JP2015529641A5 - - Google Patents

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JP2015529641A5
JP2015529641A5 JP2015521849A JP2015521849A JP2015529641A5 JP 2015529641 A5 JP2015529641 A5 JP 2015529641A5 JP 2015521849 A JP2015521849 A JP 2015521849A JP 2015521849 A JP2015521849 A JP 2015521849A JP 2015529641 A5 JP2015529641 A5 JP 2015529641A5
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Japan
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seq
antibody
tumor
variable region
cancer
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JP2015521849A
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JP6335896B2 (ja
JP2015529641A (ja
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Priority claimed from PCT/US2013/050300 external-priority patent/WO2014012007A2/en
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JP2015521849A 2012-07-13 2013-07-12 Rspo3結合剤およびその使用法 Expired - Fee Related JP6335896B2 (ja)

Applications Claiming Priority (9)

Application Number Priority Date Filing Date Title
US201261671421P 2012-07-13 2012-07-13
US61/671,421 2012-07-13
US201361753184P 2013-01-16 2013-01-16
US61/753,184 2013-01-16
US201361789156P 2013-03-15 2013-03-15
US61/789,156 2013-03-15
US201361826747P 2013-05-23 2013-05-23
US61/826,747 2013-05-23
PCT/US2013/050300 WO2014012007A2 (en) 2012-07-13 2013-07-12 Rspo3 binding agents and uses thereof

Publications (3)

Publication Number Publication Date
JP2015529641A JP2015529641A (ja) 2015-10-08
JP2015529641A5 true JP2015529641A5 (enExample) 2016-09-01
JP6335896B2 JP6335896B2 (ja) 2018-05-30

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JP2015521849A Expired - Fee Related JP6335896B2 (ja) 2012-07-13 2013-07-12 Rspo3結合剤およびその使用法

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US (3) US9181333B2 (enExample)
EP (1) EP2872175A4 (enExample)
JP (1) JP6335896B2 (enExample)
KR (1) KR20150036603A (enExample)
CN (1) CN104854132A (enExample)
AU (1) AU2013289990B2 (enExample)
BR (1) BR112015000776A2 (enExample)
CA (1) CA2878868A1 (enExample)
CL (1) CL2015000097A1 (enExample)
EA (1) EA032038B1 (enExample)
EC (1) ECSP15005280A (enExample)
HK (1) HK1208687A1 (enExample)
IL (1) IL236617A0 (enExample)
IN (1) IN2015KN00350A (enExample)
MX (1) MX2015000565A (enExample)
NI (1) NI201500002A (enExample)
NZ (1) NZ704269A (enExample)
PE (1) PE20150360A1 (enExample)
PH (1) PH12015500084A1 (enExample)
SG (1) SG11201500233PA (enExample)
TW (2) TW201906861A (enExample)
UA (1) UA117659C2 (enExample)
WO (1) WO2014012007A2 (enExample)
ZA (1) ZA201500872B (enExample)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2664738C (en) 2006-09-29 2017-03-07 Oncomed Pharmaceuticals, Inc. Compositions and methods for diagnosing and treating cancer
EP3009148B1 (en) 2007-07-02 2018-08-22 Oncomed Pharmaceuticals, Inc. Compositions and methods for treating and diagnosing cancer
US8551479B2 (en) 2010-09-10 2013-10-08 Oncomed Pharmaceuticals, Inc. Methods for treating melanoma
AU2012271413B2 (en) 2011-06-17 2017-07-13 President And Fellows Of Harvard College Frizzled 2 as a target for therapeutic antibodies in the treatment of cancer
EP3401329A1 (en) 2011-07-15 2018-11-14 OncoMed Pharmaceuticals, Inc. Rspo binding agents and uses thereof
JP6335896B2 (ja) 2012-07-13 2018-05-30 オンコメッド ファーマシューティカルズ インコーポレイテッド Rspo3結合剤およびその使用法
CN105744954B (zh) * 2013-10-18 2021-03-05 豪夫迈·罗氏有限公司 抗rspo2和/或抗rspo3抗体及其用途
BR112017000130A2 (pt) 2014-07-11 2018-01-09 Genentech Inc método para atenuar a toxicidade associada à inibição da via de notch e método de tratamento do câncer
CA2961374A1 (en) 2014-09-16 2016-03-24 Oncomed Pharmaceuticals, Inc. Treatment of fibrotic diseases
MA41123A (fr) * 2014-12-02 2017-10-10 Oncomed Pharm Inc Polythérapie pour le traitement du cancer
WO2017040660A1 (en) * 2015-08-31 2017-03-09 Oncomed Pharmaceuticals, Inc. Combination therapy for treatment of disease
CN106913880B (zh) * 2015-12-24 2021-02-12 上海交通大学 一种含有rspo1的靶向给药系统及其制备与应用
CN105925576B (zh) * 2016-03-24 2018-04-20 嘉兴市第一医院 针对哺乳动物R‑Spondin3基因靶点的小干扰RNA、短发卡RNA及载体和应用
EP3443004A1 (en) 2016-04-14 2019-02-20 H. Hoffnabb-La Roche Ag Anti-rspo3 antibodies and methods of use
WO2018035210A1 (en) * 2016-08-17 2018-02-22 Oncomed Pharmaceuticals, Inc. Methods and monitoring of treatment with an rspo antagonist
JP7370997B2 (ja) 2017-12-07 2023-10-30 ナショナル ヘルス リサーチ インスティテューツ 抗rspo3抗体
CN110339364B (zh) * 2018-04-02 2021-02-12 上海邦耀生物科技有限公司 Lgr4/rspo阻断剂与抗免疫检查点抑制剂联合用于肿瘤的免疫治疗
CN110467663B (zh) * 2019-06-18 2022-05-10 华南农业大学 Rspo3基因在母猪卵巢颗粒细胞中的应用
US20250346890A1 (en) * 2019-12-19 2025-11-13 Deutsches Krebsforschungszentrum Leukemia treatment
KR102554222B1 (ko) * 2023-03-21 2023-07-11 순천향대학교 산학협력단 신규한 항-인간 알스폰딘3 항체 및 이의 용도
CN116769030B (zh) * 2023-08-21 2023-10-20 成都大熊猫繁育研究基地 一种大熊猫松弛素3单克隆抗体及其杂交瘤细胞株和应用

Family Cites Families (104)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5681718A (en) 1986-03-14 1997-10-28 Celltech Limited Methods for enhanced production of tissue plasminogen activator in cell culture using alkanoic acids or salts thereof
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for 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
ES2108048T3 (es) 1990-08-29 1997-12-16 Genpharm Int Produccion y utilizacion de animales inferiores transgenicos capaces de producir anticuerpos heterologos.
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US20070124581A1 (en) 1992-05-17 2007-05-31 Reena Khare Cell adhesion and extracellular matrix proteins
JP2001527403A (ja) 1997-04-25 2001-12-25 ジェネティックス・インスチチュート・インコーポレーテッド 分泌蛋白およびそれらをコードするポリヌクレオチド
US6004528A (en) 1997-09-18 1999-12-21 Bergstein; Ivan Methods of cancer diagnosis and therapy targeted against the cancer stemline
WO1999015660A1 (en) 1997-09-24 1999-04-01 Merck & Co., Inc. G-protein coupled glycoprotein hormone receptor hg38
US20020065394A1 (en) 1998-03-18 2002-05-30 Kenneth Jacobs Secreted proteins and polynucleotides encoding them
DE69941330D1 (de) 1998-03-26 2009-10-08 Univ R Neue g-protein-gekoppelte rezeptoren aus säugetieren mit extrazellulären leucin-reicher region
US6485972B1 (en) 1998-10-15 2002-11-26 President And Fellows Of Harvard College WNT signalling in reproductive organs
US20030166047A1 (en) 1999-05-06 2003-09-04 Millennium Pharmaceuticals, Inc. Lgr6 nucleic acids and uses thereof
WO2001007611A2 (en) 1999-07-26 2001-02-01 Genentech, Inc. Novel polynucleotides and method for the use thereof
US6824973B2 (en) 2000-02-03 2004-11-30 Kirin Beer Kabushiki Kaisha Method of promoting stem cell proliferation or survival by contacting a cell with a stem cell factor-like polypeptide
EP1572987A4 (en) 2000-02-03 2005-11-30 Nuvelo Inc NUCLEIC ACIDS AND POLYPEPTIDES
US6924141B2 (en) 2000-03-31 2005-08-02 The General Hospital Corporation Methods of modulating hair growth
CA2405104A1 (en) 2000-04-05 2001-10-18 Kirin Beer Kabushiki Kaisha Methods and materials relating to stem cell growth factor-like polypeptides and polynucleotides
EP1156062A1 (en) 2000-05-12 2001-11-21 GPC Biotech AG Immunomodulatory human MHC class II antigen-binding peptides/proteins
AU2001263006A1 (en) 2000-05-18 2001-11-26 Hyseq, Inc. Novel nucleic acids and polypeptides
AU2001281791A1 (en) 2000-05-30 2001-12-11 Bayer Aktiengesellschaft Regulation of human lgr4-like g protein-coupled receptor
US6984522B2 (en) 2000-08-03 2006-01-10 Regents Of The University Of Michigan Isolation and use of solid tumor stem cells
US20050089518A1 (en) 2001-12-07 2005-04-28 Clarke Michael F. Prospective identification and characterization of breast cancer stem cells
US6768004B2 (en) 2001-01-11 2004-07-27 Mueller Sybille Nucleotide sequences encoding variable regions of heavy and light chains of monoclonal antibody 1F7, an anti-idiotypic antibody reactive with anti-HIV antibodies
US20040077048A1 (en) 2002-01-30 2004-04-22 Warren Bridget A. Protein modification and maintenance molecules
US7411052B2 (en) 2001-03-05 2008-08-12 Nuvelo, Inc. Methods and materials relating to stem cell growth factor-like polypeptides and polynucleotides
US20030032034A1 (en) 2001-03-05 2003-02-13 Tang Y. Tom Methods and materials relating to stem cell growth factor-like polypeptides and polynucleotides
US20100292155A1 (en) 2001-03-05 2010-11-18 Arca Biopharma, Inc. Methods and materials relating to stem cell growth factor-like polypeptides and polynucleotides
WO2002100898A2 (en) 2001-06-11 2002-12-19 Kirin Beer Kabushiki Kaisha Polypeptide having an activity to support proliferation or survival of hematopoietic stem cell and hematopoietic progenitor cell, and dna coding for the same
CA2450793A1 (en) 2001-06-20 2002-12-27 Prochon Biotech Ltd. Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof
US20030022217A1 (en) 2001-07-02 2003-01-30 Pe Corporation (Ny) Isolated human secreted proteins, nucleic acid molecules encoding human secreted proteins, and uses thereof
ATE553193T1 (de) 2001-08-30 2012-04-15 Arca Biopharma Inc Verfahren und materialien in verbindung mit stammzellen-wachstumsfaktor-ähnlichen polypeptiden und polynukleotiden
CA2462795A1 (en) 2001-10-03 2003-04-10 Incyte Genomics, Inc. Secreted proteins
US20070237770A1 (en) * 2001-11-30 2007-10-11 Albert Lai Novel compositions and methods in cancer
US20040197778A1 (en) 2002-12-26 2004-10-07 Sagres Discovery, Inc. Novel compositions and methods in cancer
CA2469941A1 (en) 2001-12-10 2003-07-03 Nuvelo, Inc. Novel nucleic acids and polypeptides
US7193069B2 (en) 2002-03-22 2007-03-20 Research Association For Biotechnology Full-length cDNA
US7439332B2 (en) 2002-04-26 2008-10-21 Kirin Pharma Kabushiki Kaisha Polypeptide having an activity to support proliferation or survival of hematopoietic stem or progenitor cells
EP1380644A1 (en) 2002-07-08 2004-01-14 Kylix B.V. The use of specified TCF target genes to identify drugs for the treatment of cancer, in particular colorectal cancer, in which TCF/beta-catenin/WNT signalling plays a central role
GB0216648D0 (en) 2002-07-18 2002-08-28 Lonza Biologics Plc Method of expressing recombinant protein in CHO cells
WO2004074436A2 (en) 2003-02-19 2004-09-02 Incyte Corporation Methods of use of a gpcr in the diagnosis and treatment of colon and lung cancer
US20050003405A1 (en) 2003-04-30 2005-01-06 Hua-Chien Chen Treatment and diagnostics of cancer
EP2003196A3 (en) 2003-06-09 2009-01-07 The Regents of the University of Michigan Compositions and methods for treating and diagnosing cancer
WO2005110009A2 (en) 2003-07-22 2005-11-24 Immunex Corporation COMPOSITIONS AND METHODS RELATING TO TSP-30a, b, c AND d
DE10339820A1 (de) 2003-08-22 2005-03-17 Hinzmann, Bernd, Dr. Verwendung von an GPR49 bindenden Substanzen zur Diagnose und Behandlung von Krebs
US9046537B2 (en) 2003-09-22 2015-06-02 Enzo Biochem, Inc. Method for treating inflammation by administering a compound which binds LDL-receptor-related protein (LRP) ligand binding domain
EP1673475B1 (en) 2003-10-10 2010-04-28 Deutsches Krebsforschungszentrum Compositions for diagnosis and therapy of diseases associated with aberrant expression of futrins (r-spondins) and/or wnt
WO2005040828A2 (en) 2003-10-24 2005-05-06 Bayer Healthcare Ag Diagnostics and therapeutics for diseases associated with g protein-coupled receptor 49 (gpr49)
JP2007526248A (ja) 2004-01-27 2007-09-13 ヌベロ インコーポレーティッド 胃腸増殖因子およびその使用方法
WO2005074633A2 (en) 2004-02-03 2005-08-18 The Regents Of The University Of Michigan Compositions and methods for characterizing, regulating, diagnosing, and treating cancer
WO2005075514A2 (en) 2004-03-10 2005-08-18 Lonza Ltd. Method for producing antibodies
US7572456B2 (en) 2004-09-13 2009-08-11 Macrogenics, Inc. Humanized antibodies against West Nile Virus and therapeutic and prophylactic uses thereof
CA2591665C (en) 2004-12-20 2015-05-05 Crucell Holland B.V. Binding molecules capable of neutralizing west nile virus and uses thereof
US7439327B2 (en) 2005-01-18 2008-10-21 Nuvelo, Inc. Stem cell factor-like proteins and uses thereof
WO2006110585A2 (en) 2005-04-07 2006-10-19 Novartis Vaccines And Diagnostics Inc. Cancer-related genes (prlr)
EP1917022A2 (en) 2005-07-26 2008-05-07 Kirin Pharma Kabushiki Kaisha Anti-tumor agents comprising r-spondins
US7541431B2 (en) 2005-09-07 2009-06-02 Maine Medical Center Cristin/R-spondin ligands active in the Wnt signaling pathway and methods, compositions and kits relating thereto
EP1942926A4 (en) 2005-10-07 2010-06-16 Nuvelo Inc STEM CELL FACTOR ARTIFICIAL PROTEIN SCFA1 AND ITS USES
US7723112B2 (en) 2005-10-31 2010-05-25 The Regents Of The University Of Michigan Compositions and methods for treating and diagnosing cancer
US7723477B2 (en) 2005-10-31 2010-05-25 Oncomed Pharmaceuticals, Inc. Compositions and methods for inhibiting Wnt-dependent solid tumor cell growth
GB0603683D0 (en) 2006-02-23 2006-04-05 Novartis Ag Organic compounds
ES2378097T3 (es) 2006-06-02 2012-04-04 Aveo Pharmaceuticals, Inc. Proteínas de unión al factor de crecimiento de hepatocitos (HGF)
ATE495195T1 (de) 2006-06-02 2011-01-15 Aveo Pharmaceuticals Inc Hepatocytenwachstumsfaktor-(hgf-)bindungsprotei e
PL2032166T3 (pl) 2006-06-13 2013-09-30 Oncomed Pharm Inc Kompozycje i sposoby diagnozowania i leczenia nowotworów
NZ574215A (en) * 2006-07-18 2012-07-27 Sanofi Aventis Antagonist antibody against epha2 for the treatment of cancer
JP2008044926A (ja) 2006-08-14 2008-02-28 Trustees Of Columbia Univ In The City Of New York Wnt信号伝達に関係した分泌タンパク質
CA2664738C (en) 2006-09-29 2017-03-07 Oncomed Pharmaceuticals, Inc. Compositions and methods for diagnosing and treating cancer
DK2081586T4 (en) 2006-10-20 2019-01-21 Deutsches Krebsforschungszentrum Stiftung Des Oeffentlichen Rechts Rspondins as modulators of angiogenesis and vasculogenesis
WO2008075796A1 (ja) 2006-12-21 2008-06-26 Kyowa Hakko Kirin Co., Ltd. 血球回復促進剤
WO2008088524A2 (en) 2006-12-28 2008-07-24 Nuvelo, Inc. Thrombospondin-domain-deficient r-spondin 1 protein as gastrointestinal tract epithelial proliferation factor
EP2164871A2 (en) 2007-06-12 2010-03-24 Wyeth a Corporation of the State of Delaware Anti-cd20 therapeutic compositions and methods
EP3009148B1 (en) 2007-07-02 2018-08-22 Oncomed Pharmaceuticals, Inc. Compositions and methods for treating and diagnosing cancer
US20120082659A1 (en) 2007-10-02 2012-04-05 Hartmut Land Methods And Compositions Related To Synergistic Responses To Oncogenic Mutations
US20100285001A1 (en) 2007-10-02 2010-11-11 University Of Rochester Method and Compositions Related to Synergistic Responses to Oncogenic Mutations
WO2009063970A1 (ja) 2007-11-14 2009-05-22 Forerunner Pharma Research Co., Ltd. 抗gpr49抗体を用いる癌の診断および治療
US8187601B2 (en) 2008-07-01 2012-05-29 Aveo Pharmaceuticals, Inc. Fibroblast growth factor receptor 3 (FGFR3) binding proteins
WO2010016766A2 (en) 2008-08-08 2010-02-11 Koninklijke Nederlandse Akademie Van Wetenschappen Antibodies recognizing endogenous human lgr5 and/or lgr6
KR101682257B1 (ko) * 2008-10-31 2016-12-05 도레이 카부시키가이샤 인간 cxcl1 단백질의 면역학적 측정 방법
US20120039912A1 (en) 2009-04-15 2012-02-16 Galapagos Sasu Rspondin-3 inhibition in bone disorders
WO2010129284A1 (en) 2009-04-27 2010-11-11 The Trustees Of The University Of Pennsylvania Inhibition of hair follicle growth by the wnt inhibitor dkk1
CN102459346B (zh) * 2009-04-27 2016-10-26 昂考梅德药品有限公司 制造异源多聚体分子的方法
CN102695499A (zh) 2009-06-18 2012-09-26 惠氏有限责任公司 小模块免疫药物的冻干制剂
US8318162B2 (en) * 2009-07-16 2012-11-27 Xoma Technology Ltd. Antibodies to high molecular weight melanoma associated antigen
RU2595409C2 (ru) 2009-09-03 2016-08-27 Мерк Шарп И Доум Корп., Анти-gitr-антитела
WO2011076932A1 (en) 2009-12-23 2011-06-30 Deutsches Krebsforschungszentrum Receptors of rspo2 and rspo3
WO2011085289A1 (en) 2010-01-11 2011-07-14 Arizona Board Of Regents, A Body Corporate Of The State Of Arizona, Acting For And On Behalf Of Arizona State University Production of a monoclonal antibody therapeutic against west nile virus in plants
NZ601743A (en) 2010-02-12 2014-11-28 Oncomed Pharm Inc Methods for identifying and isolating cells expressing a polypeptide
US20150024952A1 (en) * 2010-12-28 2015-01-22 Arlet Alarcon Molecular profiling for cancer
GB201106395D0 (en) 2011-04-14 2011-06-01 Hubrecht Inst Compounds
AU2012248158C1 (en) * 2011-04-28 2017-02-02 Sbi Biotech Co., Ltd. Anti-human receptor-type protein tyrosine phosphatase sigma antibody
EP3401329A1 (en) 2011-07-15 2018-11-14 OncoMed Pharmaceuticals, Inc. Rspo binding agents and uses thereof
CN109111523B (zh) 2011-10-14 2022-06-07 诺华股份有限公司 用于Wnt途径相关疾病的抗体和方法
US10598653B2 (en) 2011-11-01 2020-03-24 Bionomics Inc. Methods of blocking cancer stem cell growth
US9220774B2 (en) 2011-11-01 2015-12-29 Bionomics Inc. Methods of treating cancer by administering anti-GPR49 antibodies
MX366804B (es) 2012-02-11 2019-07-25 Genentech Inc Translocaciones de la r-espondina y sus metodos de uso.
AR090549A1 (es) 2012-03-30 2014-11-19 Genentech Inc Anticuerpos anti-lgr5 e inmunoconjugados
JP6335896B2 (ja) 2012-07-13 2018-05-30 オンコメッド ファーマシューティカルズ インコーポレイテッド Rspo3結合剤およびその使用法
CN105142641A (zh) 2013-03-12 2015-12-09 广州源生医药科技有限公司 用于治疗癌症的化合物
JPWO2014192974A1 (ja) 2013-05-30 2017-02-23 株式会社オーダーメードメディカルリサーチ 抗lgr6抗体を含む癌の検出用又は診断用試薬
CN105744954B (zh) 2013-10-18 2021-03-05 豪夫迈·罗氏有限公司 抗rspo2和/或抗rspo3抗体及其用途
MA41123A (fr) 2014-12-02 2017-10-10 Oncomed Pharm Inc Polythérapie pour le traitement du cancer
US9777052B2 (en) 2014-12-02 2017-10-03 The Board Of Regents Of The University Of Oklahoma R-spondin variants, compositions, and methods of use

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