WO1999067291A3 - Site specific protein modification by mutagenesis - Google Patents

Site specific protein modification by mutagenesis Download PDF

Info

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 NZ509424A priority Critical patent/NZ509424A/en
Priority to JP2000555941A priority patent/JP3578991B2/en
Priority to AU47020/99A priority patent/AU767630B2/en
Priority to EP99930486A priority patent/EP1090036B1/en
Priority to DE69935855T priority patent/DE69935855T2/en
Priority to CA002331337A priority patent/CA2331337C/en
Publication of WO1999067291A2 publication Critical patent/WO1999067291A2/en
Publication of WO1999067291A3 publication Critical patent/WO1999067291A3/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General 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
    • C07K1/1072—General 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
    • C07K1/1077—General 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
    • 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
    • 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
    • A61K47/62—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 a protein, peptide or polyamino acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7151—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for tumor necrosis factor [TNF], for lymphotoxin [LT]

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Analytical Chemistry (AREA)
  • General Chemical & Material Sciences (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
NZ509424A NZ509424A (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
AU47020/99A AU767630B2 (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

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)

* 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
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

Families Citing this family (85)

* 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
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
US7431921B2 (en) 2000-04-14 2008-10-07 Maxygen Aps Interferon beta-like molecules
SK8292002A3 (en) * 1999-11-12 2002-12-03 Maxygen Holdings Ltd A conjugate exhibiting interferon gamma activity, nucleotide sequence encoding for a polypeptide fraction of conjugate, an expression vector and a host cell containing nucleotide sequence, pharmaceutical composition comprising the same and use thereof
CN1309423C (en) 1999-11-12 2007-04-11 马克西根控股公司 Interferon gamma conjugates
US6555660B2 (en) * 2000-01-10 2003-04-29 Maxygen Holdings Ltd. G-CSF conjugates
US6831158B2 (en) 2000-01-10 2004-12-14 Maxygen Holdings Ltd. G-CSF conjugates
US6646110B2 (en) 2000-01-10 2003-11-11 Maxygen Holdings Ltd. G-CSF polypeptides and conjugates
CA2401683A1 (en) * 2000-03-02 2001-09-07 Xencor Design and discovery of protein based tnf-.alpha. variants for the treatment of tnf-.alpha. related disorders
EP1334127A1 (en) * 2000-11-02 2003-08-13 Maxygen Aps Single-chain multimeric polypeptides
ATE432288T1 (en) 2001-02-27 2009-06-15 Maxygen Aps NEW INTERFERON BETA-LIKE MOLECULES
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
MXPA04000231A (en) 2001-07-11 2004-05-04 Maxygen Holdings Ltd 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
US7737260B2 (en) * 2003-11-13 2010-06-15 Hanmi Pharm. Co., Ltd Protein complex using an immunoglobulin fragment and method for the preparation thereof
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
CA2553528C (en) * 2004-01-21 2012-12-04 Nektar Therapeutics Al, Corporation Method of preparing propionic acid-terminated polymers
GB2429207A (en) 2004-02-02 2007-02-21 Ambrx Inc Modified human interferon polypeptides and their uses
AU2005319099B2 (en) 2004-02-02 2010-09-16 Ambrx, Inc. Modified human growth hormone
US7553653B2 (en) * 2004-09-17 2009-06-30 Biomarin Pharmaceutical Inc. Variants and chemically-modified variants of phenylalanine ammonia-lyase
US8080391B2 (en) 2004-12-22 2011-12-20 Ambrx, Inc. Process of producing non-naturally encoded amino acid containing high conjugated to a water soluble polymer
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
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)
EP1836298B1 (en) 2004-12-22 2012-01-18 Ambrx, Inc. COMPOSITIONS OF AMINOACYL-tRNA SYNTHETASE AND USES THEREOF
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
ATE529442T1 (en) 2005-06-03 2011-11-15 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
AU2006315758A1 (en) * 2005-11-10 2007-05-24 Ercole Biotech, Inc. Splice switching oligomers for TNF superfamily receptors and their use in treatment of disease
US7785834B2 (en) * 2005-11-10 2010-08-31 Ercole Biotech, Inc. Soluble TNF receptors and their use in treatment of disease
PT2339014E (en) 2005-11-16 2015-10-13 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
WO2008030614A2 (en) 2006-09-08 2008-03-13 Ambrx, Inc. Suppressor trna transcription in vertebrate cells
DK2615108T3 (en) 2006-09-08 2017-01-30 Ambrx Inc Modified human plasma polypeptide or fc scaffolds and their applications
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
CA2667678A1 (en) * 2006-10-25 2008-07-24 Amgen Inc. Toxin peptide therapeutic agents
KR20140012199A (en) 2007-03-30 2014-01-29 암브룩스, 인코포레이티드 Modified fgf-21 polypeptides and their uses
CN103965347B (en) 2007-05-02 2017-07-18 Ambrx公司 Modified interferon beta polypeptides and its purposes
EP2162540A2 (en) 2007-05-22 2010-03-17 Amgen Inc. Compositions and methods for producing bioactive fusion proteins
US7537923B2 (en) * 2007-08-17 2009-05-26 Biomarin Pharmaceutical Inc. Compositions of prokaryotic phenylalanine ammonia-lyase and methods of treating cancer using compositions thereof
AU2008326324B9 (en) 2007-11-20 2012-11-15 Ambrx, Inc. Modified insulin polypeptides and their uses
EP3103880A1 (en) 2008-02-08 2016-12-14 Ambrx, Inc. Modified leptin polypeptides and their uses
EP2307038A4 (en) 2008-06-27 2013-03-27 Univ Duke Therapeutic agents comprising elastin-like peptides
UA118536C2 (en) 2008-07-23 2019-02-11 Амбркс, Інк. MODIFIED Bovine granulocyte colony-stimulating factor polypeptide and its application
US20110201022A1 (en) * 2008-07-30 2011-08-18 Biomarin Pharmaceutical Inc. Assays for detection of phenylalanine ammonia-lyase and antibodies to phenylalanine ammonia-lyase
MX348657B (en) 2008-09-26 2017-06-21 Ambrx Inc Non-natural amino acid replication-dependent microorganisms and vaccines.
EP3216800A1 (en) 2008-09-26 2017-09-13 Ambrx, Inc. Modified animal erythropoietin polypeptides and their uses
BR112012013330A2 (en) * 2009-12-02 2017-03-28 Acceleron Pharma Inc compositions and methods for increasing fc fusion protein serum half life
CN102753573A (en) 2009-12-21 2012-10-24 Ambrx公司 Modified bovine somatotropin polypeptides and their uses
NZ600363A (en) 2009-12-21 2014-07-25 Ambrx Inc Modified porcine somatotropin polypeptides and their uses
CA2782444C (en) 2010-02-04 2018-10-23 Biomarin Pharmaceutical Inc. Compositions of prokaryotic phenylalanine ammonia-lyase variants and methods of using compositions thereof
CA2797033C (en) 2010-04-22 2021-10-19 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
BR112013003522B1 (en) 2010-08-17 2021-05-25 Ambrx, Inc. modified relaxin polypeptides comprising a non-naturally encoded amino acid, their method of preparation and their use, as well as nucleic acid and host cell
TWI480288B (en) 2010-09-23 2015-04-11 Lilly Co Eli Formulations for bovine granulocyte colony stimulating factor and variants thereof
US9340590B2 (en) 2011-03-16 2016-05-17 Amgen Inc. Potent and selective inhibitors of NaV1.3 and NaV1.7
EP2694095B1 (en) 2011-04-05 2018-03-07 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
WO2014099984A1 (en) 2012-12-20 2014-06-26 Amgen Inc. Apj receptor agonists and uses thereof
WO2014165277A2 (en) 2013-03-12 2014-10-09 Amgen Inc. POTENT 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
CA2951391C (en) 2014-06-10 2021-11-02 Amgen Inc. Apelin polypeptides
IL258759B2 (en) 2015-11-03 2023-04-01 Ambrx Inc Anti-cd3-folate conjugates and their uses
CN114835793A (en) * 2015-11-16 2022-08-02 Ubi蛋白公司 Method for extending protein half-life
AU2017317183A1 (en) 2016-08-22 2019-02-07 Ambrx, Inc. Bovine fibroblast growth factor 21 and ketosis in dairy cattle
CN110637027A (en) 2017-02-08 2019-12-31 百时美施贵宝公司 Modified relaxin polypeptides comprising pharmacokinetic enhancers and uses thereof
SG11202001379WA (en) 2017-09-08 2020-03-30 Bristol Myers Squibb Co Modified fibroblast growth factor 21 (fgf-21) for use in methods for treating nonalcoholic steatohepatitis (nash)
CN117924503A (en) 2018-03-29 2024-04-26 Ambrx公司 Humanized anti-Prostate Specific Membrane Antigen (PSMA) antibody drug conjugates
CN114903978A (en) 2018-07-03 2022-08-16 百时美施贵宝公司 FGF-21 formulations
AU2019327456A1 (en) 2018-08-28 2021-04-15 Ambrx, Inc. anti-CD3 antibody folate bioconjugates and their uses
KR20210090649A (en) 2018-11-05 2021-07-20 브리스톨-마이어스 스큅 컴퍼니 Methods for Purification of PEGylated Proteins
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
AU3830895A (en) 1994-10-07 1996-05-02 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
DE69935855T2 (en) 2008-01-10
WO1999067291A2 (en) 1999-12-29
US6441136B1 (en) 2002-08-27
JP3578991B2 (en) 2004-10-20
CA2331337C (en) 2008-07-29
US6451986B1 (en) 2002-09-17
DE69935855D1 (en) 2007-05-31
US7129203B2 (en) 2006-10-31
US6433158B1 (en) 2002-08-13
CA2331337A1 (en) 1999-12-29
EP1829554A2 (en) 2007-09-05
US20070048837A1 (en) 2007-03-01
AU767630B2 (en) 2003-11-20
NZ509424A (en) 2002-05-31
US20030023049A1 (en) 2003-01-30
ES2285843T3 (en) 2007-11-16
JP2002518522A (en) 2002-06-25
ATE360033T1 (en) 2007-05-15
AU4702099A (en) 2000-01-10
EP1829554A3 (en) 2007-09-26
US20020081309A1 (en) 2002-06-27
EP1090036A2 (en) 2001-04-11
EP1090036B1 (en) 2007-04-18

Similar Documents

Publication Publication Date Title
WO1999067291A3 (en) Site specific protein modification by mutagenesis
DK0973806T3 (en) Site-protected protein modification
IL130403A (en) Oil bodies and associated proteins as affinity matrices
MY126352A (en) Modified/chimeric superantigens and their use
WO2000069900A3 (en) Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components
EP1229047A3 (en) IL-1 Receptor fusion proteins used as antagonists and methods of making and using
WO2000021574A3 (en) Site-directed dual pegylation of proteins
AU9174398A (en) Peptides
EP0947142A3 (en) Method for cross-linking protein by using enzyme
EP1939293A3 (en) Interferon-Like Protein ZCYTO21
WO1999066054A3 (en) Erythropoietin analog-human serum albumin fusion protein
WO2002095356A3 (en) Methods and compositions for analyzing proteins
WO2001044286A3 (en) Five-helix protein
BG102947A (en) Ionic conjugates with delayed release
NZ333647A (en) Truncated soluble tumor necrosis factor type-I and type-II receptors
IL127583A0 (en) Method for the production of polypeptides
AU1207301A (en) Stabilized proteins
SG65593A1 (en) Totally synthetic affinity reagents
WO2001048485A3 (en) Selecting library members capable of binding to epitopes
CA2328805A1 (en) Enzyme-protein complex
AU3257197A (en) Process for the activation of denatured protein
WO2000035950A3 (en) Reagents and methods useful for detecting diseases of the breast
GB2342652A (en) Polypeptides comprising a coiled-coil and an addition
WO2000018909A3 (en) NUCLEIC ACIDS AND PROTEINS FROM $i(CENARCHAEUM SYMBIOSUM)
WO2003091273A3 (en) Protein interaction system for multisubunit complexes

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM HR HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM HR HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW SD SL SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

ENP Entry into the national phase

Ref document number: 2331337

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2000 555941

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 47020/99

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 509424

Country of ref document: NZ

Ref document number: 1999930486

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1999930486

Country of ref document: EP

WWG Wipo information: grant in national office

Ref document number: 47020/99

Country of ref document: AU

WWG Wipo information: grant in national office

Ref document number: 1999930486

Country of ref document: EP