Nucleic acids, proteins, and antibodies

• US 20020147140A1
• Filed: 01/17/2001
• Published: 10/10/2002
• Est. Priority Date: 01/31/2000
• Status: Abandoned Application

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Rosen, Craig A., Ruben, Steven M., Barash, Steven C.
• Application Number:
  US09/764,877
• Publication Number:
  US 20020147140A1
• Time in Patent Office: Days
• US Class Current: 514/12
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material

Abstract

The present invention relates to novel musculoskeletal system related polynucleotides and the polypeptides encoded by these polynucleotides herein collectively known as “musculoskeletal system antigens,” and the use of such musculoskeletal system antigens for detecting disorders of the musculoskeletal system, particularly the presence of cancer and cancer metastases. More specifically, isolated musculoskeletal system associated nucleic acid molecules are provided encoding novel musculoskeletal system associated polypeptides. Novel musculoskeletal system polypeptides and antibodies that bind to these polypeptides are provided. Also provided are vectors, host cells, and recombinant and synthetic methods for producing human musculoskeletal system associated polynucleotides and/or polypeptides. The invention further relates to diagnostic and therapeutic methods useful for diagnosing, treating, preventing and/or prognosing disorders related to the musculoskeletal system, including cancer of musculoskeletal tissues, and therapeutic methods for treating such disorders. The invention further relates to screening methods for identifying agonists and antagonists of polynucleotides and polypeptides of the invention. The present invention further relates to methods and/or compositions for inhibiting the production and function of the polypeptides of the present invention.

Claims

1. An isolated nucleic acid molecule comprising a polynucleotide having a nucleotide sequence at least 95% identical to a sequence selected from the group consisting of:

(a) a polynucleotide fragment of SEQ ID NO;

X or a polynucleotide fragment of the cDNA sequence contained in Clone ID NO;

Z, which is hybridizable to SEQ ID NO;

X;

(b) a polynucleotide encoding a polypeptide fragment of SEQ ID NO;

Y or a polypeptide fragment encoded by the cDNA sequence contained in cDNA Clone ID NO;

Z, which is hybridizable to SEQ ID NO;

X;

(c) a polynucleotide encoding a polypeptide fragment of a polypeptide encoded by SEQ ID NO;

X or a polypeptide fragment encoded by the cDNA sequence contained in cDNA Clone ID NO;

Z, which is hybridizable to SEQ ID NO;

X;

(d) a polynucleotide encoding a polypeptide domain of SEQ ID NO;

Y or a polypeptide domain encoded by the cDNA sequence contained in cDNA Clone ID NO;

Z, which is hybridizable to SEQ ID NO;

X;

(e) a polynucleotide encoding a polypeptide epitope of SEQ ID NO;

Y or a polypeptide epitope encoded by the cDNA sequence contained in cDNA Clone ID NO;

Z, which is hybridizable to SEQ ID NO;

X;

(f) a polynucleotide encoding a polypeptide of SEQ ID NO;

Y or the cDNA sequence contained in cDNA Clone ID NO;

Z, which is hybridizable to SEQ ID NO;

X, having biological activity;

(g) a polynucleotide which is a variant of SEQ ID NO ;

X;

(h) a polynucleotide which is an allelic variant of SEQ ID NO;

X;

(i) a polynucleotide which encodes a species homologue of the SEQ ID NO;

Y;

(j) a polynucleotide capable of hybridizing under stringent conditions to any one of the polynucleotides specified in (a)-(i), wherein said polynucleotide does not hybridize under stringent conditions to a nucleic acid molecule having a nucleotide sequence of only A residues or of only T residues.

2. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding a protein.

3. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises a nucleotide sequence encoding the sequence identified as SEQ ID NO:

Y or the polypeptide encoded by the cDNA sequence contained in cDNA Clone ID NO;

Z, which is hybridizable to SEQ ID NO;

X.

4. The isolated nucleic acid molecule of claim 1, wherein the polynucleotide fragment comprises the entire nucleotide sequence of SEQ ID NO:

X or the cDNA sequence contained in cDNA Clone ID NO;

Z, which is hybridizable to SEQ ID NO;

X.

5. The isolated nucleic acid molecule of claim 2, wherein the nucleotide sequence comprises sequential nucleotide deletions from either the C-terminus or the N-terminus.

6. The isolated nucleic acid molecule of claim 3, wherein the nucleotide sequence comprises sequential nucleotide deletions from either the C-terminus or the N-terminus.

7. A recombinant vector comprising the isolated nucleic acid molecule of claim 1.

8. A method of making a recombinant host cell comprising the isolated nucleic acid molecule of claim 1.

9. A recombinant host cell produced by the method of claim 8.

10. The recombinant host cell of claim 9 comprising vector sequences.

17. A method for preventing, treating, or ameliorating a medical condition, comprising administering to a mammalian subject a therapeutically effective amount of the polynucleotide of claim 1.

18. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising:

(a) determining the presence or absence of a mutation in the polynucleotide of claim 1;

and

(b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or absence of said mutation.

11. An isolated polypeptide comprising an amino acid sequence at least 90% identical to a sequence selected from the group consisting of:

(a) a polypeptide fragment of SEQ ID NO;

Y or the encoded sequence contained in cDNA Clone ID NO;

Z;

(b) a polypeptide fragment of SEQ ID NO;

Y or the encoded sequence contained in cDNA Clone ID NO;

Z, having biological activity;

(c) a polypeptide domain of SEQ ID NO;

Y or the encoded sequence contained in cDNA Clone ID NO;

Z;

(d) a polypeptide epitope of SEQ ID NO;

Y or the encoded sequence contained in cDNA Clone ID NO;

Z;

(e) a full length protein of SEQ ID NO;

Y or the encoded sequence contained in cDNA Clone ID NO;

Z;

(f) a variant of SEQ ID NO;

Y;

(g) an allelic variant of SEQ ID NO;

Y;

or

(h) a species homologue of the SEQ ID NO;

Y.

12. The isolated polypeptide of claim 11, wherein the full length protein comprises sequential amino acid deletions from either the C-terminus or the N-terminus.

13. An isolated antibody that binds specifically to the isolated polypeptide of claim 11.

14. A recombinant host cell that expresses the isolated polypeptide of claim 11.

15. A method of making an isolated polypeptide comprising:

(a) culturing the recombinant host cell of claim 14 under conditions such that said polypeptide is expressed; and

(b) recovering said polypeptide.

16. The polypeptide produced by claim 15.

19. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject comprising:

(a) determining the presence or amount of expression of the polypeptide of claim 11 in a biological sample; and

(b) diagnosing a pathological condition or a susceptibility to a pathological condition based on the presence or amount of expression of the polypeptide.

20. A method for identifying a binding partner to the polypeptide of claim 11 comprising:

(a) contacting the polypeptide of claim 11 with a binding partner; and

(b) determining whether the binding partner effects an activity of the polypeptide.

23. The product produced by the method of claim 20.

24. A method for preventing, treating, or ameliorating a medical condition, comprising administering to a mammalian subject a therapeutically effective amount of the polypeptide of claim 11.

21. The gene corresponding to the cDNA sequence of SEQ ID NO:

Y.

22. A method of identifying an activity in a biological assay, wherein the method comprises:

(a) expressing SEQ ID NO;

X in a cell;

(b) isolating the supernatant;

(c) detecting an activity in a biological assay; and

(d) identifying the protein in the supernatant having the activity.