TWI613216B - 經生物工程之抗－ＴＧＦ－β抗體及抗原結合片段 - Google Patents
經生物工程之抗－ＴＧＦ－β抗體及抗原結合片段 Download PDFInfo
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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
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/00113—Growth factors
- A61K39/001134—Transforming growth factor [TGF]
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
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- 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
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- 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
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- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
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- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
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| Publication number | Priority date | Publication date | Assignee | Title |
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| HK1225742A1 (zh) | 2013-08-22 | 2017-09-15 | Acceleron Pharma, Inc. | TGF-β受体II型变体及其用途 |
| DK3240805T3 (da) | 2014-12-15 | 2025-02-10 | Univ California | Bispecifik or-gate kimærisk antigenreceptor, som reagerer på cd19 og cd20 |
| WO2016100233A1 (en) | 2014-12-15 | 2016-06-23 | The Regents Of The University Of California | Cytotoxic molecules responsive to intracellular ligands for selective t cell mediated killing |
| TWI733661B (zh) | 2015-03-04 | 2021-07-21 | 美商健臻公司 | 以高親合性、結合性及特異性結合轉化生長因子－β１的經修飾ＩｇＧ抗體 |
| TWI726870B (zh) | 2015-03-04 | 2021-05-11 | 美商健臻公司 | 具有高親和性、結合性及專一性之結合轉形生長因子-β１的ｓｃＦｖ-Ｆｃ二聚體 |
| EP3331550B1 (en) | 2015-08-04 | 2022-11-02 | Acceleron Pharma Inc. | Composition for treating myeloproliferative disorders |
| EP4036120A1 (en) * | 2015-10-30 | 2022-08-03 | F. Hoffmann-La Roche AG | Hinge modified antibody fragments and methods of making |
| DK3368571T5 (da) * | 2015-10-30 | 2024-09-30 | Univ California | Transformerende, vækstfaktor-beta-responsive polypeptider og fremgangsmåder til anvendelse deraf |
| EP3458608B1 (en) | 2016-05-17 | 2025-07-23 | F. Hoffmann-La Roche AG | Stromal gene signatures for diagnosis and use in immunotherapy |
| GB201610044D0 (en) | 2016-06-08 | 2016-07-20 | Ucb Biopharma Sprl | Antibodies |
| US20190216943A1 (en) * | 2016-08-11 | 2019-07-18 | Precithera, Inc. | Tgf-beta antagonist conjugates |
| CA3039136A1 (en) | 2016-09-02 | 2018-03-08 | The Regents Of The University Of California | Methods and compositions involving interleukin-6 receptor alpha-binding single chain variable fragments |
| FI3628049T3 (fi) | 2017-05-04 | 2023-07-26 | Acceleron Pharma Inc | Tgf-beeta-reseptorin tyypin ii fuusioproteiineja ja niiden käyttöjä |
| JP7544597B2 (ja) | 2017-11-06 | 2024-09-03 | ジェネンテック， インコーポレイテッド | がんの診断及び療法 |
| MA53125A (fr) | 2018-07-11 | 2021-05-19 | Scholar Rock Inc | Inhibiteurs de tgf?1 sélectifs selon l'isoforme à affinité élevée |
| KR102823692B1 (ko) | 2019-08-28 | 2025-06-20 | 추가이 세이야쿠 가부시키가이샤 | 종교차성 항잠재형 TGF-β1 항체 및 사용 방법 |
| TWI867190B (zh) * | 2020-03-19 | 2024-12-21 | 美商建南德克公司 | 同功型選擇性抗-TGF-β抗體及其使用方法 |
| US20220119513A1 (en) * | 2020-06-08 | 2022-04-21 | Zoetis Services Llc | Anti-tgfb antibodies and therapeutic uses thereof |
| WO2022115611A1 (en) | 2020-11-25 | 2022-06-02 | Catamaran Bio, Inc. | Cellular therapeutics engineered with signal modulators and methods of use thereof |
| WO2022157773A2 (en) * | 2021-01-21 | 2022-07-28 | Biolojic Design Ltd. | Dual binding antibodies, methods of producing dual binding antibodies, and uses thereof |
| CN112851819B (zh) * | 2021-01-25 | 2023-08-11 | 华中科技大学同济医学院附属同济医院 | 结合小鼠PD-L1和TGF-β的双特异性抗体及其制备方法与应用 |
| WO2022172085A2 (en) | 2021-02-15 | 2022-08-18 | Takeda Pharmaceutical Company Limited | Cell therapy compositions and methods for modulating tgf-b signaling |
| CN113480645B (zh) * | 2021-07-16 | 2022-11-11 | 甘肃中科博瑞生物工程有限公司 | 一种抗幽门螺旋杆菌重组抗体、制备方法及用途 |
| WO2023080900A1 (en) | 2021-11-05 | 2023-05-11 | Genentech, Inc. | Methods and compositions for classifying and treating kidney cancer |
| EP4599089A1 (en) | 2022-10-05 | 2025-08-13 | Genentech, Inc. | Methods and compositions for classifying and treating bladder cancer |
| WO2024077166A1 (en) | 2022-10-05 | 2024-04-11 | Genentech, Inc. | Methods and compositions for classifying and treating lung cancer |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006086469A2 (en) * | 2005-02-08 | 2006-08-17 | Genzyme Corporation | Antibodies to tgfbeta |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5571714A (en) | 1988-12-22 | 1996-11-05 | Celtrix Pharmaceuticals, Inc. | Monoclonal antibodies which bind both transforming growth factors β1 and β2 and methods of use |
| US6008011A (en) | 1991-10-31 | 1999-12-28 | Whitehead Institute For Biomedical Research | TGF-β type II receptor cDNAs |
| CA2122491A1 (en) | 1991-10-31 | 1993-05-13 | Herbert Y. Lin | Tgf-.beta. type receptor cdnas and uses therefor |
| IL110589A0 (en) | 1993-08-10 | 1994-11-11 | Bioph Biotech Entw Pharm Gmbh | Growth/differentiation factor of the TGF- beta family |
| RU2157406C2 (ru) * | 1993-08-10 | 2000-10-10 | Биофарм Гезелльшафт Цур Биотехнологишен Энтвиклунг Фон Фармака Мбх | НОВЫЙ ФАКТОР РОСТА/ДИФФЕРЕНЦИАЦИИ TGF-β-СЕМЕЙСТВА |
| GB9601081D0 (en) | 1995-10-06 | 1996-03-20 | Cambridge Antibody Tech | Specific binding members for human transforming growth factor beta;materials and methods |
| CA2301166A1 (en) | 1997-07-24 | 1999-02-04 | Yuan-Peng Zhang | Liposomal compositions for the delivery of nucleic acid catalysts |
| WO2000040227A2 (en) | 1999-01-05 | 2000-07-13 | University Of Utah | Methods for treating conditions associated with the accumulation of excess extracellular matrix |
| US7763580B2 (en) | 1999-01-05 | 2010-07-27 | University Of Utah Research Foundation | Methods for treating conditions associated with the accumulation of excess extracellular matrix |
| US6492497B1 (en) | 1999-04-30 | 2002-12-10 | Cambridge Antibody Technology Limited | Specific binding members for TGFbeta1 |
| WO2001066140A1 (en) | 2000-03-09 | 2001-09-13 | Genzyme Corporation | Use of tgf-beta antagonists to treat or to prevent loss of renal function |
| JP4564261B2 (ja) | 2002-01-22 | 2010-10-20 | ジェンザイム、コーポレーション | 慢性的移植片拒絶反応の治療と予防のためのＴＧＦ−β拮抗薬の使用 |
| WO2004098637A1 (en) | 2003-04-30 | 2004-11-18 | Genzyme Corporation | Tgf-beta antagonists combined with renin-angiotensin-aldosteron-system antagonists for treating renal insufficiency |
| US8597646B2 (en) | 2005-10-25 | 2013-12-03 | The Johns Hopkins University | Methods and compositons featuring TGF-beta antagonists for the treatment of marfan syndrome and associated disorders |
| MX2008011874A (es) * | 2006-03-17 | 2009-01-07 | Biogen Idec Inc | Composiciones estabilizadas de polipeptidos. |
| CA2649440A1 (en) | 2006-04-12 | 2007-10-25 | Genzyme Corporation | Methods of treating autoimmune diseases |
| EP2083863B1 (en) | 2006-10-03 | 2015-03-18 | Genzyme Corporation | Antibodies to tgf-beta for use in the treatment of infants at risk of developing bronchopulmonary dysplasia |
| WO2010124276A2 (en) | 2009-04-24 | 2010-10-28 | Vanderbilt Universtiy | Anti-tgf-beta induction of bone cell function and bone growth |
| PT2835053T (pt) | 2010-03-12 | 2016-07-14 | Genzyme Corp | Terapêutica combinada para o tratamento do cancro da mama |
| KR101939965B1 (ko) | 2010-09-01 | 2019-01-18 | 젠자임 코포레이션 | ＴＧＦ－β 길항제를 이용한 심근경색증의 치료 |
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2014
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Patent Citations (1)
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| WO2006086469A2 (en) * | 2005-02-08 | 2006-08-17 | Genzyme Corporation | Antibodies to tgfbeta |
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