Heparanase specific molecular probes and their use in research and medical applications

• US 7,339,038 B2
• Filed: 10/02/2003
• Issued: 03/04/2008
• Est. Priority Date: 09/02/1997
• Status: Expired due to Fees

• Current Assignee: Hadasit Medical Research Services and Development Limited, Insight Biopharmaceuticals Limited
• Original Assignee: Hadasit Medical Research Services & Development Ltd (Hadassah, The Women's Zionist Organization of America, Inc.), Insight Biopharmaceuticals Limited
• Inventors: Pecker, Iris, Friedmann, Yael, Peretz, Tuvia, Vlodavsky, Israel
• Primary Examiner(s): Chan; Christina
• Assistant Examiner(s): DiBrino; Marianne
• Application Number:
  US10/676,079
• Publication Number:
  US 20040063135A1
• Time in Patent Office: 1,615 Days
• Field of Search: 536/22.1, 536/23.5
• US Class Current: 536/22.1
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61M 15/009 using medicine packages with incorporated spraying means, e.g. aerosol cans pocket atomiser of the injector type A61M11/08
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C12N 9/2402 hydrolysing O- and S- glycosyl compounds (3.2.1)
• CPC Class Codes: C12Y 302/01166 Heparanase (3.2.1.166)
• CPC Class Codes: G01N 2333/988 Lyases (4.), e.g. aldolases, heparinase, enolases, fumarase
• CPC Class Codes: G01N 2400/40 Glycosaminoglycans, i.e. GAG or mucopolysaccharides, e.g. chondroitin sulfate, dermatan sulfate, hyaluronic acid, heparin, heparan sulfate, and related sulfated polysaccharides
• CPC Class Codes: G01N 33/573 for enzymes or isoenzymes

Abstract

A variety of heparanase specific molecular probes which can be used for research and medical applications including diagnosis and therapy. Specific applications include the use of a heparanase specific molecular probe for detection of the presence, absence or level of heparanase expression; the use of a heparanase specific molecular probe for therapy of a condition associated with expression of heparanase; the use of a heparanase specific molecular probe for quantification of heparanase in a body fluid; the use of a heparanase specific molecular probe for targeted drug delivery; and the use of a heparanase specific molecular probe as a therapeutic agent.

Claims

1. A pair of oligonucleotides comprising a sense oligonucleotide and an antisense oligonucleotide, said pair of oligonucleotides capable of directing PCR amplification resulting in a polynucleotide fragment of a polynucleotide sequence encoding a protein selected from the group consisting a) SEQ ID NO:

2 and b) SEQ ID NO;

2 having a phenylalanine residue instead of a tyrosine residue at position 246, said polynucleotide fragment being part of said polynucleotide sequence that encodes said protein.

2. The pair of oligonucleotides of claim 1. wherein said polynucleotide sequence is as set forth in SEQ ID NO:

1.

3. The pair of oligonucleotides of claim 1, wherein said pair of oligonucleotides is set forth by SEQ ID NOs:

6 and 7.

4. The pair of oligonucleotides of claim 1, wherein at least one of said sense oligonucleotide and said antisense oligonucleotide is designed having an endonuclease cleavage site, so as to enable cloning of a resulting PCR product generated therewith into a vector.

5. The pair of oligonucleotides of claim 1, wherein at least one of said sense oligonucleotide and said antisense oligonucleotide is labeled with a detectable moiety.

6. The pair of oligonucleotides of claim 5, wherein said detectable moiety is selected from the group consisting of a chromogenic moiety, a fluorogenic moiety, a light-emitting moiety and a radioactivc moiety.

7. The pair of oligonucleotides of claim 1, wherein said polynucleotide sequence is as set forth in SEQ ID NO:

1, provided that T replaccs A at position 799.

8. The pair of oligonucleotides of claim 1, wherein said protein is SEQ ID NO:

2.

9. The pair of oligonucleotides of claim 1, wherein said protein is SEQ ID NO:

2 having a phenylalanine residue instead of a tyrosine residue at position 246.