WO2001026671A1 - Procedes de traitement au moyen d'inhibiteurs doubles de metalloproteinase-2 matricielle et de metalloproteinase-9 matricielle - Google Patents

Procedes de traitement au moyen d'inhibiteurs doubles de metalloproteinase-2 matricielle et de metalloproteinase-9 matricielle Download PDF

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Publication number
WO2001026671A1
WO2001026671A1 PCT/US2000/027949 US0027949W WO0126671A1 WO 2001026671 A1 WO2001026671 A1 WO 2001026671A1 US 0027949 W US0027949 W US 0027949W WO 0126671 A1 WO0126671 A1 WO 0126671A1
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WO
WIPO (PCT)
Prior art keywords
pain
mmp
seq
polypeptide
post
Prior art date
Application number
PCT/US2000/027949
Other languages
English (en)
Inventor
Anne Romanic Arnold
Frank C. Barone
Sharon Bingham
Original Assignee
Smithkline Beecham Corporation
Smithkline Beecham Plc
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 Smithkline Beecham Corporation, Smithkline Beecham Plc filed Critical Smithkline Beecham Corporation
Publication of WO2001026671A1 publication Critical patent/WO2001026671A1/fr

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Classifications

    • 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
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
    • A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/05—Dipeptides

Definitions

  • a typical variant of a polypeptide differs in amino acid sequence from another, reference polypeptide. Generally, differences are limited so that the sequences of the reference polypeptide and the variant are closely similar overall and, in many regions, identical.
  • a variant and reference polypeptide may differ in amino acid sequence by one or more substitutions, additions, deletions in any combination.
  • a substituted or inserted amino acid residue may or may not be one encoded by the genetic code.
  • a variant of a polynucleotide or polypeptide may be a naturally occurring such as an allelic variant, or it may be a variant that is not known to occur naturally. Non- naturally occurring variants of polynucleotides and polypeptides may be made by mutagenesis techniques or by direct synthesis.
  • the polynucleotide may include the coding sequence for the mature polypeptide or a fragment thereof, by itself; the coding sequence for the mature polypeptide or fragment in reading frame with other coding sequences, such as those encoding a leader or secretory sequence, a pre-, or pro- or prepro- protein sequence, or other fusion peptide portions.
  • a marker sequence that facilitates purification of the fused polypeptide can be encoded.
  • Polynucleotides of the invention which are identical or sufficiently identical to the nucleotide sequences contained in SEQ ID NO: 1 or 3, may be used as hybridization probes for cDNA and genomic DNA, to isolate full-length cDNAs and genomic clones encoding MMP-2 or MMP-9 polypeptides and to isolate cDNA and genomic clones of other genes that have a high sequence similarity to the MMP-2 and MMP-9 genes.
  • hybridization techniques are known to those of skill in the art.
  • these nucleotide sequences are at least 95% identical to that of the referent.
  • the probes generally will comprise at least 15 nucleotides.
  • such probes will have at least 30 nucleotides and may have at least 50 nucleotides. Particularly preferred probes will range between 30 and 50 nucleotides.
  • host cells can be genetically engineered to inco ⁇ orate expression systems or portions thereof for polynucleotides of the present invention.
  • Introduction of polynucleotides into host cells can be effected by methods described in many standard laboratory manuals, such as Davis, et al, BASIC
  • Human MMP-2 and MMP-9 proteins are responsible for many biological functions, including many pathologies.
  • screening methods to identify compounds that stimulate or that inhibit the function the function or level of the polypeptide.
  • agonists or antagonists are employed for diseases and disorders including, but not limited to: stroke; hemorrhage; reperfusion injury; cerebral ischemia; cerebral infarction; enhanced or exaggerated sensitivity to pain, such as hyperalgesia, causalgia and allodynia; acute pain; burn pain; atypical facial pain; neuropathic pain; back pain; complex regional pain syndromes I and II; arthritic pain; sports injury pain; pain related to viral infection, e.g., HIV, post-polio syndrome, and post-he ⁇ etic neuralgia; phantom limb pain; labor pain; cancer pain; post-chemotherapy pain; post-stroke pain; postoperative pain; physiological pain; inflammatory pain; acute inflammatory conditions/visceral pain, e.g., angina, irritable
  • Prefened forms of systemic administration of the pharmaceutical compositions include injection, typically by intravenous injection Other injection routes, such as subcutaneous, intramuscular, or intrape ⁇ toneal, can be used Alternative means for systemic administration include transmucosal and transdermal administration using penetrants such as bile salts or fusidic acids or other detergents.
  • penetrants such as bile salts or fusidic acids or other detergents
  • oral administration may also be possible
  • Administration of these compounds may also be topical and/or localized, in the form of salves, pastes, gels, and the like
  • MMP enzyme expression was assayed by SDS-PAGE zymography using gelatin as an MMP substrate.
  • gelatin-containing zymograms equal volumes ( 10 ⁇ l) of tissue extracts normalized for protein concentration were subjected to electrophoresis, without boiling or reduction, through a 10% polyacrylamide gel co- polymerized with gelatin (0.5 mg/ml) at 4°C. After electrophoresis was complete, the gel was incubated for 1 hour at 25°C in a 2.5% Triton X-100 solution, washed two times, 20 minutes each, with water and then incubated overnight at 37°C in a 0.05 M Tris-HCI buffer, pH 8.0, containing 5 mM CaCl2.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Immunology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne un procédé de traitement d'un patient souffrant de douleur ou d'un accident vasculaire cérébral, ledit procédé comprenant une étape qui consiste à administrer au patient une quantité suffisante pour soulager la douleur d'un inhibiteur double de MMP-2 (SEQ ID NO:2) et de MMP-9 (SEQ ID NO:4) d'origine humaine en combinaison avec un support.
PCT/US2000/027949 1999-10-12 2000-10-11 Procedes de traitement au moyen d'inhibiteurs doubles de metalloproteinase-2 matricielle et de metalloproteinase-9 matricielle WO2001026671A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15878799P 1999-10-12 1999-10-12
US60/158,787 1999-10-12

Publications (1)

Publication Number Publication Date
WO2001026671A1 true WO2001026671A1 (fr) 2001-04-19

Family

ID=22569708

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/027949 WO2001026671A1 (fr) 1999-10-12 2000-10-11 Procedes de traitement au moyen d'inhibiteurs doubles de metalloproteinase-2 matricielle et de metalloproteinase-9 matricielle

Country Status (1)

Country Link
WO (1) WO2001026671A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001069261A2 (fr) * 2000-03-15 2001-09-20 Oxford Glycosciences (Uk) Ltd. Proteines, genes et leur utilisation dans le diagnostic et le traitement de la demence vasculaire
EP1283823A1 (fr) * 2000-05-24 2003-02-19 Smithkline Beecham Corporation Inhibiteurs des mmp-2/mmp-9
US7189700B2 (en) 2003-06-20 2007-03-13 Kimberly-Clark Worldwide, Inc. Anti-chrondrosarcoma compounds
EP2262840A2 (fr) * 2008-03-03 2010-12-22 Dyax Corp. Protéines de liaison à la métalloprotéinase 9 et à la métalloprotéinase 2
CN102618620A (zh) * 2012-04-11 2012-08-01 上海健耕医药科技有限公司 一种细胞水平筛选金属基质蛋白酶抑制剂的方法
US8455205B2 (en) 2008-03-03 2013-06-04 Dyax Corp. Metalloproteinase 9 binding proteins
US8501181B2 (en) 2007-12-17 2013-08-06 Dyax Corp. Compositions and methods for treating osteolytic disorders comprising MMP-14 binding proteins
US10314909B2 (en) 2011-10-21 2019-06-11 Dyax Corp. Combination therapy comprising an MMP-14 binding protein

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4923818A (en) * 1987-09-04 1990-05-08 Washington University DNA clone of human type IV collagenase
WO1998039024A1 (fr) * 1997-03-03 1998-09-11 Darwin Discovery Limited Inhibiteurs selectifs de la metalloprotease matricielle presentant des effets secondaires reduits
US6114159A (en) * 1994-03-17 2000-09-05 Max-Delbruck-Centrum Fur Molekulare Medizin DNA sequences for matrix metalloproteases, their production and use

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4923818A (en) * 1987-09-04 1990-05-08 Washington University DNA clone of human type IV collagenase
US6114159A (en) * 1994-03-17 2000-09-05 Max-Delbruck-Centrum Fur Molekulare Medizin DNA sequences for matrix metalloproteases, their production and use
WO1998039024A1 (fr) * 1997-03-03 1998-09-11 Darwin Discovery Limited Inhibiteurs selectifs de la metalloprotease matricielle presentant des effets secondaires reduits

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
COLLIER ET AL.: "On the structure and chromosome location of the 72-and 92-kDa human type IV collagenase genes", GENOMICS, vol. 9, 1991, pages 429 - 434, XP002935269 *
LEES ET AL.: "Mast cell proteinases activate precursor forms of collagenase and stromelysin, but not of gelatinases A and B", EUR. J. BIOCHEM., vol. 223, 1994, pages 171 - 177, XP002935270 *
MAKOWSKI ET AL.: "Identification and partial characterization of three calcium-and zinc-independent gelatinases constitutively present in human circulation", BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL, vol. 46, no. 5, December 1998 (1998-12-01), pages 1043 - 1053, XP002935272 *
TAMURA ET AL.: "Nitric oxide mediates interleukin-1-induced matrix degradation and basic fibroblast growth factor release in cultured rabbit articular chondrocytes: A possible mechanism of pathological neovascularization in arthritis", ENDOCRINOLOGY, vol. 137, no. 9, 1996, pages 3729 - 3737, XP002935271 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001069261A2 (fr) * 2000-03-15 2001-09-20 Oxford Glycosciences (Uk) Ltd. Proteines, genes et leur utilisation dans le diagnostic et le traitement de la demence vasculaire
WO2001069261A3 (fr) * 2000-03-15 2002-05-16 Oxford Glycosciences Uk Ltd Proteines, genes et leur utilisation dans le diagnostic et le traitement de la demence vasculaire
EP1283823A1 (fr) * 2000-05-24 2003-02-19 Smithkline Beecham Corporation Inhibiteurs des mmp-2/mmp-9
EP1283823A4 (fr) * 2000-05-24 2005-07-27 Smithkline Beecham Corp Inhibiteurs des mmp-2/mmp-9
US7189700B2 (en) 2003-06-20 2007-03-13 Kimberly-Clark Worldwide, Inc. Anti-chrondrosarcoma compounds
US7795225B2 (en) 2003-06-20 2010-09-14 Kimberly-Clark Worldwide, Inc. Anti-chrondrosarcoma compounds
US8501181B2 (en) 2007-12-17 2013-08-06 Dyax Corp. Compositions and methods for treating osteolytic disorders comprising MMP-14 binding proteins
EP2262840A2 (fr) * 2008-03-03 2010-12-22 Dyax Corp. Protéines de liaison à la métalloprotéinase 9 et à la métalloprotéinase 2
EP2262840A4 (fr) * 2008-03-03 2012-08-08 Dyax Corp Protéines de liaison à la métalloprotéinase 9 et à la métalloprotéinase 2
US8455205B2 (en) 2008-03-03 2013-06-04 Dyax Corp. Metalloproteinase 9 binding proteins
US10314909B2 (en) 2011-10-21 2019-06-11 Dyax Corp. Combination therapy comprising an MMP-14 binding protein
CN102618620A (zh) * 2012-04-11 2012-08-01 上海健耕医药科技有限公司 一种细胞水平筛选金属基质蛋白酶抑制剂的方法

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