CA2800769C - Monoclonal antibodies against her2 epitope - Google Patents
Monoclonal antibodies against her2 epitope Download PDFInfo
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- CA2800769C CA2800769C CA2800769A CA2800769A CA2800769C CA 2800769 C CA2800769 C CA 2800769C CA 2800769 A CA2800769 A CA 2800769A CA 2800769 A CA2800769 A CA 2800769A CA 2800769 C CA2800769 C CA 2800769C
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/77—Internalization into the cell
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34918210P | 2010-05-27 | 2010-05-27 | |
| US61/349,182 | 2010-05-27 | ||
| DKPA201000468 | 2010-05-27 | ||
| DKPA201000468 | 2010-05-27 | ||
| PCT/EP2011/058772 WO2011147982A2 (en) | 2010-05-27 | 2011-05-27 | Monoclonal antibodies against her2 epitope |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2800769A1 CA2800769A1 (en) | 2011-12-01 |
| CA2800769C true CA2800769C (en) | 2021-11-02 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2800769A Active CA2800769C (en) | 2010-05-27 | 2011-05-27 | Monoclonal antibodies against her2 epitope |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US9714294B2 (enExample) |
| EP (1) | EP2575880B1 (enExample) |
| JP (2) | JP6082344B2 (enExample) |
| CN (1) | CN103153339B (enExample) |
| CA (1) | CA2800769C (enExample) |
| IL (2) | IL223163A0 (enExample) |
| NZ (1) | NZ604007A (enExample) |
| WO (1) | WO2011147982A2 (enExample) |
Families Citing this family (60)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US9272029B2 (en) | 2009-03-26 | 2016-03-01 | Ibc Pharmaceuticals, Inc. | Interferon lambada-antibody complexes |
| EP2575880B1 (en) * | 2010-05-27 | 2019-01-16 | Genmab A/S | Monoclonal antibodies against her2 epitope |
| CA3051311A1 (en) | 2010-05-27 | 2011-12-01 | Genmab A/S | Monoclonal antibodies against her2 |
| RU2604490C2 (ru) | 2010-11-05 | 2016-12-10 | Займворкс Инк. | ДИЗАЙН УСТОЙЧИВОГО ГЕТЕРОДИМЕРНОГО АНТИТЕЛА С МУТАЦИЯМИ В Fc ДОМЕНЕ |
| AU2012222833B2 (en) | 2011-03-03 | 2017-03-16 | Zymeworks Inc. | Multivalent heteromultimer scaffold design and constructs |
| JP2014514314A (ja) * | 2011-04-20 | 2014-06-19 | ゲンマブ エー／エス | Ｈｅｒ２およびｃｄ３に対する二重特異性抗体 |
| CN103648523A (zh) * | 2011-05-09 | 2014-03-19 | 弗吉尼亚大学专利基金会 | 用于治疗癌症的组合物和方法 |
| UA117901C2 (uk) | 2011-07-06 | 2018-10-25 | Ґенмаб Б.В. | Спосіб посилення ефекторної функції вихідного поліпептиду, його варіанти та їх застосування |
| KR102052774B1 (ko) | 2011-11-04 | 2019-12-04 | 자임워크스 인코포레이티드 | Ｆｃ 도메인 내의 돌연변이를 갖는 안정한 이종이합체 항체 설계 |
| WO2013112801A1 (en) * | 2012-01-26 | 2013-08-01 | Ibc Pharmaceuticals, Inc. | Targeting interferon-lambda with antibodies potently enhances anti-tumor and anti-viral activities |
| JP6849868B2 (ja) * | 2012-05-10 | 2021-03-31 | ザイムワークス，インコーポレイテッド | シングルアーム一価抗体構築物およびその用途 |
| US9499634B2 (en) | 2012-06-25 | 2016-11-22 | Zymeworks Inc. | Process and methods for efficient manufacturing of highly pure asymmetric antibodies in mammalian cells |
| EP3632462A1 (en) | 2012-07-06 | 2020-04-08 | Genmab B.V. | Dimeric protein with triple mutations |
| CN104736174B (zh) | 2012-07-06 | 2019-06-14 | 根马布私人有限公司 | 具有三重突变的二聚体蛋白质 |
| IN2015DN01115A (enExample) | 2012-07-13 | 2015-06-26 | Zymeworks Inc | |
| KR102545617B1 (ko) | 2012-11-28 | 2023-06-20 | 자임워크스 비씨 인코포레이티드 | 가공된 면역글로불린 중쇄-경쇄 쌍 및 이들의 용도 |
| US9914785B2 (en) | 2012-11-28 | 2018-03-13 | Zymeworks Inc. | Engineered immunoglobulin heavy chain-light chain pairs and uses thereof |
| KR20200024345A (ko) | 2013-01-10 | 2020-03-06 | 젠맵 비. 브이 | 인간 IgG1 Fc 영역 변이체 및 그의 용도 |
| US20160114057A1 (en) * | 2013-05-24 | 2016-04-28 | Zyeworks Inc. | Modular protein drug conjugate therapeutic |
| WO2014200891A1 (en) * | 2013-06-11 | 2014-12-18 | THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTEMENT OF HEALTH & HUMAN SERVICES | Her2-specific monoclonal antibodies and conjugates thereof |
| JP6326137B2 (ja) * | 2013-11-19 | 2018-05-16 | 烟台▲榮▼昌生物工程有限公司Ｒｅｍｅｇｅｎ， Ｌｔｄ． | 抗ｈｅｒ２抗体及びその結合体 |
| MX376384B (es) | 2013-11-27 | 2025-03-07 | Zymeworks Bc Inc | Construcciones de union a antigenos biespecificas dirigidas a her2. |
| KR102357961B1 (ko) | 2013-12-17 | 2022-02-08 | 제넨테크, 인크. | 항-cd3 항체 및 이의 사용 방법 |
| JP6510532B2 (ja) | 2013-12-20 | 2019-05-08 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 二重特異性ｈｅｒ２抗体及び使用方法 |
| JP6342517B2 (ja) * | 2014-01-10 | 2018-06-13 | シントン・バイオファーマシューティカルズ・ビー．ブイ．Ｓｙｎｔｈｏｎ Ｂｉｏｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｂ．Ｖ． | 改善されたインビボ抗腫瘍活性を示すデュオカルマイシンａｄｃ |
| EP4014995A1 (en) | 2014-02-28 | 2022-06-22 | Allakos Inc. | Methods and compositions for treating siglec-8 associated diseases |
| CN105017421B (zh) * | 2014-04-16 | 2017-12-26 | 中国人民解放军海军总医院 | 一种抗her2双特异性抗体及其制备方法与应用 |
| EA201692476A1 (ru) | 2014-05-28 | 2017-07-31 | Займворкс Инк. | Модифицированные антигенсвязывающие полипептидные конструкции и их применение |
| TWI695011B (zh) | 2014-06-18 | 2020-06-01 | 美商梅爾莎納醫療公司 | 抗ｈｅｒ２表位之單株抗體及其使用之方法 |
| CN105367657B (zh) * | 2014-08-14 | 2019-09-13 | 上海生物制品研究所有限责任公司 | 抗her3抗体、其制法及其应用 |
| CA2968258A1 (en) | 2014-11-27 | 2016-06-02 | Zymeworks Inc. | Methods of using bispecific antigen-binding constructs targeting her2 |
| CN105985435B (zh) * | 2015-01-30 | 2019-10-15 | 嘉和生物药业有限公司 | 全人源her2抗体的突变抗体及其编码基因和应用 |
| CN104689335B (zh) * | 2015-02-12 | 2017-12-01 | 中国科学院上海高等研究院 | 烯基磺酰胺基作为连接子的抗体药物偶联物及其应用 |
| EP3294772B1 (en) | 2015-05-13 | 2025-11-05 | Zymeworks BC Inc. | Antigen-binding constructs targeting her2 |
| CN107921127B (zh) * | 2015-05-22 | 2022-04-08 | 纪念斯隆-凯特琳癌症中心 | 对于prame肽具有特异性的t细胞受体样抗体 |
| US10323094B2 (en) | 2015-06-16 | 2019-06-18 | Genentech, Inc. | Humanized and affinity matured antibodies to FcRH5 and methods of use |
| EP3322735A4 (en) | 2015-07-15 | 2019-03-13 | Zymeworks Inc. | ACTIVE CONJUGATED BIS-SPECIFIC ANTIGEN-BONDING CONSTRUCTS |
| CA3000869A1 (en) | 2015-10-08 | 2017-04-13 | Zymeworks Inc. | Antigen-binding polypeptide constructs comprising kappa and lambda light chains and uses thereof |
| US10604577B2 (en) | 2015-10-22 | 2020-03-31 | Allakos Inc. | Methods and compositions for treating systemic mastocytosis |
| ITUA20162242A1 (it) * | 2016-04-01 | 2017-10-01 | St Biochimico Italiano Giovanni Lorenzini Spa | Un nuovo anticorpo anti-erbb2 |
| EP3241847A1 (en) | 2016-05-06 | 2017-11-08 | MAB Discovery GmbH | Her-2 binding antibodies |
| EP3534948A1 (en) * | 2016-11-04 | 2019-09-11 | Genentech, Inc. | Treatment of her2-positive breast cancer |
| WO2018093821A1 (en) | 2016-11-15 | 2018-05-24 | Genentech, Inc. | Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies |
| CN108610419B (zh) * | 2016-12-09 | 2020-08-18 | 泰州迈博太科药业有限公司 | 一种人源化抗her2单克隆抗体 |
| JP6971319B2 (ja) | 2016-12-28 | 2021-11-24 | グリーン・クロス・ラブ・セル・コーポレイション | キメラ抗原受容体及びそれを発現するナチュラルキラー細胞 |
| EP3585431A4 (en) * | 2017-02-24 | 2020-12-16 | MacroGenics, Inc. | BISPECIFIC BINDING MOLECULES CAPABLE OF BINDING TO CD137 AND TUMOR ANTIGENS, AND THEIR USES |
| EA201992626A1 (ru) | 2017-05-05 | 2020-04-24 | Аллакос Инк. | Способы и композиции для лечения аллергических заболеваний глаз |
| EP3630841A1 (en) | 2017-06-02 | 2020-04-08 | Pfizer Inc. | Antibodies specific for flt3 and their uses |
| US11517632B2 (en) * | 2017-06-20 | 2022-12-06 | Nanomab Technology Limited | Anti-Her2 single chain antibody and coding sequence and use thereof |
| EP3712178A4 (en) | 2017-11-14 | 2021-08-11 | Green Cross Lab Cell Corporation | ANTI-HER2 ANTIBODIES OR ANTIGIBODY FRAGMENT THEREOF AND CHIMERAIR ANTIGEN RECEPTOR WITH IT |
| US11649294B2 (en) | 2017-11-14 | 2023-05-16 | GC Cell Corporation | Anti-HER2 antibody or antigen-binding fragment thereof, and chimeric antigen receptor comprising same |
| MX2020008289A (es) | 2018-02-08 | 2020-09-25 | Genentech Inc | Moleculas biespecificas de union al antigeno y metodos de uso. |
| AU2019222666B2 (en) | 2018-02-15 | 2025-12-04 | Macrogenics, Inc. | Variant CD3-binding domains and their use in combination therapies for the treatment of disease |
| CN108484772A (zh) * | 2018-04-11 | 2018-09-04 | 中国人民解放军军事科学院军事医学研究院 | 抗her2抗原的人源化抗体h5l5及其应用 |
| MA52945A (fr) | 2018-06-22 | 2021-04-28 | Genmab As | Procédé de production d'un mélange contrôlé d'au moins deux anticorps différents |
| CN110790840A (zh) * | 2018-08-01 | 2020-02-14 | 三生国健药业（上海）股份有限公司 | 结合人her2的抗体、其制备方法和用途 |
| CA3112043A1 (en) | 2018-09-10 | 2020-03-19 | Mirati Therapeutics, Inc. | Combination therapies |
| US20220204644A1 (en) * | 2019-05-02 | 2022-06-30 | Mab Discovery Gmbh | Combination of her2 antibodies |
| US12291575B2 (en) | 2021-05-14 | 2025-05-06 | Genentech, Inc. | Methods for treatment of CD20-positive proliferative disorder with mosunetuzumab and polatuzumab vedotin |
| WO2024183623A1 (zh) * | 2023-03-03 | 2024-09-12 | 盛禾(中国)生物制药有限公司 | 一种抗her2抗体在制备治疗癌症的药物中的用途 |
Family Cites Families (111)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| JPS5896026A (ja) | 1981-10-30 | 1983-06-07 | Nippon Chemiphar Co Ltd | 新規ウロキナ−ゼ誘導体およびその製造法ならびにそれを含有する血栓溶解剤 |
| US4609546A (en) | 1982-06-24 | 1986-09-02 | Japan Chemical Research Co., Ltd. | Long-acting composition |
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| JP3040121B2 (ja) | 1988-01-12 | 2000-05-08 | ジェネンテク，インコーポレイテッド | 増殖因子レセプターの機能を阻害することにより腫瘍細胞を処置する方法 |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US5705157A (en) | 1989-07-27 | 1998-01-06 | The Trustees Of The University Of Pennsylvania | Methods of treating cancerous cells with anti-receptor antibodies |
| US6884418B1 (en) | 1989-08-04 | 2005-04-26 | Berlex Laboratories, Inc. | Use of ligand-mimicking agents and anti-neoplastic drugs in cancer therapy |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| KR100272077B1 (ko) | 1990-08-29 | 2000-11-15 | 젠팜인터내셔날,인코포레이티드 | 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물 |
| US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
| US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| WO1992022645A1 (en) | 1991-06-14 | 1992-12-23 | Genpharm International, Inc. | Transgenic immunodeficient non-human animals |
| JPH06508880A (ja) | 1991-07-08 | 1994-10-06 | ユニバーシティ オブ マサチューセッツ アット アムハースト | サーモトロピック液晶セグメント化ブロックコポリマー |
| US5733743A (en) | 1992-03-24 | 1998-03-31 | Cambridge Antibody Technology Limited | Methods for producing members of specific binding pairs |
| AU6819494A (en) | 1993-04-26 | 1994-11-21 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| US6077835A (en) | 1994-03-23 | 2000-06-20 | Case Western Reserve University | Delivery of compacted nucleic acid to cells |
| US6410690B1 (en) | 1995-06-07 | 2002-06-25 | Medarex, Inc. | Therapeutic compounds comprised of anti-Fc receptor antibodies |
| KR970029803A (ko) | 1995-11-03 | 1997-06-26 | 김광호 | 반도체 메모리장치의 프리차지 회로 |
| PT896586E (pt) | 1996-03-27 | 2007-01-31 | Genentech Inc | Anticorpos de erbb3 |
| JP2001504326A (ja) | 1996-10-18 | 2001-04-03 | ジェネンテック インコーポレーテッド | 抗ＥｒｂＢ２抗体 |
| ZA9811162B (en) | 1997-12-12 | 2000-06-07 | Genentech Inc | Treatment with anti-ERBB2 antibodies. |
| US6417168B1 (en) | 1998-03-04 | 2002-07-09 | The Trustees Of The University Of Pennsylvania | Compositions and methods of treating tumors |
| AU765003B2 (en) | 1998-03-27 | 2003-09-04 | Genentech Inc. | Apo-2 ligand-anti-her-2 antibody synergism |
| CA2347067C (en) | 1998-03-31 | 2013-09-17 | Geron Corporation | Dendritic cell vaccine containing telomerase reverse transcriptase for the treatment of cancer |
| US7244826B1 (en) | 1998-04-24 | 2007-07-17 | The Regents Of The University Of California | Internalizing ERB2 antibodies |
| MXPA01007895A (es) | 1999-02-03 | 2003-07-21 | Biosante Pharmaceuticals Inc | Particulas terapeuticas de fosfato de calcio, metodos de manufactura y usos. |
| EP1187632B1 (en) | 1999-05-14 | 2008-12-03 | Genentech, Inc. | TREATMENT WITH ANTI-ErbB2 ANTIBODIES |
| US6281005B1 (en) | 1999-05-14 | 2001-08-28 | Copernicus Therapeutics, Inc. | Automated nucleic acid compaction device |
| CA2383493C (en) | 1999-06-25 | 2010-08-10 | Genentech, Inc. | Treating prostate cancer with anti-erbb2 antibodies |
| EP2977063A1 (en) | 1999-06-25 | 2016-01-27 | Genentech, Inc. | Methods of treatment using anti-ErbB antibody-maytansinoid conjugates |
| US6949245B1 (en) | 1999-06-25 | 2005-09-27 | Genentech, Inc. | Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies |
| GEP20104998B (en) | 1999-06-25 | 2010-06-10 | Genentech Inc | Humanized antibody which binds erbb2 and blocks activation by ligand receptor of erbb2 (variants) and use of the composition comprising these antibodies methods for treating cancer |
| HK1049014A1 (zh) | 1999-07-29 | 2003-04-25 | Medarex, Inc. | 抗her2/neu的人类单克隆抗体 |
| EP1212422B1 (en) | 1999-08-24 | 2007-02-21 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
| IL152656A0 (en) | 2000-05-19 | 2003-06-24 | Genentech Inc | Gene detection assay for improving the likelihood of an effective response to an erbb antagonist cancer therapy |
| AU2002235141A1 (en) | 2000-11-27 | 2002-06-03 | Geron Corporation | Glycosyltransferase vectors for treating cancer |
| DK1354034T3 (da) | 2000-11-30 | 2008-03-25 | Medarex Inc | Transgene transchromosomale gnavere til fremstilling af humane antistoffer |
| EP1243276A1 (en) | 2001-03-23 | 2002-09-25 | Franciscus Marinus Hendrikus De Groot | Elongated and multiple spacers containing activatible prodrugs |
| US6989452B2 (en) | 2001-05-31 | 2006-01-24 | Medarex, Inc. | Disulfide prodrugs and linkers and stabilizers useful therefor |
| WO2003062375A2 (en) | 2001-12-19 | 2003-07-31 | Genentech, Inc. | Stabilizing polypeptides which have been exposed to urea |
| US7332585B2 (en) | 2002-04-05 | 2008-02-19 | The Regents Of The California University | Bispecific single chain Fv antibody molecules and methods of use thereof |
| WO2003101491A1 (en) | 2002-06-03 | 2003-12-11 | Mitsubishi Pharma Corporation | PREVENTIVES AND/OR REMEDIES FOR SUBJECTS WITH THE EXPRESSION OR ACTIVATION OF Her2 AND/OR EGFR |
| HUE025086T2 (en) | 2002-10-10 | 2016-02-29 | Merck Patent Gmbh | Pharmaceutical preparations for ERB-B1 receptor |
| CA2506080A1 (en) | 2002-11-14 | 2004-05-27 | Syntarga B.V. | Prodrugs built as multiple self-elimination-release spacers |
| US7309486B1 (en) | 2002-11-15 | 2007-12-18 | Mark Zamoyski | HER cancer protocols |
| WO2005034733A2 (en) | 2003-10-08 | 2005-04-21 | North Shore-Long Island Jewish Research Institute | Methods and compositions for diagnosis and treatment of b cell chronic lymphocytic leukemia |
| WO2005063816A2 (en) | 2003-12-19 | 2005-07-14 | Genentech, Inc. | Monovalent antibody fragments useful as therapeutics |
| ES2526343T3 (es) * | 2004-06-03 | 2015-01-09 | Novimmune Sa | Anticuerpos anti-CD3 y métodos de uso de los mismos |
| KR20070034512A (ko) | 2004-06-18 | 2007-03-28 | 암브룩스, 인코포레이티드 | 신규 항원-결합 폴리펩티드 및 이의 용도 |
| AU2005287404B2 (en) | 2004-07-22 | 2009-05-07 | Genentech, Inc. | HER2 antibody composition |
| EP1810979B1 (en) | 2004-09-22 | 2012-06-20 | Kyowa Hakko Kirin Co., Ltd. | STABILIZED HUMAN IgG4 ANTIBODIES |
| AU2005314127A1 (en) | 2004-12-07 | 2006-06-15 | Genentech, Inc. | Selecting patients for therapy with a HER inhibitor |
| GB0503546D0 (en) * | 2005-02-21 | 2005-03-30 | Hellenic Pasteur Inst | Antibody |
| CN103251946A (zh) | 2005-02-23 | 2013-08-21 | 健泰科生物技术公司 | 使用her二聚化抑制剂在癌症患者中延长病情进展前时间或存活 |
| WO2006113643A2 (en) * | 2005-04-20 | 2006-10-26 | Amgen Fremont Inc. | High affinity fully human monoclonal antibodies to interleukin-8 and epitopes for such antibodies |
| MX2007013200A (es) | 2005-04-22 | 2008-03-24 | Johnson & Johnson | Composicion de inmunoliposoma para el direccionamiento hacia un receptor de la celula her2. |
| AU2006277117B2 (en) | 2005-08-05 | 2013-01-10 | Syntarga B.V. | Triazole-containing releasable linkers and conjugates comprising the same |
| AR056142A1 (es) | 2005-10-21 | 2007-09-19 | Amgen Inc | Metodos para generar el anticuerpo igg monovalente |
| US10155816B2 (en) | 2005-11-28 | 2018-12-18 | Genmab A/S | Recombinant monovalent antibodies and methods for production thereof |
| BRPI0707426A2 (pt) | 2006-02-02 | 2011-05-03 | Syntarga Bv | composto, conjugado, uso de um composto, composição farmacêutica, processo para preparar uma composição farmacêutica, e, métodos de tratamento de um mamìfero estando em necessidade do mesmo, e de tratamento ou prevenção de um tumor em um mamìfero |
| EP2975057A1 (en) * | 2006-07-10 | 2016-01-20 | Fujita Health University | Novel anti-cd73 antibody |
| ES2661952T3 (es) * | 2006-08-04 | 2018-04-04 | Medimmune Limited | Anticuerpos humanos contra ERBB2 |
| MY150756A (en) | 2006-08-21 | 2014-02-28 | Hoffmann La Roche | Tumor theraphy with an anti-vegf antibody |
| WO2008031531A1 (en) | 2006-09-15 | 2008-03-20 | F. Hoffmann-La Roche Ag | Tumor therapy with a combination of anti-her2 antibodies |
| EP2126117A2 (en) | 2007-01-18 | 2009-12-02 | University Of Southern California | Gene polymorphisms predictive for dual tki therapy |
| WO2008097229A1 (en) | 2007-02-09 | 2008-08-14 | The Government Of The Usa As Represented By The Secretary Of The Dept. Of Health And Human Services | Method for spectroscopic quantitation of her-2 in biological samples |
| PE20090681A1 (es) | 2007-03-02 | 2009-06-10 | Genentech Inc | Prediccion de respuesta a un inhibidor her |
| CA2681790A1 (en) | 2007-03-30 | 2008-10-09 | F. Hoffmann-La Roche Ag | Composition of labeled and non-labeled monoclonal antibodies |
| EP1980626A1 (en) | 2007-04-13 | 2008-10-15 | Het Nederlands Kanker Instituut | Involvement of lipid kinase, and signal transduction pathway comprising said lipid kinase, in resistance to HER2-targeting therapy |
| EP2851091B1 (en) | 2007-04-13 | 2017-12-27 | Dana-Farber Cancer Institute, Inc. | Methods for treating cancer resistant to ERBB therapeutics |
| JP2010525326A (ja) | 2007-04-19 | 2010-07-22 | ウェルスタット バイオロジックス コーポレイション | 分離されていない循環癌細胞由来のＨｅｒ−２／ｎｅｕタンパク質の上昇したレベルの検出および治療 |
| WO2008150485A2 (en) | 2007-05-29 | 2008-12-11 | Wyeth | Erbb2 binding proteins and use thereof |
| WO2008145142A1 (en) | 2007-05-31 | 2008-12-04 | Genmab A/S | Stable igg4 antibodies |
| US8529901B2 (en) | 2007-06-06 | 2013-09-10 | Hoffmann-La Roche, Inc. | Composition of a first non-labeled monoclonal antibody binding to a tumor antigen and a non-cross reactive second monoclonal antibody labeled with a NIR fluorescence label |
| ES2417148T3 (es) | 2007-06-08 | 2013-08-06 | Genentech, Inc. | Marcadores de expresión génica de la resistencia tumoral al tratamiento con inhibidor de HER2 |
| DE102007031818A1 (de) | 2007-07-07 | 2009-01-08 | Daimler Ag | Windschutzeinrichtung |
| US8680293B2 (en) | 2007-08-01 | 2014-03-25 | Syntarga B.V. | Substituted CC-1065 analogs and their conjugates |
| US9693539B2 (en) | 2007-08-10 | 2017-07-04 | E. R. Squibb & Sons, L.L.C. | HCO32 and HCO27 and related examples |
| WO2009026681A1 (en) | 2007-08-24 | 2009-03-05 | University Health Network | Methods of inhibiting tumor growth using beta 5 integrin antagonists |
| US20110256142A1 (en) | 2007-09-06 | 2011-10-20 | Genmab A/S | Novel methods and antibodies for treating cancer |
| WO2009055074A2 (en) | 2007-10-25 | 2009-04-30 | Wyeth | Erbb2 binding proteins and use thereof |
| GB0722704D0 (en) | 2007-11-20 | 2007-12-27 | Cadbury Schweppes Plc | Confectionery product |
| CN101970490A (zh) | 2007-11-27 | 2011-02-09 | 埃博灵克斯股份有限公司 | 针对异二聚体细胞因子和/或其受体的氨基酸序列以及包括所述氨基酸序列的多肽 |
| US20110020329A1 (en) * | 2007-11-30 | 2011-01-27 | Bristol-Myers Squibb Company | Conjugates of anti-rg-1 antibodies |
| TWI472339B (zh) | 2008-01-30 | 2015-02-11 | Genentech Inc | 包含結合至ｈｅｒ２結構域ii之抗體及其酸性變異體的組合物 |
| EP2240203B1 (en) | 2008-02-05 | 2014-04-09 | Bristol-Myers Squibb Company | Alpha 5 - beta 1 antibodies and their uses |
| WO2009105230A2 (en) | 2008-02-21 | 2009-08-27 | The Regents Of The University Of Colorado | Methods for treating cancer using combination therapy |
| CN102076865B (zh) | 2008-05-02 | 2016-03-16 | 西雅图基因公司 | 用于制造核心岩藻糖基化降低的抗体和抗体衍生物的方法和组合物 |
| JP2010006705A (ja) * | 2008-06-13 | 2010-01-14 | Atlas Antibodies Ab | Ｈｅｒ２サブセット |
| BRPI0812682A2 (pt) | 2008-06-16 | 2010-06-22 | Genentech Inc | tratamento de cáncer de mama metastático |
| ES2628108T3 (es) | 2008-09-03 | 2017-08-01 | F. Hoffmann-La Roche Ag | Anticuerpos multiespecíficos |
| CN101721700A (zh) | 2008-10-15 | 2010-06-09 | 哈药集团生物工程有限公司 | 一种抗人Her2抗体的冻干制剂 |
| WO2010070117A1 (en) | 2008-12-18 | 2010-06-24 | Universite Libre De Bruxelles | Treatment method by the administration of anti-her2 targeted active compounds to patients with early breast cancer and her2-negative primary tumor |
| CN101633695B (zh) | 2009-04-15 | 2012-12-12 | 北京天广实生物技术股份有限公司 | 基于erbB2蛋白胞外区C-端功能表位特征设计抗erbB2功能抗体 |
| US8446101B2 (en) | 2009-07-20 | 2013-05-21 | Gallen Ka Leung Tsui | Control switch |
| CN110066339A (zh) * | 2010-04-20 | 2019-07-30 | 根马布股份公司 | 含异二聚体抗体fc的蛋白及其制备方法 |
| CA3051311A1 (en) | 2010-05-27 | 2011-12-01 | Genmab A/S | Monoclonal antibodies against her2 |
| EP2575880B1 (en) * | 2010-05-27 | 2019-01-16 | Genmab A/S | Monoclonal antibodies against her2 epitope |
| JP6177231B2 (ja) * | 2011-04-20 | 2017-08-09 | ゲンマブ エー／エス | Ｈｅｒ２に対する二重特異性抗体 |
| JP2014514314A (ja) * | 2011-04-20 | 2014-06-19 | ゲンマブ エー／エス | Ｈｅｒ２およびｃｄ３に対する二重特異性抗体 |
| US20140170148A1 (en) * | 2011-04-20 | 2014-06-19 | Genmab A/S | Bispecific antibodies against her2 |
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| CA2800769A1 (en) | 2011-12-01 |
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| US9714294B2 (en) | 2017-07-25 |
| US20210122830A1 (en) | 2021-04-29 |
| EP2575880B1 (en) | 2019-01-16 |
| US20180022816A1 (en) | 2018-01-25 |
| WO2011147982A3 (en) | 2012-03-15 |
| NZ604007A (en) | 2015-03-27 |
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