CA3118144A1 - Co-formulations of anti-lag3 antibodies and anti-pd-1 antibodies - Google Patents
Co-formulations of anti-lag3 antibodies and anti-pd-1 antibodies Download PDFInfo
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- CA3118144A1 CA3118144A1 CA3118144A CA3118144A CA3118144A1 CA 3118144 A1 CA3118144 A1 CA 3118144A1 CA 3118144 A CA3118144 A CA 3118144A CA 3118144 A CA3118144 A CA 3118144A CA 3118144 A1 CA3118144 A1 CA 3118144A1
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- histidine
- arginine
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
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- Health & Medical Sciences (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201862756678P | 2018-11-07 | 2018-11-07 | |
| US62/756,678 | 2018-11-07 | ||
| PCT/US2019/059954 WO2020097139A1 (en) | 2018-11-07 | 2019-11-06 | Co-formulations of anti-lag3 antibodies and anti-pd-1 antibodies |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3118144A1 true CA3118144A1 (en) | 2020-05-14 |
Family
ID=70612309
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3118144A Pending CA3118144A1 (en) | 2018-11-07 | 2019-11-06 | Co-formulations of anti-lag3 antibodies and anti-pd-1 antibodies |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US12319735B2 (en:Method) |
| EP (1) | EP3876990A4 (en:Method) |
| JP (1) | JP7503056B6 (en:Method) |
| KR (1) | KR20210089215A (en:Method) |
| CN (1) | CN113316458B (en:Method) |
| AU (2) | AU2019377456A1 (en:Method) |
| BR (1) | BR112021008873A8 (en:Method) |
| CA (1) | CA3118144A1 (en:Method) |
| MX (1) | MX2021005394A (en:Method) |
| WO (1) | WO2020097139A1 (en:Method) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103649123B (zh) | 2011-06-13 | 2017-05-24 | Csl有限公司 | 抗g‑csfr抗体及其用途 |
| BR112019022873A8 (pt) | 2017-05-02 | 2023-04-11 | Merck Sharp & Dohme | Formulação, e, vaso ou dispositivo de injeção. |
| JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
| WO2019104385A1 (en) | 2017-11-29 | 2019-06-06 | Csl Limited | Method of treating or preventing ischemia-reperfusion injury |
| WO2019178645A1 (en) | 2018-03-23 | 2019-09-26 | Csl Limited | Method of treating asthma |
| JP7503056B6 (ja) | 2018-11-07 | 2024-07-16 | メルク・シャープ・アンド・ドーム・エルエルシー | 抗ｌａｇ３抗体および抗ｐｄ－１抗体の共－製剤 |
| US20230272106A1 (en) * | 2020-06-19 | 2023-08-31 | Sinocelltech Ltd | Stable formulation for recombinant anti-pd-1 monoclonal antibody |
| AU2021317805A1 (en) * | 2020-07-31 | 2023-03-16 | Jiangsu Hengrui Pharmaceuticals Co., Ltd. | Anti-PD-1 antibody pharmaceutical composition and use thereof |
| CN117042755A (zh) * | 2020-12-16 | 2023-11-10 | Csl创新私人有限公司 | 蛋白质配制剂及其用途 |
| EP4284834A1 (en) | 2021-01-29 | 2023-12-06 | Merck Sharp & Dohme LLC | Compositions of programmed death receptor 1 (pd-1) antibodies and methods of obtaining the compositions thereof |
| WO2023037383A1 (en) * | 2021-09-07 | 2023-03-16 | Dr. Reddy’S Laboratories Limited | Formulations of immune check point inhibitors |
| WO2023059900A2 (en) * | 2021-10-08 | 2023-04-13 | Invivyd, Inc. | Pharmaceutical formulations comprising anti-coronavirus s protein antibodies and uses thereof |
| EP4514854A1 (en) * | 2022-04-29 | 2025-03-05 | Merck Sharp & Dohme LLC | Stable formulations of anti-ilt4 antibodies or antigen-binding fragments thererof in combination with anti-pd-1 antibodies and methods of use thereof |
| WO2025040080A1 (en) * | 2023-08-21 | 2025-02-27 | Beigene Switzerland Gmbh | Treatment of esophageal cancer with anti-lag3, anti-pd-1 and chemotherapy |
Family Cites Families (231)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4401820A (en) | 1981-01-23 | 1983-08-30 | Tanabe Seiyaku Co., Ltd. | Process for racemizing optically active α-amino acids or a salt thereof |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5262296A (en) | 1988-03-30 | 1993-11-16 | Toray Industries, Inc. | Freeze-dried composition containing enzyme-labeled anti-human interferon-β antibody and enzyme immunoassay kit containing the composition |
| DE68908175T2 (de) | 1988-05-27 | 1994-03-03 | Centocor Inc | Gefriergetrocknete formulierung für antikörperprodukte. |
| ES2191016T3 (es) | 1992-09-16 | 2003-09-01 | Scripps Research Inst | Anticuerpos monoclonales neutralizantes humanos para el virus respiratorio sincitial. |
| DK2275119T3 (da) | 1995-07-27 | 2013-11-11 | Genentech Inc | Stabil, isotonisk lyofiliseret proteinformulering |
| US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| WO1997010846A1 (en) | 1995-09-18 | 1997-03-27 | Intracel Corporation | Neutralizing monoclonal antibodies to respiratory syncytial virus |
| US7365166B2 (en) | 1997-04-07 | 2008-04-29 | Genentech, Inc. | Anti-VEGF antibodies |
| US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
| HK1044159A1 (zh) | 1998-12-01 | 2002-10-11 | 蛋白质设计实验室股份有限公司 | 抗γ-干扰素的人化抗体 |
| WO2000048635A1 (en) | 1999-02-22 | 2000-08-24 | Baxter International Inc. | Novel albumin-free factor viii formulations |
| WO2000053631A1 (en) | 1999-03-11 | 2000-09-14 | Schering Corporation | Mammalian cytokines; related reagents and methods |
| JP4505166B2 (ja) | 1999-09-09 | 2010-07-21 | シェーリング コーポレイション | 哺乳動物インターロイキン−１２ｐ４０およびインターロイキンｂ３０、その組成物、抗体、薬学的組成物における使用 |
| US7090847B1 (en) | 1999-09-09 | 2006-08-15 | Schering Corporation | Mammalian cytokines; related reagents and methods |
| AU1102401A (en) * | 1999-10-22 | 2001-05-08 | Ludwig Institute For Cancer Research | Methods for reducing the effects of cancers that express a33 antigen using a33 antigen specific immunoglobulin products |
| US20050175986A1 (en) | 2000-05-09 | 2005-08-11 | Smit Kline Beecham Corporation | Human monoclonal antibody |
| ATE442862T2 (de) | 2000-10-12 | 2009-10-15 | Genentech Inc | Niederviskose konzentrierte proteinformulierungen |
| US8703126B2 (en) | 2000-10-12 | 2014-04-22 | Genentech, Inc. | Reduced-viscosity concentrated protein formulations |
| US6818216B2 (en) | 2000-11-28 | 2004-11-16 | Medimmune, Inc. | Anti-RSV antibodies |
| EP1801123A3 (en) | 2000-12-28 | 2007-11-21 | Altus Pharmaceuticals Inc. | Crystals of whole antibodies and fragments thereof and methods for making and using them |
| WO2002072636A2 (en) | 2000-12-28 | 2002-09-19 | Altus Biologics Inc. | Crystals of whole antibodies and fragments thereof and methods for making and using them |
| GB0113179D0 (en) | 2001-05-31 | 2001-07-25 | Novartis Ag | Organic compounds |
| CA2451185A1 (en) | 2001-06-21 | 2003-01-03 | Altus Biologics, Inc. | Spherical protein particles and methods of making and using them |
| DE60235989D1 (de) | 2001-06-26 | 2010-05-27 | Amgen Fremont Inc | Antikörper gegen opgl |
| ATE454137T1 (de) | 2001-07-25 | 2010-01-15 | Facet Biotech Corp | Stabile lyophilisierte pharmazeutische formulierung des igg-antikörpers daclizumab |
| DK1441589T3 (da) | 2001-11-08 | 2012-08-06 | Abbott Biotherapeutics Corp | Stabil, flydende, farmaceutisk sammensætning af IgG-antistoffer |
| DE10207178A1 (de) | 2002-02-19 | 2003-09-04 | Novosom Ag | Komponenten für die Herstellung amphoterer Liposomen |
| SI1478394T1 (sl) | 2002-02-27 | 2008-12-31 | Immunex Corp | STABILIZIRAN TNFR-Fc SESTAVEK Z ARGININOM |
| WO2003086310A2 (en) | 2002-04-12 | 2003-10-23 | Ramot At Tel Aviv University Ltd. | Prevention of brain inflammation as a result of induced autoimmune response |
| US7132100B2 (en) | 2002-06-14 | 2006-11-07 | Medimmune, Inc. | Stabilized liquid anti-RSV antibody formulations |
| DK2206517T3 (da) | 2002-07-03 | 2023-11-06 | Ono Pharmaceutical Co | Immunpotentierende sammensætninger omfattende af anti-PD-L1-antistoffer |
| JP2006502116A (ja) | 2002-07-12 | 2006-01-19 | メダレックス， インク． | タンパク質の酸化分解を防ぐ方法及び組成物 |
| US20040033228A1 (en) | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
| AU2003265511A1 (en) | 2002-08-21 | 2004-03-11 | Pharmacia Corporation | Injectable pharmaceutical suspension in a two-chamber vial |
| WO2004019861A2 (en) | 2002-08-28 | 2004-03-11 | Pharmacia Corporation | Stable ph optimized formulation of a modified antibody |
| US20040191243A1 (en) | 2002-12-13 | 2004-09-30 | Bei Chen | System and method for stabilizing antibodies with histidine |
| US7488802B2 (en) | 2002-12-23 | 2009-02-10 | Wyeth | Antibodies against PD-1 |
| US7563869B2 (en) | 2003-01-23 | 2009-07-21 | Ono Pharmaceutical Co., Ltd. | Substance specific to human PD-1 |
| WO2004071517A2 (en) | 2003-02-06 | 2004-08-26 | Schering Corporation | Uses of il-23 related reagents |
| PT2236154T (pt) | 2003-02-10 | 2018-06-26 | Biogen Ma Inc | Formulação de imunoglobulinas e método de preparação das mesmas |
| NZ541898A (en) | 2003-03-10 | 2008-07-31 | Schering Corp | Uses of IL-23 antagonists for the manufacture of a medicament for the treatment of tumors |
| BRPI0403964B8 (pt) | 2003-04-04 | 2021-05-25 | Genentech Inc | formulações líquidas estáveis, artigo manufaturado e uso dessas formulações para o tratamento de disfunção mediada por ige |
| JP4703566B2 (ja) | 2003-05-14 | 2011-06-15 | イムノゲン インコーポレーティッド | 薬剤複合体組成物 |
| US20070212346A1 (en) | 2003-10-09 | 2007-09-13 | Tomoyuki Igawa | Highly Concentrated Stabilized Igm Solution |
| US8277810B2 (en) | 2003-11-04 | 2012-10-02 | Novartis Vaccines & Diagnostics, Inc. | Antagonist anti-CD40 antibodies |
| PE20050925A1 (es) | 2003-11-10 | 2005-11-29 | Schering Corp | Anticuerpo recombinante humanizado anti-interleuquina 10 |
| DE10355904A1 (de) | 2003-11-29 | 2005-06-30 | Merck Patent Gmbh | Feste Formen von anti-EGFR-Antikörpern |
| EP1712240B1 (en) | 2003-12-25 | 2015-09-09 | Kyowa Hakko Kirin Co., Ltd. | Stable water-based medicinal preparation containing antibody |
| NZ548785A (en) | 2004-01-07 | 2011-08-26 | Novartis Vaccines & Diagnostic | M-CSF-Specific monoclonal antibody and uses thereof |
| CA2555791A1 (en) | 2004-02-12 | 2005-08-25 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Highly concentrated liquid formulations of anti-egfr antibodies |
| BRPI0507794A (pt) | 2004-02-17 | 2007-07-17 | Schering Corp | métodos de modular a atividade de il-23, reagentes relacionados |
| US7662384B2 (en) | 2004-03-24 | 2010-02-16 | Facet Biotech Corporation | Use of anti-α5β1 antibodies to inhibit cancer cell proliferation |
| JP4879884B2 (ja) | 2004-04-12 | 2012-02-22 | メディミューン，エルエルシー | 抗−ｉｌ−９抗体製剤及びその使用法 |
| WO2005120571A2 (en) | 2004-06-07 | 2005-12-22 | Ramot At Tel Aviv University Ltd. | Method of passive immunization against disease or disorder characterized by amyloid aggregation with diminished risk of neuroinflammation |
| AR049390A1 (es) | 2004-06-09 | 2006-07-26 | Wyeth Corp | Anticuerpos contra la interleuquina-13 humana y usos de los mismos |
| SG190665A1 (en) | 2004-07-30 | 2013-06-28 | Rinat Neuroscience Corp | Antibodies directed against amyloid-beta peptide and methods using same |
| JO3000B1 (ar) | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
| US20080057070A1 (en) | 2004-11-04 | 2008-03-06 | Chiron Corporation | Antagonist Anti-Cd40 Monoclonal Antibodies and Methods for Their Use |
| UY29350A1 (es) | 2005-01-28 | 2006-08-31 | Wyeth Corp | Formulaciones liquidas estabilizadasde polipeptido |
| GT200600031A (es) | 2005-01-28 | 2006-08-29 | Formulacion anticuerpo anti a beta | |
| DOP2006000029A (es) | 2005-02-07 | 2006-08-15 | Genentech Inc | Antibody variants and uses thereof. (variantes de un anticuerpo y usos de las mismas) |
| EP1871806A2 (en) | 2005-03-08 | 2008-01-02 | Pharmacia & Upjohn Company LLC | ANTI-MAdCAM ANTIBODY COMPOSITIONS |
| US7785595B2 (en) | 2005-04-18 | 2010-08-31 | Yeda Research And Development Company Limited | Stabilized anti-hepatitis B (HBV) antibody formulations |
| BRPI0608376A8 (pt) | 2005-04-22 | 2018-10-16 | Lilly Co Eli | composição de ligação, método de uso de uma composição de ligação, e, kit de detecção |
| CA3151350A1 (en) | 2005-05-09 | 2006-11-16 | E. R. Squibb & Sons, L.L.C. | Human monoclonal antibodies to programmed death 1 (pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics |
| RU2415151C2 (ru) | 2005-06-07 | 2011-03-27 | Эсбатек Аг | СТАБИЛЬНЫЕ И РАСТВОРИМЫЕ АНТИТЕЛА, ИНГИБИРУЮЩИЕ TNFα |
| MX2007016306A (es) | 2005-06-15 | 2008-03-07 | Schering Corp | Formulaciones de anticuerpo anti-igf1r. |
| TR201902033T4 (tr) | 2005-06-30 | 2019-03-21 | Janssen Biotech Inc | Anti-IL-23 antikorları, bileşimleri, yöntemleri ve kullanımları. |
| EP1909838A2 (en) | 2005-07-29 | 2008-04-16 | Amgen Inc. | Formulations that inhibit protein aggregation |
| CA2615122A1 (en) | 2005-08-03 | 2007-02-15 | Immunogen, Inc. | Immunoconjugate formulations |
| DE602006015830D1 (de) | 2005-08-25 | 2010-09-09 | Lilly Co Eli | Anti-il-23-antikörper |
| WO2007027714A2 (en) | 2005-08-31 | 2007-03-08 | Schering Corporation | Engineered anti-il-23 antibodies |
| WO2007033230A2 (en) | 2005-09-12 | 2007-03-22 | Novimmune S.A. | Anti-cd3 antibody formulations |
| PL1942939T5 (pl) | 2005-09-30 | 2021-10-11 | Medimmune Limited | Kompozycja przeciwciała interleukiny-13 |
| US9084777B2 (en) | 2005-12-28 | 2015-07-21 | Chugai Seiyaku Kabushiki Kaisha | Stabilized antibody-containing formulations |
| HUE049832T2 (hu) | 2005-12-29 | 2020-10-28 | Janssen Biotech Inc | Humán anti-IL-23 ellenanyagok, készítmények, eljárás és alkalmazások |
| AU2007212147A1 (en) | 2006-02-03 | 2007-08-16 | Medimmune, Llc | Protein formulations |
| KR20080104160A (ko) | 2006-03-28 | 2008-12-01 | 에프. 호프만-라 로슈 아게 | 항-ｉｇｆ-１ｒ 인간 단일클론 항체 제형 |
| SMP200800064B (it) | 2006-04-21 | 2009-11-06 | Novartis Ag | Composizioni farmaceutiche di anticorpi anti-cd40 antagonista |
| US20080003220A1 (en) | 2006-04-21 | 2008-01-03 | Amgen, Inc. | Buffering agents for biopharmaceutical formulations |
| CA2655372A1 (en) | 2006-06-13 | 2007-12-21 | Zymogenetics, Inc. | Il-17 and il-23 antagonists and methods of using the same |
| ES2827180T3 (es) | 2006-10-06 | 2021-05-20 | Amgen Inc | Formulaciones de anticuerpos estables |
| CA2666492C (en) | 2006-10-20 | 2012-07-17 | Douglas Rehder | Stable polypeptide formulations |
| CN104072612A (zh) | 2006-10-27 | 2014-10-01 | 艾伯维生物技术有限公司 | 结晶型抗-hTNFα抗体 |
| WO2008068246A1 (en) | 2006-12-05 | 2008-06-12 | Crucell Holland B.V. | Liquid anti-rabies antibody formulations |
| AR064333A1 (es) | 2006-12-14 | 2009-04-01 | Schering Corp | Anticuerpo anti-tslp de diseno |
| CA2790018C (en) | 2006-12-21 | 2015-02-03 | Amgen Inc. | Formulations |
| PE20081610A1 (es) | 2007-01-09 | 2008-12-09 | Wyeth Corp | Formulaciones de anticuerpos anti-il-13 y usos de los mismos |
| TWI426918B (zh) | 2007-02-12 | 2014-02-21 | Merck Sharp & Dohme | Ｉｌ-２３拮抗劑於治療感染之用途 |
| JP2010518858A (ja) | 2007-02-23 | 2010-06-03 | シェーリング コーポレイション | 操作された抗−ｉｌ−２３ｐ１９抗体 |
| JP2010518856A (ja) | 2007-02-23 | 2010-06-03 | シェーリング コーポレイション | 操作された抗−ＩＬ−２３ｐ１９抗体 |
| CN101679507A (zh) | 2007-03-29 | 2010-03-24 | 艾博特公司 | 结晶抗人类il-12抗体 |
| AU2008232903B9 (en) | 2007-03-30 | 2013-09-05 | Medimmune Llc | Antibodies with decreased deamidation profiles |
| US20090208492A1 (en) | 2007-06-14 | 2009-08-20 | Elan Pharmaceuticals, Inc. | Lyophilized Immunoglobulin Formulations and Methods of Preparation |
| EA020456B1 (ru) | 2007-06-14 | 2014-11-28 | Байоджен Айдек Ма Инк. | Фармацевтическая композиция, содержащая связывающееся с vla-4 антитело, для подкожной или внутримышечной доставки |
| CN102131828B (zh) | 2007-06-18 | 2015-06-17 | 默沙东有限责任公司 | 针对人程序性死亡受体pd-1的抗体 |
| JP5513380B2 (ja) | 2007-06-25 | 2014-06-04 | アムジエン・インコーポレーテツド | 肝細胞増殖因子に対する特異的結合剤の組成物 |
| UA107557C2 (xx) | 2007-07-06 | 2015-01-26 | Композиція антитіла офатумумабу | |
| US20100286038A1 (en) | 2007-09-21 | 2010-11-11 | Valentyn Antochshuk | Formulation containing cyclin-dependent kinase inhibiting compound and method of treating tumors using the same |
| EP2205276A4 (en) | 2007-09-28 | 2012-08-15 | Janssen Biotech Inc | ANTI-IL-12 / 23P40 ANTIBODIES, EPITOPES, FORMULATIONS, COMPOSITIONS, METHODS AND USES |
| AR068723A1 (es) | 2007-10-05 | 2009-12-02 | Glaxo Group Ltd | Proteina que se une a antigenos que se une a il-23 humana y sus usos |
| WO2009070642A1 (en) | 2007-11-28 | 2009-06-04 | Medimmune, Llc | Protein formulation |
| JP5881950B2 (ja) | 2007-12-21 | 2016-03-09 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 抗体処方物 |
| PE20091174A1 (es) | 2007-12-27 | 2009-08-03 | Chugai Pharmaceutical Co Ltd | Formulacion liquida con contenido de alta concentracion de anticuerpo |
| BRPI0821600A2 (pt) | 2007-12-28 | 2015-06-23 | Bioinvent Int Ab | Composição farmacêutica, artigo de fabricação, kit de partes, método de combater aterosclerose, ou uma doença cardiovascular associada à aterosclerose, e, uso de um anticorpo |
| EA201001223A1 (ru) | 2008-02-07 | 2011-06-30 | Эмджен Инк. | Стабилизированные белковые композиции |
| CN101970499B (zh) | 2008-02-11 | 2014-12-31 | 治疗科技公司 | 用于肿瘤治疗的单克隆抗体 |
| WO2009120684A1 (en) | 2008-03-25 | 2009-10-01 | Medimmune, Llc | Antibody formulation |
| CN110082533B (zh) | 2008-04-09 | 2023-01-10 | 健泰科生物技术公司 | 用于免疫相关疾病的治疗的新组合物和方法 |
| RU2010153580A (ru) | 2008-06-03 | 2012-07-20 | Эбботт Лэборетриз (Us) | Иммуноглобулины с двумя вариабельными доменами и их применение |
| JP5945096B2 (ja) | 2008-07-04 | 2016-07-05 | 小野薬品工業株式会社 | 抗ヒトｐｄ−１抗体の癌に対する治療効果を最適化するための判定マーカーの使用 |
| CA2734919C (en) | 2008-08-27 | 2016-08-16 | Schering Corporation | Lyophilized formulations of engineered anti-il-23p19 antibodies |
| WO2010032220A1 (en) | 2008-09-19 | 2010-03-25 | Pfizer Inc. | Stable liquid antibody formulation |
| MX345226B (es) | 2008-10-29 | 2017-01-20 | Ablynx Nv | Formulaciones de moleculas de union a antigeno de dominio sencillo. |
| WO2010062372A2 (en) | 2008-11-03 | 2010-06-03 | President And Fellows Of Harvard College | Methods for modulating nf-kb using gibberellins |
| PE20120204A1 (es) | 2008-11-17 | 2012-03-03 | Genentech Inc | Metodo y formulacion para reducir la agregacion de una macromolecula bajo condiciones fisiologicas |
| WO2010069858A1 (en) | 2008-12-19 | 2010-06-24 | F. Hoffmann-La Roche Ag | Pharmaceutical composition |
| AR075715A1 (es) | 2009-03-05 | 2011-04-20 | Novartis Ag | Formulacion de anticuerpo liofilizado |
| JP2012519706A (ja) | 2009-03-06 | 2012-08-30 | ジェネンテック， インコーポレイテッド | 抗体製剤 |
| MX2011009312A (es) | 2009-03-06 | 2012-02-29 | Medimmune Llc | Formulaciones de anticuerpos humanizados anti-cd19. |
| EP2230312A1 (en) | 2009-03-19 | 2010-09-22 | Helmholtz-Zentrum für Infektionsforschung GmbH | Probe compound for detecting and isolating enzymes and means and methods using the same |
| CN102458469B (zh) | 2009-05-04 | 2014-12-24 | 艾伯维生物技术有限公司 | 人抗TNF-α抗体的稳定高蛋白质浓度制剂 |
| US9155745B2 (en) | 2009-06-16 | 2015-10-13 | Universite De Geneve | Bevacizumab formulations with lower aggregation propensity, comprising corticosteroid anti-inflammatory drugs |
| AU2010263058A1 (en) | 2009-06-18 | 2012-01-12 | Wyeth Llc | Lyophilized formulations for small modular immunopharmaceuticals |
| CA2765220A1 (en) | 2009-07-14 | 2011-01-20 | Biogen Idec Ma Inc. | Methods for inhibiting yellow color and peroxide formation in a composition |
| WO2011017070A1 (en) | 2009-07-28 | 2011-02-10 | Merck Sharp & Dohme Corp. | Methods for producing high concentration lyophilized pharmaceutical formulations |
| US9345661B2 (en) | 2009-07-31 | 2016-05-24 | Genentech, Inc. | Subcutaneous anti-HER2 antibody formulations and uses thereof |
| WO2011024862A1 (ja) | 2009-08-31 | 2011-03-03 | 三洋化成工業株式会社 | タンパク質水溶液の安定化剤、この安定化剤を含有するタンパク質水溶液及び液体洗剤組成物、並びに、この安定化剤を用いるタンパク質の安定化方法 |
| ES2788869T3 (es) | 2009-09-03 | 2020-10-23 | Merck Sharp & Dohme | Anticuerpos anti-GITR |
| EP2473191B1 (en) | 2009-09-04 | 2017-08-23 | XOMA Technology Ltd. | Antibody coformulations |
| AR078161A1 (es) | 2009-09-11 | 2011-10-19 | Hoffmann La Roche | Formulaciones farmaceuticas muy concentradas de un anticuerpo anti cd20. uso de la formulacion. metodo de tratamiento. |
| PE20121646A1 (es) | 2009-11-04 | 2012-12-02 | Merck Sharp & Dohme | Anticuerpo anti-tslp modificado por tecnicas de ingeneria genetica |
| RU2609658C2 (ru) | 2009-12-21 | 2017-02-02 | Дженентек, Инк. | Состав, содержащий антитело |
| JP2013515754A (ja) | 2009-12-29 | 2013-05-09 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 新規な抗体製剤 |
| US20120294866A1 (en) | 2010-01-19 | 2012-11-22 | F. Hoffmann-La Roche Ag | Pharmaceutical formulation for proteins |
| AR080428A1 (es) | 2010-01-20 | 2012-04-11 | Chugai Pharmaceutical Co Ltd | Formulaciones liquidas estabilizadas contentivas de anticuerpos |
| WO2011116090A1 (en) | 2010-03-17 | 2011-09-22 | Abbott Research B.V. | Anti-nerve growth factor (ngf) antibody compositions |
| CN102958538A (zh) | 2010-05-03 | 2013-03-06 | 弗·哈夫曼-拉罗切有限公司 | 用于降低含有蛋白质的制剂的粘度的组合物和方法 |
| CN103402516B (zh) | 2010-06-17 | 2018-01-30 | 富津世生物技术有限公司 | 用作抗病毒药物的化合物、组合物及使用方法 |
| EP2399604A1 (en) | 2010-06-25 | 2011-12-28 | F. Hoffmann-La Roche AG | Novel antibody formulation |
| FR2962908A1 (fr) | 2010-07-20 | 2012-01-27 | Lfb Biotechnologies | Formulation d'anticorps anti-cd20 |
| WO2012018538A2 (en) | 2010-07-26 | 2012-02-09 | Schering Corporation | Bioassays for determining pd-1 modulation |
| PH12013500672A1 (en) | 2010-10-06 | 2013-06-03 | Regeneron Pharma | Stabilized formulations containing anti-interleukin-4-receptor (il-4r) antibodies |
| US9458240B2 (en) | 2010-12-10 | 2016-10-04 | Novartis Pharma Ag | Anti-BAFFR antibody formulations |
| US9145457B2 (en) | 2011-03-25 | 2015-09-29 | Amgen Inc. | Sclerostin antibody crystals and formulations thereof |
| CA2830806C (en) * | 2011-03-31 | 2020-05-12 | Merck Sharp & Dohme Corp. | Stable formulations of antibodies to human programmed death receptor pd-1 and related treatments |
| EP2694708A4 (en) | 2011-04-07 | 2014-10-01 | Glaxosmithkline Llc | FORMULATIONS WITH REDUCED VISCOSITY |
| UY34105A (es) | 2011-06-03 | 2012-07-31 | Lg Life Sciences Ltd | Formulación líquida estable de etanercept |
| EP2735315B1 (en) | 2011-07-19 | 2019-10-02 | Chugai Seiyaku Kabushiki Kaisha | Stable protein-containing preparation containing argininamide or valinamide |
| AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
| WO2013063468A1 (en) | 2011-10-27 | 2013-05-02 | Massachusetts Institute Of Technology | Amino acid derivates functionalized on the n- terminal capable of forming drug incapsulating microspheres |
| WO2013112438A1 (en) | 2012-01-23 | 2013-08-01 | Regeneron Pharmaceuticals, Inc. | Stabilized formulations containing anti-ang2 antibodies |
| CN104159614A (zh) | 2012-03-07 | 2014-11-19 | 卡迪拉保健有限公司 | TNF-α抗体的药物制剂 |
| WO2013150273A1 (en) | 2012-04-03 | 2013-10-10 | University Court Of The University Of St Andrews | High resolution imaging of extended volumes |
| PL3326649T3 (pl) | 2012-05-03 | 2022-04-25 | Boehringer Ingelheim International Gmbh | Przeciwciała anty-il-23p19 |
| US20140004131A1 (en) | 2012-05-04 | 2014-01-02 | Novartis Ag | Antibody formulation |
| EP2866833B1 (en) | 2012-06-27 | 2019-05-15 | Merck Sharp & Dohme Corp. | Crystalline anti-human il-23 antibodies |
| KR102090849B1 (ko) | 2012-07-04 | 2020-03-19 | 에프. 호프만-라 로슈 아게 | 공유 결합된 항원-항체 접합체 |
| FR2994390B1 (fr) | 2012-08-10 | 2014-08-15 | Adocia | Procede d'abaissement de la viscosite de solutions de proteines a concentration elevee |
| US20140227250A1 (en) | 2012-08-23 | 2014-08-14 | Merck Sharp & Dohme Corp. | Stable formulations of antibodies to tslp |
| US9592297B2 (en) | 2012-08-31 | 2017-03-14 | Bayer Healthcare Llc | Antibody and protein formulations |
| US8883979B2 (en) | 2012-08-31 | 2014-11-11 | Bayer Healthcare Llc | Anti-prolactin receptor antibody formulations |
| EP2919812A4 (en) | 2012-11-19 | 2016-05-18 | Merck Sharp & Dohme | Liquid formulations for TNFR: FC fusion proteins |
| WO2014093206A1 (en) | 2012-12-13 | 2014-06-19 | Merck Sharp & Dohme Corp. | Lyophilized spherical pellets of anti-il-23 antibodies |
| US9700633B2 (en) | 2013-01-28 | 2017-07-11 | Jenkem Technology Co., Ltd., Tianjin Branch | Conjugates of water soluble polymer-amino acid oligopeptide-drug, preparation method and use thereof |
| EA201591710A1 (ru) | 2013-03-13 | 2016-03-31 | Сиэтл Дженетикс, Инк. | Композиции, содержащие циклодекстрин и конъюгат антитело-лекарственное средство |
| PL3024484T3 (pl) | 2013-07-23 | 2018-11-30 | Novaliq Gmbh | Stabilizowane kompozycje przeciwciał |
| TWI649308B (zh) | 2013-07-24 | 2019-02-01 | 小野藥品工業股份有限公司 | 喹啉衍生物 |
| IL312865B2 (en) | 2013-09-11 | 2025-06-01 | Eagle Biologics Inc | Liquid protein formulations containing viscosity-lowering agents |
| BR122023024195A2 (pt) | 2013-09-20 | 2023-12-26 | Bristol-Myers Squibb Company | Usos de anticorpos anti-lag-3 e anticorpos anti-pd-1 |
| US9782470B2 (en) | 2013-10-16 | 2017-10-10 | Merck Sharp & Dohme Corp. | Method of obtaining thermostable dried vaccine formulations |
| RU2589691C2 (ru) | 2014-06-16 | 2016-07-10 | Общество с ограниченной ответственностью "Промоген-МАТ" | Стабильная композиция антитела, специфически связывающегося с her2 рецепторами, и способ ее получения |
| WO2015196091A1 (en) | 2014-06-20 | 2015-12-23 | Reform Biologics, Llc | Viscosity-reducing excipient compounds for protein formulations |
| US9907849B2 (en) | 2014-07-18 | 2018-03-06 | Advaxis, Inc. | Combination of a PD-1 antagonist and a listeria-based vaccine for treating prostate cancer |
| CN105296433B (zh) | 2014-08-01 | 2018-02-09 | 中山康方生物医药有限公司 | 一种ctla4抗体、其药物组合物及其用途 |
| DK3179992T3 (da) | 2014-08-11 | 2022-07-11 | Acerta Pharma Bv | Terapeutisk kombination af en btk-inhibitor, en pd-1-inhibitor og/eller en pd-l1-inhibitor |
| MD4733C1 (ro) | 2014-08-19 | 2021-07-31 | Merck Sharp & Dohme Corp | Anticorpi anti-TIGIT |
| JO3663B1 (ar) | 2014-08-19 | 2020-08-27 | Merck Sharp & Dohme | الأجسام المضادة لمضاد lag3 وأجزاء ربط الأنتيجين |
| EP3186281B1 (en) | 2014-08-28 | 2019-04-10 | Halozyme, Inc. | Combination therapy with a hyaluronan-degrading enzyme and an immune checkpoint inhibitor |
| WO2016035006A1 (en) | 2014-09-01 | 2016-03-10 | Dr. Reddy’S Laboratories Limited | Novel nucleotide analogs, process for the preparation of sofosbuvir and its analogs, novel forms of sofosbuvir and solid dispersion of sofosbuvir |
| CA2967368A1 (en) | 2014-11-17 | 2016-05-26 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
| US20170340733A1 (en) | 2014-12-19 | 2017-11-30 | Novartis Ag | Combination therapies |
| US20170360929A1 (en) | 2014-12-23 | 2017-12-21 | Pfizer Inc. | Stable aqueous antibody formulation for anti tnf alpha antibodies |
| KR102644115B1 (ko) | 2014-12-23 | 2024-03-05 | 브리스톨-마이어스 스큅 컴퍼니 | Tigit에 대한 항체 |
| EP3247408A4 (en) | 2015-01-20 | 2018-08-22 | Immunexcite, Inc. | Compositions and methods for cancer immunotherapy |
| AR103726A1 (es) | 2015-02-27 | 2017-05-31 | Merck Sharp & Dohme | Cristales de anticuerpos monoclonales anti-pd-1 humanos |
| WO2016140717A1 (en) | 2015-03-04 | 2016-09-09 | Merck Sharp & Dohme Corp. | Combination of a pd-1 antagonist and a vegfr/fgfr/ret tyrosine kinase inhibitor for treating cancer |
| US20180044418A1 (en) | 2015-03-20 | 2018-02-15 | Merck Sharp & Dohme Corp. | Combination of a pd-1 antagonist and vorinostat for treating cancer |
| CN108136001B (zh) | 2015-04-03 | 2022-07-29 | 佐马技术有限公司 | 使用TGF-β抑制剂和PD-1抑制剂治疗癌症 |
| PE20180394A1 (es) | 2015-04-17 | 2018-02-28 | Bristol Myers Squibb Co | Composiciones que comprenden una combinacion de un anticuerpo anti muerte programada 1 (pd-1) y otro anticuerpo |
| KR20170140316A (ko) | 2015-04-28 | 2017-12-20 | 브리스톨-마이어스 스큅 컴퍼니 | 항-pd-1 항체를 사용한 pd-l1-양성 흑색종의 치료 |
| ES2985394T3 (es) * | 2015-05-29 | 2024-11-05 | Merck Sharp & Dohme Llc | Combinación de un antagonista de PD-1 y un oligonucleótido de tipo CpG-C para el tratamiento del cáncer |
| TWI773646B (zh) | 2015-06-08 | 2022-08-11 | 美商宏觀基因股份有限公司 | 結合lag-3的分子和其使用方法 |
| CN114853891A (zh) | 2015-07-22 | 2022-08-05 | 索伦托药业有限公司 | 与lag3结合的抗体治疗剂 |
| WO2017025498A1 (en) * | 2015-08-07 | 2017-02-16 | Pieris Pharmaceuticals Gmbh | Novel fusion polypeptide specific for lag-3 and pd-1 |
| AU2016307845B2 (en) | 2015-08-14 | 2020-10-15 | Merck Sharp & Dohme Llc | Anti-TIGIT antibodies |
| WO2017040864A1 (en) | 2015-09-01 | 2017-03-09 | First Wave Biopharma | Methods and compositions for treating conditions associated with an abnormal inflammatory responses |
| CN117510633A (zh) | 2015-09-02 | 2024-02-06 | 伊缪泰普有限公司 | 抗lag-3抗体 |
| US20180251548A1 (en) | 2015-09-14 | 2018-09-06 | Compass Therapeutics Llc | Compositions and methods for treating cancer via antagonism of the cd155/tigit pathway and tgf-beta |
| US9995753B2 (en) | 2015-09-25 | 2018-06-12 | Merck Sharp & Dohme Corp. | Anti-pembrolizumab antibodies |
| US20170097333A1 (en) | 2015-09-28 | 2017-04-06 | Merck Sharp & Dohme Corp. | Cell based assay to measure the t-cell stimulating capacity of anti-lag3 antibodies and other agents |
| MX395336B (es) | 2015-09-28 | 2025-03-25 | Suzhou Suncadia Biopharmaceuticals Co Ltd | Preparacion farmaceutica de anticuerpo anti-pd-1 estable y aplicacion del mismo en medicina. |
| DK3356413T3 (da) | 2015-10-01 | 2022-04-11 | Potenza Therapeutics Inc | Anti-tigit-antigenbindingsproteiner og fremgangsmåder til anvendelse deraf |
| US11034765B2 (en) | 2015-10-02 | 2021-06-15 | Symphogen A/S | Anti-PD-1 antibodies and compositions |
| JO3555B1 (ar) | 2015-10-29 | 2020-07-05 | Merck Sharp & Dohme | جسم مضاد يبطل فعالية فيروس الالتهاب الرئوي البشري |
| ES2862425T3 (es) | 2015-11-03 | 2021-10-07 | Janssen Biotech Inc | Formulaciones subcutáneas de anticuerpos anti-CD38 y sus usos |
| US20190010224A1 (en) * | 2015-12-22 | 2019-01-10 | Merck Sharp & Dohme Corp. | Formulations of engineered anti-il-10 antibodies |
| DK3405490T3 (da) | 2016-01-21 | 2022-01-10 | Pfizer | Mono- og bispecifikke antistoffer mod epidermal vækstfaktorreceptor variant iii og cd3 og anvendelser deraf |
| AR107483A1 (es) | 2016-01-29 | 2018-05-02 | Hanmi Pharm Ind Co Ltd | Conjugado de enzimas terapéuticas |
| HUE053452T2 (hu) * | 2016-05-18 | 2021-07-28 | Boehringer Ingelheim Int | Anti-PD-1 és anti-LAG3 antitestek rák kezelésére |
| HUE068801T2 (hu) | 2016-06-14 | 2025-01-28 | Xencor Inc | Bispecifikus kontrollpont-gátló antitestek |
| WO2018091729A2 (en) | 2016-11-21 | 2018-05-24 | Zaklady Farmaceutyczne Polpharma Sa | Aqueous pharmaceutical formulations |
| RS63533B1 (sr) | 2016-12-23 | 2022-09-30 | Serum Institute Of India Pvt Ltd | Postupci za povećanje produktivnosti antitela u kulturi sisarskih ćelija i smanjenje agregacije tokom nishodne obrade, postupci formulacije i rezultujuće stabilne formulacije antitela |
| TWI761453B (zh) | 2017-03-01 | 2022-04-21 | 英商梅迪繆思有限公司 | 抗rsv單株抗體配製物 |
| CN112057419B (zh) | 2017-03-01 | 2023-08-22 | 免疫医疗有限公司 | 单克隆抗体的配制品 |
| AU2018243754B2 (en) | 2017-03-31 | 2025-04-10 | Bristol-Myers Squibb Company | Methods of treating tumor |
| US11603407B2 (en) | 2017-04-06 | 2023-03-14 | Regeneron Pharmaceuticals, Inc. | Stable antibody formulation |
| JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
| BR112019022873A8 (pt) | 2017-05-02 | 2023-04-11 | Merck Sharp & Dohme | Formulação, e, vaso ou dispositivo de injeção. |
| EP3618866A4 (en) | 2017-05-02 | 2021-07-14 | Merck Sharp & Dohme Corp. | STABLE FORMULATIONS OF ANTI-CTLA4 ANTIBODIES ALONE AND IN COMBINATION WITH ANTIBODY ANTI-RECEPTOR PROGRAMMED DEATH 1 (PD-1) AND THEIR METHODS OF USE |
| AU2018261080A1 (en) | 2017-05-02 | 2019-11-07 | Merck Sharp & Dohme Llc | Stable formulations of anti-TIGIT antibodies alone and in combination with programmed death receptor 1 (PD-1) antibodies and methods of use thereof |
| CA3065304A1 (en) | 2017-05-30 | 2018-12-06 | Bristol-Myers Squibb Company | Compositions comprising an anti-lag-3 antibody or an anti-lag-3 antibody and an anti-pd-1 or anti-pd-l1 antibody |
| DK3631454T3 (da) * | 2017-05-30 | 2023-12-04 | Bristol Myers Squibb Co | Behandling af lag-3 positive tumorer |
| AU2018328015A1 (en) | 2017-09-05 | 2020-03-05 | Merck Sharp & Dohme Corp. | Compounds for reducing the viscosity of biological formulations |
| WO2020022791A1 (ko) | 2018-07-25 | 2020-01-30 | (주)알테오젠 | 신규 히알루론산 가수분해 효소 변이체 및 이를 포함하는 약제학적 조성물 |
| CA3116592A1 (en) | 2018-10-31 | 2020-05-07 | Merck Sharp & Dohme Corp. | Anti-human pd-1 antibody crystals and methods of use thereof |
| AU2019374748A1 (en) | 2018-11-05 | 2021-05-27 | Merck Sharp & Dohme Llc | Dosing regimen of anti-LAG3 antibody and combination therapy with anti-PD-1 antibody for treating cancer |
| EP3876978A4 (en) | 2018-11-07 | 2022-09-28 | Merck Sharp & Dohme Corp. | Stable formulations of programmed death receptor 1 (pd-1) antibodies and methods of use thereof |
| JP7503056B6 (ja) | 2018-11-07 | 2024-07-16 | メルク・シャープ・アンド・ドーム・エルエルシー | 抗ｌａｇ３抗体および抗ｐｄ－１抗体の共－製剤 |
| BR112023005377A2 (pt) | 2020-09-24 | 2023-04-25 | Merck Sharp & Dohme Llc | Formulações estáveis de anticorpos de receptor de morte programada 1 (pd-1) e variantes de hialuronidase e fragmentos das mesmas e métodos de uso das mesmas |
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| JP2022512855A (ja) | 2022-02-07 |
| AU2025226754A1 (en) | 2025-09-25 |
| CN113316458B (zh) | 2024-08-02 |
| CN113316458A (zh) | 2021-08-27 |
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