Patent EA-003250-B1 (EA)
Title: Novel ifn receptor 1 binding proteins, dna encoding them, and methods of modulating cellular response to interferons
Inventor: REVEL MICHEL
IPC: C12N5/10
Filed: 1998-01-15
Abstract: 1. A recombinant DNA molecule comprising a nucleotide sequence encoding an IFNAR1 receptor binding protein capable of being induced by IFN-alpha or IFN-beta and having the nucleotide sequence is SEQ ID NO:1 or SEQ ID NO:1 variants obtained owing to genetic code degeneracy. 2. A recombinant DNA molecule comprising a nucleotide sequence encoding an IFNAR1 receptor binding protein capable of being induced by IFN-alpha or IFN-beta and having the nucleotide sequence is SEQ ID NO:7 or SEQ ID NO:7 variants obtained owing to genetic code degeneracy. 3. A recombinant DNA molecule in accordance with Claim 1 or 2, further comprising a promoter operably-linked to said sequence encoding an IFNAR1 receptor-binding protein in a sense orientation such that said DNA molecule is capable of expressing said protein when the recombinant DNA molecule is in an appropriate expression host. 4. A recombinant DNA molecule according to Claim 3, wherein said promoter is a strong constitutive promoter in human cells. 5. A recombinant DNA molecule in accordance with Claim 1, wherein said nucleotide sequence is SEQ ID NO:1. 6. A recombinant DNA molecule in accordance with Claim 2, wherein said nucleotide sequence is SEQ ID NO:7. 7. A recombinant DNA or RNA molecule comprising a DNA molecule comprising the nucleotide sequence SEQ ID NO:1 in either sense or anti-sense orientation, or a fragment thereof capable of hybridizing to mRNA encoding an interferon inducible IFNAR1 receptor binding protein and thereby preventing its expression, or an RNA molecule with a sequence complementary sequence SEQ ID NO:1. 8. A recombinant DNA or RNA molecule comprising a DNA molecule comprising the nucleotide sequence SEQ ID NO:7 in either sense or anti-sense orientation, or a fragment thereof capable of hybridizing to mRNA encoding an interferon inducible IFNAR1 receptor binding protein and thereby preventing its expression, or an RNA molecule with a sequence complementary sequence SEQ ID NO:7. 9. A recombinant DNA or RNA molecule in accordance with Claim 7 or 8, comprising an RNA molecule, complementary to sequence SEQ ID NO:1 or SEQ ID NO:7. 10. A recombinant DNA or RNA molecule in accordance with Claim 7 or 8, wherein said sequence is in the sense orientation. 11. A recombinant DNA or RNA molecule in accordance with Claim 7 or 8, wherein said sequence is in the anti-sense orientation. 12. A recombinant DNA or RNA molecule in accordance with Claim 11, comprising a recombinant DNA molecule further comprising a promoter operably linked to said sequence in an anti-sense orientation such that said DNA molecule is capable of expressing an anti-sense RNA complementary to a whole or part of a sense RNA encoding an interferon-induced IFNAR1 receptor binding protein. 13. A recombinant DNA molecule according to Claim 12, wherein said nucleotide sequence is a segment from the 5'-end of SEQ ID NO:1 or SEQ ID NO:7. 14. A recombinant DNA molecule according to any one of Claims 3, 12 or 13, wherein said promoter is an interferon-inducible promoter. 15. A recombinant DNA molecule according to any one of Claims 1-8 and 10-13, which is an expression vector. 16. A host cell capable of expressing an antisense RNA complementary to a sense RNA encoding an interferon-inducible IFNAR1 receptor binding protein, which cell includes an expression vector in accordance with Claim 15. 17. A method of prolonging tissue graft survival, comprising the steps of: introducing an expression vector comprising the recombinant DNA molecule of any one of Claims 11-13 into cells of a tissue or organ to be grafted to a patient in need thereof; and grafting the tissue or organ to the patient. 18. A method of enhancing response to exogenous interferon therapy in treating cancer, comprising the steps of: administering directly into a tumor an expression vector comprising the recombinant DNA molecule of any of Claims 4-6, and subsequently administering exogenous interferon therapy. 19. A DNA molecule encoding protein according to Claim 1, capable of IFNAR1-binding having the sequence of SEQ ID NO:2. 20. A DNA molecule encoding protein according to Claim 2, capable of IFNAR1-binding having the sequence of SEQ ID NO:8. 21. A monoclonal antibody specific for an IFNAR1-binding protein in accordance with Claim 19 or 20, or a molecule comprising the antigen binding portion of such a monoclonal antibody. 22. A method for providing an IFNAR1 receptor binding protein comprising placing a DNA in accordance with Claim 1 into an appropriate expression host in a manner whereby expression of said protein can be obtained upon culturing of said host, and culturing said host so as to obtain expression of said protein. 23. A method for providing an IFNAR1 receptor binding protein comprising placing a DNA in accordance with Claim 2 into an appropriate expression host in a manner whereby expression of said protein can be obtained upon culturing of said host, and culturing said host so as to obtain expression of said protein.