WO1999067291A3 - Site specific protein modification by mutagenesis - Google Patents

Site specific protein modification by mutagenesis Download PDF

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Publication number
WO1999067291A3
WO1999067291A3 PCT/US1999/013953 US9913953W WO9967291A3 WO 1999067291 A3 WO1999067291 A3 WO 1999067291A3 US 9913953 W US9913953 W US 9913953W WO 9967291 A3 WO9967291 A3 WO 9967291A3
Authority
WO
WIPO (PCT)
Prior art keywords
protein
polyethylene glycol
amino acid
acid residue
mutagenesis
Prior art date
Application number
PCT/US1999/013953
Other languages
French (fr)
Other versions
WO1999067291A2 (en
Inventor
Dean K Pettit
Original Assignee
Immunex Corp
Dean K Pettit
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 Immunex Corp, Dean K Pettit filed Critical Immunex Corp
Priority to AU47020/99A priority Critical patent/AU767630B2/en
Priority to NZ509424A priority patent/NZ509424A/en
Priority to EP99930486A priority patent/EP1090036B1/en
Priority to DE69935855T priority patent/DE69935855T2/en
Priority to CA002331337A priority patent/CA2331337C/en
Priority to JP2000555941A priority patent/JP3578991B2/en
Publication of WO1999067291A2 publication Critical patent/WO1999067291A2/en
Publication of WO1999067291A3 publication Critical patent/WO1999067291A3/en

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K1/00General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/1072General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
    • C07K1/1077General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
    • 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
    • A61K47/56Medicinal 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
    • A61K47/59Medicinal 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
    • A61K47/60Medicinal 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
    • 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7151Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for tumor necrosis factor [TNF], for lymphotoxin [LT]

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cell Biology (AREA)
  • Immunology (AREA)
  • Toxicology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.
PCT/US1999/013953 1998-06-22 1999-06-18 Site specific protein modification by mutagenesis WO1999067291A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
AU47020/99A AU767630B2 (en) 1998-06-22 1999-06-18 Site specific protein modification by mutagenesis
NZ509424A NZ509424A (en) 1998-06-22 1999-06-18 Site specific protein modification by mutagenesis
EP99930486A EP1090036B1 (en) 1998-06-22 1999-06-18 Site specific protein modification by mutagenesis
DE69935855T DE69935855T2 (en) 1998-06-22 1999-06-18 Site-specific protein modifiaction by mutagenesis
CA002331337A CA2331337C (en) 1998-06-22 1999-06-18 Site specific protein modification by mutagenesis
JP2000555941A JP3578991B2 (en) 1998-06-22 1999-06-18 Site-specific modification of proteins by mutagenesis

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/102,530 US6451986B1 (en) 1998-06-22 1998-06-22 Site specific protein modification
US09/102,530 1998-06-22

Publications (2)

Publication Number Publication Date
WO1999067291A2 WO1999067291A2 (en) 1999-12-29
WO1999067291A3 true WO1999067291A3 (en) 2000-03-09

Family

ID=22290346

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/013953 WO1999067291A2 (en) 1998-06-22 1999-06-18 Site specific protein modification by mutagenesis

Country Status (10)

Country Link
US (5) US6451986B1 (en)
EP (2) EP1829554A3 (en)
JP (1) JP3578991B2 (en)
AT (1) ATE360033T1 (en)
AU (1) AU767630B2 (en)
CA (1) CA2331337C (en)
DE (1) DE69935855T2 (en)
ES (1) ES2285843T3 (en)
NZ (1) NZ509424A (en)
WO (1) WO1999067291A2 (en)

Cited By (3)

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US9175083B2 (en) 2004-06-18 2015-11-03 Ambrx, Inc. Antigen-binding polypeptides and their uses
US9434778B2 (en) 2014-10-24 2016-09-06 Bristol-Myers Squibb Company Modified FGF-21 polypeptides comprising an internal deletion and uses thereof
US9567386B2 (en) 2010-08-17 2017-02-14 Ambrx, Inc. Therapeutic uses of modified relaxin polypeptides

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6451986B1 (en) * 1998-06-22 2002-09-17 Immunex Corporation Site specific protein modification
US7431921B2 (en) 2000-04-14 2008-10-07 Maxygen Aps Interferon beta-like molecules
US6531122B1 (en) 1999-08-27 2003-03-11 Maxygen Aps Interferon-β variants and conjugates
US7144574B2 (en) 1999-08-27 2006-12-05 Maxygen Aps Interferon β variants and conjugates
CN1309423C (en) 1999-11-12 2007-04-11 马克西根控股公司 Interferon gamma conjugates
PL356007A1 (en) * 1999-11-12 2004-05-31 Maxygen Holdings Ltd Interferon gamma conjugates
US6555660B2 (en) 2000-01-10 2003-04-29 Maxygen Holdings Ltd. G-CSF conjugates
US6646110B2 (en) 2000-01-10 2003-11-11 Maxygen Holdings Ltd. G-CSF polypeptides and conjugates
US6831158B2 (en) 2000-01-10 2004-12-14 Maxygen Holdings Ltd. G-CSF conjugates
AU4541101A (en) * 2000-03-02 2001-09-12 Xencor Inc Design and discovery of protein based tnf-alpha variants for the treatment of tnf-alpha related disorders
WO2002036626A1 (en) * 2000-11-02 2002-05-10 Maxygen Aps Single-chain multimeric polypeptides
BR0207576A (en) 2001-02-27 2004-04-27 Maxygen Aps Glycosylated variant of an interferon beta precursor (ifnb) polypeptide, processes for increasing the in vivo glycosylation of a precursor ifnb molecule, producing a glycosylated ifnb molecule, preparing a conjugated variant, and treating a mammal with multiple sclerosis pharmaceutical composition , variant ifnb molecule, nucleotide sequence, expression vector, conjugated glycosylation host cell, and use of a conjugate
US6958388B2 (en) 2001-04-06 2005-10-25 Maxygen, Aps Interferon gamma polypeptide variants
US7038015B2 (en) 2001-04-06 2006-05-02 Maxygen Holdings, Ltd. Interferon gamma polypeptide variants
AU2002325819B2 (en) 2001-07-11 2008-06-19 Maxygen, Inc. G-CSF Conjugates
US6908963B2 (en) 2001-10-09 2005-06-21 Nektar Therapeutics Al, Corporation Thioester polymer derivatives and method of modifying the N-terminus of a polypeptide therewith
US7138134B2 (en) * 2001-12-18 2006-11-21 Arizona Health Consulting Group, Llc Preparation and administration of jojoba product for reducing weight, fat and blood lipid levels
CA2491178A1 (en) 2002-07-03 2004-01-15 Maxygen Holdings Ltd. Full-length interferon gamma polypeptide variants
EP1491554A1 (en) * 2003-06-23 2004-12-29 CONARIS research institute AG PEGylated soluble gp130-dimers useful as a medicament
KR100775343B1 (en) * 2003-11-13 2007-11-08 한미약품 주식회사 A PHARMACEUTICAL COMPOSITION COMPRISING AN IMMUNOGLOBULIN Fc REGION AS A CARRIER
EP1756173B1 (en) * 2004-01-21 2019-04-03 Nektar Therapeutics Method of preparing propionic acid-terminated polymers
AU2005211385B2 (en) 2004-02-02 2008-12-11 Ambrx, Inc. Modified human growth hormone polypeptides and their uses
AU2005286763A1 (en) * 2004-09-17 2006-03-30 Biomarin Pharmaceutical, Inc. Variants and chemically-modified variants of phenylalanine ammonia-lyase
EP1674113A1 (en) 2004-12-22 2006-06-28 F. Hoffmann-La Roche Ag Conjugates of insulin-like growth factor-1 (IGF-1) and poly(ethylene glycol)
BRPI0519568C8 (en) 2004-12-22 2022-06-14 Ambrx Inc Aminoacyl-trna synthetase (rs), compositions comprising said aminoacyl-trna synthetase, yeast cell, fungal cell, non-eukaryotic cell, vector encoding an rs, polynucleotide, and a method for producing a polypeptide in a cell with a selected amino acid in a specified position
JP2008525032A (en) 2004-12-22 2008-07-17 アンブレツクス・インコーポレイテツド Methods for expressing and purifying recombinant human growth hormone
US7816320B2 (en) 2004-12-22 2010-10-19 Ambrx, Inc. Formulations of human growth hormone comprising a non-naturally encoded amino acid at position 35
SG160437A1 (en) 2004-12-22 2010-04-29 Ambrx Inc Modified human growth hormone
CA2602654A1 (en) * 2005-04-05 2006-10-12 Istituto Di Ricerche Di Biologia Molecolare P Angeletti Spa Method for shielding functional sites or epitopes on proteins
DE102005016824A1 (en) 2005-04-12 2006-10-19 Giesecke & Devrient Gmbh Device and method for checking value documents
US7833979B2 (en) * 2005-04-22 2010-11-16 Amgen Inc. Toxin peptide therapeutic agents
CA2607844C (en) 2005-06-01 2012-07-10 Maxygen Holdings Ltd. Pegylated g-csf polypeptides and methods of producing same
WO2006133088A2 (en) 2005-06-03 2006-12-14 Ambrx, Inc. Improved human interferon molecules and their uses
US8008453B2 (en) 2005-08-12 2011-08-30 Amgen Inc. Modified Fc molecules
US8168592B2 (en) * 2005-10-21 2012-05-01 Amgen Inc. CGRP peptide antagonists and conjugates
US7785834B2 (en) * 2005-11-10 2010-08-31 Ercole Biotech, Inc. Soluble TNF receptors and their use in treatment of disease
EP1951872A2 (en) * 2005-11-10 2008-08-06 The University of North Carolina at Chapel Hill Splice switching oligomers for tnf superfamily receptors and their use in treatment of disease
US20090018029A1 (en) 2005-11-16 2009-01-15 Ambrx, Inc. Methods and Compositions Comprising Non-Natural Amino Acids
US20130172274A1 (en) 2005-12-20 2013-07-04 Duke University Methods and compositions for delivering active agents with enhanced pharmacological properties
US8841255B2 (en) 2005-12-20 2014-09-23 Duke University Therapeutic agents comprising fusions of vasoactive intestinal peptide and elastic peptides
US7534595B2 (en) 2006-06-12 2009-05-19 Biomarin Pharmaceutical Inc. Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof
US7531341B1 (en) 2006-06-12 2009-05-12 Biomarin Pharmaceutical Inc. Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof
EP2615108B1 (en) 2006-09-08 2016-10-26 Ambrx, Inc. Modified human plasma polypeptide or fc scaffolds and thier uses
EP2064333B1 (en) 2006-09-08 2014-02-26 Ambrx, Inc. Suppressor trna transcription in vertebrate cells
US20090252703A1 (en) * 2006-10-19 2009-10-08 Gegg Jr Colin V Use of alcohol co-solvents to improve pegylation reaction yields
US20090264353A1 (en) * 2007-10-19 2009-10-22 Santaris Pharma A/S Splice Switching Oligomers for TNF Superfamily Receptors and their Use in Treatment of Disease
US7803769B2 (en) * 2006-10-25 2010-09-28 Amgen Inc. OSK1 peptide analogs and pharmaceutical compositions
DK2068909T3 (en) 2007-03-30 2012-08-06 Ambrx Inc Modified FGF-21 polypeptides and their use
BRPI0810622A2 (en) 2007-05-02 2020-10-13 Ambrx, Inc. modified interferon beta polypeptides and their uses
US8420779B2 (en) * 2007-05-22 2013-04-16 Amgen Inc. Compositions and methods for producing bioactive fusion proteins
US7560263B2 (en) * 2007-08-17 2009-07-14 Biomarin Pharmaceutical Inc. Compositions of prokaryotic phenylalanine ammonia-lyase and methods of treating cancer using compositions thereof
CN101918026B (en) 2007-11-20 2016-03-02 Ambrx公司 Modified insulin polypeptides and its purposes
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CN102131516B (en) 2008-06-27 2016-03-16 杜克大学 Comprise the therapeutic agent of elastin-like peptides
BRPI0916515B8 (en) 2008-07-23 2021-07-27 Ambrx Inc bovine granulocyte colony-stimulating factor polypeptide (bg-csf), pharmaceutical formulation and composition comprising the same
WO2010014225A2 (en) * 2008-07-30 2010-02-04 Biomarin Pharmaceutical Inc. Assays for detection of phenylalanine ammonia-lyase and antibodies to phenylalanine ammonia-lyase
UA106731C2 (en) 2008-09-26 2014-10-10 Амбркс, Інк. modified animal erythropoietin polypeptides and their application
PT2337846T (en) 2008-09-26 2018-04-05 Ambrx Inc Non-natural amino acid replication-dependent microorganisms and vaccines
WO2011068993A1 (en) * 2009-12-02 2011-06-09 Acceleron Pharma Inc. Compositions and methods for increasing serum half-life of fc fusion proteins.
CA2784793A1 (en) 2009-12-21 2011-07-21 Ambrx, Inc. Modified bovine somatotropin polypeptides and their uses
NZ600363A (en) 2009-12-21 2014-07-25 Ambrx Inc Modified porcine somatotropin polypeptides and their uses
LT3025728T (en) 2010-02-04 2018-10-25 Biomarin Pharmaceutical Inc. Method for purifying prokaryotic phenylalanine ammonia-lyase variants
US9782454B2 (en) 2010-04-22 2017-10-10 Longevity Biotech, Inc. Highly active polypeptides and methods of making and using the same
JP2012034668A (en) 2010-08-12 2012-02-23 Tohoku Univ Fragment of humanized anti-egfr antibody substituted-lysine variable region, and use thereof
PL2605789T3 (en) 2010-08-17 2019-11-29 Ambrx Inc Modified relaxin polypeptides and their uses
AR083006A1 (en) 2010-09-23 2013-01-23 Lilly Co Eli FORMULATIONS FOR THE STIMULATING FACTOR OF COLONIES OF GRANULOCITS (G-CSF) BOVINE AND VARIANTS OF THE SAME
BR112013023674A2 (en) 2011-03-16 2016-12-13 Amgen Inc potent and selective inhibitors of nav1.3 and nav1.7
US9790262B2 (en) 2011-04-05 2017-10-17 Longevity Biotech, Inc. Compositions comprising glucagon analogs and methods of making and using the same
EP2718328A4 (en) 2011-06-08 2014-12-24 Acceleron Pharma Inc Compositions and methods for increasing serum half-life
US20160067347A1 (en) 2012-12-20 2016-03-10 Amgen Inc. Apj receptor agonists and uses thereof
UY35397A (en) 2013-03-12 2014-10-31 Amgen Inc POWERFUL AND SELECTIVE INHIBITORS OF NaV1.7
EP2968469A4 (en) 2013-03-15 2016-08-31 Longevity Biotech Inc Peptides comprising non-natural amino acids and methods of making and using the same
MX370689B (en) 2014-06-10 2019-12-19 Amgen Inc Apelin polypeptides.
JP6931649B2 (en) 2015-11-03 2021-09-08 アンブルックス, インコーポレイテッドAmbrx, Inc. New anti-CD3 antibody and its use
CN108699120B (en) * 2015-11-16 2022-05-13 Ubi蛋白公司 Method for extending protein half-life
US20190201491A1 (en) 2016-08-22 2019-07-04 Elanco Us Inc. Bovine fibroblast growth factor 21 and ketosis in dairy cattle
US10266578B2 (en) 2017-02-08 2019-04-23 Bristol-Myers Squibb Company Modified relaxin polypeptides comprising a pharmacokinetic enhancer and uses thereof
AU2018329850A1 (en) 2017-09-08 2020-04-23 Bristol-Myers Squibb Company Modified fibroblast growth factor 21 (FGF-21) for use in methods for treating nonalcoholic steatohepatitis (NASH)
KR20200138759A (en) 2018-03-29 2020-12-10 암브룩스, 인코포레이티드 Humanized anti-prostate specific membrane antigen (PSMA) antibody drug conjugate
SG11202013240RA (en) 2018-07-03 2021-01-28 Bristol Myers Squibb Co Fgf21 formulations
CN111417655A (en) 2018-08-28 2020-07-14 润俊(中国)有限公司 anti-CD3 antibody folate bioconjugates and uses thereof
WO2020096958A1 (en) 2018-11-05 2020-05-14 Bristol-Myers Squibb Company Method for purifying pegylated protein
WO2021173889A1 (en) 2020-02-26 2021-09-02 Ambrx, Inc. Uses of anti-cd3 antibody folate bioconjugates
WO2023155872A1 (en) * 2022-02-18 2023-08-24 江苏众红生物工程创药研究院有限公司 Method for realizing controlled release and sustained release of activity of bioactive molecules and use for drugs
WO2024077277A1 (en) 2022-10-07 2024-04-11 Ambrx, Inc. Drug linkers and antibody conjugates thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989005824A1 (en) * 1987-12-23 1989-06-29 Genetics Institute, Inc. Site-specific homogeneous modification of polypeptides to facilitate covalent linkages to a hydrophilic moiety
WO1992016221A1 (en) * 1991-03-15 1992-10-01 Synergen, Inc. Pegylation of polypeptides
WO1997011178A1 (en) * 1995-09-21 1997-03-27 Genentech, Inc. Human growth hormone variants
WO1998035026A1 (en) * 1997-02-06 1998-08-13 Novo Nordisk A/S Polypeptide-polymer conjugates having added and/or removed attachment groups

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
US5235028A (en) 1990-08-31 1993-08-10 University Of Minnesota Polyethylene glycol derivatives for solid-phase applications
US6565841B1 (en) 1991-03-15 2003-05-20 Amgen, Inc. Pulmonary administration of granulocyte colony stimulating factor
IT1260468B (en) 1992-01-29 1996-04-09 METHOD FOR MAINTAINING THE ACTIVITY OF PROTEOLYTIC ENZYMES MODIFIED WITH POLYETHYLENGLYCOL
GB9225448D0 (en) 1992-12-04 1993-01-27 Erba Carlo Spa Improved synthesis of polymer bioactive conjugates
CA2139385C (en) * 1994-02-04 2001-12-25 Gottfried Alber Products containing g-csf and tnf binding protein
WO1996011213A1 (en) 1994-10-07 1996-04-18 Amgen Boulder Inc. Dimeric il-4 inhibitors
US5882141A (en) 1996-08-02 1999-03-16 Nibco, Inc. Low energy precision flooding irrigation apparatus and method
US6451986B1 (en) * 1998-06-22 2002-09-17 Immunex Corporation Site specific protein modification

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989005824A1 (en) * 1987-12-23 1989-06-29 Genetics Institute, Inc. Site-specific homogeneous modification of polypeptides to facilitate covalent linkages to a hydrophilic moiety
WO1992016221A1 (en) * 1991-03-15 1992-10-01 Synergen, Inc. Pegylation of polypeptides
WO1997011178A1 (en) * 1995-09-21 1997-03-27 Genentech, Inc. Human growth hormone variants
WO1998035026A1 (en) * 1997-02-06 1998-08-13 Novo Nordisk A/S Polypeptide-polymer conjugates having added and/or removed attachment groups

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
M S HERSHFIELD ET AL.: "Use of site-directed mutagenesis to enhance the epitope-shielding effect of covalent modification of proteins with polyethylene glycol", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA., vol. 88, August 1991 (1991-08-01), NATIONAL ACADEMY OF SCIENCE. WASHINGTON., US, pages 7185 - 7189, XP002097495, ISSN: 0027-8424 *
S ZALIPSKY: "Chemistry of polyethylene glycol conjugates with biologically active molecules", ADVANCED DRUG DELIVERY REVIEWS, vol. 16, 1995, AMSTERDAM, NL, pages 157 - 182, XP002037428, ISSN: 0169-409X *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9175083B2 (en) 2004-06-18 2015-11-03 Ambrx, Inc. Antigen-binding polypeptides and their uses
US9567386B2 (en) 2010-08-17 2017-02-14 Ambrx, Inc. Therapeutic uses of modified relaxin polypeptides
US9434778B2 (en) 2014-10-24 2016-09-06 Bristol-Myers Squibb Company Modified FGF-21 polypeptides comprising an internal deletion and uses thereof

Also Published As

Publication number Publication date
EP1090036B1 (en) 2007-04-18
US20070048837A1 (en) 2007-03-01
AU767630B2 (en) 2003-11-20
US6433158B1 (en) 2002-08-13
DE69935855D1 (en) 2007-05-31
US7129203B2 (en) 2006-10-31
CA2331337C (en) 2008-07-29
JP2002518522A (en) 2002-06-25
EP1829554A3 (en) 2007-09-26
US6441136B1 (en) 2002-08-27
US20020081309A1 (en) 2002-06-27
CA2331337A1 (en) 1999-12-29
US6451986B1 (en) 2002-09-17
AU4702099A (en) 2000-01-10
EP1829554A2 (en) 2007-09-05
ES2285843T3 (en) 2007-11-16
NZ509424A (en) 2002-05-31
JP3578991B2 (en) 2004-10-20
WO1999067291A2 (en) 1999-12-29
DE69935855T2 (en) 2008-01-10
EP1090036A2 (en) 2001-04-11
ATE360033T1 (en) 2007-05-15
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