KR101497045B1 - 난소 암종의 방사성면역요법을 위한 인간 항-엽산염 수용체알파 항체와 항체 단편 - Google Patents
난소 암종의 방사성면역요법을 위한 인간 항-엽산염 수용체알파 항체와 항체 단편 Download PDFInfo
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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
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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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
- 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
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
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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
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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
- C07K2317/54—F(ab')2
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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
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- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Applications Claiming Priority (3)
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| EP06019399.2 | 2006-09-15 | ||
| EP06019399A EP1900752A1 (en) | 2006-09-15 | 2006-09-15 | Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma |
| PCT/EP2007/007944 WO2008031577A1 (en) | 2006-09-15 | 2007-09-12 | Human anti-folate receptor alpha antibodies and antibody fragments for the radioimmunotherapy of ovarian carcinoma |
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| KR20090059114A KR20090059114A (ko) | 2009-06-10 |
| KR101497045B1 true KR101497045B1 (ko) | 2015-02-27 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2005214331B2 (en) | 2004-02-12 | 2011-09-15 | Eisai, Inc. | Monoclonal antibodies that specifically bind to folate receptor alpha |
| AU2006241099B2 (en) | 2005-04-22 | 2012-04-19 | Eisai, Inc. | Antibodies with immune effector activity and that internalize in folate receptor alpha-positive cells |
| SG10201501342UA (en) * | 2010-02-24 | 2015-04-29 | Immunogen Inc | Folate receptor 1 antibodies and immunoconjugates and uses thereof |
| EP2614084A4 (en) | 2010-09-09 | 2014-02-19 | Purdue Research Foundation | HUMANE FOLAT RECEPTOR BETA ANTIBODIES AND METHOD FOR THEIR USE |
| SG189957A1 (en) * | 2010-11-05 | 2013-06-28 | Morphotek Inc | Folate receptor alpha as a diagnostic and prognostic marker for folate receptor alpha-expressing cancers |
| AU2012207356A1 (en) | 2011-01-18 | 2013-08-01 | The Trustees Of The University Of Pennsylvania | Compositions and methods for treating cancer |
| US20140010756A1 (en) | 2011-03-18 | 2014-01-09 | Kagoshima University | Composition for treatment and diagnosis of pancreatic cancer |
| SI2694106T1 (en) * | 2011-04-01 | 2018-04-30 | Immunogen, Inc. | Methods for increasing the effectiveness of treatment with FOLR1 receptor cancer |
| SI2731972T1 (en) | 2011-07-15 | 2018-04-30 | Eisai R&D Management Co., Ltd. | Anti-folate receptor alpha antibodies and uses thereof |
| WO2013026839A1 (en) * | 2011-08-23 | 2013-02-28 | Roche Glycart Ag | Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use |
| US9629918B2 (en) | 2012-02-29 | 2017-04-25 | Purdue Research Foundation | Folate receptor alpha binding ligands |
| US9200073B2 (en) * | 2012-08-31 | 2015-12-01 | Immunogen, Inc. | Diagnostic assays and kits for detection of folate receptor 1 |
| WO2014055771A1 (en) | 2012-10-05 | 2014-04-10 | The Trustees Of The University Of Pennsylvania | Human alpha-folate receptor chimeric antigen receptor |
| US20150320799A1 (en) | 2012-12-20 | 2015-11-12 | Purdue Research Foundation | Chimeric antigen receptor-expressing t cells as anti-cancer therapeutics |
| CA3222465A1 (en) | 2013-08-30 | 2015-03-05 | Immunogen, Inc. | Antibodies and assays for detection of folate receptor 1 |
| PT3055332T (pt) * | 2013-10-08 | 2019-12-09 | Immunogen Inc | Regimes de dosagem de imunoconjugados anti-folr1 |
| KR101646577B1 (ko) * | 2014-08-14 | 2016-08-09 | 원광대학교산학협력단 | 엽산수용체 표적용 화합물 또는 이의 약학적으로 허용가능한 염과, 이를 유효성분으로 포함하는 암 예방, 진단 또는 치료용 조성물 |
| CN107074955B (zh) | 2014-11-20 | 2021-06-22 | 豪夫迈·罗氏有限公司 | 针对FolR1和CD3的T细胞活化性双特异性抗原结合分子 |
| LT3789402T (lt) | 2014-11-20 | 2022-09-26 | F. Hoffmann-La Roche Ag | Kompleksinė terapija, naudojant t ląsteles aktyvinančias bispecifines antigeną surišančias molekules ir pd-1 ašį surišančius antagonistus |
| RS60615B1 (sr) | 2014-11-20 | 2020-08-31 | Hoffmann La Roche | Zajednički laki lanci i postupci upotrebe |
| CN116440279A (zh) | 2015-09-17 | 2023-07-18 | 伊缪诺金公司 | 包含抗folr1免疫缀合物的治疗组合 |
| JP7282521B2 (ja) | 2016-04-08 | 2023-05-29 | パーデュー・リサーチ・ファウンデイション | Ｃａｒ ｔ細胞療法のための方法および組成物 |
| EP3496757A4 (en) | 2016-08-12 | 2020-04-15 | L.E.A.F Holdings Group LLC | POLYGLUTAMATE ANTIFOLATES AND USES THEREOF. |
| WO2018031980A1 (en) | 2016-08-12 | 2018-02-15 | L.E.A.F. Holdings Group Llc | Polyglutamated antifolates and uses thereof |
| CN110944651A (zh) | 2017-02-08 | 2020-03-31 | 蜻蜓疗法股份有限公司 | 用于自然杀伤细胞激活的多特异性结合蛋白及其治疗癌症的治疗性用途 |
| ES2955074T3 (es) | 2017-02-20 | 2023-11-28 | Dragonfly Therapeutics Inc | Proteínas que se unen a HER2, NKG2D Y CD16 |
| WO2018160622A1 (en) | 2017-02-28 | 2018-09-07 | Endocyte, Inc. | Compositions and methods for car t cell therapy |
| WO2019094648A1 (en) | 2017-11-08 | 2019-05-16 | L.E.A.F. Holdings Group Llc | Platinum complexes and uses thereof |
| AU2019209432A1 (en) | 2018-01-22 | 2020-08-06 | Seattle Children's Hospital (dba Seattle Children's Research Institute) | Methods of use for CAR T cells |
| CA3090236A1 (en) | 2018-02-08 | 2019-08-15 | Dragonfly Therapeutics, Inc. | Combination therapy of cancer involving multi-specific binding proteins that activate natural killer cells |
| SG11202007482WA (en) | 2018-02-08 | 2020-09-29 | Dragonfly Therapeutics Inc | Antibody variable domains targeting the nkg2d receptor |
| KR102832460B1 (ko) | 2018-02-20 | 2025-07-11 | 드래곤플라이 쎄라퓨틱스, 인크. | Cd33, nkg2d, 및 cd16에 결합하는 다중-특이적 결합 단백질, 및 이의 사용 방법 |
| WO2019165237A1 (en) | 2018-02-23 | 2019-08-29 | Endocyte, Inc. | Sequencing method for car t cell therapy |
| CN115925952A (zh) | 2018-03-13 | 2023-04-07 | 东莞凡恩世生物医药有限公司 | 抗叶酸受体1抗体及其用途 |
| MX2021001527A (es) | 2018-08-08 | 2021-06-15 | Dragonfly Therapeutics Inc | Proteínas de unión a nkg2d, cd16 y a un antígeno asociado a tumor. |
| MA53293A (fr) | 2018-08-08 | 2021-11-17 | Dragonfly Therapeutics Inc | Protéines de liaison multi-spécifiques se liant à bcma, nkg2d et cd16, et méthodes d'utilisation |
| EA202091888A1 (ru) | 2018-08-08 | 2020-10-23 | Драгонфлай Терапьютикс, Инк. | Вариабельные домены антител, нацеленные на рецептор nkg2d |
| KR20220004687A (ko) | 2019-04-29 | 2022-01-11 | 이뮤노젠 아이엔씨 | 이중파라토프 fr-알파 항체 및 면역접합체 |
| CA3149914A1 (en) | 2019-08-06 | 2021-02-11 | L.E.A.F. Holdings Group Llc | Processes of preparing polyglutamated antifolates and uses of their compositions |
| CN111393528B (zh) * | 2020-01-19 | 2023-01-31 | 中国药科大学 | 一种靶向叶酸受体α的单链抗体及其应用 |
| MX2022013944A (es) | 2020-05-06 | 2022-11-30 | Dragonfly Therapeutics Inc | Proteinas que se unen al receptor activador de celulas asesinas naturales grupo 2 miembro d (nkg2d), cumulo de diferenciacion (cd16) y miembro a de la familia de dominios de lectina tipo c 12 (clec12a). |
| WO2022187539A1 (en) | 2021-03-03 | 2022-09-09 | Dragonfly Therapeutics, Inc. | Methods of treating cancer using multi-specific binding proteins that bind nkg2d, cd16 and a tumor-associated antigen |
| CN117700557B (zh) * | 2024-02-05 | 2024-04-30 | 卡秋(江苏)生物科技有限公司 | 一种特异性结合叶酸受体α的抗体或抗原结合片段 |
| CN119757601A (zh) * | 2025-01-06 | 2025-04-04 | 哈尔滨脉图精准技术有限公司 | 一种用于卵巢癌诊断的代谢标志物组合及其应用 |
Citations (1)
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| WO2005080431A2 (en) | 2004-02-12 | 2005-09-01 | Morphotek, Inc. | Monoclonal antibodies that specifically bind to folate receptor alpha |
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| WO2003074679A2 (en) * | 2002-03-01 | 2003-09-12 | Xencor | Antibody optimization |
| DK1517921T3 (da) * | 2002-06-28 | 2006-10-09 | Domantis Ltd | Immunglobulin-enkeltvariable antigen-bindende domæner og dobbeltspecifikke konstruktioner deraf |
| KR101461408B1 (ko) * | 2005-10-06 | 2014-11-13 | 어드밴스드 엑셀러레이터 어플리케이션즈 에스.에이. | 신규 선택 시스템 |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005080431A2 (en) | 2004-02-12 | 2005-09-01 | Morphotek, Inc. | Monoclonal antibodies that specifically bind to folate receptor alpha |
Non-Patent Citations (1)
| Title |
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| CANCER RESEARCH. 1998, Vol. 58, pp.991-996. * |
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| WO2008031577A1 (en) | 2008-03-20 |
| CA2662005A1 (en) | 2008-03-20 |
| IL197300A0 (en) | 2011-08-01 |
| BRPI0716811B1 (pt) | 2020-11-24 |
| ES2644423T3 (es) | 2017-11-28 |
| JP2010503386A (ja) | 2010-02-04 |
| US8388972B2 (en) | 2013-03-05 |
| EP1900752A1 (en) | 2008-03-19 |
| IL197300A (en) | 2016-02-29 |
| NZ575093A (en) | 2012-04-27 |
| KR20090059114A (ko) | 2009-06-10 |
| CA2662005C (en) | 2018-01-02 |
| RU2009114161A (ru) | 2010-10-20 |
| BRPI0716811A2 (pt) | 2013-11-05 |
| AU2007296899B2 (en) | 2012-09-13 |
| AU2007296899A1 (en) | 2008-03-20 |
| BRPI0716811B8 (pt) | 2021-05-25 |
| MX2009002711A (es) | 2009-06-18 |
| JP5513114B2 (ja) | 2014-06-04 |
| EP2061813B1 (en) | 2017-07-19 |
| EP2061813A1 (en) | 2009-05-27 |
| RU2464277C2 (ru) | 2012-10-20 |
| US20100055034A1 (en) | 2010-03-04 |
| WO2008031577A8 (en) | 2009-07-02 |
| ZA200901328B (en) | 2010-05-26 |
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