CA2312004A1 - Site-specific preparation of polyethylene glycol-grf conjugates - Google Patents

Site-specific preparation of polyethylene glycol-grf conjugates Download PDF

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Publication number
CA2312004A1
CA2312004A1 CA002312004A CA2312004A CA2312004A1 CA 2312004 A1 CA2312004 A1 CA 2312004A1 CA 002312004 A CA002312004 A CA 002312004A CA 2312004 A CA2312004 A CA 2312004A CA 2312004 A1 CA2312004 A1 CA 2312004A1
Authority
CA
Canada
Prior art keywords
hgrf
conjugates
site
specific preparation
grf
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002312004A
Other languages
French (fr)
Other versions
CA2312004C (en
Inventor
Francesco Maria Veronese
Paolo Caliceti
Oddone Schiavon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Serono SA
Original Assignee
Applied Research Systems Ars Holding N.V.
Francesco Maria Veronese
Paolo Caliceti
Oddone Schiavon
Laboratoires Serono S.A.
Merck Serono Sa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Applied Research Systems Ars Holding N.V., Francesco Maria Veronese, Paolo Caliceti, Oddone Schiavon, Laboratoires Serono S.A., Merck Serono Sa filed Critical Applied Research Systems Ars Holding N.V.
Publication of CA2312004A1 publication Critical patent/CA2312004A1/en
Application granted granted Critical
Publication of CA2312004C publication Critical patent/CA2312004C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal 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
    • A61K47/51—Medicinal 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
    • A61K47/56—Medicinal 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal 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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH

Abstract

A method is described for the site-specific preparation of hGRF-PHG conjugates containing one or more PEG units (per mole of hGRF) covalently bound to Lys12 and/or Lys21 and/or N.alpha., characterized in that the conjugation reaction between the hGRF peptide and activated PEG is carried out in solution and the desired hGRF-PEG conjugate can be purified by chromatography. The conjugates prepared by this method, as well as their use in the treatment, prevention or diagnosis of growth hormone deficiency, are also an object of the present invention.
CA002312004A 1997-12-03 1998-12-01 Site-specific preparation of polyethylene glycol-grf conjugates Expired - Lifetime CA2312004C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP97121264A EP0922446A1 (en) 1997-12-03 1997-12-03 Solution-phase site-specific preparation of GRF-PEG conjugates
EP97121264.2 1997-12-03
PCT/EP1998/007748 WO1999027897A1 (en) 1997-12-03 1998-12-01 Site-specific preparation of polyethylene glycol-grf conjugates

Publications (2)

Publication Number Publication Date
CA2312004A1 true CA2312004A1 (en) 1999-06-10
CA2312004C CA2312004C (en) 2009-05-19

Family

ID=8227732

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002312004A Expired - Lifetime CA2312004C (en) 1997-12-03 1998-12-01 Site-specific preparation of polyethylene glycol-grf conjugates

Country Status (30)

Country Link
US (3) US6528485B1 (en)
EP (2) EP0922446A1 (en)
JP (2) JP2001524505A (en)
KR (1) KR100561768B1 (en)
CN (1) CN1149967C (en)
AR (1) AR017780A1 (en)
AT (1) ATE236607T1 (en)
AU (1) AU755285B2 (en)
BG (1) BG64815B1 (en)
BR (1) BR9815159A (en)
CA (1) CA2312004C (en)
DE (1) DE69813291T2 (en)
DK (1) DK1037587T3 (en)
EA (1) EA004269B1 (en)
EE (1) EE200000319A (en)
ES (1) ES2194376T3 (en)
HK (1) HK1034203A1 (en)
HU (1) HUP0100507A3 (en)
IL (2) IL136551A0 (en)
NO (1) NO327238B1 (en)
NZ (1) NZ504570A (en)
PL (1) PL192082B1 (en)
PT (1) PT1037587E (en)
SI (1) SI1037587T1 (en)
SK (1) SK8242000A3 (en)
TR (1) TR200001615T2 (en)
TW (1) TWI254641B (en)
UA (1) UA73716C2 (en)
WO (1) WO1999027897A1 (en)
ZA (1) ZA9811068B (en)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20010055581A1 (en) 1994-03-18 2001-12-27 Lawrence Tamarkin Composition and method for delivery of biologically-active factors
US6407218B1 (en) * 1997-11-10 2002-06-18 Cytimmune Sciences, Inc. Method and compositions for enhancing immune response and for the production of in vitro mabs
US7229841B2 (en) * 2001-04-30 2007-06-12 Cytimmune Sciences, Inc. Colloidal metal compositions and methods
AU2001295589B2 (en) * 2000-10-05 2005-10-13 Ares Trading S.A. Regioselective liquid phase pegylation
EP1234583A1 (en) 2001-02-23 2002-08-28 F. Hoffmann-La Roche Ag PEG-conjugates of HGF-NK4
US20030171285A1 (en) * 2001-11-20 2003-09-11 Finn Rory F. Chemically-modified human growth hormone conjugates
DE60315949T2 (en) 2002-01-16 2008-06-12 Biocompatibles Uk Ltd., Farnham polymer conjugates
US7998705B2 (en) * 2002-08-06 2011-08-16 FUJIFILM Diosynth Biotechnologies U.S.A., Inc Increased dynamic binding capacity in ion exchange chromatography by addition of polyethylene glycol
CA2496687A1 (en) * 2002-09-18 2004-04-01 Centre Hospitalier De L'universite De Montreal (Chum) Ghrh analogues
GB0301014D0 (en) * 2003-01-16 2003-02-19 Biocompatibles Ltd Conjugation reactions
US7662915B2 (en) * 2003-01-18 2010-02-16 Pegsphere Co., Ltd. Peptides having protected amines of untargeted sites, methods for production thereof and of specifically conjugated PEG peptides using the same
WO2005010163A2 (en) * 2003-07-15 2005-02-03 Barros Research Institute Compositions and methods for immunotherapy of human immunotherapy of human immunodeficiency virus (hiv)
JP2008500005A (en) * 2003-07-15 2008-01-10 バロス リサーチ インスティテュート Compositions and methods for immunotherapy of cancer and infectious diseases
JP2008504216A (en) * 2003-12-02 2008-02-14 サイトイミューン サイエンシズ インコーポレイテッド Methods and compositions for the production of monoclonal antibodies
US20050175584A1 (en) * 2004-01-28 2005-08-11 Paciotti Giulio F. Functionalized colloidal metal compositions and methods
CN100355784C (en) * 2004-02-12 2007-12-19 江苏恒瑞医药股份有限公司 Method for preparing polyethylene glycol-modified alpha-interferon 1b
US20050261475A1 (en) * 2004-02-13 2005-11-24 Harvard Medical School Solid-phase capture-release-tag methods for phosphoproteomic analyses
US6986264B1 (en) * 2004-07-15 2006-01-17 Carrier Corporation Economized dehumidification system
KR20180110192A (en) 2004-11-12 2018-10-08 바이엘 헬스케어 엘엘씨 Site-directed modification of fviii
JP2009503191A (en) 2005-07-26 2009-01-29 ローディア インコーポレイティド Polymers with pendant poly (alkyleneoxy) substituents and their use in personal care applications
US20070238656A1 (en) * 2006-04-10 2007-10-11 Eastman Kodak Company Functionalized poly(ethylene glycol)
CA2653748A1 (en) 2006-05-02 2007-11-15 Allozyne, Inc. Non-natural amino acid substituted polypeptides
US20080096819A1 (en) 2006-05-02 2008-04-24 Allozyne, Inc. Amino acid substituted molecules
US8765924B2 (en) * 2006-08-04 2014-07-01 Prolong Pharmaceuticals, Inc. Modified erythropoietin
US20080083154A1 (en) * 2006-10-05 2008-04-10 Timothy M Gregory Bait retention fish hook
CA2707840A1 (en) 2007-08-20 2009-02-26 Allozyne, Inc. Amino acid substituted molecules
US20110014118A1 (en) * 2007-09-21 2011-01-20 Lawrence Tamarkin Nanotherapeutic colloidal metal compositions and methods
KR20100123674A (en) * 2007-09-21 2010-11-24 싸이티뮨 사이언스, 인크. Nanotherapeutic colloidal metal compositions and methods
CA2706700A1 (en) 2007-11-08 2009-05-14 Cytimmune Sciences, Inc. Compositions and methods for generating antibodies
ES2723098T3 (en) * 2008-11-04 2019-08-21 Janssen Pharmaceutica Nv CRHR2 peptide agonists and uses thereof
PL2408800T3 (en) * 2009-03-20 2016-11-30 Method for preparing a site-specific conjugate of a physiologically active polypeptide
US20100267635A1 (en) * 2009-04-20 2010-10-21 Theratechonolgies Inc. Use of protease inhibitors and grf molecules in combination therapy
US20100267636A1 (en) * 2009-04-20 2010-10-21 Theratechnologies Inc. Use of cytochrome p450-metabolized drugs and grf molecules in combination therapy
CA2766634A1 (en) 2009-06-22 2011-01-13 Burnham Institute For Medical Research Methods and compositions using peptides and proteins with c-terminal elements
BR112012010661A2 (en) 2009-11-04 2016-11-22 Janssen Pharmaceutica Nv method for treating heart failure with stressecopine-like peptides
WO2012118778A1 (en) 2011-02-28 2012-09-07 Sanford-Burnham Medical Research Institute Truncated car peptides and methods and compositions using truncated car peptides
WO2012142706A1 (en) 2011-04-21 2012-10-26 Theratechnologies Inc. Growth hormone releasing factor (grf) analogs and uses thereof
AU2012262488A1 (en) 2011-05-31 2014-01-16 Airware, Inc. Re-calibration of AB NDIR gas sensors
US10179801B2 (en) 2011-08-26 2019-01-15 Sanford-Burnham Medical Research Institute Truncated LYP-1 peptides and methods and compositions using truncated LYP-1 peptides
WO2013190520A2 (en) 2012-06-22 2013-12-27 The General Hospital Corporation Gh-releasing agents in the treatment of vascular stenosis and associated conditions
US10064940B2 (en) 2013-12-11 2018-09-04 Siva Therapeutics Inc. Multifunctional radiation delivery apparatus and method
CA2986927C (en) 2015-05-28 2023-12-19 Institut National De La Recherche Scientifique Inhibitors of prototypic galectin dimerization and uses thereof
PT3445778T (en) * 2016-04-19 2020-10-15 Griffon Pharmaceuticals Int Sa C/O Biopole Sa Pegylated bioactive peptides and uses thereof
CN110317826B (en) * 2019-05-22 2020-11-10 中国农业大学 Application of substance for regulating content or activity of PvGRF9 in regulation of plant stem growth and development
WO2021133407A1 (en) 2019-12-27 2021-07-01 Compagnie Generale Des Etablissements Michelin Rubber mix with high specific surface area and high structure acetylene carbon black
US11623949B2 (en) 2021-01-28 2023-04-11 Talem Therapeutics Llc Anti-spike glycoprotein antibodies and the therapeutic use thereof
WO2024081918A1 (en) 2022-10-14 2024-04-18 Talem Therapeutics Llc Anti-trkb/cd3 antibodies and uses thereof

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4563352A (en) * 1982-10-04 1986-01-07 The Salk Institute For Biological Studies Human pancreatic GRF
ES2085297T3 (en) * 1989-05-27 1996-06-01 Sumitomo Pharma PROCEDURE FOR PREPARING DERIVATIVES OF POLY (ETHYLENE GLYCOL) AND MODIFIED PROTEIN.
ZA914983B (en) * 1990-06-29 1992-03-25 Hoffmann La Roche His-grf-analogs
JP3051145B2 (en) * 1990-08-28 2000-06-12 住友製薬株式会社 Novel polyethylene glycol derivative modified peptide
WO1992018531A1 (en) * 1991-04-09 1992-10-29 F. Hoffmann-La Roche Ag Growth hormone releasing factor analogs
EP0518295A3 (en) * 1991-06-14 1993-09-01 Millipore Corporation Allyl side chain protection in peptide synthesis
FR2687681B1 (en) * 1992-02-20 1995-10-13 Transgene Sa POLYETHYLENEGLYCOL-HIRUDINE CONJUGATES, THEIR PREPARATION PROCESS AND THEIR USE FOR THE TREATMENT OF THROMBOSES.
US5932462A (en) * 1995-01-10 1999-08-03 Shearwater Polymers, Inc. Multiarmed, monofunctional, polymer for coupling to molecules and surfaces
WO1997017367A1 (en) * 1995-11-03 1997-05-15 Theratechnologies Inc. Method of grf peptides synthesis

Also Published As

Publication number Publication date
NZ504570A (en) 2003-10-31
BR9815159A (en) 2000-10-10
NO20002664L (en) 2000-07-13
NO327238B1 (en) 2009-05-18
KR20010032494A (en) 2001-04-25
EP1037587A1 (en) 2000-09-27
CN1280483A (en) 2001-01-17
EP1037587B1 (en) 2003-04-09
US6528485B1 (en) 2003-03-04
PL192082B1 (en) 2006-08-31
HUP0100507A2 (en) 2001-08-28
UA73716C2 (en) 2005-09-15
IL136551A0 (en) 2001-06-14
TR200001615T2 (en) 2000-12-21
ES2194376T3 (en) 2003-11-16
EA200000601A1 (en) 2000-12-25
JP2001524505A (en) 2001-12-04
AU755285B2 (en) 2002-12-05
DK1037587T3 (en) 2003-07-28
CA2312004C (en) 2009-05-19
PT1037587E (en) 2003-08-29
ZA9811068B (en) 1999-06-28
NO20002664D0 (en) 2000-05-24
DE69813291D1 (en) 2003-05-15
HUP0100507A3 (en) 2001-11-28
IL136551A (en) 2008-12-29
JP5431874B2 (en) 2014-03-05
US20040029794A1 (en) 2004-02-12
HK1034203A1 (en) 2001-10-19
ATE236607T1 (en) 2003-04-15
CN1149967C (en) 2004-05-19
US7317002B2 (en) 2008-01-08
BG104484A (en) 2000-12-29
DE69813291T2 (en) 2003-11-13
AR017780A1 (en) 2001-10-24
US20050159353A1 (en) 2005-07-21
EE200000319A (en) 2001-08-15
PL341139A1 (en) 2001-03-26
US6869932B2 (en) 2005-03-22
EP0922446A1 (en) 1999-06-16
SK8242000A3 (en) 2001-01-18
AU1563399A (en) 1999-06-16
KR100561768B1 (en) 2006-03-16
JP2010024245A (en) 2010-02-04
EA004269B1 (en) 2004-02-26
SI1037587T1 (en) 2003-08-31
WO1999027897A9 (en) 1999-09-30
TWI254641B (en) 2006-05-11
BG64815B1 (en) 2006-05-31
WO1999027897A1 (en) 1999-06-10

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Effective date: 20181203