CN109414514B - Pet成像免疫调节剂 - Google Patents

Pet成像免疫调节剂 Download PDF

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Publication number
CN109414514B
CN109414514B CN201780042462.1A CN201780042462A CN109414514B CN 109414514 B CN109414514 B CN 109414514B CN 201780042462 A CN201780042462 A CN 201780042462A CN 109414514 B CN109414514 B CN 109414514B
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compound
tissue
subject
imaging
disease
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CN109414514A (zh
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D·J·唐纳利
K·M·博伊
Y·张
J·金
A·佩纳
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Bristol Myers Squibb Co
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • 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
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/02—Arrangements for diagnosis sequentially in different planes; Stereoscopic radiation diagnosis
    • A61B6/03—Computed tomography [CT]
    • A61B6/037—Emission tomography
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B6/00—Apparatus or devices for radiation diagnosis; Apparatus or devices for radiation diagnosis combined with radiation therapy equipment
    • A61B6/12—Arrangements for detecting or locating foreign bodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2123/00—Preparations for testing in vivo
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Epidemiology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Pathology (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Surgery (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Oncology (AREA)
  • Neurosurgery (AREA)
  • Hematology (AREA)
  • Hospice & Palliative Care (AREA)
  • Communicable Diseases (AREA)
  • Psychiatry (AREA)
  • Cardiology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
CN201780042462.1A 2016-05-19 2017-05-17 Pet成像免疫调节剂 Active CN109414514B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662338872P 2016-05-19 2016-05-19
US62/338,872 2016-05-19
PCT/US2017/033004 WO2017201111A1 (en) 2016-05-19 2017-05-17 Pet-imaging immunomodulators

Publications (2)

Publication Number Publication Date
CN109414514A CN109414514A (zh) 2019-03-01
CN109414514B true CN109414514B (zh) 2022-03-11

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CN201780042462.1A Active CN109414514B (zh) 2016-05-19 2017-05-17 Pet成像免疫调节剂

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EP (2) EP3458111B1 (enExample)
JP (1) JP6953444B2 (enExample)
KR (1) KR102378288B1 (enExample)
CN (1) CN109414514B (enExample)
AU (1) AU2017268291B2 (enExample)
BR (1) BR112018073642A2 (enExample)
CA (1) CA3024844A1 (enExample)
CY (1) CY1124241T1 (enExample)
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HR (1) HRP20210644T8 (enExample)
HU (1) HUE054306T2 (enExample)
IL (1) IL262962B (enExample)
LT (1) LT3458111T (enExample)
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PL (1) PL3458111T3 (enExample)
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RS (1) RS61742B1 (enExample)
SG (1) SG11201810177VA (enExample)
SI (1) SI3458111T1 (enExample)
SM (1) SMT202100238T1 (enExample)
WO (1) WO2017201111A1 (enExample)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9856292B2 (en) 2014-11-14 2018-01-02 Bristol-Myers Squibb Company Immunomodulators
US10143746B2 (en) 2016-03-04 2018-12-04 Bristol-Myers Squibb Company Immunomodulators
US10358463B2 (en) 2016-04-05 2019-07-23 Bristol-Myers Squibb Company Immunomodulators
WO2018048882A1 (en) 2016-09-06 2018-03-15 The Research Foundation For The State University Of New York Positron imaging tomography imaging agent composition and method for bacterial infection
EP3548515A1 (en) 2016-12-01 2019-10-09 Regeneron Pharmaceuticals, Inc. Radiolabeled anti-pd-l1 antibodies for immuno-pet imaging
CN110366432A (zh) * 2016-12-23 2019-10-22 约翰霍普金斯大学 基于pd-l1表达的肿瘤和免疫细胞成像
BR112019016336A2 (pt) 2017-02-10 2020-03-31 Regeneron Pharmaceuticals, Inc. Conjugado de anticorpo radiorrotulado, método para imageamento de um tecido que expressa lag3 e para tratar um tumor, e, composto.
WO2018237153A1 (en) 2017-06-23 2018-12-27 Bristol-Myers Squibb Company Immunomodulators acting as antagonists of pd-1
KR102880156B1 (ko) 2017-07-24 2025-11-05 리제너론 파마슈티칼스 인코포레이티드 항cd8 항체 및 이의 용도
JP7257393B2 (ja) 2017-10-03 2023-04-13 ブリストル－マイヤーズ スクイブ カンパニー 免疫調節剤
CN110504017B (zh) * 2019-07-30 2022-06-10 哈尔滨医科大学 一种示踪剂的制备和使用方法
JP2023510737A (ja) 2020-01-06 2023-03-15 ブリストル－マイヤーズ スクイブ カンパニー 免疫調節剤
EP4121442A1 (en) * 2020-03-16 2023-01-25 Bristol-Myers Squibb Company Immunomodulators
CN115362166A (zh) 2020-03-30 2022-11-18 百时美施贵宝公司 免疫调节剂
US12159403B2 (en) * 2021-06-18 2024-12-03 The United States Government As Represented By The Department Of Veteran Affairs Combination of features from biopsies and scans to predict prognosis in SCLC
WO2024129479A2 (en) * 2022-12-12 2024-06-20 Merck Sharp & Dohme Llc Cyclic peptides as pet imaging agents of granzyme b

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013010573A1 (en) * 2011-07-18 2013-01-24 Universitaet Muenster Compounds with matrix-metalloproteinase inhibitory activity
CN105209479A (zh) * 2013-03-15 2015-12-30 百时美施贵宝公司 Pd-1/pd-l1和cd80(b7-1)/pd-l1蛋白质/蛋白质相互作用的大环抑制剂

Family Cites Families (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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.
US5101827A (en) 1985-07-05 1992-04-07 Immunomedics, Inc. Lymphographic and organ imaging method and kit
US4735210A (en) 1985-07-05 1988-04-05 Immunomedics, Inc. Lymphographic and organ imaging method and kit
US5776093A (en) 1985-07-05 1998-07-07 Immunomedics, Inc. Method for imaging and treating organs and tissues
US5128119A (en) 1989-06-12 1992-07-07 Immunomedics, Inc. Methods for technetium/rhenium labeling of f(ab1)2 fragments
US5328679A (en) 1988-04-01 1994-07-12 Immunomedics, Inc. Methods for technetium/rhenium labeling of proteins
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US5746996A (en) 1994-06-03 1998-05-05 Immunomedics, Inc. Thiolation of peptides for radionuclide-based radiodetection and radiotherapy
IL113610A0 (en) 1994-06-03 1995-08-31 Immunomedics Inc A method of radiolabeling a protein, radiolabeled proteins prepared thereby and diagnostic kits containing the same
US5753206A (en) 1995-06-07 1998-05-19 Immunomedics, Inc. Radiometal-binding analogues of luteinizing hormone releasing hormone
US5869451A (en) 1995-06-07 1999-02-09 Glaxo Group Limited Peptides and compounds that bind to a receptor
EP0954340B1 (en) 1996-05-03 2007-06-27 Immunomedics, Inc. Targeted combination immunotherapy of cancer
ES2297862T3 (es) 1996-07-12 2008-05-01 Immunomedics, Inc. Analogos de peptidos que se unen a radiometales.
US6277818B1 (en) 1998-10-29 2001-08-21 Angstrom Pharmaceuticals, Inc. Cyclic peptide ligands that target urokinase plasminogen activator receptor
DE69837095T2 (de) 1997-09-03 2007-11-22 Immunomedics, Inc. Fluorierung von proteinen und peptiden für positronemissionstomographie
EP2141175B1 (en) 2007-03-26 2016-07-27 The University of Tokyo Process for synthesizing cyclic peptide compound
CA2735006A1 (en) 2008-08-25 2010-03-11 Amplimmune, Inc. Pd-1 antagonists and methods of use thereof
US8907053B2 (en) 2010-06-25 2014-12-09 Aurigene Discovery Technologies Limited Immunosuppression modulating compounds
JP5818237B2 (ja) 2010-09-09 2015-11-18 国立大学法人 東京大学 Ｎ−メチルアミノ酸およびその他の特殊アミノ酸を含む特殊ペプチド化合物ライブラリーの翻訳構築と活性種探索法
JP6206943B2 (ja) 2010-12-03 2017-10-04 国立大学法人 東京大学 ペプチドライブラリーの製造方法、ペプチドライブラリー、及びスクリーニング方法
CN103732238A (zh) 2011-06-08 2014-04-16 奥瑞基尼探索技术有限公司 用于免疫调节的治疗性化合物
US9422339B2 (en) 2012-03-29 2016-08-23 Aurigene Discovery Technologies Limited Immunomodulating cyclic compounds
CA2875733C (en) 2012-06-06 2019-09-10 Polyphor Ag Beta-hairpin peptidomimetics
JP2013253842A (ja) 2012-06-06 2013-12-19 Univ Of Tokyo ｐＨ依存的に標的分子に結合するペプチドのスクリーニング方法
JP6483082B2 (ja) 2013-03-15 2019-03-13 ジェネンテック， インコーポレイテッド Ｐｄ−１及びｐｄ−ｌ１に関連する状態を治療するためのバイオマーカー及び方法
KR20160075506A (ko) 2013-09-06 2016-06-29 오리진 디스커버리 테크놀로지스 리미티드 면역조절제로서 사이클릭 펩티도미메틱 화합물
WO2015044900A1 (en) 2013-09-27 2015-04-02 Aurigene Discovery Technologies Limited Therapeutic immunomodulating compounds
MA40132B1 (fr) 2014-09-11 2019-04-30 Bristol Myers Squibb Co Inhibiteurs macrocycliques des interactions protéine/protéine pd-1/pd-l1 et cd80(b7-1)/pd-li
US9732119B2 (en) 2014-10-10 2017-08-15 Bristol-Myers Squibb Company Immunomodulators
US9856292B2 (en) * 2014-11-14 2018-01-02 Bristol-Myers Squibb Company Immunomodulators
CN107207379B (zh) 2014-11-25 2021-08-10 百时美施贵宝公司 用于生物制品的18f-放射性标记的方法和组合物
EP3224277B1 (en) * 2014-11-25 2020-08-26 Bristol-Myers Squibb Company Novel pd-l1 binding polypeptides for imaging
US9861680B2 (en) 2014-12-18 2018-01-09 Bristol-Myers Squibb Company Immunomodulators
US9944678B2 (en) 2014-12-19 2018-04-17 Bristol-Myers Squibb Company Immunomodulators
US20160222060A1 (en) 2015-02-04 2016-08-04 Bristol-Myers Squibb Company Immunomodulators
US9809625B2 (en) 2015-03-18 2017-11-07 Bristol-Myers Squibb Company Immunomodulators
US10143746B2 (en) 2016-03-04 2018-12-04 Bristol-Myers Squibb Company Immunomodulators
US10358463B2 (en) 2016-04-05 2019-07-23 Bristol-Myers Squibb Company Immunomodulators
WO2017210335A1 (en) 2016-06-01 2017-12-07 Bristol-Myers Squibb Company Imaging methods using 18f-radiolabeled biologics
ES2910832T3 (es) 2016-11-07 2022-05-13 Bristol Myers Squibb Co Inmunomoduladores
WO2018237153A1 (en) 2017-06-23 2018-12-27 Bristol-Myers Squibb Company Immunomodulators acting as antagonists of pd-1
JP7257393B2 (ja) 2017-10-03 2023-04-13 ブリストル－マイヤーズ スクイブ カンパニー 免疫調節剤

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013010573A1 (en) * 2011-07-18 2013-01-24 Universitaet Muenster Compounds with matrix-metalloproteinase inhibitory activity
CN105209479A (zh) * 2013-03-15 2015-12-30 百时美施贵宝公司 Pd-1/pd-l1和cd80(b7-1)/pd-l1蛋白质/蛋白质相互作用的大环抑制剂

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AU2017268291A1 (en) 2019-01-17
IL262962A (en) 2018-12-31
HRP20210644T8 (hr) 2021-06-25
CN109414514A (zh) 2019-03-01
US11103605B2 (en) 2021-08-31
EP3827849A1 (en) 2021-06-02
HUE054306T2 (hu) 2021-08-30
CA3024844A1 (en) 2017-11-23
EP3458111A1 (en) 2019-03-27
LT3458111T (lt) 2021-05-25
ES2864091T3 (es) 2021-10-13
KR20190009330A (ko) 2019-01-28
US20210386876A1 (en) 2021-12-16
HRP20210644T1 (hr) 2021-05-28
RS61742B1 (sr) 2021-05-31
SI3458111T1 (sl) 2021-07-30
MX2018014028A (es) 2019-04-04
BR112018073642A2 (pt) 2019-02-26
MA53402A (fr) 2021-06-02
CY1124241T1 (el) 2022-07-22
EA038019B1 (ru) 2021-06-23
EP3458111B1 (en) 2021-03-03
IL262962B (en) 2020-04-30
JP2019520328A (ja) 2019-07-18
AU2017268291B2 (en) 2022-09-29
PL3458111T3 (pl) 2021-06-28
EA201892635A1 (ru) 2019-04-30
US20190117801A1 (en) 2019-04-25
WO2017201111A1 (en) 2017-11-23
PT3458111T (pt) 2021-04-09
SMT202100238T1 (it) 2021-05-07
DK3458111T3 (da) 2021-04-26
KR102378288B1 (ko) 2022-03-23
JP6953444B2 (ja) 2021-10-27
SG11201810177VA (en) 2018-12-28

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