Human osteoclast derived cathepsin

التفاصيل البيبلوغرافية
العنوان: Human osteoclast derived cathepsin
Document Number: 20050019889
تاريخ النشر: January 27, 2005
Appl. No: 10/726645
Application Filed: December 04, 2003
مستخلص: Disclosed is a human osteoclast-derived cathepsin (Cathepsin O) polypeptide and DNA(RNA) encoding such cathepsin O polypeptides. Also provided is a procedure for producing such polypeptide by recombinant techniques. The present invention also discloses antibodies, antagonists and inhibitors of such polypeptide which may be used to prevent the action of such polypeptide and therefore may be used therapeutically to treat bone diseases such as osteoporosis and cancers, such as tumor metastases.
Inventors: Hastings, Gregg A. (Westlake Village, CA, US); Adams, Mark D. (North Potomac, MD, US); Fraser, Claire M. (Potomac, MD, US); Lee, Norman H. (Woodstock, MD, US); Kirkness, Ewen F. (Olney, MD, US); Blake, Judith A. (Laurel, MD, US); Fitzgerald, Lisa M. (Germantown, MD, US); Drake, Fred H. (Glenmore, PA, US); Gowan, Maxine (Valley Forge, PA, US)
Assignees: Human Genome Sciences, Inc. (Rockville, MD, US), SmithKline Beecham Corporation (Philadelphia, PA, US)
Claim: 1. An isolated polynucleotide encoding for Cathepsin O, said polynucleotide selected from the group consisting of (a) a polynucleotide encoding for the Cathepsin O polypeptide having the deduced amino acid sequence of FIG. 1 or a fragment, analog or derivative of said polypeptide; and (b) a polynucleotide encoding for the Cathepsin O polypeptide having the amino acid sequence encoded by the cDNA contained in ATCC Deposit No. 75671 or a fragment, analog or derivative of said polypeptide.
Claim: 2. The polynucleotide of claim 1 wherein the polynucleotide is DNA.
Claim: 3. The polynucleotide of claim 1 wherein the polynucleotide is RNA.
Claim: 4. The polynucleotide of claim 1 wherein the polynucleotide is genomic DNA.
Claim: 5. The polynucleotide of claim 2 wherein said polynucleotide encodes for Cathepsin O having the deduced amino acid sequence of FIG. 1.
Claim: 6. The polynucleotide of claim 2 wherein said polynucleotide encodes for the Cathepsin O polypeptide encoded by the cDNA of ATCC Deposit No. 75671.
Claim: 7. The polynucleotide of claim 1 having the coding sequence for Cathepsin O as shown in FIG. 1.
Claim: 8. The polynucleotide of claim 2 having the coding sequence for Cathepsin O deposited as ATCC Deposit No. 75671.
Claim: 9. A vector containing the DNA of claim 2.
Claim: 10. A host cell genetically engineered with the vector of claim 9.
Claim: 11. A process for producing a polypeptide comprising: expressing from the host cell of claim 10 the polypeptide encoded by said DNA.
Claim: 12. A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of claim 9.
Claim: 13. An isolated DNA hybridizable to the DNA of claim 2 and encoding a polypeptide having Cathepsin O activity.
Claim: 14. A polypeptide selected from the group consisting of (i) a Cathepsin O polypeptide having the deduced amino acid sequence of FIG. 1 and fragments, analogs and derivatives thereof and (ii) a Cathepsin O polypeptide encoded by the cDNA of ATCC Deposit No. 75671 and fragments, analogs and derivatives of said polypeptide.
Claim: 15. The polypeptide of claim 14 wherein the polypeptide is Cathepsin O having the deduced amino acid sequence of FIG. 1.
Claim: 16. An antibody against the polypeptide of claim 14.
Claim: 17. An antagonist/inhibitor against the polypeptide of claim 14.
Claim: 18. A method for the treatment of a patient having need to inhibit Cathepsin O comprising: administering to the patient a therapeutically effective amount of an antagonist against the polypeptide of claim 14.
Claim: 19. A pharmaceutical composition comprising the polypeptide of claim 14 and a pharmaceutically acceptable carrier.
Claim: 20. A method for the treatment of a patient having need to inhibit Cathepsin O comprising: administering to the patient a therapeutically effective amount of an antisense construct against the DNA or RNA which encodes for Cathepsin O such that transcription and translation into Cathepsin O is inhibited.
Claim: 21. A method for the treatment of a patient having need to inhibit Cathepsin O comprising: administering to the patient a therapeutically effective amount of the antibody of claim 16.
Claim: 22. A method for the treatment of a patient having need to inhibit Cathepsin O comprising: administering to the patient a therapeutically effective amount of the antagonist/inhibitor of claim 17.
Claim: 23. A method for identifying inhibitors of Cathepsin O comprising: combining a potential inhibitor of the Cathepsin O polypeptide with peptide-based substrate of the formula X-(Y).sub.n-Z, wherein (i) X is an amino protecting group; (ii) Y is any naturally or non-naturally occurring amino acid; (iii) n is any whole integer; and (iv) Z is any chromogenic or fluorogenic tag; allowing an effective amount of time for the Cathepsin O to cleave the Y amino acid group; passing the peptide-based substrate through a fluorimeter, if a fluorogenic tag is used or a spectrophotometer, if a chromogenic tag is used; and detecting the production of fluorescence or color released by Z.
Claim: 24. The method of claim 21, wherein said patient has cancer.
Claim: 25. A method of detecting Cathepsin O protein in a biological sample comprising: (a) contacting the biological sample with the antibody of claim 16; and (b) detecting the Cathepsin O protein in the biological sample.
Current U.S. Class: 435226/000
رقم الانضمام: edspap.20050019889
قاعدة البيانات: USPTO Patent Applications