JP2009541398A - 医薬目的のための新規な多官能性化合物 - Google Patents

医薬目的のための新規な多官能性化合物 Download PDF

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Publication number
JP2009541398A
JP2009541398A JP2009517014A JP2009517014A JP2009541398A JP 2009541398 A JP2009541398 A JP 2009541398A JP 2009517014 A JP2009517014 A JP 2009517014A JP 2009517014 A JP2009517014 A JP 2009517014A JP 2009541398 A JP2009541398 A JP 2009541398A
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peptide
binder
effector
linker
compound
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Japanese (ja)
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アンドレ コルターマン,
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/64Cyclic peptides containing only normal peptide links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/39Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/641Branched, dendritic or hypercomb peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6425Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/646Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/06Linear peptides containing only normal peptide links having 5 to 11 amino acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K7/00Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04Linear peptides containing only normal peptide links
    • C07K7/08Linear peptides containing only normal peptide links having 12 to 20 amino acids

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Immunology (AREA)
  • Mycology (AREA)
  • Virology (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cell Biology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
JP2009517014A 2006-06-30 2007-07-02 医薬目的のための新規な多官能性化合物 Pending JP2009541398A (ja)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US80629806P 2006-06-30 2006-06-30
EP06013640 2006-06-30
EP06013641 2006-06-30
PCT/EP2007/005836 WO2008000517A2 (en) 2006-06-30 2007-07-02 Conjugates for innate immunotherapy of cancer

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2014095688A Division JP2014166186A (ja) 2006-06-30 2014-05-07 医薬目的のための新規な多官能性化合物

Publications (1)

Publication Number Publication Date
JP2009541398A true JP2009541398A (ja) 2009-11-26

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Family Applications (3)

Application Number Title Priority Date Filing Date
JP2009517014A Pending JP2009541398A (ja) 2006-06-30 2007-07-02 医薬目的のための新規な多官能性化合物
JP2014095688A Withdrawn JP2014166186A (ja) 2006-06-30 2014-05-07 医薬目的のための新規な多官能性化合物
JP2016114025A Pending JP2017002039A (ja) 2006-06-30 2016-06-08 医薬目的のための新規な多官能性化合物

Family Applications After (2)

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JP2014095688A Withdrawn JP2014166186A (ja) 2006-06-30 2014-05-07 医薬目的のための新規な多官能性化合物
JP2016114025A Pending JP2017002039A (ja) 2006-06-30 2016-06-08 医薬目的のための新規な多官能性化合物

Country Status (5)

Country Link
US (1) US8470963B2 (enExample)
EP (3) EP3669894A3 (enExample)
JP (3) JP2009541398A (enExample)
CN (1) CN101528263B (enExample)
WO (1) WO2008000517A2 (enExample)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015513358A (ja) * 2012-03-22 2015-05-11 ザ キュレイターズ オブ ザ ユニバーシティ オブ ミズーリ 金結合性及びegfr受容体親和性を有するペプチド、並びに金ナノ構造に結合したペプチド
JP2019523782A (ja) * 2016-05-24 2019-08-29 シンタプ セラピューティクス ゲーエムベーハー 合成化合物
JP2020523413A (ja) * 2017-06-16 2020-08-06 イーライ リリー アンド カンパニー 操作された抗体化合物およびこれらの抱合体

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8815804B2 (en) * 2006-02-06 2014-08-26 Sanford-Burnham Medical Research Institute Methods and compositions related to targeting tumors and wounds
CA2682580A1 (en) 2007-03-30 2008-10-09 Duke University A method of modulating the activity of a nucleic acid molecule
US20120010153A1 (en) 2009-01-14 2012-01-12 Andre Koltermann Novel tumor-targeting compounds
IN2012DN02345A (enExample) * 2009-09-16 2015-08-21 Univ Duke
US10066323B2 (en) 2014-04-16 2018-09-04 Duke University Electrospun cationic nanofibers and methods of making and using the same
US12514872B2 (en) 2015-11-04 2026-01-06 Duke University Polycationic polymers for use in treating and detecting cancer
WO2018119422A1 (en) 2016-12-22 2018-06-28 Duke University Polycationic microfibers and methods of using the same
CN112672747B (zh) 2018-07-19 2025-02-18 加利福尼亚大学董事会 用于激活骨祖细胞中细胞信号传导的肽
CN109055476B (zh) * 2018-08-07 2021-07-09 河南大学 一种生物活性肽p11在治疗甲状腺癌的药物中效果分析方法
CN109679981A (zh) * 2019-02-21 2019-04-26 武汉大学 一种甲酰基肽定向进化噬菌体及其制备方法与应用
CN111474370B (zh) * 2020-04-22 2021-04-06 天津医科大学总医院 检测甲酰肽或甲酰肽受体-1配体含量的方法及应用
WO2022189361A1 (en) * 2021-03-08 2022-09-15 Universiteit Gent Conjugates including multiple saccharidic chains on a linear protein and uses in mammals feed
CN115448980A (zh) * 2021-06-08 2022-12-09 戴德森医疗财团法人嘉义基督教医院 表面链结标靶多肽的类病毒颗粒及其用途
WO2025262329A1 (en) 2024-06-21 2025-12-26 Syntab Therapeutics Gmbh Synthetic molecules comprising tlr2 ligands

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4427660A (en) * 1982-03-03 1984-01-24 Research Corporation Formyl-methionyl chemotatic peptide antibiotic conjugates useful in treating infections
US20030099629A1 (en) * 1999-03-11 2003-05-29 Immunomedics, Inc. Recombinant onconase and chemical conjugates and fusion proteins of recombinant onconase

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA1055932A (en) 1975-10-22 1979-06-05 Hematech Inc. Blood substitute based on hemoglobin
IT1164225B (it) 1983-05-13 1987-04-08 Anic Spa Analoghi retro-invertiti del pentapeptide potenziante la bradichina bpp5a e metodi per la loro preparazione
WO1993022343A1 (en) * 1992-05-01 1993-11-11 The Rockfeller University Multiple antigen peptide system having adjuvant properties and vaccines prepared therefrom
US5767078A (en) 1995-06-07 1998-06-16 Johnson; Dana L. Agonist peptide dimers
KR100459984B1 (ko) 1995-06-07 2005-06-20 아피맥스 테크놀로지스, 엔.브이. 에리트로포이에틴수용체(epo-r)에결합하는화합물및펩티드
DE19853778C1 (de) 1998-11-21 2000-09-21 Basf Ag DNA-Sequenzen kodierend einen Glutamat/Malat-Translokator, Plasmide Bakterien, Hefen und Pflanzen enthaltend diesen Transporter
AU2030000A (en) 1998-11-25 2000-06-13 Cadus Pharmaceutical Corporation Methods and compositions for identifying receptor effectors
US6017537A (en) * 1998-12-18 2000-01-25 Connaught Laboratories, Inc. Formyl methionyl peptide vaccine adjuvant
US6703480B1 (en) 1999-11-24 2004-03-09 Palani Balu Peptide dimers as agonists of the erythropoientin (EPO) receptor, and associated methods of synthesis and use
AU7490401A (en) 2000-05-26 2001-12-11 Ortho Mcneil Pharm Inc Neuroprotective peptides
IL156942A0 (en) 2001-01-16 2004-02-08 Univ Ramot Compounds, pharmaceutical compositions and methods for treatment of bacteremia and/or septicemia
US7265084B2 (en) * 2001-10-10 2007-09-04 Neose Technologies, Inc. Glycopegylation methods and proteins/peptides produced by the methods
EP1532159A4 (en) * 2002-06-20 2009-10-21 Univ Maryland Biotech Inst MALEIMIDES CLUSTERS ON SCAFFOLDING FOR PLURIVALENT PEPTIDE ASSEMBLIES
WO2004024761A1 (en) 2002-09-11 2004-03-25 Fresenius Kabi Deutschland Gmbh Hasylated polypeptides, especially hasylated erythropoietin
CN1820024B (zh) 2003-05-12 2011-06-22 阿费麦克斯公司 新的聚(乙二醇)修饰的化合物及其用途
EP1629007B1 (en) 2003-05-12 2009-04-15 Affymax, Inc. Novel peptides that bind to the erythropoietin receptor
KR101227666B1 (ko) 2003-05-12 2013-01-31 아피맥스, 인크. 에리스로포이에틴 수용체에 결합하는 펩티드
EP2204193A3 (en) 2003-05-12 2010-08-18 Affymax, Inc. Novel spacer moiety for poly(ethylene glycol)-modified peptide-based compounds
EP1538164A1 (en) * 2003-12-04 2005-06-08 Vectron Therapeutics AG RGD targeting moiety its production and use

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4427660A (en) * 1982-03-03 1984-01-24 Research Corporation Formyl-methionyl chemotatic peptide antibiotic conjugates useful in treating infections
US20030099629A1 (en) * 1999-03-11 2003-05-29 Immunomedics, Inc. Recombinant onconase and chemical conjugates and fusion proteins of recombinant onconase

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
JPN5009011440; OBRIST R: INTERNATIONAL JOURNAL OF IMMUNOPHARMACOLOGY V5 N4, 19830101, P307-314, ELMSFORD *
JPN5009011441; OBRIST R: CELLULAR IMMUNOLOGY V81 N1, 19830101, P169-174, ACADEMIC PRESS *
JPN5009011442; HETLAND G: INTERNATIONAL JOURNAL OF IMMUNOTHERAPY V11 N3, 19950101, P85-93, BIOSCIENCE EDIPRINT INC. *
JPN7013000053; Biochemical and biophysical research communications Vol.155, 1988, p.1139-1144 *
JPN7013000054; Eur.J.Immunol. Vol.35, 2005, p.2486-2495 *
JPN7013000055; FASEB Journal Vol.19, 2005, p.1978-1985 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2015513358A (ja) * 2012-03-22 2015-05-11 ザ キュレイターズ オブ ザ ユニバーシティ オブ ミズーリ 金結合性及びegfr受容体親和性を有するペプチド、並びに金ナノ構造に結合したペプチド
JP2019523782A (ja) * 2016-05-24 2019-08-29 シンタプ セラピューティクス ゲーエムベーハー 合成化合物
US11318208B2 (en) 2016-05-24 2022-05-03 Syntab Therapeutics Gmbh Synthetic compound
JP7449091B2 (ja) 2016-05-24 2024-03-13 シンタプ セラピューティクス ゲーエムベーハー 合成化合物
JP2020523413A (ja) * 2017-06-16 2020-08-06 イーライ リリー アンド カンパニー 操作された抗体化合物およびこれらの抱合体
JP7073487B2 (ja) 2017-06-16 2022-05-23 イーライ リリー アンド カンパニー 操作された抗体化合物およびこれらの抱合体
JP2022106970A (ja) * 2017-06-16 2022-07-20 イーライ リリー アンド カンパニー 操作された抗体化合物およびこれらの抱合体
JP2022106975A (ja) * 2017-06-16 2022-07-20 イーライ リリー アンド カンパニー 操作された抗体化合物およびこれらの抱合体
JP2022106976A (ja) * 2017-06-16 2022-07-20 イーライ リリー アンド カンパニー 操作された抗体化合物およびこれらの抱合体
JP7467526B2 (ja) 2017-06-16 2024-04-15 イーライ リリー アンド カンパニー 操作された抗体化合物およびこれらの抱合体
JP2024054197A (ja) * 2017-06-16 2024-04-16 イーライ リリー アンド カンパニー 操作された抗体化合物およびこれらの抱合体
JP7553504B2 (ja) 2017-06-16 2024-09-18 イーライ リリー アンド カンパニー 操作された抗体化合物およびこれらの抱合体

Also Published As

Publication number Publication date
CN101528263A (zh) 2009-09-09
EP3669894A3 (en) 2020-08-26
US8470963B2 (en) 2013-06-25
CN101528263B (zh) 2013-01-23
WO2008000517A3 (en) 2009-04-02
EP2035041B1 (en) 2020-01-08
EP2035041A2 (en) 2009-03-18
JP2017002039A (ja) 2017-01-05
US20100233161A1 (en) 2010-09-16
EP2275142A3 (en) 2011-05-11
JP2014166186A (ja) 2014-09-11
EP3669894A2 (en) 2020-06-24
EP2275142A2 (en) 2011-01-19
WO2008000517A2 (en) 2008-01-03

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