 2000-11-03 | 2002-05-10 | Biomedicines, Inc. | Method for short-term and long-term drug dosimetry |
| WO2002045737A2 (en) * | 2000-12-07 | 2002-06-13 | Board Of Regents, The University Of Texas System | Methods of treatment involving human mda-7 |
| US7232563B2 (en) | 2001-08-12 | 2007-06-19 | Pepgen Corporation | Hybrid interferon/interferon tau proteins, compositions and methods of use |
| AU2002365436B8 (en) * | 2001-11-09 | 2008-04-03 | Intarcia Therapeutics, Inc. | Method for treating diseases with omega interferon |
| US20040009939A1 (en) * | 2002-03-05 | 2004-01-15 | Board Of Regent, The University Of Texas System | Methods of enhancing immune induction involving MDA-7 |
| WO2004022593A2 (en) * | 2002-09-09 | 2004-03-18 | Nautilus Biotech | Rational evolution of cytokines for higher stability, the cytokines and encoding nucleic acid molecules |
| US20040126360A1 (en) * | 2002-10-09 | 2004-07-01 | Manning Mark C. | Oral formulations for proteins and polypeptides |
| US7731947B2 (en) | 2003-11-17 | 2010-06-08 | Intarcia Therapeutics, Inc. | Composition and dosage form comprising an interferon particle formulation and suspending vehicle |
| AU2004218407A1 (en) * | 2003-03-03 | 2004-09-16 | Board Of Regents, The University Of Texas System | Methods and compositions involving MDA-7 |
| US20050003533A1 (en) | 2003-05-08 | 2005-01-06 | Pawel Kalinski | Mature type-1 polarized dendritic cells with enhanced IL-12 production and methods of serum-free production and use |
| CA2548220A1 (en) * | 2003-12-01 | 2005-09-09 | Introgen Therapeutics, Inc. | Use of mda-7 to inhibit infection by pathogenic organisms |
| WO2005074546A2 (en) | 2004-02-02 | 2005-08-18 | Ambrx, Inc. | Modified human growth hormone polypeptides and their uses |
| US20070281041A1 (en) * | 2004-03-02 | 2007-12-06 | Introgen Therapeutics, Inc. | Compositions and Methods Involving MDA-7 for the Treatment of Cancer |
| WO2006083761A2 (en) | 2005-02-03 | 2006-08-10 | Alza Corporation | Solvent/polymer solutions as suspension vehicles |
| US11246913B2 (en) | 2005-02-03 | 2022-02-15 | Intarcia Therapeutics, Inc. | Suspension formulation comprising an insulinotropic peptide |
| AU2006211960A1 (en) * | 2005-02-08 | 2006-08-17 | Board Of Regents, The University Of Texas System | Compositions and methods involving MDA-7 for the treatment of cancer |
| JP2008543943A (ja) * | 2005-06-20 | 2008-12-04 | ペプゲン コーポレイション | ヒトインターフェロンアルファ類似体とインターフェロンタウの低毒性長期循環性キメラ |
| US7695710B2 (en) * | 2005-06-20 | 2010-04-13 | Pepgen Corporation | Antitumor and antiviral combination therapies using low-toxicity, long-circulating human interferon-alpha analogs |
| RU2288474C1 (ru) * | 2005-12-28 | 2006-11-27 | Федеральное государственное учреждение науки "Московский научно-исследовательский институт эпидемиологии и микробиологии имени Г.Н. Габричевского Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека" (ФГУН МНИИЭМ им. Г.Н. Габричевского Роспотребнадзора) | Способ определения токсического действия оральной мукозальной интерферонотерапии |
| WO2007098106A2 (en) * | 2006-02-17 | 2007-08-30 | Pepgen Coporation | Respiratory tract delivery of interferon-tau |
| ATE481963T1 (de) | 2006-05-30 | 2010-10-15 | Intarcia Therapeutics Inc | Zweiteiliger flussmodulator mit einem internen kanal für ein osmotisches ausgabesystem |
| AU2007284759B2 (en) | 2006-08-09 | 2010-10-28 | Intarcia Therapeutics, Inc. | Osmotic delivery systems and piston assemblies |
| WO2008121461A2 (en) * | 2007-02-26 | 2008-10-09 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Vaccine for activating helper function of cd8+ tcells |
| US20080260820A1 (en) * | 2007-04-19 | 2008-10-23 | Gilles Borrelly | Oral dosage formulations of protease-resistant polypeptides |
| MX2009011123A (es) | 2007-04-23 | 2009-11-02 | Intarcia Therapeutics Inc | Formulaciones de suspensiones de peptidos insulinotropicos y sus usos. |
| EP3103880A1 (en) | 2008-02-08 | 2016-12-14 | Ambrx, Inc. | Modified leptin polypeptides and their uses |
| DK2240155T3 (da) | 2008-02-13 | 2012-09-17 | Intarcia Therapeutics Inc | Indretninger, formuleringer og fremgangsmåder til levering af flere gavnlige midler |
| WO2010142017A1 (en) | 2009-06-09 | 2010-12-16 | Defyrus, Inc . | Administration of interferon for prophylaxis against or treatment of pathogenic infection |
| KR102093612B1 (ko) | 2009-09-28 | 2020-03-26 | 인타르시아 세라퓨틱스 인코포레이티드 | 실질 항정상태 약물 전달의 신속 확립 및/또는 종결 |
| US20120208755A1 (en) | 2011-02-16 | 2012-08-16 | Intarcia Therapeutics, Inc. | Compositions, Devices and Methods of Use Thereof for the Treatment of Cancers |
| WO2012177892A2 (en) * | 2011-06-21 | 2012-12-27 | University Of Florida Research Foundation, Inc. | Type i interferon mimetics as therapeutics for cancer, viral infections, and multiple sclerosis |
| US9889085B1 (en) | 2014-09-30 | 2018-02-13 | Intarcia Therapeutics, Inc. | Therapeutic methods for the treatment of diabetes and related conditions for patients with high baseline HbA1c |
| KR102650751B1 (ko) | 2015-06-03 | 2024-03-22 | 인타르시아 세라퓨틱스 인코포레이티드 | 임플란트 배치 및 제거 시스템들 |
| CA3024479A1 (en) | 2016-05-16 | 2017-11-23 | Intarcia Therapeutics, Inc. | Glucagon-receptor selective polypeptides and methods of use thereof |
| USD860451S1 (en) | 2016-06-02 | 2019-09-17 | Intarcia Therapeutics, Inc. | Implant removal tool |
| USD840030S1 (en) | 2016-06-02 | 2019-02-05 | Intarcia Therapeutics, Inc. | Implant placement guide |
| MX2019008006A (es) | 2017-01-03 | 2019-08-29 | Intarcia Therapeutics Inc | Metodos que comprenden la administracion continua de un agonista del receptor de glp-1 y la co-administracion de un farmaco. |
| CN112043685A (zh) * | 2020-09-18 | 2020-12-08 | 深圳科兴药业有限公司 | 重组人干扰素α1b突变体吸入溶液及其制备方法 |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2016015B (en) | 1978-01-22 | 1982-05-06 | Hayashibara Co | Method of preparing interferon and preparations containing interferon |
| US4460574A (en) | 1980-06-16 | 1984-07-17 | Yabrov Alexander A | Prophylaxis or treatment of interferon-sensitive diseases |
| US4414150A (en) | 1980-11-10 | 1983-11-08 | Genentech, Inc. | Hybrid human leukocyte interferons |
| US4456748A (en) | 1981-02-23 | 1984-06-26 | Genentech, Inc. | Hybrid human leukocyte interferons |
| US4507281A (en) | 1981-10-13 | 1985-03-26 | Exovir, Inc. | Interferon-containing compositions |
| EP0098876A1 (en) | 1982-01-19 | 1984-01-25 | Cetus Corporation | Multiclass hybrid interferons |
| US6936694B1 (en) | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
| US4892743A (en) | 1983-12-21 | 1990-01-09 | Schering Corporation | Novel hybrid interferon species |
| EP0146903A3 (en) | 1983-12-19 | 1987-07-22 | Schering Corporation | Production of a vector encoding a novel hybrid interferon species |
| US4636383A (en) | 1984-08-29 | 1987-01-13 | Schering Corporation | Interferon-cyclaradine combination |
| US4724232A (en) | 1985-03-16 | 1988-02-09 | Burroughs Wellcome Co. | Treatment of human viral infections |
| DE3607835A1 (de) | 1986-03-10 | 1987-09-24 | Boehringer Ingelheim Int | Hybridinterferone, deren verwendung als arzneimittel und als zwischenprodukte zur herstellung von antikoerpern und deren verwendung sowie verfahren zu ihrer herstellung |
| US4846782A (en) | 1986-03-14 | 1989-07-11 | Schering Corporation | Treatment of cancer with interferon and radiotherapy |
| EP0240224A3 (en) | 1986-03-31 | 1989-02-01 | Interferon Sciences, Inc. | An alpha interferon analogue |
| ZA878295B (en) | 1986-11-06 | 1988-05-03 | Amarillo Cell Culture Co. Inc. | Treatment of immuno-resistant disease |
| US5705363A (en) | 1989-03-02 | 1998-01-06 | The Women's Research Institute | Recombinant production of human interferon τ polypeptides and nucleic acids |
| TW391983B (en) | 1992-10-30 | 2000-06-01 | Univ Florida | Human interferon TAU, processes thereof and pharmaceutical uses thereof |
| US5939286A (en) * | 1995-05-10 | 1999-08-17 | University Of Florida | Hybrid interferon tau/alpha polypeptides, their recombinant production, and methods using them |
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- 1998-10-20 EP EP98952350A patent/EP1025124B1/en not_active Expired - Lifetime
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| KR100861007B1 (ko) | 2008-09-30 |
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| US6204022B1 (en) | 2001-03-20 |
| KR100586625B1 (ko) | 2006-06-07 |
| JP2008247926A (ja) | 2008-10-16 |
| KR20060015701A (ko) | 2006-02-17 |
| CN1276797A (zh) | 2000-12-13 |
| TW593336B (en) | 2004-06-21 |
| JP2001520238A (ja) | 2001-10-30 |
| EP1025124B1 (en) | 2008-07-30 |
| KR20010031206A (ko) | 2001-04-16 |
| EP1025124A1 (en) | 2000-08-09 |
| DE69839812D1 (de) | 2008-09-11 |
| WO1999020653A1 (en) | 1999-04-29 |
| ATE402957T1 (de) | 2008-08-15 |
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