CN109562195A - 用pd-l1结合多肽进行pet成像 - Google Patents
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- CN109562195A CN109562195A CN201780046557.0A CN201780046557A CN109562195A CN 109562195 A CN109562195 A CN 109562195A CN 201780046557 A CN201780046557 A CN 201780046557A CN 109562195 A CN109562195 A CN 109562195A
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- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0455—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- C—CHEMISTRY; METALLURGY
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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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
- C07K16/2803—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 immunoglobulin superfamily
- C07K16/2818—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 immunoglobulin superfamily against CD28 or CD152
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- A—HUMAN NECESSITIES
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111116595A (zh) * | 2019-12-30 | 2020-05-08 | 福建医科大学附属第一医院 | 以tspo为靶点的放射性分子探针及其制备方法和应用 |
| WO2022028557A1 (zh) * | 2020-08-07 | 2022-02-10 | 上海再极医药科技有限公司 | 18f标记的联苯类化合物、其中间体、制备方法、药物组合物及应用 |
| CN114057589A (zh) * | 2020-08-07 | 2022-02-18 | 上海再极医药科技有限公司 | 18f标记的联苯类化合物、其中间体、制备方法、药物组合物及应用 |
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| WO2015143156A1 (en) | 2014-03-20 | 2015-09-24 | Bristol-Myers Squibb Company | Stabilized fibronectin based scaffold molecules |
| JP6701217B2 (ja) | 2014-11-25 | 2020-05-27 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 生物学的製剤の１８ｆ−放射性標識方法および組成物 |
| KR102632418B1 (ko) | 2014-11-25 | 2024-01-31 | 브리스톨-마이어스 스큅 컴퍼니 | 영상화를 위한 신규 pd-l1 결합 폴리펩티드 |
| CN109562195A (zh) | 2016-06-01 | 2019-04-02 | 百时美施贵宝公司 | 用pd-l1结合多肽进行pet成像 |
| WO2017210335A1 (en) | 2016-06-01 | 2017-12-07 | Bristol-Myers Squibb Company | Imaging methods using 18f-radiolabeled biologics |
| BR112019025188A2 (pt) | 2017-06-01 | 2020-06-23 | Cytomx Therapeutics, Inc. | Anticorpos anti-pdl1 ativáveis e métodos de uso dos mesmos |
| WO2019165143A1 (en) * | 2018-02-21 | 2019-08-29 | Cytomx Therapeutics, Inc. | Positron emission tomography imaging of activatable binding polypeptides and related compositions thereof |
| WO2019227490A1 (en) * | 2018-06-01 | 2019-12-05 | Tayu Huaxia Biotech Medical Group Co., Ltd. | Compositions and methods for imaging |
| WO2019228514A1 (en) | 2018-06-01 | 2019-12-05 | Tayu Huaxia Biotech Medical Group Co., Ltd. | Compositions and uses thereof for treating disease or condition |
| CN113795511B (zh) | 2019-01-23 | 2024-07-23 | 大有华夏生物医药集团有限公司 | 抗pd-l1双抗体及其用途 |
| CN110746493A (zh) * | 2019-09-06 | 2020-02-04 | 中国药科大学 | 一种pd-l1拮抗剂多肽及其应用 |
| WO2021174045A1 (en) | 2020-02-28 | 2021-09-02 | Bristol-Myers Squibb Company | Radiolabeled fibronectin based scaffolds and antibodies and theranostic uses thereof |
| JP2023522961A (ja) * | 2020-04-21 | 2023-06-01 | フラッグシップ パイオニアリング， インコーポレイテッド | 二機能性分子およびその使用方法 |
| US20250135047A1 (en) * | 2021-08-06 | 2025-05-01 | The Johns Hopkins University | Improved aluminum fluoride radiosynthesis of [18f]dk222 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1946417A (zh) * | 2003-12-05 | 2007-04-11 | 阿德内克休斯治疗公司 | 2型血管内皮生长因子受体的抑制剂 |
| WO2013181634A2 (en) * | 2012-05-31 | 2013-12-05 | Sorrento Therapeutics Inc. | Antigen binding proteins that bind pd-l1 |
| CN107406494A (zh) * | 2014-11-25 | 2017-11-28 | 百时美施贵宝公司 | 用于成像的新型pd‑l1结合多肽 |
Family Cites Families (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| USRE30985E (en) | 1978-01-01 | 1982-06-29 | Serum-free cell culture media | |
| US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
| US4560655A (en) | 1982-12-16 | 1985-12-24 | Immunex Corporation | Serum-free cell culture medium and process for making same |
| US4657866A (en) | 1982-12-21 | 1987-04-14 | Sudhir Kumar | Serum-free, synthetic, completely chemically defined tissue culture media |
| US4767704A (en) | 1983-10-07 | 1988-08-30 | Columbia University In The City Of New York | Protein-free culture medium |
| US5374548A (en) | 1986-05-02 | 1994-12-20 | Genentech, Inc. | Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor |
| MX9203291A (es) | 1985-06-26 | 1992-08-01 | Liposome Co Inc | Metodo para acoplamiento de liposomas. |
| US5672502A (en) | 1985-06-28 | 1997-09-30 | Celltech Therapeutics Limited | Animal cell culture |
| US4927762A (en) | 1986-04-01 | 1990-05-22 | Cell Enterprises, Inc. | Cell culture medium with antioxidant |
| US6048728A (en) | 1988-09-23 | 2000-04-11 | Chiron Corporation | Cell culture medium for enhanced cell growth, culture longevity, and product expression |
| US5108921A (en) | 1989-04-03 | 1992-04-28 | Purdue Research Foundation | Method for enhanced transmembrane transport of exogenous molecules |
| FR2646437B1 (fr) | 1989-04-28 | 1991-08-30 | Transgene Sa | Nouvelles sequences d'adn, leur application en tant que sequence codant pour un peptide signal pour la secretion de proteines matures par des levures recombinantes, cassettes d'expression, levures transformees et procede de preparation de proteines correspondant |
| US5122469A (en) | 1990-10-03 | 1992-06-16 | Genentech, Inc. | Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins |
| PT752248E (pt) | 1992-11-13 | 2001-01-31 | Idec Pharma Corp | Aplicacao terapeutica de anticorpos quimericos e marcados radioactivamente contra antigenios de diferenciacao restrita de linfocitos b humanos para o tratamento do linfoma de celulas b |
| AU1444095A (en) | 1993-12-27 | 1995-07-17 | Baxter International Inc. | Water soluble non-immunogenic polyamide cross-linking agents |
| US6261804B1 (en) | 1997-01-21 | 2001-07-17 | The General Hospital Corporation | Selection of proteins using RNA-protein fusions |
| DE69835143T2 (de) | 1997-01-21 | 2007-06-06 | The General Hospital Corp., Boston | Selektion von proteinen mittels rns-protein fusionen |
| US7115396B2 (en) | 1998-12-10 | 2006-10-03 | Compound Therapeutics, Inc. | Protein scaffolds for antibody mimics and other binding proteins |
| US6818418B1 (en) | 1998-12-10 | 2004-11-16 | Compound Therapeutics, Inc. | Protein scaffolds for antibody mimics and other binding proteins |
| EP1074563A1 (en) | 1999-08-02 | 2001-02-07 | F. Hoffmann-La Roche Ag | Chimeric polypeptides enhancing dimer formation through electrostatic interactions and disulfide bond, method for production and uses thereof |
| US20050287153A1 (en) | 2002-06-28 | 2005-12-29 | Genentech, Inc. | Serum albumin binding peptides for tumor targeting |
| US20050019826A1 (en) | 2000-03-31 | 2005-01-27 | Roselyne Tournaire | Peptides blocking vascular endothelial growth factor(vegf)-mediated angiogenesis, polynucleotides encoding said pepetides and methods of use thereof |
| US7556925B2 (en) * | 2001-04-04 | 2009-07-07 | University Of Rochester | ανβ3 integrin-binding polypeptide monobodies and their use |
| KR20030033007A (ko) | 2001-05-31 | 2003-04-26 | 코울터 파머수티컬, 인코포레이티드 | 세포독소, 약물전구체, 링커 및 이에 유용한 안정화제 |
| US7696320B2 (en) | 2004-08-24 | 2010-04-13 | Domantis Limited | Ligands that have binding specificity for VEGF and/or EGFR and methods of use therefor |
| WO2005112919A2 (en) | 2004-05-19 | 2005-12-01 | Medarex, Inc. | Self-immolative linkers and drug conjugates |
| US7691962B2 (en) | 2004-05-19 | 2010-04-06 | Medarex, Inc. | Chemical linkers and conjugates thereof |
| US7714016B2 (en) | 2005-04-08 | 2010-05-11 | Medarex, Inc. | Cytotoxic compounds and conjugates with cleavable substrates |
| EP2439273B1 (en) | 2005-05-09 | 2019-02-27 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
| KR101888321B1 (ko) | 2005-07-01 | 2018-08-13 | 이. 알. 스퀴부 앤드 선즈, 엘.엘.씨. | 예정 사멸 리간드 1 (피디-엘1)에 대한 인간 모노클로날 항체 |
| CN101312748A (zh) | 2005-09-26 | 2008-11-26 | 梅达莱克斯公司 | 抗体-药物轭合物和使用方法 |
| US7847105B2 (en) | 2005-10-26 | 2010-12-07 | Medarex, Inc. | Methods and compounds for preparing CC-1065 analogs |
| CA2627190A1 (en) | 2005-11-10 | 2007-05-24 | Medarex, Inc. | Duocarmycin derivatives as novel cytotoxic compounds and conjugates |
| CA2670471A1 (en) | 2006-11-22 | 2008-06-05 | Adnexus, A Bristol-Myers Squibb R&D Company (A Delaware Corporation) | Targeted therapeutics based on engineered proteins for tyrosine kinases receptors, including igf-ir |
| EP2111237B1 (en) | 2006-12-11 | 2015-03-18 | BRACCO IMAGING S.p.A. | Fibrin-binding peptides and conjugates thereof |
| TWI412367B (zh) | 2006-12-28 | 2013-10-21 | Medarex Llc | 化學鏈接劑與可裂解基質以及其之綴合物 |
| US8398956B2 (en) | 2007-01-11 | 2013-03-19 | Immunomedics, Inc. | In vivo copper-free click chemistry for delivery of therapeutic and/or diagnostic agents |
| CA2678514A1 (en) | 2007-02-21 | 2008-08-28 | Medarex, Inc. | Chemical linkers with single amino acids and conjugates thereof |
| EP2036576A1 (en) | 2007-09-17 | 2009-03-18 | Bayer Schering Pharma Aktiengesellschaft | ED-B fibronectin as stratification marker for antitumor drugs |
| CN101918027A (zh) | 2007-11-02 | 2010-12-15 | 森托科尔奥索生物科技公司 | 半合成GLP-1肽-Fc融合构造、方法及其用途 |
| EP2072525A1 (en) | 2007-12-21 | 2009-06-24 | Affibody AB | New polypeptides having affinity for HER2 |
| CA2710835A1 (en) | 2007-12-27 | 2009-07-09 | Novartis Ag | Improved fibronectin-based binding molecules and their use |
| JP2011517314A (ja) | 2008-02-14 | 2011-06-02 | ブリストル−マイヤーズ スクイブ カンパニー | Ｅｇｆｒに結合する操作されたタンパク質に基づく標的化された治療薬 |
| WO2009133208A1 (en) | 2008-05-02 | 2009-11-05 | Novartis Ag | Improved fibronectin-based binding molecules and uses thereof |
| CN102099373A (zh) | 2008-05-22 | 2011-06-15 | 百时美施贵宝公司 | 基于纤连蛋白的多价支架结构域蛋白 |
| TWI496582B (zh) | 2008-11-24 | 2015-08-21 | 必治妥美雅史谷比公司 | 雙重專一性之ｅｇｆｒ／ｉｇｆｉｒ結合分子 |
| US9217210B2 (en) | 2009-03-24 | 2015-12-22 | North Carolina State University | Process of making composite inorganic/polymer nanofibers |
| TW201138808A (en) | 2010-05-03 | 2011-11-16 | Bristol Myers Squibb Co | Serum albumin binding molecules |
| EP2576615B1 (en) | 2010-05-26 | 2016-03-30 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins having improved stability |
| US9469676B2 (en) | 2011-04-13 | 2016-10-18 | Bristol-Myers Squibb Company | Fc fusion proteins comprising novel linkers or arrangements |
| WO2013010573A1 (en) | 2011-07-18 | 2013-01-24 | Universitaet Muenster | Compounds with matrix-metalloproteinase inhibitory activity |
| WO2013067029A2 (en) | 2011-10-31 | 2013-05-10 | Bristol-Myers Squibb Company | Fibronectin binding domains with reduced immunogenicity |
| WO2013173223A1 (en) | 2012-05-15 | 2013-11-21 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
| PL3564258T3 (pl) | 2012-09-13 | 2021-10-25 | Bristol-Myers Squibb Company | Oparte na fibronektynie białka z domeną rusztowania, które wiążą się z miostatyną |
| ES2972124T3 (es) | 2012-12-03 | 2024-06-11 | Curasight As | Péptidos marcados con un radionúclido que emite positrones para obtención de imágenes de PET del uPAR humana |
| US20150361159A1 (en) | 2013-02-01 | 2015-12-17 | Bristol-Myers Squibb Company | Fibronectin based scaffold proteins |
| EP2953968B1 (en) | 2013-02-06 | 2018-07-25 | Bristol-Myers Squibb Company | Fibronectin type iii domain proteins with enhanced solubility |
| SG11201506407VA (en) | 2013-02-15 | 2015-09-29 | Univ Jefferson | Kit for tumor imaging |
| US9433689B2 (en) | 2013-03-12 | 2016-09-06 | The Board Of Trustees Of The Leland Stanford Junio | Probes and methods of imaging non-Hodgkins lymphoma |
| WO2015073746A2 (en) | 2013-11-13 | 2015-05-21 | Whitehead Institute For Biomedical Research | 18f labeling of proteins using sortases |
| WO2015143156A1 (en) | 2014-03-20 | 2015-09-24 | Bristol-Myers Squibb Company | Stabilized fibronectin based scaffold molecules |
| ES2913840T3 (es) | 2014-03-20 | 2022-06-06 | Bristol Myers Squibb Co | Dominios de tipo III de fibronectina de unión a seroalbúmina |
| US9963443B2 (en) | 2014-06-09 | 2018-05-08 | Takeda Pharmaceutical Company Limited | Radiolabeled compounds |
| HRP20201153T1 (hr) | 2014-08-08 | 2021-01-22 | The Board Of Trustees Of The Leland Stanford Junior University | Pd-1 sredstva visokog afiniteta i načini uporabe |
| US9856292B2 (en) * | 2014-11-14 | 2018-01-02 | Bristol-Myers Squibb Company | Immunomodulators |
| JP6701217B2 (ja) | 2014-11-25 | 2020-05-27 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 生物学的製剤の１８ｆ−放射性標識方法および組成物 |
| WO2016162368A1 (en) | 2015-04-07 | 2016-10-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Non-invasive imaging of tumor pd-l1 expression |
| JP6893504B2 (ja) | 2015-09-23 | 2021-06-23 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 速い解離速度を有する血清アルブミン結合フィブロネクチンタイプｉｉｉドメイン |
| EP3353198B1 (en) | 2015-09-23 | 2020-06-17 | Bristol-Myers Squibb Company | Glypican-3binding fibronectin based scafflold molecules |
| MX382321B (es) | 2015-10-30 | 2025-03-13 | Affibody Ab | Nuevo polipéptido con afinidad por pd-l1. |
| JP6990652B2 (ja) * | 2015-10-30 | 2022-02-03 | アフィボディ・アーベー | 新規ポリペプチド |
| EP3402537B1 (en) | 2016-01-15 | 2021-01-06 | Rigshospitalet | Quantitative pet imaging of tissue factor expression using 18f-labelled active site inhibited factor vii |
| CN109562195A (zh) | 2016-06-01 | 2019-04-02 | 百时美施贵宝公司 | 用pd-l1结合多肽进行pet成像 |
| WO2017210335A1 (en) | 2016-06-01 | 2017-12-07 | Bristol-Myers Squibb Company | Imaging methods using 18f-radiolabeled biologics |
-
2017
- 2017-05-31 CN CN201780046557.0A patent/CN109562195A/zh active Pending
- 2017-05-31 JP JP2018563054A patent/JP7016323B2/ja active Active
- 2017-05-31 KR KR1020187037833A patent/KR102397783B1/ko active Active
- 2017-05-31 WO PCT/US2017/035227 patent/WO2017210302A1/en not_active Ceased
- 2017-05-31 US US16/305,284 patent/US11344639B2/en active Active
- 2017-05-31 EP EP17730305.4A patent/EP3463486A1/en not_active Withdrawn
-
2022
- 2022-04-04 US US17/712,729 patent/US20220347324A1/en not_active Abandoned
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1946417A (zh) * | 2003-12-05 | 2007-04-11 | 阿德内克休斯治疗公司 | 2型血管内皮生长因子受体的抑制剂 |
| WO2013181634A2 (en) * | 2012-05-31 | 2013-12-05 | Sorrento Therapeutics Inc. | Antigen binding proteins that bind pd-l1 |
| CN107406494A (zh) * | 2014-11-25 | 2017-11-28 | 百时美施贵宝公司 | 用于成像的新型pd‑l1结合多肽 |
Non-Patent Citations (3)
| Title |
|---|
| ANDERS JOSEFSSON等: "Imaging, Biodistribution, and Dosimetry of Radionuclide-Labeled PD-L1 Antibody in an Immunocompetent Mouse Model of Breast Cancer", 《CANCER RES》 * |
| ARUTSELVAN NATARAJAN等: "A Novel Engineered Anti-CD20 Tracer Enables Early Time PET Imaging in a Humanized Transgenic Mouse Model of B-cell Non-Hodgkins Lymphoma", 《CLIN CANCER RES》 * |
| D.LIPOVSEK: "Adnectins: engineered target-binding protein therapeutics", 《PROTEIN ENGINEERING, DESIGN & SELECTION》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111116595A (zh) * | 2019-12-30 | 2020-05-08 | 福建医科大学附属第一医院 | 以tspo为靶点的放射性分子探针及其制备方法和应用 |
| WO2022028557A1 (zh) * | 2020-08-07 | 2022-02-10 | 上海再极医药科技有限公司 | 18f标记的联苯类化合物、其中间体、制备方法、药物组合物及应用 |
| CN114057589A (zh) * | 2020-08-07 | 2022-02-18 | 上海再极医药科技有限公司 | 18f标记的联苯类化合物、其中间体、制备方法、药物组合物及应用 |
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|---|---|
| EP3463486A1 (en) | 2019-04-10 |
| WO2017210302A1 (en) | 2017-12-07 |
| US20220347324A1 (en) | 2022-11-03 |
| US11344639B2 (en) | 2022-05-31 |
| KR20190015376A (ko) | 2019-02-13 |
| JP2019525891A (ja) | 2019-09-12 |
| KR102397783B1 (ko) | 2022-05-12 |
| US20190184042A1 (en) | 2019-06-20 |
| JP7016323B2 (ja) | 2022-02-21 |
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