Claims
- 1. A substantially purified polypeptide comprising a Siglec-12 polypeptide, wherein the amino acid sequence of the Siglec-12 polypeptide is at least 80% identical to a sequence as set forth in SEQ ID NO:2, wherein the Siglec-12 polypeptide binds a sialic acid moiety.
- 2. The substantially purified polypeptide of claim 1, wherein the amino acid sequence is at least 90% identical to a sequence as set forth in SEQ ID NO:2.
- 3. The substantially purified polypeptide of claim 1, wherein the amino acid sequence is a sequence as set forth in SEQ ID NO:2.
- 4. The substantially purified polypeptide of claim 1, wherein the sequence is from about amino acid 14 to 686 of SEQ ID NO:2.
- 5. The substantially purified polypeptide of claim 1, wherein the sequence is from about amino acid 14 to 549 of SEQ ID NO:2.
- 6. A substantially purified polypeptide comprising a Siglec-12 extracellular domain, wherein the amino acid sequence of the Siglec-12 extracellular domain is at least 80% identical to a sequence as set forth from about amino acid 14 to 549 of SEQ ID NO:2, wherein the Siglec-12 extracellular domain binds a sialic acid moiety.
- 7. A fusion polypeptide comprising a first polypeptide comprising an amino acid sequence as set forth from about amino acid 14 to 549 of SEQ ID NO:2 operably linked to a second polypeptide.
- 8. The fusion polypeptide of claim 7, wherein the second polypeptide is an Fc polypeptide.
- 9. The fusion polypeptide of claim 7, wherein the second polypeptide is a leucine zipper polypeptide.
- 10. The fusion polypeptide of claim 7, comprising a linker polypeptide separating the first polypeptide and the second polypeptide.
- 11. An isolated polynucleotide encoding a polypeptide of claim 1.
- 12. An isolated polynucleotide encoding a polypeptide of claim 6.
- 13. An isolated polynucleotide encoding a fusion polypeptide of claim 7.
- 14. An isolated polynucleotide comprising a sequence selected from the group consisting of:
a) SEQ ID NO:1; b) SEQ ID NO:1 from about nucleotide 40 to 2058; c) SEQ ID NO:1 from about nucleotide 40 to 1647; d) sequences complementary to SEQ ID NO:1; e) sequences complementary to SEQ ID NO:1 from nucleotide 40 to 2058; f) sequences complementary to SEQ ID NO:1 from nucleotide 40 to 1647; g) any of (a)-(f), wherein T can also be U; and h) fragments of (a)-(g) that are at least 50 bases in length and that will hybridize under moderate to highly stringent conditions to a nucleic acid which encodes a polypeptide consisting of a sequence as set forth in SEQ ID NO:2.
- 15. A vector comprising a polynucleotide of claim 14.
- 16. The vector of claim 15, wherein the vector is a plasmid.
- 17. The vector of claim 15, wherein the vector is a viral vector.
- 18. A host cell containing the vector of claim 15.
- 19. A recombinant host cell comprising a polynucleotide of claim 14 under the control of a heterologous regulatory sequence.
- 20. The host cell of claim 19, wherein the cell is prokaryotic.
- 21. The host cell of claim 19, wherein the cell is eukaryotic.
- 22. A method of producing a polypeptide comprising culturing a host cell of claim 19 under condition that promote expression of the polypeptide.
- 23. A polypeptide produced by culturing a host cell of claim 19 under conditions that promote expression of the polypeptide.
- 24. A substantially purified antibody that specifically binds to a polypeptide consisting of a sequence as set forth in SEQ ID NO:2.
- 25. The substantially purified antibody of claim 24, wherein the antibody is a monoclonal antibody.
- 26. The substantially purified antibody of claim 24, wherein the antibody is a human or a humanized antibody.
- 27. A pharmaceutical composition comprising the antibody of claim 24.
- 28. A pharmaceutical composition comprising a polypeptide selected from the group consisting of:
(a) a polypeptide comprising a sequence as set forth in SEQ ID NO:2 from about amino acid 14 to 686; and (b) a polypeptide comprising a sequence as set forth in SEQ ID NO:2 from about amino acid 14 to 549, and a pharmaceutical carrier, excipient or diluent.
- 29. A method for identifying an agent which modulates expression of a polynucleotide comprising contacting a sample containing a polynucleotide comprising a sequence as set forth in SEQ ID NO:1 with a test agent and measuring the expression of the polynucleotide compared to a control, wherein a change in expression compared to the control is indicative of an agent that modulates expression of the polynucleotide.
- 30. The method of claim 29, wherein the agent is selected from the group consisting of a polypeptide, a peptide, a peptidomimetic, a nucleic acid, and a small molecule.
- 31. The method of claim 29, wherein the sample is a biological sample from a subject.
- 32. The method of claim 29, wherein the sample comprises cells.
- 33. The method of claim 29, wherein the change in expression is an increase in expression.
- 34. The method of claim 29, wherein the measuring is by PCR or Northern Blot.
- 35. The method of claim 29, wherein the measuring is by detecting a polypeptide expressed by the polynucleotide.
- 36. A method for identifying an agent which modulates the activity of a polypeptide comprising contacting a sample containing a polypeptide comprising a sequence selected from the group consisting of (a) SEQ ID NO:2, (b) SEQ ID NO:2 from 14 to 686, and (c) SEQ ID NO:2 from 14 to 549, with a test agent and measuring the activity of the polypeptide compared to a control, wherein a change in activity compared to the control is indicative of an agent that modulates activity of the polypeptide.
- 37. The method of claim 36, wherein the agent is selected from the group consisting of a polypeptide, a peptide, a peptidomimetic, a nucleic acid, and a small molecule.
- 38. The method of claim 36, wherein the sample is a biological sample from a subject.
- 39. The method of claim 36, wherein the sample comprises cells.
- 40. The method of claim 42, wherein the change in activity is an increase in activity.
- 41. The method of claim 36, wherein the measuring is by quantitating the amount of polypeptide in the sample.
- 42. A method of treating a siglec-associated disorder or disease comprising contacting a subject with a Siglec-12 polypeptide or Siglec-12 polynucleotide in an amount effective to treat the siglec-associated disorder or disease.
- 43. The method of claim 42, wherein the siglec-associated disorder is selected from the group consisting of a rheumatologic disorder, a bone marrow or solid organ transplant disorder, a graft-versus-host disorder, an inflammatory disorder, an autoimmune disorder, a neurologic disorder, a cell proliferative disorder, an infection, a cardiovascular disorder, a hematologic disorder, liver disorder, and a bone disorder.
- 44. The method of claim 42, wherein the Siglec-12 polypeptide has a sequence as set forth in SEQ ID NO:2 or a bioactive fragment thereof.
- 45. The method of claim 44, wherein the bioactive fragment has a sequence as set forth in SEQ ID NO:2 from about amino acid 14 to 549.
- 46. The method of claim 42, wherein the Siglec-12 polynucleotide has a sequence as set forth in SEQ ID NO:1.
- 47. The substantially purified antibody of claim 24 conjugated to a toxin or a radioisotope.
- 48. A method of treating a subject having a tumor that expresses a Siglec-12 polypeptide, comprising administering to the subject an antibody of claim 47.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority under 35 U.S.C. §119 to U.S. Provisional Application Serial No. 60/294,199, filed May 29, 2001, the disclosure of which is incorporated herein by references.
Provisional Applications (1)
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Number |
Date |
Country |
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60294199 |
May 2001 |
US |