CA2367457A1 - Protein for blocking platelet adhesion - Google Patents
Protein for blocking platelet adhesion Download PDFInfo
- Publication number
- CA2367457A1 CA2367457A1 CA002367457A CA2367457A CA2367457A1 CA 2367457 A1 CA2367457 A1 CA 2367457A1 CA 002367457 A CA002367457 A CA 002367457A CA 2367457 A CA2367457 A CA 2367457A CA 2367457 A1 CA2367457 A1 CA 2367457A1
- Authority
- CA
- Canada
- Prior art keywords
- polypeptide
- protein
- dna sequence
- collagen
- seq
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
Classifications
-
- 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
-
- 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
- C07K14/43504—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates
- C07K14/43536—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from invertebrates from worms
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Toxicology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Materials For Medical Uses (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
A naturally occurring protein isolated from the saliva of the medicinal leec h Hirudo medicinalis is described which strongly binds to collagen thus acting as an inhibitor of natural platelet adhesion to collagen. The protein has a molecular weight of about 12 000, an acidic isoelectric point and contains s ix cysteins. The protein was sequenced and the gene was cloned from a H. medicinalis cDNA-library. Procedures for producing such polypeptide by recombinant techniques are disclosed. The recombinant and the natural occurring proteins are potent inhibitors of collagen-dependent platelet adhesion and therefore useful for the therapeutic treatment of various conditions related to hard disease and diseases of the circulation system. Furthermore the protein is useful for coating natural or artificial collagen surfaces in order to render them nonadhesive for cells and prevent the activation of cells.
Claims (25)
1. A polypeptide isolated from H. medicinalis having a molecular weight of about 12 000 ~1kD with the biological activity of an inhibitor of collagen-dependent platelet adhesion.
2. A polypeptide of claim 1 having an isoelectric point of pH 3.7 ~ 0.5
3. A polypeptide of claim 1 or 2 having six cysteine molecules capable of forming -S-S- brigdes
4. A polypeptide of claim 1 which comprises an amino acid sequences of SEQ.
ID. NO. 1.
ID. NO. 1.
5. A polypeptide comprising an amino acid sequence according to claim 4 which is at least 80% identical to the amino acid sequence of SEQ. ID. NO. 1 over its entire length.
6. An isolated polynucleotide encoding a polypeptide of claims 1-5.
7. An isolated polynucleotide comprising a DNA sequence of SEQ. ID. NO. 2, or a DNA sequence complementary to said DNA sequence wherein said polynucleotide is encoding a polypeptide of claim 1-5.
8. The polynucleotide of claim 7 wherein said polynucleotide comprises a DNA
sequence that is at least 80% identical to that of SEQ ID NO: 1 over its entire length.
sequence that is at least 80% identical to that of SEQ ID NO: 1 over its entire length.
9. An expression vector comprising a DNA sequence of claims 6-8.
10. A host cell comprising the expression vector of claim 9.
11. An expression system comprising a host cell of claim 10.
12. A process for producing a polypeptide of claims 1-5 comprising a host of claim 10 culturing said host under conditions sufficient for the production of said polypeptide and recovering the polypeptide from the culture supernatant or cell residue.
13. An antibody immunospecific for a polypeptide of claims 1-5.
14. A pharmaceutical formulation which comprises a polypeptide according to claims 1-5 and a pharmaceutical acceptable carrier or excipient therefore.
15. A pharmaceutical active agent of claim 14 for the treatment of thromboembolic processes
16. A pharmaceutical formulation of claims 14 or 15 comprising additional drugs wherein the additional drug is selected from aspirin, heparin or streptokinase or a combination thereof.
17. Use of a polypeptide according to claims 1-5 for the manufacture of a medicament for the treatment of thromboembolic diseases.
18. Use of a polypeptide according to claims 1-5 for coating artifical surfaces.
19. Use of a polypeptide according to claims 1-5 for modifying intraocular lenses in order to lessen the thrombogenicity of the lens material.
20. Use of a polypeptide according to claims 1-5 for contacting the lens surface
21. Use of a polypeptide according to claims 1-5 for covalent crosslinking to modify said lens material.
22. Use of antibodies according to claim 13 and polypeptide according to claim to measure samples derived from claim 12 or a treated subject.
23. A method for identifying compounds which inhibit (antagonize) or agonize the polypeptide of claim 1 -5 by observing the binding, or stimulation or inhibition of a functional response.
24. An agonist identified by the method of claim 23.
25. An antagonist identified by the method of claim 23.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99105530 | 1999-03-18 | ||
| EP99105530.2 | 1999-03-18 | ||
| EP99109503 | 1999-05-12 | ||
| EP99109503.5 | 1999-05-12 | ||
| PCT/EP2000/002117 WO2000056885A1 (en) | 1999-03-18 | 2000-03-10 | Protein for blocking platelet adhesion |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2367457A1 true CA2367457A1 (en) | 2000-09-28 |
| CA2367457C CA2367457C (en) | 2010-09-21 |
Family
ID=26152935
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2367457A Expired - Fee Related CA2367457C (en) | 1999-03-18 | 2000-03-10 | Protein for blocking platelet adhesion |
Country Status (27)
| Country | Link |
|---|---|
| US (3) | US6774107B1 (en) |
| EP (1) | EP1161530B1 (en) |
| JP (1) | JP4805461B2 (en) |
| KR (1) | KR100788219B1 (en) |
| CN (1) | CN1185344C (en) |
| AR (1) | AR023099A1 (en) |
| AT (1) | ATE295883T1 (en) |
| AU (1) | AU767172B2 (en) |
| BR (1) | BR0009074A (en) |
| CA (1) | CA2367457C (en) |
| CO (1) | CO5241328A1 (en) |
| CZ (1) | CZ301524B6 (en) |
| DE (1) | DE60020220T2 (en) |
| DK (1) | DK1161530T3 (en) |
| ES (1) | ES2240067T3 (en) |
| HK (1) | HK1045330B (en) |
| HU (1) | HU228068B1 (en) |
| MX (1) | MXPA01009363A (en) |
| MY (1) | MY123371A (en) |
| NO (1) | NO330769B1 (en) |
| PL (1) | PL200384B1 (en) |
| PT (1) | PT1161530E (en) |
| RU (1) | RU2292351C2 (en) |
| SI (1) | SI1161530T1 (en) |
| SK (1) | SK287496B6 (en) |
| TR (1) | TR200102729T2 (en) |
| WO (1) | WO2000056885A1 (en) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4805461B2 (en) * | 1999-03-18 | 2011-11-02 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Protein for blocking platelet adhesion |
| MY128992A (en) * | 2000-08-25 | 2007-03-30 | Merck Patent Gmbh | Saratin for inhibiting platelet adhesion to collagen |
| CA2453986A1 (en) * | 2001-07-18 | 2003-01-30 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Glycoprotein vi fusion proteins |
| US7053051B2 (en) | 2003-10-28 | 2006-05-30 | Medtronic, Inc. | Methods of preparing crosslinked materials and bioprosthetic devices |
| US8017634B2 (en) | 2003-12-29 | 2011-09-13 | President And Fellows Of Harvard College | Compositions for treating obesity and insulin resistance disorders |
| EP1799828B1 (en) * | 2004-10-12 | 2013-05-01 | Board of Trustees of Michigan State University | Biosynthesis of phloroglucinol and preparation of 1,3-dihydroxybenzene therefrom |
| CA2611102A1 (en) * | 2005-05-26 | 2006-11-30 | Thomas Jefferson University | Method to treat and prevent posterior capsule opacification |
| US20110034396A1 (en) * | 2005-09-28 | 2011-02-10 | Biovascular, Inc. | Methods and compositions for inhibiting cell migration and treatment of inflammatory conditions |
| CA2623565A1 (en) | 2005-09-28 | 2007-04-05 | Biovascular, Inc. | Methods and compositions for blocking platelet and cell adhesion, cell migration and inflammation |
| US20080015145A1 (en) * | 2006-07-11 | 2008-01-17 | Maria Gyongyossy-Issa | Mimotope receptors and inhibitors for platelet-platelet and platelet-endothelium interactions |
| GB2462022B (en) | 2008-06-16 | 2011-05-25 | Biovascular Inc | Controlled release compositions of agents that reduce circulating levels of platelets and methods thereof |
| CA2966011C (en) | 2008-10-15 | 2021-10-19 | Ionis Pharmaceuticals, Inc. | Modulation of factor 11 expression |
| WO2012003461A2 (en) | 2010-07-02 | 2012-01-05 | Draths Corporation | Phloroglucinol synthases and methods of making and using the same |
| WO2012006244A1 (en) | 2010-07-06 | 2012-01-12 | Draths Corporation | Method for producing phloroglucinol and dihydrophloroglucinol |
| WO2012006245A1 (en) | 2010-07-06 | 2012-01-12 | Draths Corporation | Phloroglucinol reductase and methods of making and using the same |
| HUE058226T2 (en) | 2010-08-19 | 2022-07-28 | Zoetis Belgium S A | Anti-ngf antibodies and their use |
| US8790651B2 (en) | 2011-07-21 | 2014-07-29 | Zoetis Llc | Interleukin-31 monoclonal antibody |
| DE202012012998U1 (en) | 2011-08-31 | 2014-06-13 | Daniel Elias | Bioactive, regenerative mixture for the preparation of a supplementary food |
| EP2859018B1 (en) | 2012-06-06 | 2021-09-22 | Zoetis Services LLC | Caninized anti-ngf antibodies and methods thereof |
| CA2879443A1 (en) | 2012-07-19 | 2014-01-23 | Zoetis Llc | Bovine influenza virus compositions |
| AU2013295770A1 (en) | 2012-07-27 | 2015-01-29 | Zoetis Services Llc | Tick toxin compositions |
| US11167017B2 (en) | 2016-08-17 | 2021-11-09 | Pharmaq As | Sea lice vaccine |
| BR102017005783A2 (en) * | 2017-03-21 | 2018-10-02 | Fund Butantan | process for obtaining esculptin and fragments thereof, recombinant sculptin and its uses |
| WO2019177690A1 (en) | 2018-03-12 | 2019-09-19 | Zoetis Services Llc | Anti-ngf antibodies and methods thereof |
| MX2020009639A (en) | 2018-03-16 | 2021-01-08 | Zoetis Services Llc | Peptide vaccines against interleukin-31. |
| EP3765500A2 (en) | 2018-03-16 | 2021-01-20 | Zoetis Services LLC | Interleukin-31 monoclonal antibodies for veterinary use |
| BR112020020957B1 (en) | 2018-05-09 | 2022-05-10 | Ionis Pharmaceuticals, Inc | Oligomeric compounds, population and pharmaceutical composition thereof and their uses |
| WO2021050701A1 (en) | 2019-09-11 | 2021-03-18 | Zoetis Services Llc | Recombinant herpesvirus of turkey vectors expressing antigens of avian pathogens and uses thereof |
| US20220119513A1 (en) | 2020-06-08 | 2022-04-21 | Zoetis Services Llc | Anti-tgfb antibodies and therapeutic uses thereof |
| US20210386854A1 (en) | 2020-06-15 | 2021-12-16 | Zoetis Services Llc | Cell Line for Production of Marek's Disease Virus Vaccine and Methods of Making and Using the Same |
| JP2023544839A (en) | 2020-10-07 | 2023-10-25 | ゾエティス・サービシーズ・エルエルシー | Anti-NGF antibody and its usage method |
| TW202221039A (en) | 2020-10-19 | 2022-06-01 | 美商碩騰服務公司 | Antibodies to canine and feline oncostatin m receptor beta and uses thereof |
| CA3232382A1 (en) | 2021-09-27 | 2023-03-30 | Zoetis Services Llc | Anti- tgf.beta.1,2,3 antibodies and therapeutic uses thereof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5705355A (en) * | 1984-03-27 | 1998-01-06 | Transgene, S.A. | Hirudin, pharmaceutical compositions comprising it and their use |
| US4898734A (en) * | 1988-02-29 | 1990-02-06 | Massachusetts Institute Of Technology | Polymer composite for controlled release or membrane formation |
| IL86857A (en) * | 1988-06-24 | 1994-04-12 | Yissum Res Dev Co | Platelet-aggregating inhibitory agents from leech saliva and pharmaceutical preparations containing the same |
| US5182260A (en) * | 1989-01-27 | 1993-01-26 | Biogen, Inc. | Dna sequences encoding snake venom inhibitors of platelet activation processes for producing those inhibitors and compositions using them |
| CA2052486A1 (en) * | 1990-10-09 | 1992-04-10 | Thomas M. Connolly | Protein for inhibiting collagen-stimulated platelet aggregation |
| GB9022040D0 (en) * | 1990-10-10 | 1990-11-21 | Biopharm Ltd | Platelet adhesion inhibitor |
| DE4136513A1 (en) * | 1991-11-06 | 1993-05-13 | Basf Ag | NEW THROMBIN INHIBITORIC PROTEIN FROM RUBBER BUGS |
| CZ287472B6 (en) * | 1993-07-01 | 2000-12-13 | Merck Patent Gmbh | Purified protein, process of its preparation and use as well as pharmaceutical preparation based thereon |
| PT1118325E (en) * | 1993-07-29 | 2006-05-31 | Us Health | USES OF PACLITAXEL AND ITS DERIVATIVES IN THE PREPARATION OF A MEDICINAL PRODUCT FOR THE TREATMENT OF RESTENOSE |
| EP0781334A1 (en) * | 1994-09-12 | 1997-07-02 | Schering Aktiengesellschaft | Process for manufacture of a modified collagen-induced platelet aggregation inhibitor pallidipin |
| WO1996013585A1 (en) * | 1994-10-28 | 1996-05-09 | Clodica S.A. | A novel family of protease inhibitors, and other biologic active substances |
| JP4805461B2 (en) * | 1999-03-18 | 2011-11-02 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | Protein for blocking platelet adhesion |
| MY128992A (en) * | 2000-08-25 | 2007-03-30 | Merck Patent Gmbh | Saratin for inhibiting platelet adhesion to collagen |
-
2000
- 2000-03-10 JP JP2000606744A patent/JP4805461B2/en not_active Expired - Fee Related
- 2000-03-10 DE DE60020220T patent/DE60020220T2/en not_active Expired - Lifetime
- 2000-03-10 DK DK00909351T patent/DK1161530T3/en active
- 2000-03-10 KR KR1020017011881A patent/KR100788219B1/en not_active IP Right Cessation
- 2000-03-10 CN CNB008052115A patent/CN1185344C/en not_active Expired - Fee Related
- 2000-03-10 CA CA2367457A patent/CA2367457C/en not_active Expired - Fee Related
- 2000-03-10 ES ES00909351T patent/ES2240067T3/en not_active Expired - Lifetime
- 2000-03-10 BR BR0009074-3A patent/BR0009074A/en not_active IP Right Cessation
- 2000-03-10 PT PT00909351T patent/PT1161530E/en unknown
- 2000-03-10 SI SI200030723T patent/SI1161530T1/en unknown
- 2000-03-10 US US09/936,737 patent/US6774107B1/en not_active Expired - Fee Related
- 2000-03-10 AU AU31662/00A patent/AU767172B2/en not_active Ceased
- 2000-03-10 HU HU0200353A patent/HU228068B1/en not_active IP Right Cessation
- 2000-03-10 WO PCT/EP2000/002117 patent/WO2000056885A1/en active Search and Examination
- 2000-03-10 MX MXPA01009363A patent/MXPA01009363A/en active IP Right Grant
- 2000-03-10 EP EP00909351A patent/EP1161530B1/en not_active Expired - Lifetime
- 2000-03-10 AT AT00909351T patent/ATE295883T1/en active
- 2000-03-10 CZ CZ20013341A patent/CZ301524B6/en not_active IP Right Cessation
- 2000-03-10 TR TR2001/02729T patent/TR200102729T2/en unknown
- 2000-03-10 SK SK1290-2001A patent/SK287496B6/en not_active IP Right Cessation
- 2000-03-10 PL PL350147A patent/PL200384B1/en not_active IP Right Cessation
- 2000-03-10 RU RU2001126921/13A patent/RU2292351C2/en not_active IP Right Cessation
- 2000-03-14 MY MYPI20000991A patent/MY123371A/en unknown
- 2000-03-17 AR ARP000101192A patent/AR023099A1/en active IP Right Grant
- 2000-03-17 CO CO00019687A patent/CO5241328A1/en not_active Application Discontinuation
-
2001
- 2001-09-17 NO NO20014506A patent/NO330769B1/en not_active IP Right Cessation
-
2002
- 2002-09-16 HK HK02106777.4A patent/HK1045330B/en not_active IP Right Cessation
-
2004
- 2004-05-17 US US10/846,668 patent/US6962801B2/en not_active Expired - Fee Related
-
2005
- 2005-06-16 US US11/153,433 patent/US7090986B2/en not_active Expired - Fee Related
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20170310 |