EA020456B1 - Фармацевтическая композиция, содержащая связывающееся с vla-4 антитело, для подкожной или внутримышечной доставки - Google Patents
Фармацевтическая композиция, содержащая связывающееся с vla-4 антитело, для подкожной или внутримышечной доставки Download PDFInfo
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- EA020456B1 EA020456B1 EA201070015A EA201070015A EA020456B1 EA 020456 B1 EA020456 B1 EA 020456B1 EA 201070015 A EA201070015 A EA 201070015A EA 201070015 A EA201070015 A EA 201070015A EA 020456 B1 EA020456 B1 EA 020456B1
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- natalizumab
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| CA2765220A1 (en) * | 2009-07-14 | 2011-01-20 | Biogen Idec Ma Inc. | Methods for inhibiting yellow color and peroxide formation in a composition |
| BR112012021576A2 (pt) | 2010-02-26 | 2016-10-25 | Novo Nordisk As | composições estáveis contendo anticorpo. |
| EA201892184A1 (ru) | 2010-03-01 | 2019-03-29 | БАЙЕР ХЕЛЬСКЕР ЛЛСи | Оптимизированные моноклональные антитела против ингибитора пути тканевого фактора |
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| WO2013006461A1 (en) * | 2011-07-01 | 2013-01-10 | Biogen Idec Ma Inc. | Cholesterol-based media supplementals for cell culture |
| US9302002B2 (en) | 2011-10-18 | 2016-04-05 | Coherus Biosciences, Inc. | Etanercept formulations stabilized with combinations of sugars and polyols |
| US10493151B2 (en) | 2011-10-18 | 2019-12-03 | Coherus Biosciences, Inc. | Etanercept formulations stabilized with sodium chloride |
| AU2013221635B2 (en) * | 2012-02-16 | 2017-12-07 | Santarus, Inc. | Anti-VLA1 (CD49a) antibody pharmaceutical compositions |
| US20150150979A1 (en) * | 2012-06-21 | 2015-06-04 | Ucb Pharma, S.A. | Pharmaceutical formulation |
| CA2878508A1 (en) | 2012-07-09 | 2014-01-16 | Coherus Biosciences, Inc. | Etanercept formulations exhibiting marked reduction in sub-visible particles |
| US9592297B2 (en) | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
| PL2895188T3 (pl) | 2012-09-11 | 2018-06-29 | Coherus Biosciences, Inc. | Prawidłowo pofałdowany etanercept o wysokiej czystości i doskonałej wydajności |
| CN103217525B (zh) * | 2013-03-21 | 2015-04-29 | 上海执诚生物科技股份有限公司 | 一种含有提高胱抑素c胶乳包被抗体的稳定性的组合物、稳定剂及其制备方法和用途 |
| EP3062814A1 (en) * | 2013-10-29 | 2016-09-07 | Albumedix A/S | Antibody composition |
| CN105793850B (zh) * | 2013-11-29 | 2020-04-24 | 豪夫迈·罗氏有限公司 | 抗体选择装置和方法 |
| CA2938933A1 (en) | 2014-03-12 | 2015-09-17 | Prothena Biosciences Limited | Anti-laminin4 antibodies specific for lg4-5 |
| WO2015136468A1 (en) * | 2014-03-13 | 2015-09-17 | Prothena Biosciences Limited | Combination treatment for multiple sclerosis |
| EP3149030A2 (en) * | 2014-06-02 | 2017-04-05 | Laboratoire Francais du Fractionnement et des Biotechnologies Societe Anonyme | Production of fc fragments |
| EP3207061A1 (en) * | 2014-10-18 | 2017-08-23 | Pfizer Inc | Anti-il-7r antibody compositions |
| WO2017205101A1 (en) | 2016-05-27 | 2017-11-30 | Alexion Pharmaceuticals, Inc. | Methods for treatment of refractory generalized myasthenia gravis |
| GB201612317D0 (en) | 2016-07-15 | 2016-08-31 | Philogen Spa | Antibody compositions |
| US11608357B2 (en) | 2018-08-28 | 2023-03-21 | Arecor Limited | Stabilized antibody protein solutions |
| GB201703062D0 (en) * | 2017-02-24 | 2017-04-12 | Arecor Ltd | Stabilized antibody protein solutions |
| EP3372242A1 (en) | 2017-03-06 | 2018-09-12 | Ares Trading S.A. | Liquid pharmaceutical composition |
| EP3372241A1 (en) | 2017-03-06 | 2018-09-12 | Ares Trading S.A. | Liquid pharmaceutical composition |
| JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
| WO2018204374A1 (en) | 2017-05-02 | 2018-11-08 | Merck Sharp & Dohme Corp. | Formulations of anti-lag3 antibodies and co-formulations of anti-lag3 antibodies and anti-pd-1 antibodies |
| JP7518764B2 (ja) | 2017-10-26 | 2024-07-18 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | 発作性夜間ヘモグロビン尿症（ＰＮＨ）および非典型溶血性尿毒症症候群（ａＨＵＳ）の処置のための抗Ｃ５抗体の投薬量および投与 |
| EP3773696A4 (en) * | 2018-04-10 | 2021-12-29 | Dr. Reddy's Laboratories Ltd. | Stable formulations of therapeutic antibody |
| CN119080931A (zh) | 2018-06-04 | 2024-12-06 | 马萨诸塞州渤健公司 | 具有降低的效应功能的抗vla-4抗体 |
| JP7538723B2 (ja) * | 2018-06-28 | 2024-08-22 | アレクシオン ファーマシューティカルズ， インコーポレイテッド | 抗ｃ５抗体の産生方法 |
| KR20210089215A (ko) | 2018-11-07 | 2021-07-15 | 머크 샤프 앤드 돔 코포레이션 | 항-lag3 항체 및 항-pd-1 항체의 공동-제제 |
| WO2021007504A2 (en) * | 2019-07-10 | 2021-01-14 | Regeneron Pharmaceuticals, Inc. | Methods and compositions comprising reduced level of host cell proteins |
| CN113134081A (zh) * | 2020-01-20 | 2021-07-20 | 上海君实生物医药科技股份有限公司 | 抗btla抗体药物组合物及其用途 |
| WO2022092183A1 (ja) * | 2020-10-30 | 2022-05-05 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | 医薬組成物 |
| MX2023005596A (es) | 2020-11-14 | 2023-08-15 | Biogen Ma Inc | Regímenes de dosificación bifásica subcutánea para anticuerpos anti-vla-4. |
| JP2024513974A (ja) | 2021-04-13 | 2024-03-27 | バイオジェン・エムエイ・インコーポレイテッド | 慢性活動性白質病変／放射線学的孤立性症候群を治療するための組成物及び方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995019790A1 (en) * | 1994-01-25 | 1995-07-27 | Athena Neurosciences, Inc. | Humanized antibodies against leukocyte adhesion molecule vla-4 |
| WO2004071439A2 (en) * | 2003-02-10 | 2004-08-26 | Elan Pharmaceuticals, Inc. | Immunoglobulin formulation and method of preparation thereof |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) * | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| IE52535B1 (en) | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
| US4475196A (en) * | 1981-03-06 | 1984-10-02 | Zor Clair G | Instrument for locating faults in aircraft passenger reading light and attendant call control system |
| US4447233A (en) * | 1981-04-10 | 1984-05-08 | Parker-Hannifin Corporation | Medication infusion pump |
| US4439196A (en) * | 1982-03-18 | 1984-03-27 | Merck & Co., Inc. | Osmotic drug delivery system |
| US4447224A (en) * | 1982-09-20 | 1984-05-08 | Infusaid Corporation | Variable flow implantable infusion apparatus |
| US4487603A (en) * | 1982-11-26 | 1984-12-11 | Cordis Corporation | Implantable microinfusion pump system |
| US4486194A (en) * | 1983-06-08 | 1984-12-04 | James Ferrara | Therapeutic device for administering medicaments through the skin |
| US4596556A (en) * | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
| JPS62196921A (ja) | 1986-02-25 | 1987-08-31 | Nec Corp | 位相検出回路 |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| DE3883899T3 (de) | 1987-03-18 | 1999-04-22 | Sb2, Inc., Danville, Calif. | Geänderte antikörper. |
| US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
| US4790824A (en) * | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
| US5530101A (en) * | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| US5312335A (en) * | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
| US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| EP0940468A1 (en) * | 1991-06-14 | 1999-09-08 | Genentech, Inc. | Humanized antibody variable domain |
| US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
| SG47043A1 (en) | 1993-01-06 | 1998-03-20 | Kinerton Ltd | Ionic molecular conjugates of biodegradeble polyesters and bioactive polypeptides |
| SG44845A1 (en) | 1993-01-12 | 1997-12-19 | Biogen Inc | Recombitant anti-vla4 antibody molecules |
| AU687790B2 (en) * | 1993-02-09 | 1998-03-05 | Biogen Idec Ma Inc. | Treatment for insulin dependent diabetes |
| US5827690A (en) * | 1993-12-20 | 1998-10-27 | Genzyme Transgenics Corporatiion | Transgenic production of antibodies in milk |
| US5840299A (en) * | 1994-01-25 | 1998-11-24 | Athena Neurosciences, Inc. | Humanized antibodies against leukocyte adhesion molecule VLA-4 |
| EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
| US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
| DE19541844C1 (de) | 1995-11-09 | 1997-07-24 | Gsf Forschungszentrum Umwelt | Verfahren zur Herstellung von menschlichen Antikörpern und deren Verwendung |
| DK0929578T3 (da) * | 1996-02-09 | 2003-08-25 | Abbott Lab Bermuda Ltd | Humane antistoffer, der binder human TNFalfa |
| EP1500329B1 (en) | 1996-12-03 | 2012-03-21 | Amgen Fremont Inc. | Human antibodies that specifically bind human TNF alpha |
| US6914128B1 (en) | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
| WO2001055112A1 (en) | 2000-01-27 | 2001-08-02 | American Cyanamid Company | Method for preparing alpha-sulfonyl hydroxamic acid derivatives |
| US8288322B2 (en) | 2000-04-17 | 2012-10-16 | Dyax Corp. | Methods of constructing libraries comprising displayed and/or expressed members of a diverse family of peptides, polypeptides or proteins and the novel libraries |
| CA2478458A1 (en) | 2004-08-20 | 2006-02-20 | Michael Panzara | Treatment of pediatric multiple sclerosis |
| CN101102792A (zh) * | 2004-11-19 | 2008-01-09 | 比奥根艾迪克Ma公司 | 治疗多发性硬化 |
| WO2008021954A2 (en) | 2006-08-09 | 2008-02-21 | Biogen Idec Ma Inc. | Method for distribution of a drug |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995019790A1 (en) * | 1994-01-25 | 1995-07-27 | Athena Neurosciences, Inc. | Humanized antibodies against leukocyte adhesion molecule vla-4 |
| WO2004071439A2 (en) * | 2003-02-10 | 2004-08-26 | Elan Pharmaceuticals, Inc. | Immunoglobulin formulation and method of preparation thereof |
Non-Patent Citations (7)
| Title |
|---|
| DAUGHERTY ANN L. ET AL.: "Formulation and delivery issues for monoclonal antibody therapeutics". ADVANCED DRUG DELIVERY REVIEWS, vol. 58, no. 5-6, August 2006 (2006-08), pages 686-706, XF005611422, ISSN: 0169-409X, the whole document * |
| HARRIS R.J. ET AL.: "Commercial manufacturing scale formulation and analytical characterization of therapeutic recombinant antibodies". DRUG DEVELOPMENT RESEARCH, NEW YORK, NY, US. vol. 61, no. 3, 1 March 2004 (2004-03-01), pages 137-154, XP002324970, ISSN: 0272-4391, the whole document * |
| RUDIKOFF S. ET AL.: "Single amino acid substitution altering antigen-binding specificity". PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE, WASHINGTON, DC.; US, vol. 79, 1 March 1982 (1982-03-01), pages 1979-1983, XP007901436, ISSN: 0027-8424, the whole document * |
| SHIRE STEVEN J. ET AL.: "Challenges in the development of high protein concentration formulations". JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 93, no. 6, June 2004 (2004-06), pages 1390-1402, XP009108986, ISSN: 0022-3549, the whole document * |
| VOLLMER T.L. ET AL.: "An open-label safety and drug interaction study of natalizumab (Antegren(TM)) in combination with interferon-beta (Avonex(R)) in patients with multiple sclerosis". MULTIPLE SCLEROSIS, vol. 10, no, 5, 2004, pages 511-520, XP009109055, ISSN: 1352-4585, the whole document * |
| WAHG W. ET AL.: "ANTIBODY STRUCTURE, INSTABILITY, AND FORMULATION". JOURNAL OF PHARMACEUTICAL SCIENCE, vol. 96, no. 1, 1 January 2007 (2007-01-01), pages 1-26, XP009084505, ISSN: 0022-3549, the whole document * |
| WAKANKAR ADITYA A. ET AL.: "The effect of cosolutes on the isomerization of aspartic acid residues and conformational stability in a monoclonal antibody". JOURNAL OF PHARMACEUTICAL SCIENCE, vol. 96, no. 7, 1 July 2007 (2007-07-01), pages 1708-1718, XP009108930, ISSN: 0022-3549, the whole document * |
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