JP6864953B2 - Axlに対するヒトモノクローナル抗体 - Google Patents
Axlに対するヒトモノクローナル抗体 Download PDFInfo
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- JP6864953B2 JP6864953B2 JP2017530761A JP2017530761A JP6864953B2 JP 6864953 B2 JP6864953 B2 JP 6864953B2 JP 2017530761 A JP2017530761 A JP 2017530761A JP 2017530761 A JP2017530761 A JP 2017530761A JP 6864953 B2 JP6864953 B2 JP 6864953B2
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- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
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- A—HUMAN NECESSITIES
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- 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
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- C—CHEMISTRY; METALLURGY
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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Description
本発明は、AXLに対するヒトモノクローナル抗体及び抗体−薬剤コンジュゲートを提供する。特に、本発明の抗体は、完全にヒト抗体であり、ヒトAXLに対して高い親和性で結合し、マウス型とヒト型とのAXL間で交叉反応することができ、レセプターの内部移行及び分解を誘引し、このレセプターのホモ二量体化を支持することができ、AXLのリン酸化を阻害し、in vitroにおける細胞増殖を阻害し、抵抗性AXL過剰発現CML細胞及びイマチニブ抵抗性GIST細胞のニロチニブに対する感受性を回復させ、in nivoにおける腫瘍成長を低下させるような、1つ以上の機能性により特徴付けられる。特に、本発明は、実施例に記載されたD4抗体から得られた抗体を提供する。
D4のL−CDR2は、配列番号:2における、52位のアミノ酸残基から58位のアミノ酸残基の範囲の配列により定義される。
シクロアルケニル会合残基F、H、W、及びY
疎水性残基A、C、F、G、H、I、L、M、R、T、V、W、及びY
負に荷電した残基D及びE
極性残基C、D、E、H、K、N、Q、R、S、及びT
正に荷電した残基H、K、及びR
小型残基A、C、D、G、N、P、S、T、及びV
非常に小型の残基A、G、及びS
ターン形成に関わる残基A、C、D、E、G、H、K、N、Q、R、S、P、及びT
フレキシブルな残基Q、T、K、S、G、P、D、E、及びR
−F(ab’)2フラグメント(同フラグメントは、ヒンジ領域においてジスルフィド架橋により連結された、2つのFabフラグメントを含む二価のフラグメントである。これらは、例えば、全長抗体をペプシンで処理することにより生成することができる)、
−Fab’又はFabフラグメント(同フラグメントは、VL、VH、CL、及びCH1ドメインからなる一価のフラグメントである。Fabフラグメントは、例えば、IgG抗体をパパインで処理することにより得ることができる。Fab’フラグメントは、例えば、F(ab’)2フラグメントのジスルフィド架橋を、還元剤、例えば、ジチオスレイトールを使用して還元することにより得ることができる)、
−Fdフラグメント(同フラグメントは、VH及びCH1ドメインから本質的になる)、
−Fvフラグメント(同フラグメントは、抗体の1つのアームのVL及びVHドメインとその一本鎖抗体とから本質的になる。一本鎖抗体(一本鎖Fv(scFv)抗体としても公知)は、FvフラグメントのVL及びVHドメインが、リコンビナント法を使用して、これらのドメインを1つのタンパク質鎖として発現させることができる合成リンカーにより連結されている構築物である。同構築物中において、VL及びVH領域ペアは、一価の分子を形成する(例えば、Bird et al., Science 242, 423-426 (1988)及びHuston et al., PNAS USA 85, 5879-5883 (1988)を参照のこと))、
−配列番号:1又は配列番号:2のVL又はVH鎖ならびに配列番号:1又は配列番号:2に対して少なくとも70%の同一性を有するアミノ酸配列を含むか、又は、これらからなるフラグメント
本発明者らは、AXLレセプターの細胞外ドメインに特異的な完全なヒトmAbを、研究室において生成し、細胞膜表面上でAXLレセプターの内部移行及び分解を誘引可能であり(図1)、マウス型とヒト型とのAXL間で交叉反応可能(図6)なもの(すなわち、D4ヒトモノクローナル抗体)をスクリーニングしてきた。この抗体は、このレセプターのホモ二量体化を誘引可能である(図2)。その結果として、このmAbで処理した腫瘍細胞は、その細胞表面におけるAXLレセプターの存在を劇的に減少させるのを示した。処理された細胞は、GAS6(AXLの天然リガンド)に対して応答できない。これにより、AXLリン酸化の阻害及びin vitroにおける細胞増殖の強力な阻害ももたらされた。本発明者らは、本発明者らの抗AXL mAbによる処理により、抵抗性AXL過剰発現CML細胞のニロチニブに対する感受性が回復されることを証明した(図3)。さらに、同じ効果は、処理されたイマチニブ抵抗性GIST細胞において観察された(図4)。
全てのin vivoにおける実験を、French guidelines for experimental animal studies(協定番号C34-172-27)に遵守して行った。6週齢のメスの無胸腺ヌードマウスを、Harlanから購入した。膵臓ガン細胞(3.5×106個、BXPC3)を、無胸腺ヌードマウスの右腹部に移植した。担ガンマウスを、腫瘍が体積約100mm3に達した時点で、種々の処置群にランダム化した。マウスを、媒体(0.9% NaCl);マウス抗AXLモノクローナル抗体20G7−D9(D9)、又は、注入あたりに300μg ヒトモノクローナル抗体D4単独(4週間連続で1週間に2回)の腹腔内注入により処置した。腫瘍体積を、カリパーにより、1週間に1回測定した。抗AXL抗体、及び特に、ヒト抗体D4は、膵臓異種移植片の腫瘍成長を低下させる(図5)。
この出願全体を通して、種々の参考文献が、本発明が属する技術水準を説明している。これらの参考文献の開示は、参照により、本開示に組み入れられる。
Claims (14)
- −配列番号:1における、31位のアミノ酸残基から35位のアミノ酸残基の範囲の配列により定義されるH−CDR1、
−配列番号:1における、50位のアミノ酸残基から66位のアミノ酸残基の範囲の配列により定義されるH−CDR2、及び
−配列番号:1における、99位のアミノ酸残基から108位のアミノ酸残基の範囲の配列により定義されるH−CDR3
を含む重鎖、及び
−配列番号:2における、23位のアミノ酸残基から36位のアミノ酸残基の範囲の配列により定義されるL−CDR1、
−配列番号:2における、52位のアミノ酸残基から58位のアミノ酸残基の範囲の配列により定義されるL−CDR2、及び
−配列番号:2における、91位のアミノ酸残基から100位のアミノ酸残基の範囲の配列により定義されるL−CDR3
を含む軽鎖を含む、AXLに対するヒトモノクローナル抗体。 - 配列番号:1に対して少なくとも70%の同一性を有する重鎖と、配列番号:2に対して少なくとも70%の同一性を有する軽鎖とを含む抗体である、請求項1記載のヒトモノクローナル抗体。
- 配列番号:1に同一の重鎖を含む抗体である、請求項1記載のヒトモノクローナル抗体。
- 配列番号:2に同一の軽鎖を含む抗体である、請求項1記載のヒトモノクローナル抗体。
- 配列番号:1に同一の重鎖と、配列番号:2に同一の軽鎖とを含む抗体である、請求項1記載のヒトモノクローナル抗体。
- Fv、Fab、F(ab’)2、Fab’、dsFv、scFv、及びsc(Fv)2からなる群より選択される、請求項1記載のヒトモノクローナル抗体のフラグメント。
- 請求項1記載のヒトモノクローナル抗体の重鎖及び軽鎖をコードする、
核酸分子。 - 請求項7記載の核酸分子を含む、
ベクター。 - 請求項7記載の核酸分子又は請求項8記載のベクターを含む、
ホスト細胞。 - サイトトキシン、化学療法剤、サイトカイン、免疫抑制剤、免疫刺激剤、溶解型ペプチド、及び放射性同位体からなる群より選択される治療部分にコンジュゲートしている、請求項1記載のヒトモノクローナル抗体。
- オーリスタチンにコンジュゲートしている、請求項10記載のヒトモノクローナル抗体。
- 医薬として使用するための、請求項1又は10記載のヒトモノクローナル抗体。
- ガンの処置を必要とする対象においてガンを処置する方法における使用のための、請求項1又は10記載のヒトモノクローナル抗体。
- 請求項1又は10記載のヒトモノクローナル抗体を含む、
医薬組成物。
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EP14306982 | 2014-12-09 | ||
EP14306982.1 | 2014-12-09 | ||
PCT/EP2015/079003 WO2016091891A1 (en) | 2014-12-09 | 2015-12-08 | Human monoclonal antibodies against axl |
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JP6864953B2 true JP6864953B2 (ja) | 2021-04-28 |
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EP (1) | EP3229836B1 (ja) |
JP (1) | JP6864953B2 (ja) |
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Families Citing this family (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2015286569B2 (en) | 2014-07-11 | 2021-04-15 | Genmab A/S | Antibodies binding AXL |
GB201610902D0 (en) | 2016-06-22 | 2016-08-03 | Bergen Teknologioverforing As And Bergenbio As | Anti-Axl Antagonistic Antibodies |
EP3481868A1 (en) * | 2016-07-08 | 2019-05-15 | Genmab A/S | New dosage regimens for antibody drug conjugates based on anti-axl antibodies |
NZ758119A (en) * | 2017-04-14 | 2024-03-22 | Tallac Therapeutics Inc | Immunomodulating polynucleotides, antibody conjugates thereof, and methods of their use |
EP3498293A1 (en) | 2017-12-15 | 2019-06-19 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Treatment of monogenic diseases with an anti-cd45rc antibody |
CN110483639A (zh) | 2018-05-15 | 2019-11-22 | 复旦大学 | 靶向axl的抗体及抗体-药物偶联物及其制备方法和用途 |
CN113045664B (zh) * | 2019-11-28 | 2023-05-12 | 尚健单抗(北京)生物技术有限公司 | 一种分离的结合抗原axl的蛋白及其用途 |
CA3169523A1 (en) | 2020-02-28 | 2021-09-02 | Jaume Pons | Transglutaminase-mediated conjugation |
CN116715774B (zh) * | 2023-05-12 | 2023-11-24 | 武汉爱博泰克生物科技有限公司 | 针对人axl的兔单克隆抗体及其制备方法和应用 |
Family Cites Families (145)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CU22545A1 (es) | 1994-11-18 | 1999-03-31 | Centro Inmunologia Molecular | Obtención de un anticuerpo quimérico y humanizado contra el receptor del factor de crecimiento epidérmico para uso diagnóstico y terapéutico |
US4943533A (en) | 1984-03-01 | 1990-07-24 | The Regents Of The University Of California | Hybrid cell lines that produce monoclonal antibodies to epidermal growth factor receptor |
EP0154316B1 (en) | 1984-03-06 | 1989-09-13 | Takeda Chemical Industries, Ltd. | Chemically modified lymphokine and production thereof |
US4861719A (en) | 1986-04-25 | 1989-08-29 | Fred Hutchinson Cancer Research Center | DNA constructs for retrovirus packaging cell lines |
EP0307434B2 (en) | 1987-03-18 | 1998-07-29 | Scotgen Biopharmaceuticals, Inc. | Altered antibodies |
US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
GB8725529D0 (en) | 1987-10-30 | 1987-12-02 | Delta Biotechnology Ltd | Polypeptides |
US5278056A (en) | 1988-02-05 | 1994-01-11 | The Trustees Of Columbia University In The City Of New York | Retroviral packaging cell lines and process of using same |
DE68921982T4 (de) | 1988-06-14 | 1996-04-25 | Cetus Oncology Corp | Kupplungsmittel und sterisch gehinderte, mit disulfid gebundene konjugate daraus. |
DE68925966T2 (de) | 1988-12-22 | 1996-08-29 | Kirin Amgen Inc | Chemisch modifizierte granulocytenkolonie erregender faktor |
CA2066428C (en) | 1989-09-08 | 2000-11-28 | Bert Vogelstein | Structural alterations of the egf receptor gene in human gliomas |
US5670488A (en) | 1992-12-03 | 1997-09-23 | Genzyme Corporation | Adenovirus vector for gene therapy |
US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
US5635483A (en) | 1992-12-03 | 1997-06-03 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Tumor inhibiting tetrapeptide bearing modified phenethyl amides |
US5780588A (en) | 1993-01-26 | 1998-07-14 | Arizona Board Of Regents | Elucidation and synthesis of selected pentapeptides |
US5618829A (en) | 1993-01-28 | 1997-04-08 | Mitsubishi Chemical Corporation | Tyrosine kinase inhibitors and benzoylacrylamide derivatives |
CA2156725A1 (en) | 1993-02-22 | 1994-09-01 | Warren S. Pear | Production of high titer helper-free retroviruses by transient transfection |
US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
JPH08511420A (ja) | 1993-06-16 | 1996-12-03 | セルテック・セラピューテイクス・リミテッド | 抗 体 |
JPH09500125A (ja) | 1993-07-15 | 1997-01-07 | キャンサー リサーチ キャンペーン テクノロジー リミテッド | タンパク質チロシンキナーゼインヒビターのプロドラッグ |
FR2712812B1 (fr) | 1993-11-23 | 1996-02-09 | Centre Nat Rech Scient | Composition pour la production de produits thérapeutiques in vivo. |
ATE207366T1 (de) | 1993-12-24 | 2001-11-15 | Merck Patent Gmbh | Immunokonjugate |
US5804396A (en) | 1994-10-12 | 1998-09-08 | Sugen, Inc. | Assay for agents active in proliferative disorders |
US5663149A (en) | 1994-12-13 | 1997-09-02 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Human cancer inhibitory pentapeptide heterocyclic and halophenyl amides |
IL116816A (en) | 1995-01-20 | 2003-05-29 | Rhone Poulenc Rorer Sa | Cell for the production of a defective recombinant adenovirus or an adeno-associated virus and the various uses thereof |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
US6121022A (en) | 1995-04-14 | 2000-09-19 | Genentech, Inc. | Altered polypeptides with increased half-life |
US5639757A (en) | 1995-05-23 | 1997-06-17 | Pfizer Inc. | 4-aminopyrrolo[2,3-d]pyrimidines as tyrosine kinase inhibitors |
CA2222231A1 (en) | 1995-06-07 | 1996-12-19 | Imclone Systems Incorporated | Antibody and antibody fragments for inhibiting the growth of tumors |
US6013516A (en) | 1995-10-06 | 2000-01-11 | The Salk Institute For Biological Studies | Vector and method of use for nucleic acid delivery to non-dividing cells |
PL190489B1 (pl) | 1996-04-12 | 2005-12-30 | Warner Lambert Co | Nieodwracalne inhibitory kinaz tyrozyny, kompozycja farmaceutyczna je zawierająca i ich zastosowanie |
US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
US6235883B1 (en) | 1997-05-05 | 2001-05-22 | Abgenix, Inc. | Human monoclonal antibodies to epidermal growth factor receptor |
ZA986732B (en) | 1997-07-29 | 1999-02-02 | Warner Lambert Co | Irreversible inhibitiors of tyrosine kinases |
US6100254A (en) | 1997-10-10 | 2000-08-08 | Board Of Regents, The University Of Texas System | Inhibitors of protein tyrosine kinases |
US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
AU3657899A (en) | 1998-04-20 | 1999-11-08 | James E. Bailey | Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity |
HUP0104865A3 (en) | 1999-01-15 | 2004-07-28 | Genentech Inc | Polypeptide variants with altered effector function |
US6740665B1 (en) | 1999-02-10 | 2004-05-25 | Ramachandran Murali | Tyrosine kinase inhibitors and methods of using the same |
US6245759B1 (en) | 1999-03-11 | 2001-06-12 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
EP2275540B1 (en) | 1999-04-09 | 2016-03-23 | Kyowa Hakko Kirin Co., Ltd. | Method for controlling the activity of immunologically functional molecule |
US6498165B1 (en) | 1999-06-30 | 2002-12-24 | Merck & Co., Inc. | Src kinase inhibitor compounds |
AU6605200A (en) | 1999-06-30 | 2001-01-31 | Merck & Co., Inc. | Src kinase inhibitor compounds |
CA2376951A1 (en) | 1999-06-30 | 2001-01-04 | Peter J. Sinclair | Src kinase inhibitor compounds |
BR0013899A (pt) | 1999-09-10 | 2003-07-08 | Merck & Co Inc | Composto, composição farmacêutica, processos de tratamento ou prevenção de câncer, de uma doença em que a angiogênese esteja implicada, da vascularização retinal, da retinopatia diabética, da degeneração macular relacionada a idade, de doenças inflamatórias, de uma doença ou condições dependentes da tirosina quinase, de patologias associadas com ossos, e, processos para produzir uma composição farmacêutica, e de reduzir ou prevenir dano tecidual em seguida a um evento isquêmico cerebral |
IL148891A0 (en) | 1999-10-19 | 2002-09-12 | Merck & Co Inc | Tyrosine kinase inhibitors |
AU778042B2 (en) | 1999-10-19 | 2004-11-11 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
US6794393B1 (en) | 1999-10-19 | 2004-09-21 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
US6420382B2 (en) | 2000-02-25 | 2002-07-16 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
US6313138B1 (en) | 2000-02-25 | 2001-11-06 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
KR100787073B1 (ko) | 2000-06-28 | 2007-12-21 | 글리코파이, 인크. | 변형된 당단백질의 제조방법 |
US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
US6599902B2 (en) | 2001-05-30 | 2003-07-29 | Sugen, Inc. | 5-aralkysufonyl-3-(pyrrol-2-ylmethylidene)-2-indolinone derivatives as kinase inhibitors |
JP2004535437A (ja) | 2001-06-22 | 2004-11-25 | メルク エンド カムパニー インコーポレーテッド | チロシンキナーゼ阻害剤 |
US6958340B2 (en) | 2001-08-01 | 2005-10-25 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
US6927293B2 (en) | 2001-08-30 | 2005-08-09 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
WO2003026577A2 (en) | 2001-09-24 | 2003-04-03 | Seattle Genetics, Inc. | P-amidobenzylethers in drug delivery agents |
ES2326964T3 (es) | 2001-10-25 | 2009-10-22 | Genentech, Inc. | Composiciones de glicoproteina. |
EP1545613B9 (en) | 2002-07-31 | 2012-01-25 | Seattle Genetics, Inc. | Auristatin conjugates and their use for treating cancer, an autoimmune disease or an infectious disease |
US7109304B2 (en) | 2003-07-31 | 2006-09-19 | Immunomedics, Inc. | Humanized anti-CD19 antibodies |
HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
EP2210607B1 (en) | 2003-09-26 | 2011-08-17 | Exelixis Inc. | N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide for the treatment of cancer |
KR101520209B1 (ko) | 2003-11-06 | 2015-05-13 | 시애틀 지네틱스, 인크. | 리간드에 접합될 수 있는 모노메틸발린 화합물 |
EP1718667B1 (en) | 2004-02-23 | 2013-01-09 | Genentech, Inc. | Heterocyclic self-immolative linkers and conjugates |
WO2005084390A2 (en) | 2004-03-02 | 2005-09-15 | Seattle Genetics, Inc. | Partially loaded antibodies and methods of their conjugation |
US7709645B2 (en) | 2004-07-27 | 2010-05-04 | Sgx Pharmaceuticals, Inc. | Pyrrolo-pyridine kinase modulators |
SI1773885T1 (sl) | 2004-08-05 | 2010-08-31 | Genentech Inc | Humanizirani anti-CMET antagonisti |
CN101018780B (zh) | 2004-08-26 | 2012-01-11 | 辉瑞大药厂 | 作为蛋白激酶抑制剂的吡唑取代的氨基杂芳基化合物 |
US8911726B2 (en) | 2004-09-22 | 2014-12-16 | Kyowa Hakko Kirin Co., Ltd | Stabilized human Igg4 antibodies |
US8288352B2 (en) | 2004-11-12 | 2012-10-16 | Seattle Genetics, Inc. | Auristatins having an aminobenzoic acid unit at the N terminus |
TW200738638A (en) | 2005-06-23 | 2007-10-16 | Merck & Co Inc | Tyrosine kinase inhibitors |
JP4119478B1 (ja) | 2005-06-23 | 2008-07-16 | メルク エンド カムパニー インコーポレーテッド | チロシンキナーゼインヒビター |
WO2007000860A1 (ja) | 2005-06-28 | 2007-01-04 | Pioneer Corporation | 放送受信装置、妨害検出装置および妨害検出方法 |
AU2006269940C1 (en) | 2005-07-18 | 2013-11-07 | Seagen Inc. | Beta-glucuronide-linker drug conjugates |
KR100950737B1 (ko) | 2005-08-24 | 2010-03-31 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 신규 피리딘 유도체 및 피리미딘 유도체(3) |
US20070089836A1 (en) | 2005-10-24 | 2007-04-26 | Applied Materials, Inc. | Semiconductor process chamber |
CA2629468A1 (en) | 2005-11-15 | 2007-05-24 | Bayer Pharmaceuticals Corporation | Pyrazolyl urea derivatives useful in the treatment of cancer |
AU2006320580B2 (en) | 2005-11-30 | 2011-06-23 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-Met and uses thereof |
MX2008008277A (es) | 2005-12-21 | 2009-03-04 | Janssen Pharmaceutica Nv | Triazolopiridazinas como moduladores de tirosina cinasa. |
US20070213319A1 (en) | 2006-01-11 | 2007-09-13 | Angion Biomedica Corporation | Modulators of hepatocyte growth factor/c-Met activity |
US7908091B2 (en) | 2006-03-17 | 2011-03-15 | Prometheus Laboratories Inc. | Methods of predicting and monitoring tyrosine kinase inhibitor therapy |
CA2646048A1 (en) | 2006-03-30 | 2007-11-08 | Novartis Ag | Compositions and methods of use for antibodies of c-met |
US7601716B2 (en) | 2006-05-01 | 2009-10-13 | Cephalon, Inc. | Pyridopyrazines and derivatives thereof as ALK and c-Met inhibitors |
NL2000613C2 (nl) | 2006-05-11 | 2007-11-20 | Pfizer Prod Inc | Triazoolpyrazinederivaten. |
EP2032578A2 (en) | 2006-05-30 | 2009-03-11 | Pfizer Products Incorporated | Triazolopyridazine derivatives |
EP2040546A4 (en) | 2006-06-22 | 2009-12-23 | Merck & Co Inc | TYROSINE KINASE INHIBITORS |
TW200813021A (en) | 2006-07-10 | 2008-03-16 | Merck & Co Inc | Tyrosine kinase inhibitors |
US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
PE20121506A1 (es) | 2006-07-14 | 2012-11-26 | Amgen Inc | Compuestos triazolopiridinas como inhibidores de c-met |
TW200817410A (en) | 2006-08-07 | 2008-04-16 | Incyte Corp | Triazolotriazines as kinase inhibitors |
DE102006037478A1 (de) | 2006-08-10 | 2008-02-14 | Merck Patent Gmbh | 2-(Heterocyclylbenzyl)-pyridazinonderivate |
US20080255155A1 (en) | 2006-10-18 | 2008-10-16 | Stephane Raeppel | Kinase inhibitors and uses thereof |
TWI432427B (zh) | 2006-10-23 | 2014-04-01 | Cephalon Inc | 作為ALK及c-MET抑制劑之2,4-二胺基嘧啶之融合雙環衍生物 |
WO2008049855A2 (en) | 2006-10-27 | 2008-05-02 | Glaxo Group Limited | 7-azaindole derivatives as c-met kinase inhibitors |
GB0621607D0 (en) | 2006-10-31 | 2006-12-06 | Chroma Therapeutics Ltd | Inhibitors of c-Met |
WO2008067119A2 (en) | 2006-11-27 | 2008-06-05 | Smithkline Beecham Corporation | Novel compounds |
JP2010513231A (ja) | 2006-12-14 | 2010-04-30 | バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト | たんぱく質キナーゼインヒビターとして有用なジヒドロピリジン誘導体 |
AU2007338792B2 (en) | 2006-12-20 | 2012-05-31 | Amgen Inc. | Substituted heterocycles and methods of use |
ES2392156T3 (es) | 2006-12-20 | 2012-12-05 | Amgen Inc. | Heterociclos sustituidos y métodos de uso |
US7759344B2 (en) | 2007-01-09 | 2010-07-20 | Amgen Inc. | Bis-aryl amide derivatives and methods of use |
WO2008088881A1 (en) | 2007-01-19 | 2008-07-24 | Xcovery, Inc. | Kinase inhibitor compounds |
WO2008103277A2 (en) | 2007-02-16 | 2008-08-28 | Amgen Inc. | Nitrogen-containing heterocyclyl ketones and their use as c-met inhibitors |
EP2626372B1 (en) | 2007-03-29 | 2018-03-21 | Genmab A/S | Bispecific antibodies and methods for production thereof |
JP2010528991A (ja) | 2007-05-21 | 2010-08-26 | エスジーエックス ファーマシューティカルズ、インコーポレイテッド | 複素環式キナーゼ調節因子 |
JP6071165B2 (ja) | 2007-05-31 | 2017-02-01 | ゲンマブ エー/エス | 安定なIgG4抗体 |
DE102007025717A1 (de) | 2007-06-01 | 2008-12-11 | Merck Patent Gmbh | Arylether-pyridazinonderivate |
DE102007025718A1 (de) | 2007-06-01 | 2008-12-04 | Merck Patent Gmbh | Pyridazinonderivate |
DE102007026341A1 (de) | 2007-06-06 | 2008-12-11 | Merck Patent Gmbh | Benzoxazolonderivate |
GB0713259D0 (en) | 2007-07-09 | 2007-08-15 | Astrazeneca Ab | Pyrazine derivatives 954 |
DE102007032507A1 (de) | 2007-07-12 | 2009-04-02 | Merck Patent Gmbh | Pyridazinonderivate |
EP2014681A1 (en) | 2007-07-12 | 2009-01-14 | Pierre Fabre Medicament | Novel antibodies inhibiting c-met dimerization, and uses thereof |
PA8792501A1 (es) | 2007-08-09 | 2009-04-23 | Sanofi Aventis | Nuevos derivados de 6-triazolopiridacina-sulfanil benzotiazol y bencimidazol,su procedimiento de preparación,su aplicación como medicamentos,composiciones farmacéuticas y nueva utilización principalmente como inhibidores de met. |
DE102007038957A1 (de) | 2007-08-17 | 2009-02-19 | Merck Patent Gmbh | 6-Thioxo-pyridazinderivate |
WO2009024825A1 (en) | 2007-08-21 | 2009-02-26 | Astrazeneca Ab | 2-pyrazinylbenzimidazole derivatives as receptor tyrosine kinase inhibitors |
AU2008293038B2 (en) | 2007-08-29 | 2013-08-29 | Mirati Therapeutics, Inc. | Inhibitors of protein tyrosine kinase activity |
DE102007041115A1 (de) | 2007-08-30 | 2009-03-05 | Merck Patent Gmbh | Thiadiazinonderivate |
WO2009033084A1 (en) | 2007-09-06 | 2009-03-12 | Array Biopharma Inc. | Pyrazolo-pyridines as tyrosine kinase inhibitors |
DE602008005786D1 (de) | 2007-10-03 | 2011-05-05 | Vertex Pharma | C-met-proteinkinasehemmer |
FR2922550B1 (fr) | 2007-10-19 | 2009-11-27 | Sanofi Aventis | Nouveaux derives de 6-aryl/heteroalkyloxy benzothiazole et benzimidazole, application comme medicaments, compositions pharmaceutiques et nouvelle utilisation notamment comme inhibiteurs de cmet |
KR20100089090A (ko) | 2007-10-25 | 2010-08-11 | 아스트라제네카 아베 | 세포 증식 장애의 치료에 유용한 피리딘 및 피라진 유도체 |
JP5769969B2 (ja) | 2007-11-12 | 2015-08-26 | ユー3・ファーマ・ゲーエムベーハー | Axl抗体 |
BRPI0820543A2 (pt) * | 2007-11-15 | 2015-06-16 | Chugai Pharmaceutical Co Ltd | Anticorpo monoclonal capaz de ligar a anexelekto, e uso do mesmo |
JP2009132660A (ja) | 2007-11-30 | 2009-06-18 | Eisai R & D Management Co Ltd | 食道癌治療用組成物 |
DE102007061963A1 (de) | 2007-12-21 | 2009-06-25 | Merck Patent Gmbh | Pyridazinonderivate |
GB0801416D0 (en) | 2008-01-25 | 2008-03-05 | Piramed Ltd | Pharmaceutical compounds |
EP2265270A1 (en) | 2008-02-04 | 2010-12-29 | OSI Pharmaceuticals, Inc. | 2-aminopyridine kinase inhibitors |
AR070317A1 (es) | 2008-02-06 | 2010-03-31 | Osi Pharm Inc | Furo (3,2-c) piridina y tieno (3,2-c) piridinas |
SG190572A1 (en) | 2008-04-29 | 2013-06-28 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
PA8849001A1 (es) | 2008-11-21 | 2010-06-28 | Lilly Co Eli | Anticuerpos de c-met |
EP2233500A1 (en) | 2009-03-20 | 2010-09-29 | LFB Biotechnologies | Optimized Fc variants |
EP2430050A1 (en) * | 2009-05-11 | 2012-03-21 | U3 Pharma GmbH | Humanized axl antibodies |
MA33405B1 (fr) * | 2009-05-15 | 2012-07-03 | Chugai Pharmaceutical Co Ltd | Anticorps anti-axl |
TW201106972A (en) | 2009-07-27 | 2011-03-01 | Genentech Inc | Combination treatments |
EP2287197A1 (en) | 2009-08-21 | 2011-02-23 | Pierre Fabre Medicament | Anti-cMET antibody and its use for the detection and the diagnosis of cancer |
KR101671378B1 (ko) | 2009-10-30 | 2016-11-01 | 삼성전자 주식회사 | c-Met에 특이적으로 결합하는 항체 및 그의 용도 |
KR101748707B1 (ko) | 2009-11-27 | 2017-06-20 | 삼성전자주식회사 | c-Met에 특이적으로 결합하는 항체 및 그를 이용한 암 진단용 키트 |
US9150663B2 (en) | 2010-04-20 | 2015-10-06 | Genmab A/S | Heterodimeric antibody Fc-containing proteins and methods for production thereof |
RU2577986C2 (ru) * | 2010-06-18 | 2016-03-20 | Дженентек, Инк. | Антитела против axl и способы их применения |
CA2813411C (en) | 2010-11-05 | 2016-08-02 | Rinat Neuroscience Corporation | Engineered polypeptide conjugates and methods for making thereof using transglutaminase |
CN103747803B (zh) * | 2011-06-22 | 2016-10-12 | 国家医疗保健研究所 | 抗axl抗体及其用途 |
EP2723376B1 (en) * | 2011-06-22 | 2018-12-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-axl antibodies and uses thereof |
EP2589609A1 (en) * | 2011-11-03 | 2013-05-08 | Pierre Fabre Medicament | Antigen binding protein and its use as addressing product for the treatment of cancer |
JP6445444B2 (ja) * | 2012-11-05 | 2018-12-26 | ピエール、ファーブル、メディカマン | 新規抗原結合タンパク質および癌の治療のためのアドレッシング産物(addressingproduct)としてのそれらの使用 |
GB201410825D0 (en) * | 2014-06-18 | 2014-07-30 | Bergenbio As | Anti-axl antibodies |
GB201410826D0 (en) * | 2014-06-18 | 2014-07-30 | Bergenbio As | Anti-axl antibodies |
-
2015
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