CA2910693C - Anti-il-4/anti-il-13 bispecific antibody formulations - Google Patents
Anti-il-4/anti-il-13 bispecific antibody formulations Download PDFInfo
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- CA2910693C CA2910693C CA2910693A CA2910693A CA2910693C CA 2910693 C CA2910693 C CA 2910693C CA 2910693 A CA2910693 A CA 2910693A CA 2910693 A CA2910693 A CA 2910693A CA 2910693 C CA2910693 C CA 2910693C
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| US10434088B2 (en) | 2013-05-03 | 2019-10-08 | Selecta Biosciences, Inc. | Methods related to administering immunosuppressants and therapeutic macromolecules at a reduced pharmacodynamically effective dose |
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| BR112018014123A2 (pt) * | 2016-01-12 | 2018-12-11 | Dr. Reddy's Laboratories Limited | formulação farmacêutica aquosa estável. |
| EA037960B1 (ru) | 2016-04-27 | 2021-06-15 | Эббви Инк. | Способ лечения эозинофильного эзофагита с применением антитела против il-13 |
| US20180193003A1 (en) | 2016-12-07 | 2018-07-12 | Progenity Inc. | Gastrointestinal tract detection methods, devices and systems |
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| WO2018183932A1 (en) | 2017-03-30 | 2018-10-04 | Progenity Inc. | Treatment of a disease of the gastrointestinal tract with a il-13 inhibitor |
| US11603407B2 (en) * | 2017-04-06 | 2023-03-14 | Regeneron Pharmaceuticals, Inc. | Stable antibody formulation |
| JOP20190255A1 (ar) | 2017-04-28 | 2019-10-27 | Amgen Inc | صيغ أجسام مضادة لـ rankl بشري، وطرق لاستخدامها |
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| EP3795590A4 (en) | 2018-05-17 | 2022-05-04 | Astellas Pharma Inc. | COMPLEX WITH ANTI-HUMAN MUC1 ANTIBODY FAB FRAGMENT, PEPTIDE LINKER AND/OR LIGAND |
| EP3849513A1 (en) * | 2018-09-11 | 2021-07-21 | Ichnos Sciences SA | Compositions comprising a bispecific antibody, bufffer and one or more stabilizing agents |
| CN112789028A (zh) * | 2018-10-01 | 2021-05-11 | 美国安进公司 | 用于减少双特异性抗体的聚集的方法 |
| US12065503B2 (en) | 2018-10-10 | 2024-08-20 | Astellas Pharma Inc. | Pharmaceutical composition containing tagged site-antihuman antibody fab fragment complex |
| KR102131519B1 (ko) * | 2018-10-30 | 2020-07-07 | 가톨릭대학교 산학협력단 | 간암 전이 진단 또는 예후 예측용 바이오마커 및 이의 용도 |
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| JOP20210229A1 (ar) | 2019-02-18 | 2023-01-30 | Lilly Co Eli | صيغة جسم مضاد علاجي |
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| CN121197633A (zh) | 2019-12-13 | 2025-12-26 | 比特比德科有限责任公司 | 用于将治疗剂递送至胃肠道的可摄取装置 |
| US20210308058A1 (en) * | 2020-03-11 | 2021-10-07 | Selecta Biosciences, Inc. | Methods and compositions related to synthetic nanocarriers |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4444887A (en) | 1979-12-10 | 1984-04-24 | Sloan-Kettering Institute | Process for making human antibody producing B-lymphocytes |
| US4716111A (en) | 1982-08-11 | 1987-12-29 | Trustees Of Boston University | Process for producing human antibodies |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| GB8928874D0 (en) | 1989-12-21 | 1990-02-28 | Celltech Ltd | Humanised antibodies |
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| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| EP0519596B1 (en) | 1991-05-17 | 2005-02-23 | Merck & Co. Inc. | A method for reducing the immunogenicity of antibody variable domains |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| US5869619A (en) | 1991-12-13 | 1999-02-09 | Xoma Corporation | Modified antibody variable domains |
| US5639641A (en) | 1992-09-09 | 1997-06-17 | Immunogen Inc. | Resurfacing of rodent antibodies |
| AU5632296A (en) | 1995-04-27 | 1996-11-18 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| WO1996034096A1 (en) | 1995-04-28 | 1996-10-31 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5916771A (en) | 1996-10-11 | 1999-06-29 | Abgenix, Inc. | Production of a multimeric protein by cell fusion method |
| EP2305027B1 (en) | 1996-12-03 | 2014-07-02 | Amgen Fremont Inc. | Transgenic mammals having human Ig loci including plural VH and Vkappa regions and antibodies produced therefrom |
| ATE200679T1 (de) | 1997-04-14 | 2001-05-15 | Micromet Ag | Neues verfahren zur herstellung von anti-humanen antigenrezeptoren und deren verwendungen |
| US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
| US20040023338A1 (en) | 2001-10-26 | 2004-02-05 | Heavner George A. | IL-4 mutein proteins, antibodies, compositions, methods and uses |
| EP1578912A4 (en) | 2001-10-26 | 2007-12-26 | Centocor Inc | IL-13 MUTEIN PROTEINS, ANTIBODIES, COMPOSITIONS, METHODS AND USES |
| US20040033228A1 (en) | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
| TWI307630B (en) * | 2004-07-01 | 2009-03-21 | Glaxo Group Ltd | Immunoglobulins |
| US20060148009A1 (en) | 2004-10-12 | 2006-07-06 | Xencor, Inc. | Prediction and assessment of immunogenicity |
| AR064826A1 (es) * | 2007-01-09 | 2009-04-29 | Wyeth Corp | Formulaciones de anticuerpos anti-il-13 y usos de los mismos. dispositivos, parche y jeringa |
| EP2050764A1 (en) * | 2007-10-15 | 2009-04-22 | sanofi-aventis | Novel polyvalent bispecific antibody format and uses thereof |
| WO2009070642A1 (en) | 2007-11-28 | 2009-06-04 | Medimmune, Llc | Protein formulation |
| EP2196476A1 (en) | 2008-12-10 | 2010-06-16 | Novartis Ag | Antibody formulation |
| US20120121580A1 (en) * | 2009-07-28 | 2012-05-17 | Merck Sharp & Dohme Corp. | Methods for producing high concentration lyophilized pharmaceutical formulations |
| SG183983A1 (en) * | 2010-03-17 | 2012-10-30 | Abbott Res Bv | Anti-nerve growth factor (ngf) antibody compositions |
| AR085911A1 (es) * | 2011-03-16 | 2013-11-06 | Sanofi Sa | Dosis terapeutica segura de una proteina similar a un anticuerpo con region v dual |
| TWI743461B (zh) | 2011-03-28 | 2021-10-21 | 法商賽諾菲公司 | 具有交叉結合區定向之雙重可變區類抗體結合蛋白 |
| JOP20200043A1 (ar) * | 2011-05-10 | 2017-06-16 | Amgen Inc | طرق معالجة أو منع الاضطرابات المختصة بالكوليسترول |
| JO3625B1 (ar) * | 2011-09-22 | 2020-08-27 | Amgen Inc | بروتينات رابطة للأنتيجين cd27l |
| CN102961745B (zh) * | 2012-09-27 | 2015-02-18 | 苏州康聚生物科技有限公司 | 抗体组合物制剂及其应用 |
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