Confluence regulated adhesion molecules useful in modulating vascular permeability
View Patent ↗The invention relates to new polypeptide in isolated form belonging to a subfamily of the human Immunoglobulin Superfamily, which polypeptide shows at least 70% sequence homology with the amino acid sequence of the murine Confluency Regulated Adhesion Molecules 1 or 2 (CRAM-1 or CRAM-2) as depicted in FIG. 3 upper and second row, respectively, and antibodies thereto as well as their use in treatment of inflammation and tumors.
1. An isolated polypeptide comprising:
a) SEQ ID NO: 13;
b) amino acids 1-291 of SEQ ID NO: 13; or
c) the amino acid sequence encoded by:
i) a nucleic acid encoding the amino acid sequence as set forth in SEQ ID NO:13;
ii) a nucleic acid which hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding the amino acid sequence as set forth in SEQ ID NO:13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence increases transendothelial migration of leukocytes; or
iii) a nucleic acid encoding a polypeptide comprising amino acids 1-291 of SEQ ID NO: 13.
2. The isolated polypeptide according to claim 1 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NO: 13.
3. The isolated polypeptide according to claim 1 , wherein said polypeptide comprises amino acids 1-291 of SEQ ID NO: 13.
4. The isolated polypeptide according to claim 1 , wherein said polypeptide comprises the amino acid sequence encoded by a nucleic acid, which hybridizes under highly stringent conditions to the full complement of a nucleic acid encoding the amino acid sequence as set forth in SEQ ID NO:13, said highly stringent conditions comprising hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence increases transendothelial migration of leukocytes.
5. A composition comprising:
a) a polypeptide comprising SEQ ID NO: 13;
b) a polypeptide comprising amino acids 1-291 of SEQ ID NO: 13; or
c) the amino acid sequence encoded by:
i) a nucleic acid encoding the amino acid sequence as set forth in SEQ ID NO: 13;
ii) a nucleic acid which hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding the amino acid sequence as set forth in SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence increases transendothelial migration of leukocytes; or
iii) a nucleic acid encoding a polypeptide comprising amino acids 1-291 of SEQ ID NO: 13.
6. The composition according to claim 5 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NO: 13.
7. The composition according to claim 5 , wherein said polypeptide comprises amino acids 1-291 of SEQ ID NO: 13.
8. The composition according to claim 5 , wherein said polypeptide comprises the amino acid sequence encoded by a nucleic acid, which hybridizes under highly stringent conditions to the full complement of a nucleic acid encoding the amino acid sequence as set forth in SEQ ID NO: 13, said highly stringent conditions comprising hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence increases transendothelial migration of leukocytes.
9. An isolated polypeptide comprising:
a) amino acids 1-159 of SEQ ID NO: 13, wherein said polypeptide inhibits transendothelial migration of leukocytes;
b) amino acids 25-241 of SEQ ID NO: 13, wherein said polypeptide inhibits transendothelial migration of leukocytes;
c) amino acids 1-238 of SEQ ID NO: 13, wherein said polypeptide inhibits transendothelial migration of leukocytes; or
d) the amino acid sequence encoded by a nucleic acid which hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 1-159 of SEQ ID NO: 13, amino acids 25-241 of SEQ ID NO: 13, or amino acids 1-238 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.100 SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes.
10. The isolated polypeptide according to claim 9 , wherein said isolated polypeptide comprises amino acids 1-159 of SEQ ID NO: 13 and inhibits transendothelial migration of leukocytes.
11. The isolated polypeptide according to claim 9 , wherein said isolated polypeptide comprises amino acids 25-241 of SEQ ID NO: 13 and said polypeptide inhibits transendothelial migration of leukocytes.
12. The isolated polypeptide according to claim 9 , wherein said isolated polypeptide comprises amino acids 1-238 of SEQ ID NO: 13 and said polypeptide inhibits transendothelial migration of leukocytes.
13. An isolated fusion protein comprising:
a) amino acids 25-241 of SEQ ID NO:13;
b) amino acids 1-159 of SEQ ID NO: 13; or
c) amino acids 1-238 of SEQ ID NO: 13;
wherein said fusion protein inhibits transendothelial migration of leukocytes.
14. The isolated fusion protein according to claim 13 , wherein said fusion protein comprises amino acids 1-159 of SEQ ID NO: 13 and said fusion protein inhibits transendothelial migration of leukocytes.
15. The isolated fusion protein according to claim 13 , wherein said fusion protein comprises amino acids 25-241 of SEQ ID NO: 13 and said fusion protein inhibits transendothelial migration of leukocytes.
16. The isolated fusion protein according to claim 13 , wherein said fusion protein comprises amino acids 1-238 of SEQ ID NO: 13 and said fusion protein inhibits transendothelial migration of leukocytes.
17. A composition comprising:
a) an isolated polypeptide comprising amino acids 1-159 of SEQ ID NO: 13, wherein said polypeptide inhibits transendothelial migration of leukocytes;
b) an isolated polypeptide comprising amino acids 25-241 of SEQ ID NO: 13, wherein said polypeptide inhibits transendothelial migration of leukocytes;
c) an isolated polypeptide comprising amino acids 1-238 of SEQ ID NO: 13, wherein said polypeptide inhibits transendothelial migration of leukocytes; or
d) an isolated polypeptide comprising the amino acid sequence encoded by a nucleic acid which hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 1-159 of SEQ ID NO: 13, amino acids 25-241 of SEQ ID NO: 13, or amino acids 1-238 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes.
18. The composition according to claim 17 , wherein said isolated polypeptide comprises amino acids 1-159 of SEQ ID NO: 13 and inhibits transendothelial migration of leukocytes.
19. The composition according to claim 17 , wherein said isolated polypeptide comprises amino acids 25-241 of SEQ ID NO: 13 and inhibits transendothelial migration of leukocytes.
20. The composition according to claim 17 , wherein said isolated polypeptide comprises amino acids 1-238 of SEQ ID NO: 13 and inhibits transendothelial migration of leukocytes.
21. A composition comprising a fusion protein comprising:
a) a polypeptide comprising amino acids 25-241 of SEQ ID NO: 13;
b) a polypeptide comprising amino acids 1-159 of SEQ ID NO: 13; or
c) a polypeptide comprising amino acids 1-238 of SEQ ID NO: 13;
wherein said fusion protein inhibits transendothelial migration of leukocytes.
22. The composition according to claim 21 , wherein said fusion protein comprises amino acids 1-159 of SEQ ID NO: 13 and said fusion protein inhibits transendothelial migration of leukocytes.
23. The composition according to claim 21 , wherein said fusion protein comprises amino acids 25-241 of SEQ ID NO: 13 and said fusion protein inhibits transendothelial migration of leukocytes.
24. The composition according to claim 21 , wherein said fusion protein comprises amino acids 1-238 of SEQ ID NO: 13 and said fusion protein inhibits transendothelial migration of leukocytes.
25. The isolated polypeptide according to claim 9 , wherein said polypeptide is the amino acid sequence encoded by a nucleic acid which hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 1-159 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes.
26. The isolated polypeptide according to claim 9 , wherein said polypeptide is the amino acid sequence encoded by a nucleic acid which hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 25-241 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes.
27. The isolated polypeptide according to claim 9 , wherein said polypeptide is the amino acid sequence encoded by a nucleic acid which hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 1-238 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes.
28. The composition according to claim 17 , wherein said isolated polypeptide is the amino acid sequence encoded by a nucleic acid which hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 1-159 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes.
29. The composition according to claim 17 , wherein said isolated polypeptide is the amino acid sequence encoded by a nucleic acid which hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 25-241 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes.
30. The composition according to claim 17 , wherein said polypeptide is the amino acid sequence encoded by a nucleic acid which hybridizes under highly stringent conditions to a nucleic acid that is the full complement of the nucleic acid encoding amino acids 1-238 of SEQ ID NO: 13, said highly stringent conditions include hybridization at 62° C. in buffer containing 50% formamide and a final wash at 67° C. in 0.5× SSC and 0.1% SDS and wherein said amino acid sequence inhibits transendothelial migration of leukocytes.