IL127115A - A substance for the treatment of diseases related to bone metabolism problem - Google Patents
A substance for the treatment of diseases related to bone metabolism problemInfo
- Publication number
- IL127115A IL127115A IL127115A IL12711598A IL127115A IL 127115 A IL127115 A IL 127115A IL 127115 A IL127115 A IL 127115A IL 12711598 A IL12711598 A IL 12711598A IL 127115 A IL127115 A IL 127115A
- Authority
- IL
- Israel
- Prior art keywords
- obm
- protein
- ocif
- cells
- human
- Prior art date
Links
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Classifications
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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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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
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- G—PHYSICS
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Landscapes
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| JP33224197 | 1997-12-02 | ||
| PCT/JP1998/001728 WO1998046644A1 (fr) | 1997-04-15 | 1998-04-15 | Nouvelle proteine et methode de production associee |
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Families Citing this family (58)
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| IL117175A (en) | 1995-02-20 | 2005-11-20 | Sankyo Co | Osteoclastogenesis inhibitory factor protein |
| US7632922B1 (en) * | 1995-12-22 | 2009-12-15 | Amgen, Inc. | Osteoprotegerin |
| US20050147611A1 (en) * | 1995-12-22 | 2005-07-07 | Amgen Inc. | Combination therapy for conditions leading to bone loss |
| DE122010000046I1 (de) * | 1996-12-13 | 2011-05-05 | Schering Corp | Oberflächenantigene aus Säugern |
| DE951551T1 (de) * | 1996-12-23 | 2000-09-14 | Immunex Corp., Seattle | Ligand für rezeptor aktivator of nf-kappa b, ligand ist mitglied der tnf superfamilie |
| US6271349B1 (en) | 1996-12-23 | 2001-08-07 | Immunex Corporation | Receptor activator of NF-κB |
| ES2263204T5 (es) | 1997-04-15 | 2013-10-14 | Daiichi Sankyo Company, Limited | Nueva proteína y proceso para producir la misma |
| US6316408B1 (en) * | 1997-04-16 | 2001-11-13 | Amgen Inc. | Methods of use for osetoprotegerin binding protein receptors |
| AU2011202547B2 (en) * | 1997-04-16 | 2014-08-28 | Amgen Inc. | Osteoprotegerin binding proteins and receptors |
| US5843678A (en) * | 1997-04-16 | 1998-12-01 | Amgen Inc. | Osteoprotegerin binding proteins |
| RO128635A2 (ro) * | 1997-04-16 | 2013-07-30 | Amgen Inc. | Anticorp sau fragment al acestuia care se leagă la opgbp şi utilizarea acestuia, utilizarea unei forme solubile de odar, şi metodă de identificare a unui compus care descreşte activitatea opgbp |
| EP2009025B1 (en) | 1998-05-14 | 2011-07-27 | Immunex Corporation | Method of inhibiting osteoclast activity |
| IL142557A0 (en) | 1998-10-28 | 2002-03-10 | Snow Brand Milk Products Co Ltd | Remedies for bone metabolic errors |
| AUPQ314799A0 (en) * | 1999-09-29 | 1999-10-21 | University Of Western Australia, The | Bone cell factor |
| US20030103978A1 (en) * | 2000-02-23 | 2003-06-05 | Amgen Inc. | Selective binding agents of osteoprotegerin binding protein |
| MXPA02008144A (es) † | 2000-02-23 | 2002-11-29 | Amgen Inc | Agentes de enlace selectivos antagonistas de la proteina de enlace de osteoprotegerina. |
| DE01973455T1 (de) | 2000-09-22 | 2004-04-22 | Immunex Corp., Seattle | Screeningverfahren für agonisten und antagonisten des rezeptoraktivators von nf-kappa b |
| WO2002062990A1 (fr) * | 2001-02-07 | 2002-08-15 | Sankyo Company, Limited | Anticorps et utilisation de cet anticorps |
| WO2002079256A1 (fr) * | 2001-03-26 | 2002-10-10 | Sankyo Company, Limited | Anticorps et son utilisation |
| AU2002253133B2 (en) | 2001-04-03 | 2008-02-28 | Societe Des Produits Nestle S.A. | Osteoprotegerin in milk |
| DK2270052T3 (en) | 2001-06-26 | 2018-07-02 | Amgen Inc | Antibodies to OPGL |
| JP4761710B2 (ja) | 2002-04-05 | 2011-08-31 | アムジェン インコーポレイテッド | 選択的opgl経路インヒビターとしてのヒト抗opgl中和抗体 |
| US7462700B2 (en) * | 2002-12-10 | 2008-12-09 | Schering-Plough Animal Health Corporation | Canine RANKL and methods for preparing and using the same |
| US20050009097A1 (en) * | 2003-03-31 | 2005-01-13 | Better Marc D. | Human engineered antibodies to Ep-CAM |
| US7318925B2 (en) | 2003-08-08 | 2008-01-15 | Amgen Fremont, Inc. | Methods of use for antibodies against parathyroid hormone |
| CN1838968A (zh) | 2003-08-08 | 2006-09-27 | 艾伯吉尼斯公司 | 针对甲状旁腺激素(pth)之抗体和其用途 |
| AR045563A1 (es) * | 2003-09-10 | 2005-11-02 | Warner Lambert Co | Anticuerpos dirigidos a m-csf |
| PT2311873T (pt) | 2004-01-07 | 2018-11-20 | Novartis Vaccines & Diagnostics Inc | Anticorpo monoclonal específico para m-csf e respetivos usos |
| TWI359026B (en) * | 2004-02-12 | 2012-03-01 | Sankyo Co | Pharmaceutical composition for the osteoclast rela |
| RU2324425C2 (ru) * | 2005-08-30 | 2008-05-20 | Государственное образовательное учреждение "Институт усовершенствования врачей" Министерства здравоохранения и социального развития | Способ профилактики рождения больных остеопетрозом детей |
| PE20070684A1 (es) | 2005-11-14 | 2007-08-06 | Amgen Inc | MOLECULAS QUIMERICAS DE ANTICUERPO RANKL-PTH/PTHrP |
| US8168181B2 (en) | 2006-02-13 | 2012-05-01 | Alethia Biotherapeutics, Inc. | Methods of impairing osteoclast differentiation using antibodies that bind siglec-15 |
| WO2007093050A1 (en) * | 2006-02-13 | 2007-08-23 | Olga Ornatsky | Gene expression assays conducted by elemental analysis |
| EP2020445B1 (en) | 2006-05-12 | 2013-01-02 | Keio University | Detection of inflammatory disease and composition for prevention or treatment of inflammatory disease |
| WO2008044379A1 (fr) | 2006-10-11 | 2008-04-17 | Oriental Yeast Co., Ltd. | Modèle animal de perte osseuse |
| WO2008044797A1 (fr) | 2006-10-11 | 2008-04-17 | Oriental Yeast Co., Ltd. | Animal modèle d'ostéopénie |
| AU2007305855A1 (en) | 2006-10-11 | 2008-04-17 | Oriental Yeast Co., Ltd. | Agent containing fused protein of soluble RANKL with epitope tag |
| WO2008150025A1 (ja) | 2007-06-05 | 2008-12-11 | Oriental Yeast Co., Ltd. | 新しい骨量増加薬 |
| SG10201605897RA (en) | 2007-10-11 | 2016-09-29 | Daiichi Sankyo Co Ltd | ANTIBODY TARGETING OSTEOCLAST-RELATED PROTEIN Siglec-15 |
| US8778359B2 (en) * | 2008-07-30 | 2014-07-15 | Emergent Biosolutions Inc. | Stable anthrax vaccine formulations |
| WO2010038610A1 (ja) | 2008-09-30 | 2010-04-08 | オリエンタル酵母工業株式会社 | 新しい軟骨細胞増殖及び分化誘導剤 |
| JP2012520098A (ja) * | 2009-03-30 | 2012-09-06 | エフ.ホフマン−ラ ロシュ アーゲー | ガラスの曇りを防ぐための方法 |
| MX2011007342A (es) * | 2009-04-09 | 2011-07-21 | Daiichi Sankyo Co Ltd | Anticuerpo anti-lectina similar a inmunoglobulina de union a acido sialico-15. |
| WO2011017294A1 (en) * | 2009-08-07 | 2011-02-10 | Schering Corporation | Human anti-rankl antibodies |
| EP2433644A1 (en) | 2010-09-22 | 2012-03-28 | IMBA-Institut für Molekulare Biotechnologie GmbH | Breast cancer therapeutics |
| EP2434285A1 (en) | 2010-09-22 | 2012-03-28 | IMBA-Institut für Molekulare Biotechnologie GmbH | Breast cancer diagnostics |
| BR112013008255A2 (pt) | 2010-10-05 | 2018-09-25 | Daiichi Sankyo Co Ltd | anticorpo isolado ou um fragmento funcional do mesmo, uso de um anticorpo isolado ou de um fragmento funcional do mesmo, composição farmacêutica, polinucleotídeo, vetor, célula transformada, e, método para produzir anticorpo |
| US20130280260A1 (en) * | 2010-10-13 | 2013-10-24 | Tokyo Women's Medical University | Osteoclastogenesis inhibitor containing anti-vdac antibody |
| CA2831247C (en) | 2011-03-31 | 2020-07-21 | Oriental Yeast Co., Ltd. | Cancer immunopotentiating agent containing rankl antagonist |
| CN104349785A (zh) * | 2012-03-21 | 2015-02-11 | 达纳-法伯癌症研究所有限公司 | 人淋巴系器官源性抑制性基质细胞的分离和用途 |
| NZ631509A (en) | 2012-03-30 | 2016-09-30 | Daiichi Sankyo Co Ltd | Cdr-modified anti-siglec-15 antibody |
| US9493562B2 (en) | 2012-07-19 | 2016-11-15 | Alethia Biotherapeutics Inc. | Anti-Siglec-15 antibodies |
| CN105555291B (zh) | 2013-08-07 | 2021-08-24 | 助育公司 | 用于治疗雄性不育症的抗体、化合物及其衍生物 |
| EP3086780A4 (en) | 2013-12-27 | 2017-08-09 | Emergent Product Development Gaithersburg Inc. | Temperature stable vaccine formulations |
| BR112019004901A2 (pt) * | 2016-09-13 | 2019-06-25 | E&S Healthcare Co., Ltd. | anticorpo monoclonal ou um fragmento de ligação ao antígeno do mesmo, seu método de preparação, molécula de ácido nucleico, vetor recombinante, célula hospedeira, kit de diagnóstico e método para fornecer informações |
| CN108410990B (zh) * | 2018-05-30 | 2021-07-06 | 中国医学科学院北京协和医院 | Igfbp3在制备诊断i型神经纤维瘤合并脊柱畸形病产品中的应用 |
| CN111205354B (zh) * | 2020-01-22 | 2021-01-22 | 天津科技大学 | 一种提高异源蛋白分泌量的信号肽突变体及其构建方法与用途 |
| CN111333709B (zh) * | 2020-03-17 | 2023-09-08 | 吉林大学 | 旋毛虫肌幼虫期丝氨酸蛋白酶抑制剂的b细胞表位多肽、杂交瘤细胞株、单克隆抗体及应用 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4179337A (en) * | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4710457A (en) * | 1983-06-29 | 1987-12-01 | Sloan-Kettering Institute For Cancer Research | Monoclonal antibody for human hematopoietic glycoproteins and method |
| US4710473A (en) * | 1983-08-10 | 1987-12-01 | Amgen, Inc. | DNA plasmids |
| EP0192658A4 (en) | 1984-07-30 | 1987-07-13 | Salk Inst For Biological Studi | RETROVIRAL GENE TRANSFER VECTORS. |
| US4959314A (en) * | 1984-11-09 | 1990-09-25 | Cetus Corporation | Cysteine-depleted muteins of biologically active proteins |
| US5846534A (en) * | 1988-02-12 | 1998-12-08 | British Technology Group Limited | Antibodies to the antigen campath-1 |
| US6027729A (en) * | 1989-04-20 | 2000-02-22 | Chiron Corporation | NANBV Diagnostics and vaccines |
| AU648505B2 (en) | 1989-05-19 | 1994-04-28 | Amgen, Inc. | Metalloproteinase inhibitor |
| AU651421B2 (en) * | 1990-11-30 | 1994-07-21 | Celtrix Pharmaceuticals, Inc. | Use of a bone morphogenetic protein in synergistic combination with TGF-beta for bone repair |
| US5118667A (en) * | 1991-05-03 | 1992-06-02 | Celtrix Pharmaceuticals, Inc. | Bone growth factors and inhibitors of bone resorption for promoting bone formation |
| CA2068389A1 (en) | 1991-05-13 | 1992-11-14 | Masahiko Sato | Method for inhibiting bone resorption |
| MX9204303A (es) * | 1991-07-23 | 1993-11-01 | Rhone Poulenc Rorer Int | Factor regulador del crecimiento de osteoclasto. |
| IL99120A0 (en) | 1991-08-07 | 1992-07-15 | Yeda Res & Dev | Multimers of the soluble forms of tnf receptors,their preparation and pharmaceutical compositions containing them |
| EP0746609A4 (en) | 1991-12-17 | 1997-12-17 | Genpharm Int | NON-HUMAN TRANSGENIC ANIMALS CAPABLE OF PRODUCING HETEROLOGOUS ANTIBODIES |
| US5623053A (en) * | 1992-01-10 | 1997-04-22 | California Institute Of Technology | Soluble mammal-derived Fc receptor which binds at a pH ranging from about 5.5 to 6.5 and releases at a pH ranging from about 7.5 to 8.5 |
| US5447851B1 (en) * | 1992-04-02 | 1999-07-06 | Univ Texas System Board Of | Dna encoding a chimeric polypeptide comprising the extracellular domain of tnf receptor fused to igg vectors and host cells |
| JPH07509223A (ja) | 1992-04-30 | 1995-10-12 | アムジェン インコーポレイテッド | インターロイキン−1媒介疾患および腫瘍壊死因子媒介疾患の治療方法 |
| US5585479A (en) * | 1992-07-24 | 1996-12-17 | The United States Of America As Represented By The Secretary Of The Navy | Antisense oligonucleotides directed against human ELAM-I RNA |
| US5578569A (en) * | 1993-03-12 | 1996-11-26 | Tam; Cherk S. | Method of increasing bone growth |
| US5457035A (en) * | 1993-07-23 | 1995-10-10 | Immunex Corporation | Cytokine which is a ligand for OX40 |
| CA2171610A1 (en) | 1993-09-14 | 1995-03-23 | Gideon A. Rodan | Cdna encoding a novel human protein tyrosine phosphatase |
| US6268212B1 (en) | 1993-10-18 | 2001-07-31 | Amgen Inc. | Tissue specific transgene expression |
| AU4440496A (en) | 1995-02-10 | 1996-08-22 | Smithkline Beecham Corporation | Use of src SH2 specific compounds to treat a bone resorption disease |
| IL117175A (en) | 1995-02-20 | 2005-11-20 | Sankyo Co | Osteoclastogenesis inhibitory factor protein |
| US20030166097A1 (en) * | 1995-03-15 | 2003-09-04 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor |
| WO1996028546A1 (en) | 1995-03-15 | 1996-09-19 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor |
| US7094564B1 (en) * | 1995-03-15 | 2006-08-22 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor |
| AU6090896A (en) | 1995-06-07 | 1997-01-15 | Osteosa Inc. | Osteoclast growth regulatory factor |
| US5843901A (en) * | 1995-06-07 | 1998-12-01 | Advanced Research & Technology Institute | LHRH antagonist peptides |
| AU5985996A (en) | 1995-06-07 | 1997-01-15 | Osteosa Inc. | Osteoclast growth regulatory factor |
| US6369027B1 (en) * | 1995-12-22 | 2002-04-09 | Amgen Inc. | Osteoprotegerin |
| US6613544B1 (en) * | 1995-12-22 | 2003-09-02 | Amgen Inc. | Osteoprotegerin |
| US5662948A (en) * | 1996-01-29 | 1997-09-02 | Chrysler Corporation | Adjustable and removable trimline inserts for a molding tool |
| US6750091B1 (en) * | 1996-03-01 | 2004-06-15 | Micron Technology | Diode formation method |
| JPH1057071A (ja) | 1996-08-19 | 1998-03-03 | Snow Brand Milk Prod Co Ltd | 新規dna及びそれを用いた蛋白質の製造方法 |
| DE122010000046I1 (de) * | 1996-12-13 | 2011-05-05 | Schering Corp | Oberflächenantigene aus Säugern |
| FR2757507B1 (fr) | 1996-12-20 | 1999-01-29 | Inst Francais Du Petrole | Procede de separation de paraxylene comprenant une adsorption avec injection d'eau et une cristallisation |
| AU5901598A (en) * | 1996-12-20 | 1998-07-17 | Board Of Regents, The University Of Texas System | Compositions and methods of use for osteoclast inhibitory factors |
| DE951551T1 (de) * | 1996-12-23 | 2000-09-14 | Immunex Corp., Seattle | Ligand für rezeptor aktivator of nf-kappa b, ligand ist mitglied der tnf superfamilie |
| US6271349B1 (en) * | 1996-12-23 | 2001-08-07 | Immunex Corporation | Receptor activator of NF-κB |
| ES2263204T5 (es) | 1997-04-15 | 2013-10-14 | Daiichi Sankyo Company, Limited | Nueva proteína y proceso para producir la misma |
| US6316408B1 (en) * | 1997-04-16 | 2001-11-13 | Amgen Inc. | Methods of use for osetoprotegerin binding protein receptors |
| RO128635A2 (ro) * | 1997-04-16 | 2013-07-30 | Amgen Inc. | Anticorp sau fragment al acestuia care se leagă la opgbp şi utilizarea acestuia, utilizarea unei forme solubile de odar, şi metodă de identificare a unui compus care descreşte activitatea opgbp |
| US5843678A (en) * | 1997-04-16 | 1998-12-01 | Amgen Inc. | Osteoprotegerin binding proteins |
| JP2002514079A (ja) | 1997-05-01 | 2002-05-14 | アムジエン・インコーポレーテツド | キメラopgポリペプチド |
| WO1998054201A1 (en) | 1997-05-29 | 1998-12-03 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor-like protein 8 |
| US6087555A (en) | 1997-10-15 | 2000-07-11 | Amgen Inc. | Mice lacking expression of osteoprotegerin |
| US6790823B1 (en) | 1998-04-23 | 2004-09-14 | Amgen Inc. | Compositions and methods for the prevention and treatment of cardiovascular diseases |
| EP2009025B1 (en) | 1998-05-14 | 2011-07-27 | Immunex Corporation | Method of inhibiting osteoclast activity |
| WO2001003719A2 (en) | 1999-07-09 | 2001-01-18 | Amgen Inc. | Combination therapy for conditions leading to bone loss |
| CA2349406C (en) | 1999-09-03 | 2011-01-11 | Amgen Inc. | Compositions and methods for the prevention or treatment of cancer and bone loss associated with cancer |
| US20030144187A1 (en) | 1999-09-03 | 2003-07-31 | Colin R. Dunstan | Opg fusion protein compositions and methods |
| US20030103978A1 (en) * | 2000-02-23 | 2003-06-05 | Amgen Inc. | Selective binding agents of osteoprotegerin binding protein |
| DK2270052T3 (en) * | 2001-06-26 | 2018-07-02 | Amgen Inc | Antibodies to OPGL |
| JP4761710B2 (ja) * | 2002-04-05 | 2011-08-31 | アムジェン インコーポレイテッド | 選択的opgl経路インヒビターとしてのヒト抗opgl中和抗体 |
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1998
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- 1998-04-15 HU HU0000717A patent/HU229476B1/hu active Protection Beyond IP Right Term
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- 1998-04-15 DE DE122010000049C patent/DE122010000049I1/de active Pending
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- 1998-04-15 EP EP20100186133 patent/EP2336168A1/en not_active Withdrawn
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2002
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