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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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 |
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| CA3118144A1 true CA3118144A1 (en) | 2020-05-14 |
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| CA3118144A Pending CA3118144A1 (en) | 2018-11-07 | 2019-11-06 | Co-formulations of anti-lag3 antibodies and anti-pd-1 antibodies |
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Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2605595C2 (ru) | 2011-06-13 | 2016-12-20 | СиЭсЭл Лимитид | Антитела против g-csfr и их применение |
| 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 |
| 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 |
| PH12022552898A1 (en) * | 2020-06-19 | 2023-12-04 | Sinocelltech Ltd | Stable formulation for recombinant anti-pd-1 monoclonal antibody |
| MX2023001160A (es) * | 2020-07-31 | 2023-02-22 | Jiangsu Hengrui Pharmaceuticals Co Ltd | Composicion farmaceutica del anticuerpo anti-pd-1 y uso del mismo. |
| EP4262750A4 (en) * | 2020-12-16 | 2024-12-04 | CSL Innovation Pty Ltd | Protein formulations and uses thereof |
| CA3206669A1 (en) | 2021-01-29 | 2022-08-04 | Mark A. BROWER | 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 |
| US20240425567A1 (en) * | 2021-10-08 | 2024-12-26 | Invivyd, Inc. | Pharmaceutical formulations comprising anti-coronavirus s protein antibodies and uses thereof |
| AU2023259126A1 (en) * | 2022-04-29 | 2024-10-31 | 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 |
| EP0365685B1 (en) | 1988-03-30 | 1995-01-18 | Toray Industries, Inc. | Freeze-dried composition comprising a horseradish peroxidase-labelled Fab' fragment of an anti-human interferon-beta monclonal antibody and trehalose; EIA kit containing the composition |
| DE68908175T2 (de) | 1988-05-27 | 1994-03-03 | Centocor Inc | Gefriergetrocknete formulierung für antikörperprodukte. |
| WO1994006448A1 (en) | 1992-09-16 | 1994-03-31 | The Scripps Research Institute | Human neutralizing monoclonal antibodies to respiratory syncytial virus |
| US6267958B1 (en) | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| CN1151842C (zh) | 1995-07-27 | 2004-06-02 | 基因技术股份有限公司 | 稳定等渗的冻干蛋白制剂 |
| WO1997010846A1 (en) | 1995-09-18 | 1997-03-27 | Intracel Corporation | Neutralizing monoclonal antibodies to respiratory syncytial virus |
| US20070059302A1 (en) | 1997-04-07 | 2007-03-15 | Genentech, Inc. | Anti-vegf antibodies |
| US6171586B1 (en) | 1997-06-13 | 2001-01-09 | Genentech, Inc. | Antibody formulation |
| JP2002531466A (ja) | 1998-12-01 | 2002-09-24 | プロテイン デザイン ラブス， インコーポレイテッド | γ−インターフェロンに対するヒト化抗体 |
| ES2541470T3 (es) | 1999-02-22 | 2015-07-20 | University Of Connecticut | Formulaciones de factor VIII libres de albúmina |
| WO2000053631A1 (en) | 1999-03-11 | 2000-09-14 | Schering Corporation | Mammalian cytokines; related reagents and methods |
| AU780163B2 (en) | 1999-09-09 | 2005-03-03 | Merck Sharp & Dohme Corp. | Mammalian interleukin-12 P40 and interleukin B30, combinations thereof, antibodies, uses in pharmaceutical compositions |
| US7090847B1 (en) | 1999-09-09 | 2006-08-15 | Schering Corporation | Mammalian cytokines; related reagents and methods |
| WO2001030393A2 (en) * | 1999-10-22 | 2001-05-03 | 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 |
| AU1344102A (en) | 2000-10-12 | 2002-04-22 | Genentech Inc | Reduced-viscosity concentrated protein formulations |
| 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 |
| KR20100031769A (ko) | 2000-12-28 | 2010-03-24 | 알투스 파마슈티컬스 인코포레이티드 | 전항체 및 이의 단편의 결정과 이의 제조 및 사용 방법 |
| GB0113179D0 (en) | 2001-05-31 | 2001-07-25 | Novartis Ag | Organic compounds |
| EP1492554B1 (en) | 2001-06-21 | 2019-08-21 | Althea Technologies, Inc. | Spherical protein particles |
| SG10201603108QA (en) | 2001-06-26 | 2016-05-30 | Amgen Inc | Antibodies To OPGL |
| DE60235013D1 (de) | 2001-07-25 | 2010-02-25 | Facet Biotech Corp | Stabile lyophilisierte pharmazeutische formulierung des igg-antikörpers daclizumab |
| EP1441589B1 (en) | 2001-11-08 | 2012-05-09 | Abbott Biotherapeutics Corp. | Stable liquid pharmaceutical formulation of igg antibodies |
| DE10207178A1 (de) | 2002-02-19 | 2003-09-04 | Novosom Ag | Komponenten für die Herstellung amphoterer Liposomen |
| DK1946776T3 (en) | 2002-02-27 | 2017-03-13 | Immunex Corp | STABILIZED TNFR-FC COMPOSITION COMPREHENSIVE ARGININE |
| AU2003226356A1 (en) | 2002-04-12 | 2003-10-27 | 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 |
| PT1537878E (pt) | 2002-07-03 | 2010-11-18 | Ono Pharmaceutical Co | Composições de imunopotenciação |
| CA2492143A1 (en) | 2002-07-12 | 2004-01-22 | Medarex, Inc. | Methods and compositions for preventing oxidative degradation of proteins |
| US20040033228A1 (en) | 2002-08-16 | 2004-02-19 | Hans-Juergen Krause | Formulation of human antibodies for treating TNF-alpha associated disorders |
| ATE345277T1 (de) | 2002-08-21 | 2006-12-15 | Pharmacia Corp | Injizierbare pharmazeutische suspension in einer phiole mit zwei kammern |
| AU2003265361A1 (en) | 2002-08-28 | 2004-03-19 | 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 |
| AU2003288675B2 (en) | 2002-12-23 | 2010-07-22 | Medimmune Limited | Antibodies against PD-1 and uses therefor |
| WO2004072286A1 (ja) | 2003-01-23 | 2004-08-26 | Ono Pharmaceutical Co., Ltd. | ヒトｐｄ−１に対し特異性を有する物質 |
| WO2004071517A2 (en) | 2003-02-06 | 2004-08-26 | Schering Corporation | Uses of il-23 related reagents |
| EP3417875B1 (en) | 2003-02-10 | 2020-06-17 | Biogen MA Inc. | Immunoglobulin formulation and method of preparation thereof |
| SI1601694T1 (sl) | 2003-03-10 | 2010-01-29 | Schering Corp | Uporabe IL-23 antagonistov; sorodni reagenti |
| MXPA05010555A (es) | 2003-04-04 | 2006-03-09 | Genentech Inc | Formulaciones de proteina y anticuerpo de alta concentracion. |
| CN102940889A (zh) | 2003-05-14 | 2013-02-27 | 伊缪诺金公司 | 药物缀合物组合物 |
| ATE518888T1 (de) | 2003-10-09 | 2011-08-15 | Chugai Pharmaceutical Co Ltd | Stabilisierte lösung mit hoher igm-konzentration |
| US8277810B2 (en) | 2003-11-04 | 2012-10-02 | Novartis Vaccines & Diagnostics, Inc. | Antagonist anti-CD40 antibodies |
| WO2005047324A2 (en) | 2003-11-10 | 2005-05-26 | Schering Corp | ANTI-INTERLEUKIN ANTIBODY-10 |
| DE10355904A1 (de) | 2003-11-29 | 2005-06-30 | Merck Patent Gmbh | Feste Formen von anti-EGFR-Antikörpern |
| US20070184050A1 (en) | 2003-12-25 | 2007-08-09 | Kirin Beer Kabushiki Kaisha | Stable water-based medicinal preparation containing antibody |
| EP3476861A1 (en) | 2004-01-07 | 2019-05-01 | Novartis Vaccines and Diagnostics, Inc. | M-csf-specific monoclonal antibody and uses thereof |
| EP1713502A1 (de) | 2004-02-12 | 2006-10-25 | MERCK PATENT GmbH | Hochkonzentrierte, flüssige formulierungen von anti-egfr-antikörpern |
| JP4903061B2 (ja) | 2004-02-17 | 2012-03-21 | シェーリング コーポレイション | Ｉｌ−２３活性を調節する方法；関連する試薬 |
| WO2005092073A2 (en) | 2004-03-24 | 2005-10-06 | Pdl Biopharma, Inc. | Use of anti-alpha5beta1 antibodies to inhibit cancer cell proliferation |
| CA2562771C (en) | 2004-04-12 | 2013-04-09 | Medimmune, Inc. | Anti-il-9 antibody formulations and uses thereof |
| EP1766396B1 (en) | 2004-06-07 | 2010-08-11 | 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 |
| AP2007003890A0 (en) | 2004-07-30 | 2007-02-28 | Rinat Neuroscience Corp | Antibodies directed against amy-loid-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 |
| JP2008528638A (ja) | 2005-01-28 | 2008-07-31 | ワイス | ポリペプチドの安定化液体処方 |
| 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) |
| WO2006096461A2 (en) | 2005-03-08 | 2006-09-14 | Pharmacia & Upjohn Company Llc | Composition comprising an antibody against macrophage colony-stimulating factor (m-csf) and a chelating agent |
| US7785595B2 (en) | 2005-04-18 | 2010-08-31 | Yeda Research And Development Company Limited | Stabilized anti-hepatitis B (HBV) antibody formulations |
| DE602006021292D1 (de) | 2005-04-22 | 2011-05-26 | Lilly Co Eli | Tgf-beta-1-spezifische antikörper |
| SI2161336T1 (sl) | 2005-05-09 | 2013-11-29 | Ono Pharmaceutical Co., Ltd. | Humana monoklonska protitelesa za programirano smrt 1 (PD-1) in postopki za zdravljenje raka ob uporabi anti-PD-1 protiteles samih ali v kombinaciji z drugimi imunoterapevtiki |
| KR101539545B1 (ko) | 2005-06-07 | 2015-07-24 | 에스바테크 - 어 노바티스 컴파니 엘엘씨 | ＴＮＦα를 억제하는 안정적이고 가용성인 항체 |
| BRPI0611800A2 (pt) | 2005-06-15 | 2008-12-09 | Schering Corp | formulaÇço estÁvel de anticorpo |
| US7491391B2 (en) | 2005-06-30 | 2009-02-17 | Centocor, Inc. | Anti-IL-23 antibodies, compositions, methods and uses |
| EP1909838A2 (en) | 2005-07-29 | 2008-04-16 | Amgen Inc. | Formulations that inhibit protein aggregation |
| KR101566393B1 (ko) | 2005-08-03 | 2015-11-05 | 이뮤노젠 아이엔씨 | 면역접합체 제형 |
| CA2619052A1 (en) | 2005-08-25 | 2007-03-01 | Eli Lily And Company | Anti-il-23 antibiodies |
| SG165322A1 (en) | 2005-08-31 | 2010-10-28 | Schering Corp | Engineered anti-il-23 antibodies |
| EP1933868A2 (en) | 2005-09-12 | 2008-06-25 | NovImmune SA | 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 |
| EP1971366B1 (en) | 2005-12-29 | 2014-07-30 | Janssen Biotech, Inc. | Human anti-il-23 antibodies, compositions, methods and uses |
| KR20080098504A (ko) | 2006-02-03 | 2008-11-10 | 메디뮨 엘엘씨 | 단백질 제제 |
| RU2008142359A (ru) | 2006-03-28 | 2010-05-10 | Ф.Хоффманн-Ля Рош Аг (Ch) | Композиция человеческого моноклонального антитела к igf-1r |
| JP2009534390A (ja) | 2006-04-21 | 2009-09-24 | アムジェン インコーポレイテッド | 生物医薬品製剤のための緩衝剤 |
| US8945564B2 (en) | 2006-04-21 | 2015-02-03 | Novartis Ag | Antagonist anti-CD40 antibody pharmaceutical compositions |
| CA2655372A1 (en) | 2006-06-13 | 2007-12-21 | Zymogenetics, Inc. | Il-17 and il-23 antagonists and methods of using the same |
| EP2081553B1 (en) | 2006-10-06 | 2020-08-12 | Amgen Inc. | Stable antibody formulations |
| EP2094247B1 (en) | 2006-10-20 | 2022-06-29 | Amgen Inc. | Stable polypeptide formulations |
| NZ613356A (en) | 2006-10-27 | 2015-02-27 | Abbvie Biotechnology Ltd | Crystalline anti-htnfalpha antibodies |
| EA017549B1 (ru) | 2006-12-05 | 2013-01-30 | Круселл Холланд Б.В. | Стабильные жидкие композиции антител против вируса бешенства |
| AU2007334499B2 (en) | 2006-12-14 | 2014-04-24 | Merck Sharp & Dohme Corp. | Engineered anti-TSLP antibody |
| EP2129401B8 (en) | 2006-12-21 | 2020-01-15 | Amgen Inc. | Stable buffered formulations containing polypeptides |
| WO2008086395A2 (en) | 2007-01-09 | 2008-07-17 | Wyeth | Anti-il-13 antibody formulations and uses thereof |
| TWI426918B (zh) | 2007-02-12 | 2014-02-21 | Merck Sharp & Dohme | Ｉｌ-２３拮抗劑於治療感染之用途 |
| KR101520110B1 (ko) | 2007-02-23 | 2015-05-18 | 머크 샤프 앤드 돔 코포레이션 | 가공된 항-ＩＬ-23ｐ19 항체 |
| CA2678863A1 (en) | 2007-02-23 | 2008-08-28 | Schering Corporation | Engineered anti-il-23p19 antibodies |
| US8168760B2 (en) | 2007-03-29 | 2012-05-01 | Abbott Laboratories | Crystalline anti-human IL-12 antibodies |
| MX2009010389A (es) | 2007-03-30 | 2010-01-20 | Medimmune Llc | Formulacion de anticuerpos. |
| 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 |
| MX2009014199A (es) | 2007-06-18 | 2010-05-24 | Organon Nv | Anticuerpos para el receptor 1 de muerte programada pd-1 de humano. |
| AU2008269086B2 (en) | 2007-06-25 | 2014-06-12 | Amgen Inc. | Compositions of specific binding agents to hepatocyte growth factor |
| 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 |
| US9308257B2 (en) | 2007-11-28 | 2016-04-12 | 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 |
| NZ586303A (en) | 2007-12-28 | 2012-03-30 | Bioinvent Int Ab | Antibody-containing formulation for the use for treating cardiovascular diseases associated with atherosclerosis |
| JP2011519347A (ja) | 2008-02-07 | 2011-07-07 | アムジエン・インコーポレーテツド | 安定化されたタンパク質組成物 |
| RU2531758C2 (ru) | 2008-02-11 | 2014-10-27 | Куретек Лтд. | Моноклональные антитела для лечения опухолей |
| WO2009120684A1 (en) | 2008-03-25 | 2009-10-01 | Medimmune, Llc | Antibody formulation |
| CA3179151A1 (en) | 2008-04-09 | 2009-10-15 | Genentech, Inc. | Novel compositions and methods for the treatment of immune related diseases |
| AR072001A1 (es) | 2008-06-03 | 2010-07-28 | Abbott Lab | Inmunoglobulina con dominio variable dual y usos de la misma |
| 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 |
| AU2009288419B2 (en) | 2008-08-27 | 2015-08-06 | Merck Sharp & Dohme Llc | Lyophilized formulatons of engineered anti-IL-23p19 antibodies |
| CN102159204B (zh) | 2008-09-19 | 2015-04-01 | 辉瑞公司 | 稳定的液体抗体制剂 |
| KR101581986B1 (ko) | 2008-10-29 | 2016-01-04 | 아블린쓰 엔.브이. | 단일 도메인 항원 결합 분자의 제형 |
| WO2010062372A2 (en) | 2008-11-03 | 2010-06-03 | President And Fellows Of Harvard College | Methods for modulating nf-kb using gibberellins |
| PE20142332A1 (es) | 2008-11-17 | 2015-01-29 | 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 |
| CN102414221A (zh) | 2009-03-06 | 2012-04-11 | 健泰科生物技术公司 | 抗体配制剂 |
| CA2754266A1 (en) | 2009-03-06 | 2010-09-10 | Medimmune, Llc | Humanized anti-cd19 antibody formulations |
| 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 |
| RU2560701C2 (ru) | 2009-05-04 | 2015-08-20 | Эббви Байотекнолоджи Лтд. | Стабильные композиции с высокими концентрациями белков антител человека против tnf-альфа |
| US9155745B2 (en) | 2009-06-16 | 2015-10-13 | Universite De Geneve | Bevacizumab formulations with lower aggregation propensity, comprising corticosteroid anti-inflammatory drugs |
| JP2012530721A (ja) | 2009-06-18 | 2012-12-06 | ワイス・エルエルシー | 小モジュール免疫薬のための凍結乾燥製剤 |
| JP2012533548A (ja) | 2009-07-14 | 2012-12-27 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | 組成物における黄色形成および過酸化物形成を阻害する方法 |
| EP2458990B1 (en) | 2009-07-28 | 2016-03-30 | 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 |
| BR112012004823B1 (pt) | 2009-09-03 | 2021-11-30 | Merck Sharp & Dohme Corp | Anticorpo ou fragmento de ligação de antígeno do mesmo, uso de um anticorpo ou um fragmento de ligação de antígeno do mesmo, e composição farmacêutica |
| 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. |
| MX2012005180A (es) | 2009-11-04 | 2012-06-08 | Merck Sharp & Dohme | Anticuerpo anti-linfopoyetina estromal timica (anti-tslp) modificado por tecnicas de ingenieria genetica. |
| RU2609658C2 (ru) | 2009-12-21 | 2017-02-02 | Дженентек, Инк. | Состав, содержащий антитело |
| KR20120110175A (ko) | 2009-12-29 | 2012-10-09 | 에프. 호프만-라 로슈 아게 | 항체 제제 |
| US20120294866A1 (en) | 2010-01-19 | 2012-11-22 | F. Hoffmann-La Roche Ag | Pharmaceutical formulation for proteins |
| TWI609698B (zh) | 2010-01-20 | 2018-01-01 | Chugai Pharmaceutical Co Ltd | 穩定化的含抗體溶液製劑 |
| NZ602054A (en) | 2010-03-17 | 2014-10-31 | Abbott Res Bv | Anti-nerve growth factor (ngf) antibody compositions |
| KR20130060227A (ko) | 2010-05-03 | 2013-06-07 | 제넨테크, 인크. | 단백질-함유 제제의 점도 감소에 유용한 조성물 및 방법 |
| 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 |
| US8945559B2 (en) | 2010-10-06 | 2015-02-03 | Regeneron Pharmaceuticals, Inc. | Stabilized formulations containing anti-interleukin-4 receptor (IL-4R) antibodies |
| EP2648750B1 (en) | 2010-12-10 | 2017-01-25 | Novartis AG | Antibody formulation |
| CR20160147A (es) | 2011-03-25 | 2016-08-03 | Amgen Inc | Formulaciones de anticuerpos |
| EP3398612A1 (en) * | 2011-03-31 | 2018-11-07 | Merck Sharp & Dohme Corp. | Stable formulations of antibodies to human programmed death receptor pd-1 and related treatments |
| JP2014510152A (ja) | 2011-04-07 | 2014-04-24 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー | 粘度が低減された処方物 |
| UY34105A (es) | 2011-06-03 | 2012-07-31 | Lg Life Sciences Ltd | Formulación líquida estable de etanercept |
| JP6176849B2 (ja) | 2011-07-19 | 2017-08-09 | 中外製薬株式会社 | アルギニンアミドまたはその類似化合物を含む安定なタンパク質含有製剤 |
| AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
| JP6151707B2 (ja) | 2011-10-27 | 2017-06-21 | マサチューセッツ インスティテュート オブ テクノロジー | 薬物内包微小球の形成が可能なｎ−末端で官能基化されたアミノ酸誘導体 |
| MX357393B (es) | 2012-01-23 | 2018-07-06 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti - ang2. |
| 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 |
| US10444520B2 (en) | 2012-04-03 | 2019-10-15 | University Court Of The University Of St Andrews | High resolution imaging of extended volumes |
| EP4039275A1 (en) | 2012-05-03 | 2022-08-10 | Boehringer Ingelheim International GmbH | Anti-il-23p19 antibodies |
| US20140004131A1 (en) | 2012-05-04 | 2014-01-02 | Novartis Ag | Antibody formulation |
| ES2729603T3 (es) | 2012-06-27 | 2019-11-05 | Merck Sharp & Dohme | Anticuerpos IL-23 antihumanos cristalinos |
| BR112014029403A2 (pt) | 2012-07-04 | 2018-10-09 | F. Hoffmann-La Roche Ag | conjugados, anticorpo e formulação farmacêutica |
| FR2994390B1 (fr) | 2012-08-10 | 2014-08-15 | Adocia | Procede d'abaissement de la viscosite de solutions de proteines a concentration elevee |
| WO2014031718A1 (en) | 2012-08-23 | 2014-02-27 | 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 |
| US9649383B2 (en) | 2012-11-19 | 2017-05-16 | Merck Sharp & Dohme Corp. | 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 |
| KR20210024245A (ko) | 2013-03-13 | 2021-03-04 | 시애틀 지네틱스, 인크. | 사이클로덱스트린 및 항체-약물 포합체 제형 |
| 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 |
| JP6595458B2 (ja) * | 2013-09-20 | 2019-10-23 | ブリストル−マイヤーズ スクイブ カンパニー | 腫瘍を処置するための抗ｌａｇ−３抗体と抗ｐｄ−１抗体との組合せ |
| WO2015057541A1 (en) | 2013-10-16 | 2015-04-23 | 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 |
| KR20170052569A (ko) | 2014-07-18 | 2017-05-12 | 어드박시스, 인크. | 전립선암 치료용 pd-1 길항제 및 리스테리아 기반 백신의 병용 |
| 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 |
| SI3179992T1 (sl) | 2014-08-11 | 2022-09-30 | Acerta Pharma B.V. | Terapevtske kombinacije zaviralca BTK, zaviralca PD-1 in/ali zaviralca PD-L1 |
| JO3663B1 (ar) * | 2014-08-19 | 2020-08-27 | Merck Sharp & Dohme | الأجسام المضادة لمضاد lag3 وأجزاء ربط الأنتيجين |
| MY198017A (en) | 2014-08-19 | 2023-07-26 | Merck Sharp & Dohme | Anti-tigit antibodies |
| HUE043847T2 (hu) | 2014-08-28 | 2019-09-30 | Halozyme Inc | Hialuronán-lebontó enzimmel és egy immun checkpoint inhibitorral végzett kombinációs terápia |
| 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 |
| AU2015350242A1 (en) | 2014-11-17 | 2017-06-29 | 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 |
| WO2016103093A1 (en) | 2014-12-23 | 2016-06-30 | Pfizer Inc. | Stable aqueous antibody formulation for anti tnf alpha antibodies |
| CN107207594B (zh) | 2014-12-23 | 2019-05-07 | 百时美施贵宝公司 | 针对tigit的抗体 |
| JP2018502123A (ja) | 2015-01-20 | 2018-01-25 | イミューンエクサイト， インコーポレイテッド | 癌免疫療法のための組成物及び方法 |
| AR103726A1 (es) | 2015-02-27 | 2017-05-31 | Merck Sharp & Dohme | Cristales de anticuerpos monoclonales anti-pd-1 humanos |
| KR20250020678A (ko) | 2015-03-04 | 2025-02-11 | 머크 샤프 앤드 돔 엘엘씨 | 암을 치료하기 위한 pd-1 길항제 및 vegfr/fgfr/ret 티로신 키나제 억제제의 조합 |
| WO2016153839A1 (en) | 2015-03-20 | 2016-09-29 | Merck Sharp & Dohme Corp. | Combination of a pd-1 antagonist and vorinostat for treating cancer |
| ES2820768T3 (es) | 2015-04-03 | 2021-04-22 | Xoma Technology Ltd | Tratamiento del cáncer usando inhibidores de TGF-beta y PD-1 |
| SMT202000442T1 (it) * | 2015-04-17 | 2020-09-10 | Bristol Myers Squibb Co | Composizioni comprendenti una combinazione di ipilimumab e nivolumab |
| JP2018515474A (ja) | 2015-04-28 | 2018-06-14 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 抗ｐｄ−１抗体を使用するｐｄ−ｌ１陽性黒色腫の処置 |
| KR20180014009A (ko) * | 2015-05-29 | 2018-02-07 | 머크 샤프 앤드 돔 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 cpg-c 유형 올리고뉴클레오티드의 조합 |
| 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 |
| TWI733687B (zh) | 2015-07-22 | 2021-07-21 | 美商索倫多醫療公司 | 結合ｌａｇ３之抗體治療劑 |
| EP3331901A1 (en) | 2015-08-07 | 2018-06-13 | 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 |
| EP3344274A4 (en) | 2015-09-01 | 2019-05-22 | First Wave Bio, Inc. | METHOD AND COMPOSITIONS FOR TREATING DISEASES RELATED TO ABNORMAL INFLAMMATORY REACTIONS |
| US11680104B2 (en) | 2015-09-02 | 2023-06-20 | Immutep S.A.S. | Anti-LAG-3 antibodies |
| 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 |
| US10786567B2 (en) * | 2015-09-28 | 2020-09-29 | Suzhou Suncediabiopharmaeuticals Co., Ltd. | Stable anti-PD-1 antibody pharmaceutical preparation and application thereof in medicine |
| RU2729379C1 (ru) | 2015-10-01 | 2020-08-06 | Потенза Терапевтикс, Инк. | Анти-tigit антигенсвязывающие белки и способы их применения |
| LT3368572T (lt) | 2015-10-02 | 2022-07-25 | Symphogen A/S | Anti-pd-1 antikūnai ir kompozicijos |
| JO3555B1 (ar) | 2015-10-29 | 2020-07-05 | Merck Sharp & Dohme | جسم مضاد يبطل فعالية فيروس الالتهاب الرئوي البشري |
| HRP20220680T1 (hr) | 2015-11-03 | 2022-07-08 | Janssen Biotech, Inc. | Potkožne formulacije protutijela anti-cd38 i njihove uporabe |
| WO2017112621A1 (en) | 2015-12-22 | 2017-06-29 | Merck Sharp & Dohme Corp. | Formulations of engineered anti-il-10 antibodies |
| EP3405490B1 (en) | 2016-01-21 | 2021-10-20 | Pfizer Inc. | Mono and bispecific antibodies for epidermal growth factor receptor variant iii and cd3 and their uses |
| AR107483A1 (es) | 2016-01-29 | 2018-05-02 | Hanmi Pharm Ind Co Ltd | Conjugado de enzimas terapéuticas |
| MY193112A (en) * | 2016-05-18 | 2022-09-26 | Boehringer Ingelheim Int | Anti pd-1 and anti-lag3 antibodies for cancer treatment |
| KR102838691B1 (ko) | 2016-06-14 | 2025-07-25 | 젠코어 인코포레이티드 | 이중특이적 체크포인트 억제제 항체 |
| EP3541413A2 (en) | 2016-11-21 | 2019-09-25 | Polpharma Biologics S.A. | Aqueous pharmaceutical formulations |
| CR20190291A (es) | 2016-12-23 | 2019-11-05 | Serum Institute Of India Pvt Ltd | Métodos mejorados para estimular la productividad de anticuerpos en el cultivo de células de mamiferos y reducir la agregación durante los procesos de formulación post-tratamiento (downstream) y formulaciones de anticuerpos estables obtenidas a partir de los mismos |
| WO2018158332A1 (en) | 2017-03-01 | 2018-09-07 | Medimmune Limited | Formulations of monoclonal antibodies |
| TW202228779A (zh) | 2017-03-01 | 2022-08-01 | 英商梅迪繆思有限公司 | 抗rsv單株抗體配製物 |
| KR102775647B1 (ko) | 2017-03-31 | 2025-03-06 | 브리스톨-마이어스 스큅 컴퍼니 | 종양을 치료하는 방법 |
| US11603407B2 (en) | 2017-04-06 | 2023-03-14 | Regeneron Pharmaceuticals, Inc. | Stable antibody formulation |
| 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 |
| JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
| US20200262922A1 (en) | 2017-05-02 | 2020-08-20 | Merck Sharp & Dohme Corp. | Stable formulations of anti-ctla4 antibodies alone and in combination with programmed death receptor 1 (pd-1) antibodies and methods of use thereof |
| 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 |
| JP2020522691A (ja) * | 2017-05-30 | 2020-07-30 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｌａｇ−３陽性腫瘍の処置 |
| AU2018275209A1 (en) | 2017-05-30 | 2019-10-17 | 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 |
| WO2019050780A1 (en) | 2017-09-05 | 2019-03-14 | Merck Sharp & Dohme Corp. | COMPOUNDS FOR REDUCING THE VISCOSITY OF BIOLOGICAL FORMULATIONS |
| CN118755703A (zh) | 2018-07-25 | 2024-10-11 | 阿特根公司 | 新型透明质酸水解酶突变体和包含其的药物组合物 |
| WO2020092233A1 (en) | 2018-10-31 | 2020-05-07 | Merck Sharp & Dohme Corp. | Anti-human pd-1 antibody crystals and methods of use thereof |
| MX2021005266A (es) | 2018-11-05 | 2021-06-18 | Merck Sharp & Dohme Llc | Regimen de dosificacion del anticuerpo anti-gen de activacion de linfocitos 3 (anti-lag3) y terapia combinada con anticuerpo anti-muerte progamada-1 (anti-pd-1) para el tratamiento del 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 |
| JP2023545926A (ja) | 2020-09-24 | 2023-11-01 | メルク・シャープ・アンド・ドーム・エルエルシー | プログラム死受容体１（ｐｄ－１）抗体とヒアルロニダーゼ変異体とそれらのフラグメントとの安定製剤およびその使用方法 |
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| JP7503056B6 (ja) | 2024-07-16 |
| US20220002410A1 (en) | 2022-01-06 |
| CN113316458B (zh) | 2024-08-02 |
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