WO1999043809A3 - Protease-activated receptor 4 and uses thereof - Google Patents

Protease-activated receptor 4 and uses thereof Download PDF

Info

Publication number
WO1999043809A3
WO1999043809A3 PCT/US1999/002983 US9902983W WO9943809A3 WO 1999043809 A3 WO1999043809 A3 WO 1999043809A3 US 9902983 W US9902983 W US 9902983W WO 9943809 A3 WO9943809 A3 WO 9943809A3
Authority
WO
WIPO (PCT)
Prior art keywords
receptor
protease
activated receptor
par4
cdnas
Prior art date
Application number
PCT/US1999/002983
Other languages
French (fr)
Other versions
WO1999043809A2 (en
Inventor
Shaun R Coughlin
Mark Kahn
Original Assignee
Univ California
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 Univ California filed Critical Univ California
Priority to EP99906934A priority Critical patent/EP1056854A2/en
Priority to CA002321142A priority patent/CA2321142A1/en
Priority to AU26728/99A priority patent/AU2672899A/en
Priority to KR1020007009552A priority patent/KR20010041418A/en
Priority to JP2000533549A priority patent/JP2002504369A/en
Publication of WO1999043809A2 publication Critical patent/WO1999043809A2/en
Publication of WO1999043809A3 publication Critical patent/WO1999043809A3/en
Priority to NO20004274A priority patent/NO20004274L/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6429—Thrombin (3.4.21.5)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21005—Thrombin (3.4.21.5)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Medicinal Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Rheumatology (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Cell Biology (AREA)
  • Dermatology (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Toxicology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Physics & Mathematics (AREA)

Abstract

Disclosed are cDNAs and genomic DNAs encoding protease-activated receptor 4 (PAR4) from mouse and human, and the recombinant polypeptides expressed from such cDNAs. The recombinant receptor polypeptides, receptor fragments and analogs expressed on the surface of cells are used in methods of screening candidate compounds for their ability to act as agonists or antagonists to the effects of interaction between thrombin and PAR4. Agonists are used as therapeutics to treat wounds, promote clotting, and as reagents to activate platelets in diagnostic tests. Antagonists are used as therapeutics to control blood coagulation, treat heart attack and stroke, and block inflammatory and proliferative responses to injury as occur in normal wound healing and variety of diseases including atherosclerosis, restenosis, pulmonary inflammation (ARDS) and glomerulosclerosis. Antibodies specific for a protease-activated receptor 4 (or receptor fragment or analog) and their use as a therapeutic are also disclosed.
PCT/US1999/002983 1998-02-27 1999-02-11 Protease-activated receptor 4 and uses thereof WO1999043809A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
EP99906934A EP1056854A2 (en) 1998-02-27 1999-02-11 Protease-activated receptor 4 and uses thereof
CA002321142A CA2321142A1 (en) 1998-02-27 1999-02-11 Protease-activated receptor 4 and uses thereof
AU26728/99A AU2672899A (en) 1998-02-27 1999-02-11 Protease-activated receptor 4 and uses thereof
KR1020007009552A KR20010041418A (en) 1998-02-27 1999-02-11 Protease-activated receptor 4 and uses thereof
JP2000533549A JP2002504369A (en) 1998-02-27 1999-02-11 Protease-activated receptor 4 and uses thereof.
NO20004274A NO20004274L (en) 1998-02-27 2000-08-25 Protease-activated receptor 4 and its use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US3239798A 1998-02-27 1998-02-27
US09/032,397 1998-02-27

Publications (2)

Publication Number Publication Date
WO1999043809A2 WO1999043809A2 (en) 1999-09-02
WO1999043809A3 true WO1999043809A3 (en) 1999-10-14

Family

ID=21864751

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1999/002983 WO1999043809A2 (en) 1998-02-27 1999-02-11 Protease-activated receptor 4 and uses thereof

Country Status (7)

Country Link
EP (1) EP1056854A2 (en)
JP (1) JP2002504369A (en)
KR (1) KR20010041418A (en)
AU (1) AU2672899A (en)
CA (1) CA2321142A1 (en)
NO (1) NO20004274L (en)
WO (1) WO1999043809A2 (en)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5892014A (en) 1996-10-30 1999-04-06 The Regents Of The University Of California DNA encoding a protease-activated receptor 3
US6111075A (en) * 1998-04-01 2000-08-29 Zymogenetics, Inc. Protese-activated receptor PAR4 (ZCHEMR2)
WO2000015243A1 (en) * 1998-09-15 2000-03-23 The University Of Melbourne A method of treatment and agents useful for same
US7026155B2 (en) 1999-02-02 2006-04-11 Regents Of The University Of California Method of reducing bacterial proliferation
GB9925005D0 (en) 1999-10-22 1999-12-22 Univ Nottingham The treatment of wounds
WO2001058930A1 (en) * 2000-02-09 2001-08-16 Zymogenetics, Inc. Par4 peptides and polypeptides
AU2001238366A1 (en) * 2000-02-17 2001-08-27 The Regents Of The University Of California Methods of modulating protease-activated receptor-4 (par4) activation via cathepsin
WO2001094411A1 (en) * 2000-06-05 2001-12-13 The Regents Of The University Of California Peptides modulating protease activated receptors and methods of using same
US6841354B2 (en) * 2000-12-21 2005-01-11 Philadelphia, Health & Education Corporation Screening assay for anti-thrombotic/anti-platelet activity
US7179887B2 (en) 2001-03-02 2007-02-20 Ortho-Mcneil Pharmaceutical, Inc. Guinea pig proteinase-activated receptor 4 and its activating peptide
WO2004080372A2 (en) * 2003-03-11 2004-09-23 Bayer Healthcare Ag Diagnostics and therapeutics for diseases associated with g-protein coupled proteinase activated receptor 4 (par4)
US20070243632A1 (en) 2003-07-08 2007-10-18 Coller Barry S Methods for measuring platelet reactivity of patients that have received drug eluting stents
ATE536889T1 (en) 2003-07-08 2011-12-15 Accumetrics Inc CONTROLLED PLATEMBOCYTE ACTIVATION TO MONITOR TREATMENT OF ADP ANTAGONISTS
KR20100017576A (en) * 2007-05-03 2010-02-16 아큐메트릭스, 인크. Methods of measuring inhibition of platelet aggregation by thrombin receptor antagonists
GB2450747A (en) * 2007-07-06 2009-01-07 Univ Sheffield Treatment of sensorineural hearing loss
US8975384B2 (en) 2008-01-31 2015-03-10 Osaka University Tag peptide and use thereof
US10266488B2 (en) 2013-10-10 2019-04-23 Eastern Virginia Medical School 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase
US11319528B2 (en) 2015-07-13 2022-05-03 University Of Utah Research Foundation Methods of making red blood cells and platelets in vitro and uses thereof
KR20200063159A (en) * 2017-09-11 2020-06-04 모나쉬 유니버시티 Human thrombin receptor PAR4 binding protein
KR20210072034A (en) * 2018-10-05 2021-06-16 유타대학연구재단 Method for preparing platelets comprising modified receptors and uses thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040040A2 (en) * 1995-06-06 1996-12-19 Incyte Pharmaceuticals, Inc. Thrombin receptor homolog
WO1998018456A1 (en) * 1996-10-30 1998-05-07 The Regents Of The University Of California Protease-activated receptor 3 and uses thereof
WO1998031810A2 (en) * 1997-01-21 1998-07-23 Schering Corporation Mammalian chemokines; receptors; reagents; uses

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996040040A2 (en) * 1995-06-06 1996-12-19 Incyte Pharmaceuticals, Inc. Thrombin receptor homolog
WO1998018456A1 (en) * 1996-10-30 1998-05-07 The Regents Of The University Of California Protease-activated receptor 3 and uses thereof
WO1998031810A2 (en) * 1997-01-21 1998-07-23 Schering Corporation Mammalian chemokines; receptors; reagents; uses

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ISHIHARA, HIROAKI ET AL: "Protease - activated receptor 3 is a second thrombin receptor in humans.", NATURE (LONDON), (1997) VOL. 386, NO. 6624, PP. 502-506., XP002112285 *
KAHN M L ET AL: "A dual thrombin receptor system for platelet activation.", NATURE, (1998 AUG 13) 394 (6694) 690-4., XP002112287 *
XU W F ET AL: "Cloning and characterization of human protease - activated receptor 4.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, (1998 JUN 9) 95 (12) 6642-6., XP002112286 *

Also Published As

Publication number Publication date
NO20004274D0 (en) 2000-08-25
AU2672899A (en) 1999-09-15
NO20004274L (en) 2000-10-13
JP2002504369A (en) 2002-02-12
CA2321142A1 (en) 1999-09-02
EP1056854A2 (en) 2000-12-06
KR20010041418A (en) 2001-05-15
WO1999043809A2 (en) 1999-09-02

Similar Documents

Publication Publication Date Title
WO1999043809A3 (en) Protease-activated receptor 4 and uses thereof
Stiernberg et al. The role of thrombin and thrombin receptor activating peptide (TRAP-508) in initiation of tissue repair
PT939804E (en) ALPHA NEUTROQUIN
EP0278776A3 (en) Methods and deoxyribonucleic acid for the preparation of tissue factor protein
ATE354638T1 (en) HUMAN TISSUE INHIBITOR OF METALLOPROTEINASE-4
CA2188463A1 (en) Pharmaceutical compositions containing activated protein c-resistant factor v for the treatment of bleeding disorders
WO2001057081A3 (en) Narc-1, subtilase-like homologs
WO1998033920A3 (en) Tissue factor pathway inhibitor-3
WO1998030694A3 (en) TUMOR NECROSIS FACTOR RECEPTORS 6α AND 6$g(b)
KR970707141A (en) Tumor necrosis factor-gamma
JP3159216B2 (en) Leukocyte-derived growth factor
KR970705635A (en) Human chemokine beta-9
AU615635B2 (en) Antistasin having anticoagulant and antimetastatic properties
WO1998006841A3 (en) Two human nsp-like proteins
EP0833897A2 (en) Prothrombin derivatives
WO2004100886A3 (en) POLYNUCLEOTIDES AND POLYPEPTIDES ASSOCIATED WITH THE NF-kB PATHWAY
EP0812913A3 (en) HR-1 receptor, a receptor of the cytokine receptors family
EP1162457A3 (en) Multiple coagulation test system and method of using a multiple coagulation test system
WO2003027231A3 (en) Polynucleotide encoding adapter protein, pmn29
EP1443055A3 (en) Interleukins-21 and 22
Castaman et al. Clinical effectiveness of desmopressin in a case of acquired von Willebrand's syndrome associated with benign monoclonal gammopathy
DE69841751D1 (en) Chemokin alpha-5
WO2004005487A3 (en) Polynucleotides encoding a novel testis-specific tubulin tyrosine-ligase-like protein, bgs42
WO1990003181A3 (en) Peptide antagonists for use in cancer therapy, and the use of mas oncogene and its product
DE59909356D1 (en) PHARMACEUTICAL PREPARATION CONTAINING A RECEPTOR ANTAGONIST FOR THE TREATMENT OF BLOOD COagulation disorders

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AU CA JP KR NO

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AU CA JP KR NO

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
ENP Entry into the national phase

Ref document number: 2321142

Country of ref document: CA

Ref country code: CA

Ref document number: 2321142

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 26728/99

Country of ref document: AU

ENP Entry into the national phase

Ref country code: JP

Ref document number: 2000 533549

Kind code of ref document: A

Format of ref document f/p: F

WWE Wipo information: entry into national phase

Ref document number: 1020007009552

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 1999906934

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1999906934

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1020007009552

Country of ref document: KR

WWW Wipo information: withdrawn in national office

Ref document number: 1999906934

Country of ref document: EP

WWR Wipo information: refused in national office

Ref document number: 1020007009552

Country of ref document: KR