JPH11503616A - オステオプロテゲリン - Google Patents
オステオプロテゲリンInfo
- Publication number
- JPH11503616A JPH11503616A JP9523861A JP52386197A JPH11503616A JP H11503616 A JPH11503616 A JP H11503616A JP 9523861 A JP9523861 A JP 9523861A JP 52386197 A JP52386197 A JP 52386197A JP H11503616 A JPH11503616 A JP H11503616A
- Authority
- JP
- Japan
- Prior art keywords
- opg
- polypeptide
- met
- seq
- bone
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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Abstract
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Claims (1)
- 【特許請求の範囲】 1.OPGの生物学的活性のうち少なくとも1つを含むポリペプチドをコード する単離された核酸であって、該核酸が: (a)図2B−2C(配列番号:120)、9A−9B(配列番号:122) 、および9C−9D(配列番号:124)で示される核酸またはその相補的鎖; (b)図2B−2C(配列番号:120)、9A−9B(配列番号:122) 、および9C−9D(配列番号:124)で示されるペプチド−コーディング領 域とストリンジェント条件下でハイブリダイズする核酸; (c)包括的に図1Aに示されたヌクレオチド148ないし337とストリン ジェント条件下でハイブリダイズする核酸;および (d)(a)、(b)および(c)の核酸に対して縮重した核酸; よりなる群から選択される該単離された核酸。 2.cDNA、ゲノミックDNA、合成DNAまたはRNAである請求項1記 載の核酸。 3.請求項1記載の核酸によってコードされたポリペプチド。 4.エシェリキア・コリ(Escherichia coli)発現に好まし い1以上のコドンを含む請求項1記載の核酸。 5.それに結合した検出可能な標識を有する請求項1記載の核酸。 6.図2B−2C(配列番号:120)、9A−9B(配列番号:122)、 および9C−9D(配列番号:124)のポリペプチド−コーディング領域を含 む請求項1記載の核酸。 7.ヌクレオチド158−1297からの図9C−D(配列番号:124)で 示された配列を有する請求項6記載の核酸。 8.請求項1記載の核酸を含む発現ベクター。 9.該核酸が図9C−9D(配列番号:124)で示されたポリペプチド−コ ーディング領域を含む請求項8記載の発現ベクター。 10.請求項8記載の発現ベクターで形質転換またはトランスフェクトされた 宿主細胞。 11.真核生物細胞である請求項10記載の宿主細胞。 12.CHO、COS、293、3T3、CV−1およびBHK細胞よりなる 群から選択される請求項11記載の宿主細胞。 13.原核生物細胞である請求項10記載の宿主細胞。 14.エシェリキア・コリ(Escherichia coli)である請求 項13記載の宿主細胞。 15.請求項8記載の発現ベクターを含むトランスジェニック哺乳動物。 16.齧歯類である請求項15記載のトランスジェニック哺乳動物。 17.マウスである請求項16記載のトランスジェニック哺乳動物。 18.適当な栄養条件下で、請求項1記載の核酸で形質転換またはトランスフ ェクトされた宿主細胞を増殖させ;次いで、 該核酸の発現のポリペプチド産物を単離することを特徴とするOPGの生産方 法。 19.OPGを含む精製され単離されたポリペプチド。 20.哺乳動物OPGである請求項19記載のポリペプチド。 21.ヒトOPGである請求項20記載のポリペプチド。 22.実質的に他のヒト蛋白質を含まない請求項19記載のポリペプチド。 23.図2B−2C(配列番号:121)、9A−9B(配 列番号:123)、および9C−9D(配列番号:125)で示されるアミノ酸 配列を有する請求項21記載のポリペプチドまたはその誘導体。 24.包括的に残基22−401からの図9C−9D(配列番号:125)で 示されるアミノ酸配列を有する請求項23記載のポリペプチド。 25.包括的に残基32−401からの図9C−9D(配列番号:125)で 示されるアミノ酸配列を有する請求項23記載のポリペプチド。 26.外因性DNA配列の発現の産物であることによって特徴付けられる請求 項19記載のポリペプチド。 27.該DNAがcDNA、ゲノミックDNAまたは合成DNAである請求項 26記載のポリペプチド。 28.水溶性ポリマーで修飾されている請求項19記載のポリペプチド。 29.該水溶性ポリマーがポリエチレングリコールである請求項28記載のポ リペプチド。 30.腫瘍壊死因子受容体細胞外領域のシステインリッチドメインに特徴的な 4つのシステイン−リッチドメインを含む少 なくとも約164アミノ酸のアミノ酸配列;および増大した骨密度の活性を含む ポリペプチド。 31.残基22のアミノ末端を有する図2B−2C(配列番号:121)、9 A−9B(配列番号:123)または9C−9D(配列番号:125)で示され るアミノ酸配列を含み、1ないし216アミノ酸がカルボキシル末端から欠失さ れているポリペプチド。 32.包括的に残基22−185、22−189、22−194、または22 −201からのアミノ酸配列を含む請求項31記載のポリペプチド。 33.さらにカルボキシル末端から伸びるヒトIgG1のFc領域を含む請求 項32記載のポリペプチド。 34.残基22のアミノ末端を有する図2B−2C(配列番号:121)、9 A−9B(配列番号:123)または9C−9D(配列番号:125)で示され るアミノ酸配列を含み、1ないし10アミノ酸がアミノ末端から欠失されており 、所望により1ないし216アミノ酸がカルボキシル末端から欠失されていても よいポリペプチド。 35.包括的に残基27−185、27−189、27−1 94、27−401、または32−401からのアミノ酸配列を含む請求項34 記載のポリペプチド。 36.さらに、カルボキシル末端から伸びるヒトIgG1のFc領域を含む請 求項35記載のポリペプチド。 37. huOPG[22−201]−Fc、 huOPG[22−401]−Fc、 huOPG[22−180]−Fc、 huOPG met[22−401]−Fc、 huOPG Fc−met[22−401]、 huOPG met[22−185]、 huOPG met[22−189]、 huOPG met[22−194]、 huOPG met[27−185]、 huOPG met[27−189]、 huOPG met[27−194]、 huOPG met[32−401]、 huOPG met−lys[22−401]、 huOPG met[22−401]、 huOPG met[22−401]−Fc (P25A)、 huOPG met[22−401] (P25A)、 huOPG met[22−401] (P26A)、 huOPG met[22−401] (P26D)、 huOPG met[22−194] (P25A)、 huOPG met[22−194] (P26A)、 huOPG met met−(lys)3[22−401]、 huOPG met met−arg−gly−ser−(his)6[22 −401] よりなる群から選択されるポリペプチド。 38.請求項37記載のポリペプチドをコードする核酸。 39.OPGに特異的に結合する抗体またはその断片。 40.モノクローナル抗体である請求項39記載の抗体。 41.OPGへの抗体の結合を可能とする条件下で請求項39記載の抗体と共 に試料をインキュベートし;次いで、 結合した抗体を検出することを特徴とする生物学的試料中のOPGの存在を検 出する方法。 42.結合を可能とする条件下で候補物質と共にOPGをインキュベートし; 次いで、 結合物質を測定することを特徴とするOPGに結合する候補物質の能力を評価 する方法。 43.OPGをコードする核酸で動物を修飾することを特徴とする動物におい てOPGのレベルを調節する方法。 44.該核酸がOPGの組織レベルにおける増加を促進する請求項43記載の 方法。 45.該動物がヒトである請求項44記載の方法。 46.医薬上許容される担体、アジュバント、可溶化剤、安定化剤および/ま たは抗酸化剤中の治療上有効量のOPGを含む医薬組成物。 47.該OPGがヒトOPGである請求項46記載の組成物。 48.該OPGが図9Bで示されるアミノ酸配列を有する請求項47記載の組 成物。 49.治療上有効量の請求項19記載のポリペプチドを投与することを特徴と する骨障害を治療する方法。 50.該ポリペプチドがヒトOPGである請求項49記載の方法。 51.該骨障害が過剰な骨喪失である請求項49記載の方法。 52.該骨障害が骨粗鬆症、骨のパジェット病、高カルシウ ム血症、副甲状腺機能亢進症、ステロイド−誘発骨減少症、慢性関節リウマチに よる骨喪失、骨髄炎による骨喪失、骨溶解転移、および歯周骨喪失よりなる群か ら選択される請求項51記載の方法。 53.さらに、骨形態発生蛋白質BMP−1ないしBMP−12、TGF−β ファミリーのメンバー、IL−1阻害剤、TNFα阻害剤、副甲状腺ホルモンお よびそのアナログ、副甲状腺ホルモン関連蛋白質およびそのアナログ、Eシリー ズのプロスタグランジン、ビスホスホネート、および骨増強性ミネラルよりなる 群から選択される物質の治療上有効量を投与することを特徴とする請求項49記 載の方法。 54.複数のオステオプロテゲリンモノマーよりなるオステオプロテゲリン多 量体。 55.ダイマーである請求項54記載の多量体。 56.鎖内ジスルフィド結合によって形成された請求項54記載の多量体。 57.ヒトIgG1に由来するのFc領域との組合せによって形成された請求 項54記載の多量体。 58.オステオプロテゲリンモノマーおよび不活性な多量体 を実質的に含まない請求項54記載の多量体。 59.該モノマーが残基22−401からの図9C−9D[配列番号:125 ]で示されるアミノ酸配列を含む請求項54記載の多量体、またはその誘導体。 60.該モノマーが残基22−194からの図9C−9D[配列番号:125 ]で示されるアミノ酸配列を含む請求項54記載の多量体。
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US08/577,788 US6613544B1 (en) | 1995-12-22 | 1995-12-22 | Osteoprotegerin |
US08/706,945 US6369027B1 (en) | 1995-12-22 | 1996-09-03 | Osteoprotegerin |
US08/706,945 | 1996-09-03 | ||
PCT/US1996/020621 WO1997023614A1 (en) | 1995-12-22 | 1996-12-20 | Osteoprotegerin |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003508491A (ja) * | 1999-09-03 | 2003-03-04 | アムジエン・インコーポレーテツド | 癌および癌に関連する骨損失の予防または治療のための組成物および方法 |
JP2008522593A (ja) * | 2004-12-13 | 2008-07-03 | エヴォジェニックス・リミテッド | オステオプロテゲリン・バリアントタンパク質 |
JP4380067B2 (ja) * | 1998-04-23 | 2009-12-09 | 味の素株式会社 | 抗血栓活性物質及びグリコカリシンの検出法 |
JP2015514082A (ja) * | 2012-03-31 | 2015-05-18 | アール−ファーム・クローズド・ジョイント・ストック・カンパニーR−Pharm, CJSC | オステオプロテゲリン由来の組成物およびその使用 |
JP2017131228A (ja) * | 2017-02-24 | 2017-08-03 | アール−ファーム・クローズド・ジョイント・ストック・カンパニーR−Pharm, CJSC | オステオプロテゲリン由来の組成物およびその使用 |
US20230235109A1 (en) * | 2020-04-17 | 2023-07-27 | The Board Of Trustees Of The Leland Stanford Junior University | Polymer excipients for biopharmaceutical formulations |
Families Citing this family (79)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6919434B1 (en) | 1995-02-20 | 2005-07-19 | Sankyo Co., Ltd. | Monoclonal antibodies that bind OCIF |
IL117175A (en) * | 1995-02-20 | 2005-11-20 | Sankyo Co | Osteoclastogenesis inhibitory factor protein |
US7078493B1 (en) | 1995-03-15 | 2006-07-18 | Human Genome Sciences, Inc. | Antibodies to human tumor necrosis factor receptor-like genes |
US7005413B1 (en) | 1995-12-22 | 2006-02-28 | Amgen Inc. | Combination therapy for conditions leading to bone loss |
US7632922B1 (en) * | 1995-12-22 | 2009-12-15 | Amgen, Inc. | Osteoprotegerin |
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 |
CA2273852C (en) | 1996-12-06 | 2009-09-29 | Amgen Inc. | Combination therapy using an il-1 inhibitor for treating il-1 mediated diseases |
US6271349B1 (en) | 1996-12-23 | 2001-08-07 | Immunex Corporation | Receptor activator of NF-κB |
DE69740107D1 (de) | 1996-12-23 | 2011-03-10 | Immunex Corp | Rezeptor aktivator von nf-kappa b, rezeptor is mitglied der tnf rezeptor superfamilie |
NZ332995A (en) * | 1997-04-15 | 2000-07-28 | Snow Brand Milk Products Co Ltd | A protein which binds to osteoclastogenesis inhibitory factor (OCIF) |
ATE363533T1 (de) | 1997-04-16 | 2007-06-15 | Amgen Inc | Osteoprotegerin bindende proteine und rezeptoren |
US6316408B1 (en) | 1997-04-16 | 2001-11-13 | Amgen Inc. | Methods of use for osetoprotegerin binding protein receptors |
AU7469998A (en) * | 1997-05-01 | 1998-11-24 | Amgen, Inc. | Chimeric opg polypeptides |
WO1999004001A1 (en) * | 1997-07-21 | 1999-01-28 | Zymogenetics, Inc. | Tumor necrosis factor receptor ztnfr-5 |
EP1019502A2 (en) * | 1997-08-06 | 2000-07-19 | Regeneron Pharmaceuticals, Inc. | Human orphan receptor ntr-1 |
US6346388B1 (en) | 1997-08-13 | 2002-02-12 | Smithkline Beecham Corporation | Method of identifying agonist and antagonists for tumor necrosis related receptors TR1 and TR2 |
WO1999011790A1 (en) * | 1997-09-04 | 1999-03-11 | Zymogenetics, Inc. | Tumor necrosis factor receptor ztnfr-6 |
DK1015587T3 (da) * | 1997-09-18 | 2008-08-25 | Genentech Inc | DcR3 polypeptid, en TNFR-homolog |
AU739304B2 (en) * | 1997-09-24 | 2001-10-11 | Sankyo Company Limited | Method of diagnosing metabolic bone diseases |
US6087555A (en) * | 1997-10-15 | 2000-07-11 | Amgen Inc. | Mice lacking expression of osteoprotegerin |
JPH11155420A (ja) * | 1997-12-02 | 1999-06-15 | Snow Brand Milk Prod Co Ltd | トランスジェニック動物 |
WO1999031128A2 (en) * | 1997-12-16 | 1999-06-24 | Incyte Pharmaceuticals, Inc. | Human tumor necrosis factor-r2-like proteins |
US6077689A (en) | 1997-12-24 | 2000-06-20 | Amgen Inc. | Enhanced solubility of recombinant proteins |
WO1999041374A2 (en) * | 1998-02-17 | 1999-08-19 | Incyte Pharmaceuticals, Inc. | Human short-chain tnf-receptor family protein |
US6103472A (en) * | 1998-02-20 | 2000-08-15 | Amgen Inc. | Methods and compositions for identifying novel secreted mammalian polypeptides in yeast |
US6150098A (en) * | 1998-02-20 | 2000-11-21 | Amgen Inc. | Methods for identifying novel secreted mammalian polypeptides |
US6790823B1 (en) * | 1998-04-23 | 2004-09-14 | Amgen Inc. | Compositions and methods for the prevention and treatment of cardiovascular diseases |
AU762574B2 (en) | 1998-05-14 | 2003-06-26 | Immunex Corporation | Method of inhibiting osteoclast activity |
US6210924B1 (en) | 1998-08-11 | 2001-04-03 | Amgen Inc. | Overexpressing cyclin D 1 in a eukaryotic cell line |
CN1318105A (zh) * | 1998-09-15 | 2001-10-17 | M&E生物技术公司 | 负调节Osteoprotegerin配体活性的方法 |
US6420339B1 (en) | 1998-10-14 | 2002-07-16 | Amgen Inc. | Site-directed dual pegylation of proteins for improved bioactivity and biocompatibility |
HU228582B1 (en) | 1998-10-23 | 2013-04-29 | Kirin Amgen Inc | Dimeric thrombopoietin peptide mimetics binding to mp1 receptor and having thrombopoietic activity |
US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
US7488590B2 (en) | 1998-10-23 | 2009-02-10 | Amgen Inc. | Modified peptides as therapeutic agents |
NZ511506A (en) * | 1998-10-28 | 2004-02-27 | Sankyo Co | Remedies for bone metabolic errors comprising OCIF |
US6245740B1 (en) | 1998-12-23 | 2001-06-12 | Amgen Inc. | Polyol:oil suspensions for the sustained release of proteins |
JP2005517379A (ja) * | 1999-01-18 | 2005-06-16 | オステオミーター・ビオテク・エー/エス | 遺伝的疾病素因 |
US20030007972A1 (en) * | 1999-02-24 | 2003-01-09 | Edward Tobinick | Cytokine antagonists and other biologics for the treatment of bone metastases |
US7259253B2 (en) * | 1999-05-14 | 2007-08-21 | Quark Biotech, Inc. | Genes associated with mechanical stress, expression products therefrom, and uses thereof |
AU6078500A (en) * | 1999-07-09 | 2001-01-30 | Amgen, Inc. | Combination therapy for conditions leading to bone loss |
AUPQ167599A0 (en) * | 1999-07-19 | 1999-08-12 | St. Vincent's Institute Of Medical Research | Inhibitor of osteoclast precursor formation |
IL130989A0 (en) * | 1999-07-20 | 2001-01-28 | Compugen Ltd | Variants of alternative splicing |
US6673771B1 (en) | 1999-07-28 | 2004-01-06 | The Trustees Of The University Of Pennsylvania | Methods of inhibiting osteoclast activity |
US8106098B2 (en) | 1999-08-09 | 2012-01-31 | The General Hospital Corporation | Protein conjugates with a water-soluble biocompatible, biodegradable polymer |
AU6946300A (en) * | 1999-08-30 | 2001-03-26 | Mayo Foundation For Medical Education And Research | Use of dna encoding osteoprotegerin to prevent or inhibit metabolic bone disorders |
AU2005237128B2 (en) * | 1999-09-03 | 2008-09-11 | 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 |
US6808902B1 (en) * | 1999-11-12 | 2004-10-26 | Amgen Inc. | Process for correction of a disulfide misfold in IL-1Ra Fc fusion molecules |
EP1238077A1 (en) * | 1999-12-16 | 2002-09-11 | Amgen Inc., | Tnfr/opg-like molecules and uses thereof |
US20030103978A1 (en) * | 2000-02-23 | 2003-06-05 | Amgen Inc. | Selective binding agents of osteoprotegerin binding protein |
ES2391124T3 (es) | 2000-06-28 | 2012-11-21 | Amgen Inc. | Moléculas de receptor de linfopoyetina estromal tímica y usos de las mismas |
DE01973455T1 (de) * | 2000-09-22 | 2004-04-22 | Immunex Corp., Seattle | Screeningverfahren für agonisten und antagonisten des rezeptoraktivators von nf-kappa b |
AU2002231602A1 (en) * | 2001-02-09 | 2002-08-28 | Maxygen Holdings Ltd. | Rank ligand-binding polypeptides |
ES2337716T3 (es) | 2001-04-03 | 2010-04-28 | Societe Des Produits Nestle S.A. | Osteoprotegerina en la leche. |
JP2005515159A (ja) * | 2001-06-06 | 2005-05-26 | イミュネックス・コーポレーション | 癌を治療するためのrankアンタゴニストの使用 |
YU103003A (sh) | 2001-06-26 | 2006-05-25 | Abgenix Inc. | Antitela za opgl |
EP1270015A3 (en) * | 2001-06-29 | 2004-02-25 | Sankyo Company Limited | A complex comprising OCIF and Polysaccharide |
KR100427299B1 (ko) * | 2001-08-10 | 2004-04-14 | 한국생명공학연구원 | 인체 골 재흡수 억제인자(hOPG)를 생산하는 재조합플라스미드 pGHOPG(KCTC 1019BP) |
US20030049694A1 (en) * | 2001-09-10 | 2003-03-13 | Chung-Hsiun Wu | Production of fusion proteins and use for identifying binding molecules |
US6800462B2 (en) * | 2001-09-10 | 2004-10-05 | Abgenomics Corporation | Production of recombinant proteins in vivo and use for generating antibodies |
US7521053B2 (en) | 2001-10-11 | 2009-04-21 | Amgen Inc. | Angiopoietin-2 specific binding agents |
US7205275B2 (en) | 2001-10-11 | 2007-04-17 | Amgen Inc. | Methods of treatment using specific binding agents of human angiopoietin-2 |
US7138370B2 (en) | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
JP4336467B2 (ja) * | 2001-10-15 | 2009-09-30 | 株式会社林原生物化学研究所 | 破骨細胞形成抑制因子の産生を調節し得る物質のスクリーニング方法 |
US20030191056A1 (en) | 2002-04-04 | 2003-10-09 | Kenneth Walker | Use of transthyretin peptide/protein fusions to increase the serum half-life of pharmacologically active peptides/proteins |
MXPA04009681A (es) | 2002-04-05 | 2005-01-11 | Amgen Inc | Anticuerpos humanos neutralizantes anti-ligando de osteoprotegerina como inhibidores selectivos de la ruta del ligando de osteoprotegerina. |
US20080249068A1 (en) * | 2002-09-05 | 2008-10-09 | Deluca Hector F | Method of Extending the Dose Range of Vitamin D Compounds |
US7259143B2 (en) * | 2002-09-05 | 2007-08-21 | Wisconsin Alumni Research Foundation | Method of extending the dose range of vitamin D compounds |
AU2003297833A1 (en) | 2002-12-10 | 2004-06-30 | Schering-Plough Ltd. | Canine rankl and methods for preparing and using the same |
TWI293882B (en) | 2003-03-24 | 2008-03-01 | Sankyo Co | Polymeric modifiers and pharmaceutical compositions |
US8143380B2 (en) | 2004-07-08 | 2012-03-27 | Amgen Inc. | Therapeutic peptides |
US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
US9283260B2 (en) | 2006-04-21 | 2016-03-15 | Amgen Inc. | Lyophilized therapeutic peptibody formulations |
CA2687141C (en) | 2007-05-22 | 2014-04-01 | Amgen Inc. | Compositions and methods for producing bioactive fusion proteins |
EP2464377B1 (en) | 2009-08-14 | 2016-07-27 | The Government of the United States of America as represented by The Secretary of the Department of Health and Human Services | Use of il-15 to increase thymic output and to treat lymphopenia |
PT2621519T (pt) | 2010-09-28 | 2017-10-04 | Aegerion Pharmaceuticals Inc | Polipéptido de fusão de leptina-abd com duração de ação melhorada |
US9812699B2 (en) | 2011-10-05 | 2017-11-07 | Oned Material Llc | Silicon nanostructure active materials for lithium ion batteries and processes, compositions, components and devices related thereto |
EP3574017A1 (en) | 2017-01-27 | 2019-12-04 | Kymab Limited | Anti-opg antibodies |
CN111004318B (zh) * | 2019-12-30 | 2022-03-04 | 北京博康健基因科技有限公司 | rhPTH(1-34)蛋白原液的纯化方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996005309A2 (en) * | 1994-08-17 | 1996-02-22 | The Rockefeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
WO1996026217A1 (fr) * | 1995-02-20 | 1996-08-29 | Snow Brand Milk Products Co., Ltd. | Proteine nouvelle et ses procedes de production |
WO1996028546A1 (en) * | 1995-03-15 | 1996-09-19 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
US6936694B1 (en) | 1982-05-06 | 2005-08-30 | Intermune, Inc. | Manufacture and expression of large structural genes |
US4710473A (en) | 1983-08-10 | 1987-12-01 | Amgen, Inc. | DNA plasmids |
FR2640537B1 (fr) | 1988-12-21 | 1992-02-21 | Levy Guy | Installation et procede utilisant l'effet laser, pour la coupe ou la vaporisation de materiaux et tissus divers |
ATE135370T1 (de) | 1988-12-22 | 1996-03-15 | Kirin Amgen Inc | Chemisch modifizierte granulocytenkolonie erregender faktor |
AU648505B2 (en) | 1989-05-19 | 1994-04-28 | Amgen, Inc. | Metalloproteinase inhibitor |
US5395760A (en) * | 1989-09-05 | 1995-03-07 | Immunex Corporation | DNA encoding tumor necrosis factor-α and -β receptors |
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 |
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 |
JP3284481B2 (ja) | 1993-08-20 | 2002-05-20 | 本田技研工業株式会社 | 車両用油圧作動式変速機の油圧制御回路 |
US6268212B1 (en) | 1993-10-18 | 2001-07-31 | Amgen Inc. | Tissue specific transgene expression |
JP3433495B2 (ja) | 1993-12-30 | 2003-08-04 | カシオ計算機株式会社 | 表示制御装置および表示制御方法 |
US8615703B2 (en) | 2010-06-04 | 2013-12-24 | Micron Technology, Inc. | Advanced bitwise operations and apparatus in a multi-level system with nonvolatile memory |
-
1996
- 1996-09-03 US US08/706,945 patent/US6369027B1/en not_active Expired - Fee Related
- 1996-12-19 AR ARP960105797A patent/AR004400A1/es unknown
- 1996-12-20 AU AU14686/97A patent/AU710587B2/en not_active Ceased
- 1996-12-20 MX MX9706193A patent/MX9706193A/es not_active IP Right Cessation
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- 1996-12-20 YU YU69196A patent/YU69196A/sr unknown
- 1996-12-20 EP EP08003204A patent/EP1990415A1/en not_active Withdrawn
- 1996-12-20 WO PCT/US1996/020621 patent/WO1997023614A1/en active Application Filing
- 1996-12-20 EP EP10181616A patent/EP2332974A3/en not_active Withdrawn
- 1996-12-20 TR TR96/01036A patent/TR199601036A2/xx unknown
- 1996-12-20 NZ NZ332915A patent/NZ332915A/xx unknown
- 1996-12-20 CZ CZ19972538A patent/CZ292587B6/cs not_active IP Right Cessation
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- 1996-12-20 CN CNB961934417A patent/CN1318588C/zh not_active Expired - Fee Related
- 1996-12-20 RO RO97-01539A patent/RO121386B1/ro unknown
- 1996-12-20 AT AT96309363T patent/ATE409745T1/de active
- 1996-12-20 DK DK96309363T patent/DK0784093T3/da active
- 1996-12-20 DE DE19654610A patent/DE19654610A1/de not_active Ceased
- 1996-12-20 NZ NZ326579A patent/NZ326579A/xx unknown
- 1996-12-20 ES ES96309363T patent/ES2316152T3/es not_active Expired - Lifetime
- 1996-12-20 SK SK1107-97A patent/SK110797A3/sk not_active Application Discontinuation
- 1996-12-20 KR KR1019970705843A patent/KR100463584B1/ko not_active IP Right Cessation
- 1996-12-20 CA CA2210467A patent/CA2210467C/en not_active Expired - Fee Related
- 1996-12-20 EP EP96945279A patent/EP0870023A1/en not_active Withdrawn
- 1996-12-20 EP EP96309363A patent/EP0784093B1/en not_active Expired - Lifetime
- 1996-12-20 EE EE9700164A patent/EE04643B1/xx not_active IP Right Cessation
-
1997
- 1997-08-05 BG BG101813A patent/BG63347B1/bg unknown
- 1997-08-11 IL IL121520A patent/IL121520A/en not_active IP Right Cessation
- 1997-08-12 NO NO973699A patent/NO973699L/no not_active Application Discontinuation
-
1998
- 1998-01-16 HK HK98100367A patent/HK1001526A1/xx not_active IP Right Cessation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1996005309A2 (en) * | 1994-08-17 | 1996-02-22 | The Rockefeller University | Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof |
WO1996026217A1 (fr) * | 1995-02-20 | 1996-08-29 | Snow Brand Milk Products Co., Ltd. | Proteine nouvelle et ses procedes de production |
WO1996028546A1 (en) * | 1995-03-15 | 1996-09-19 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptor |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4380067B2 (ja) * | 1998-04-23 | 2009-12-09 | 味の素株式会社 | 抗血栓活性物質及びグリコカリシンの検出法 |
JP2003508491A (ja) * | 1999-09-03 | 2003-03-04 | アムジエン・インコーポレーテツド | 癌および癌に関連する骨損失の予防または治療のための組成物および方法 |
JP2011225581A (ja) * | 1999-09-03 | 2011-11-10 | Amgen | 癌および癌に関連する骨損失の予防または治療のための組成物および方法 |
JP2008522593A (ja) * | 2004-12-13 | 2008-07-03 | エヴォジェニックス・リミテッド | オステオプロテゲリン・バリアントタンパク質 |
JP2015514082A (ja) * | 2012-03-31 | 2015-05-18 | アール−ファーム・クローズド・ジョイント・ストック・カンパニーR−Pharm, CJSC | オステオプロテゲリン由来の組成物およびその使用 |
JP2017131228A (ja) * | 2017-02-24 | 2017-08-03 | アール−ファーム・クローズド・ジョイント・ストック・カンパニーR−Pharm, CJSC | オステオプロテゲリン由来の組成物およびその使用 |
US20230235109A1 (en) * | 2020-04-17 | 2023-07-27 | The Board Of Trustees Of The Leland Stanford Junior University | Polymer excipients for biopharmaceutical formulations |
US11945892B2 (en) | 2020-04-17 | 2024-04-02 | The Board Of Trustees Of The Leland Stanford Junior Univeristy | Polymer excipients for biopharmaceutical formulations |
US12077621B2 (en) | 2020-04-17 | 2024-09-03 | The Board Of Trustees Of The Leland Stanford Junior Univeristy | Polymer excipients for biopharmaceutical formulations |
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