WO1996035788A3 - Kunitz type protease inhibitors - Google Patents

Kunitz type protease inhibitors Download PDF

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Publication number
WO1996035788A3
WO1996035788A3 PCT/US1996/006384 US9606384W WO9635788A3 WO 1996035788 A3 WO1996035788 A3 WO 1996035788A3 US 9606384 W US9606384 W US 9606384W WO 9635788 A3 WO9635788 A3 WO 9635788A3
Authority
WO
WIPO (PCT)
Prior art keywords
analogues
kpi
protease inhibitors
type protease
kunitz type
Prior art date
Application number
PCT/US1996/006384
Other languages
French (fr)
Other versions
WO1996035788A2 (en
Inventor
Tyler R White
Deborah Damm
David D Lesikar
Kethleen Mcfadden
Brett L Garrick
Original Assignee
Scios Inc
Tyler R White
Deborah Damm
David D Lesikar
Kethleen Mcfadden
Brett L Garrick
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 Scios Inc, Tyler R White, Deborah Damm, David D Lesikar, Kethleen Mcfadden, Brett L Garrick filed Critical Scios Inc
Priority to EP96920140A priority Critical patent/EP0827539A2/en
Priority to JP8534170A priority patent/JPH11504938A/en
Priority to AU58540/96A priority patent/AU5854096A/en
Publication of WO1996035788A2 publication Critical patent/WO1996035788A2/en
Publication of WO1996035788A3 publication Critical patent/WO1996035788A3/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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8114—Kunitz type inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A61K38/57—Protease inhibitors from animals; from humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Wood Science & Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Plant Pathology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

Analogues of the Kunitz Protease Inhibitor (KPI) domain of amyloid precursor protein bind to and inhibit activity of serine proteases, including kallikrein, plasmin and coagulation factors such as factors VIIa, IXa, Xa, XIa and XIIa. Pharmaceutical compositions containing the KPI analogues, along with methods for using such compositions, are useful for ameliorating and treating clinical conditions associated with increased serine protease activity, such as blood loss related to cardiopulmonary bypass surgery. Nucleic acid sequences encoding these analogues and systems for expression of the peptides of the invention are provided.
PCT/US1996/006384 1995-05-08 1996-05-08 Kunitz type protease inhibitors WO1996035788A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP96920140A EP0827539A2 (en) 1995-05-08 1996-05-08 Kunitz type protease inhibitors
JP8534170A JPH11504938A (en) 1995-05-08 1996-05-08 Kunitz-type protease inhibitor
AU58540/96A AU5854096A (en) 1995-05-08 1996-05-08 Kunitz type protease inhibitors

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US43655595A 1995-05-08 1995-05-08
US08/436,555 1995-05-08
US64373196A 1996-05-06 1996-05-06
US08/643,731 1996-05-06

Publications (2)

Publication Number Publication Date
WO1996035788A2 WO1996035788A2 (en) 1996-11-14
WO1996035788A3 true WO1996035788A3 (en) 1996-12-12

Family

ID=27031013

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/006384 WO1996035788A2 (en) 1995-05-08 1996-05-08 Kunitz type protease inhibitors

Country Status (6)

Country Link
EP (1) EP0827539A2 (en)
JP (1) JPH11504938A (en)
KR (1) KR19990008458A (en)
AU (1) AU5854096A (en)
CA (1) CA2220497A1 (en)
WO (1) WO1996035788A2 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8921314B2 (en) 2008-10-15 2014-12-30 Angiochem, Inc. Conjugates of GLP-1 agonists and uses thereof
US9161988B2 (en) 2009-07-02 2015-10-20 Angiochem Inc. Multimeric peptide conjugates and uses thereof
US9173891B2 (en) 2009-04-20 2015-11-03 Angiochem, Inc. Treatment of ovarian cancer using an anticancer agent conjugated to an angiopep-2 analog
US9221867B2 (en) 2003-01-06 2015-12-29 Angiochem Inc. Method for transporting a compound across the blood-brain barrier
US9365634B2 (en) 2007-05-29 2016-06-14 Angiochem Inc. Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5663143A (en) * 1988-09-02 1997-09-02 Dyax Corp. Engineered human-derived kunitz domains that inhibit human neutrophil elastase
US6057287A (en) 1994-01-11 2000-05-02 Dyax Corp. Kallikrein-binding "Kunitz domain" proteins and analogues thereof
IL126115A (en) 1996-03-11 2007-03-08 Aerovance Inc Substantially purified protein having serine protease inhibitory activity and pharmaceutical compositions thereof
EP1082430A1 (en) * 1998-05-28 2001-03-14 ZymoGenetics, Inc. Kunitz domain polypeptide and materials and methods for making it
AU4229599A (en) * 1998-06-03 1999-12-20 Scios Inc. Protease inhibitor peptides
DK1941867T3 (en) 2002-06-07 2012-01-02 Dyax Corp Polypeptide with Modified Kunitz Domain
US7153829B2 (en) 2002-06-07 2006-12-26 Dyax Corp. Kallikrein-inhibitor therapies
US7235530B2 (en) 2004-09-27 2007-06-26 Dyax Corporation Kallikrein inhibitors and anti-thrombolytic agents and uses thereof
ES2383901T5 (en) 2005-02-18 2015-02-25 Angiochem Inc. Aprotinin polypeptides to transport a compound through the blood-brain barrier
ES2424242T3 (en) 2005-07-15 2013-09-30 Angiochem Inc. Use of aprotinin polypeptides as carriers in pharmaceutical conjugates
EP2231702A1 (en) * 2007-12-21 2010-09-29 Ifxa A/s Protease inhibitor
US9914754B2 (en) 2008-12-05 2018-03-13 Angiochem Inc. Conjugates of neurotensin or neurotensin analogs and uses thereof
WO2010080833A1 (en) 2009-01-06 2010-07-15 Dyax Corp. Treatment of mucositis with kallikrein inhibitors
CA3168591A1 (en) 2010-01-06 2011-07-14 Takeda Pharmaceutical Company Limited Plasma kallikrein binding proteins
KR102502293B1 (en) 2011-01-06 2023-02-21 다케다 파머수티컬 컴패니 리미티드 Plasma kallikrein binding proteins
EP2885318A4 (en) 2012-08-14 2016-03-30 Angiochem Inc Peptide-dendrimer conjugates and uses thereof
ES2826827T3 (en) 2015-06-15 2021-05-19 Angiochem Inc Methods for the treatment of leptomeningeal carcinomatosis
EP3387012A4 (en) * 2015-12-10 2019-05-15 The National Institute for Biotechnology in the Negev Ltd. Variants of amyloid beta-protein precursor inhibitor domain
NZ744233A (en) 2015-12-11 2023-11-24 Takeda Pharmaceuticals Co Plasma kallikrein inhibitors and uses thereof for treating hereditary angioedema attack
CN110051830A (en) * 2019-03-14 2019-07-26 苏州新凝生物医药科技有限公司 A kind of protease nexin II KPI protein mutant application

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0393431A1 (en) * 1989-04-18 1990-10-24 Bayer Ag Homologues of Alzheimer protease inhibitor prepared genetechnologically, host-strains and expression vectors for their preparation and use as a medicament
WO1993014120A1 (en) * 1992-01-07 1993-07-22 Novo Nordisk A/S A human kunitz-type protease inhibitor variant
WO1993014119A1 (en) * 1992-01-07 1993-07-22 Novo Nordisk A/S Human kunitz-type protease inhibitor variants
WO1995023860A2 (en) * 1994-03-04 1995-09-08 Genentech, Inc. KUNITZ DOMAIN INHIBITOR PROTEINS DERIVED FROM ALZHEIMER'S AMYLOID β-PROTEIN PRECURSOR INHIBITOR

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0393431A1 (en) * 1989-04-18 1990-10-24 Bayer Ag Homologues of Alzheimer protease inhibitor prepared genetechnologically, host-strains and expression vectors for their preparation and use as a medicament
WO1993014120A1 (en) * 1992-01-07 1993-07-22 Novo Nordisk A/S A human kunitz-type protease inhibitor variant
WO1993014119A1 (en) * 1992-01-07 1993-07-22 Novo Nordisk A/S Human kunitz-type protease inhibitor variants
WO1995023860A2 (en) * 1994-03-04 1995-09-08 Genentech, Inc. KUNITZ DOMAIN INHIBITOR PROTEINS DERIVED FROM ALZHEIMER'S AMYLOID β-PROTEIN PRECURSOR INHIBITOR

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
DENNIS M S ET AL: "Kunitz domain inhibitors of tissue factor-factor VIIa: I. Potent inhibitors selected from libraries by phage display.", JOURNAL OF BIOLOGICAL CHEMISTRY 269 (35). 1994. 22129-22136. ISSN: 0021-9258, XP002015893 *
DENNIS M S ET AL: "Kunitz domain inhibitors of tissue factor-factor VIIa: II. Potent and specific inhibitors by competitive phage selection.", JOURNAL OF BIOLOGICAL CHEMISTRY 269 (35). 1994. 22137-22144. ISSN: 0021-9258, XP002015892 *
DENNIS M S ET AL: "Potent and Selective Kunitz Domain Inhibitors of Plasma Kallikrein Designed by Phage Display.", JOURNAL OF BIOLOGICAL CHEMISTRY 270 (43). 1995. 25411-25417. ISSN: 0021-9258, XP002015896 *
HYNES T R ET AL: "X-RAY CRYSTAL STRUCTURE OF THE PROTEASE INHIBITOR DOMAIN OF ALZHEIMER 'S AMYLOID BETA-PROTEIN PRECURSOR.", BIOCHEMISTRY 29 (43). 1990. 10018-10022. CODEN: BICHAW ISSN: 0006-2960, XP002015891 *
J. PERONA ET AL: "Crystal structures of rat anionic trypsin complexed with the protein inhibitors APPI and BPTI", JOURNAL OF MOLECULAR BIOLOGY, vol. 230, 1993, pages 919 - 933, XP000608106 *
KIDO H ET AL: "PROTEASE-SPECIFICITY OF KUNITZ INHIBITOR DOMAIN OF ALZHEIMER 'S DISEASE AMYLOID PROTEIN PRECURSOR.", BIOCHEM BIOPHYS RES COMMUN 167 (2). 1990. 716-721. CODEN: BBRCA9 ISSN: 0006-291X, XP002015895 *
S. SINHA ET AL: "Conversion of the Alzheimer's beta-Amyloid precursor protein (APP) Kunitz domain into a potent human neutrophil elastase inhibitor", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 266, no. 31, 5 November 1991 (1991-11-05), MD US, pages 21011 - 21013, XP002015894 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9221867B2 (en) 2003-01-06 2015-12-29 Angiochem Inc. Method for transporting a compound across the blood-brain barrier
US9365634B2 (en) 2007-05-29 2016-06-14 Angiochem Inc. Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues
US8921314B2 (en) 2008-10-15 2014-12-30 Angiochem, Inc. Conjugates of GLP-1 agonists and uses thereof
US9173891B2 (en) 2009-04-20 2015-11-03 Angiochem, Inc. Treatment of ovarian cancer using an anticancer agent conjugated to an angiopep-2 analog
US9161988B2 (en) 2009-07-02 2015-10-20 Angiochem Inc. Multimeric peptide conjugates and uses thereof

Also Published As

Publication number Publication date
AU5854096A (en) 1996-11-29
WO1996035788A2 (en) 1996-11-14
JPH11504938A (en) 1999-05-11
KR19990008458A (en) 1999-01-25
CA2220497A1 (en) 1996-11-14
EP0827539A2 (en) 1998-03-11

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