Patent EA-003635-B1 (EA)
Title: Ifnar2/ifn complex
Inventor: TEPPER MARK
IPC: C12P21/04
Filed: 1998-12-18
Abstract: 1. A complex, comprising Type I interferon (IFN) and a subunit of the human interferon .alpha./.beta. receptor (IFNAR), which is capable of binding to the Type I IFN of the complex, , wherein said Type I IFN has a sequence consisting essentially of the sequence of: a) a native Type I IFN; b) a fragment of a) which has Type I IFN biological activity; c) a variant of a) or b) which has at least 70% sequence identity with a) or b) and which has Type IFN biological activity; d) a variant of a) or b) which is encoded by a DNA sequence which hybridizes to the compliment of the native DNA sequence encoding a) or b) under moderately stringent conditions and which has Type I IFN biological activity; or e) a salt or functional derivative of a), b), c), or d) which has Type I IFN biological activity; and wherein said IFNAR has a sequence consisting essentially of the sequence of: f) a native human IFNAR polypeptide chain; g) a fragment of f) which has IFNAR biological activity; h) a variant of f) or g) which has at least 70% sequence identity with f) or g) and which has IFNAR biological activity; i) a variant of f) or g) which is encoded by a DNA sequence which hybridizes to the compliment of the native DNA sequence encoding f) or g) under moderately stringent conditions and which has IFNAR biological activity; or j) a salt or functional derivative of f), g), h), or i) which has IFNAR biological activity. 2. A complex in accordance with claim 1, wherein said Type I IFN is bound to said IFNAR by a covalent bond. 3. A complex in accordance with claim 1, wherein said complex comprises a fusion protein in which said Type I IFN is bound to said IFNAR by a peptide bond. 4. A complex in accordance with claim 5, wherein said Type 1 IFN is linked to said IFNAR by means of a peptide linker. 5. A complex in accordance with claim 4, wherein said peptide linker is (GGGGS)n wherein n=1-5. 6. A complex in accordance with any one of claims 1 to 5, wherein said Type I IFN is an IFN.alpha., an IFN.beta., or an IFN.omega. 7. A complex in accordance with claim 5, wherein said Type I IFN is IFN.beta. 8. A complex in accordance with any one of claims 1 to 7, wherein said IFNAR is the beta subunit of the human interferon .alpha./.beta. receptor (IFNAR2). 9. A DNA molecule encoding a fusion protein in accordance with any one of claims 3 to 5. 10. A vector comprising a DNA molecule in accordance with claim 9. 11. A host cell transformed with a vector carrying a DNA in accordance with claim 10 in a manner which permits expression of said fusion protein. 12. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a complex of a Type I interferon (IFN) in accordance with any one of claims 1 to 8. 13. Use of a complex in accordance with any one of claims 1 to 8 as a medicament. 14. Use of a complex in accordance with any one of claims 1 to 8 in antiviral, antineoplastic or immunomodulatory therapy. 15. Use of a complex in accordance with any one of claims 1 to 8 for prolonging the in vivo effect in a patient. 16. A pharmaceutical composition comprising a complex in accordance with claim 1 manufactured by a separate, simultaneous or sequential administering of a Type I interferon (IFN) and a subunit of the human interferon .alpha./.beta. receptor (IFNAR) to a patient in need of antiviral, antineoplastic or immunomodulatory therapy, in which said Type I interferon (IFN) is: a) a native Type I IFN; b) a fragment of a) which has Type I IFN biological activity. 17. A pharmaceutical composition in accordance with claim 16, wherein said Type I IFN and said IFNAR are administered separately and said complex in accordance with any one of claims 1 to 8 is formed in vivo. 18. A pharmaceutical composition in accordance with claim 16 or 17, wherein IFN is an IFN.alpha., an IFN.beta., or an IFN.omega. 19. A complex in accordance with claim 18, wherein IFN is IFN.beta. 20. A complex in accordance with any one of claims 16 to 19, wherein said IFNAR is the beta subunit of the human interferon .alpha./.beta. receptor (IFNAR2). 21. Use of the human interferon .alpha./.beta. receptor (IFNAR) in the manufacture of a medicament comprising a complex in accordance with claim 1 for potentiating the biological effects of Type I interferon (IFN), wherein said IFNAR has a sequence consisting essentially of the sequence of: a) a native human IFNAR polypeptide chain; b) a fragment of a) which has IFNAR biological activity; c) a variant of a) or b) which has at least 70% sequence identity with a) or b) and which has IFNAR biological activity; d) a variant of a) or b) which is encoded by a DNA sequence which hybridizes to the compliment of the native DNA sequence encoding a) or b) under moderately stringent conditions and which has IFNAR biological activity; or e) a salt or functional derivative of a), b), c), which has IFNAR biological activity. 22. Use of a complex of Type I interferon (IFN) and a subunit of the human interferon .alpha./.beta. receptor (IFNAR) which is capable of binding to the Type I IFN of the complex, in the manufacture of a medicament comprising a complex in accordance with claim 1 for prolonging the in vivo effect of Type I IFN, wherein said medicament is prepared in vivo by a separate, simultaneous or sequential administering of the compounds of said complex to a patient in need thereof, wherein said Type I interferon (IFN) has a sequence consisting essentially of the sequence of: a) a native Type I IFN; b) a fragment of a) which has Type I IFN biological activity; c) a variant of a) or b) which has at least 70% sequence identity with a) or b) and which has Type IFN biological activity; d) a variant of a) or b) which is encoded by a DNA sequence which hybridizes to the compliment of the native DNA sequence encoding a) or b) under moderately stringent conditions and which has Type I IFN biological activity; or e) a salt or functional derivative of a), b), c), and wherein said IFNAR has a sequence consisting essentially of the sequence of: a) a native human IFNAR polypeptide chain; b) a fragment of a) which has IFNAR biological activity; c) a variant of a) or b) which has at least 70% sequence identity with a) or b) and which has IFNAR biological activity; d) a variant of a) or b) which is encoded by a DNA sequence which hybridizes to the compliment of the native DNA sequence encoding a) or b) under moderately stringent conditions and which has IFNAR biological activity; or e) a salt or functional derivative of a), b), c), which has IFNAR biological activity. 23. Use of a complex in accordance with any one of claims 1 to 8 in manufacturing a medicament for prolonging the in vivo effect of Type I IFN 24. A method of making a fusion protein comprising culturing a host cell in accordance with claim 11 and recovering the fusion protein expressed thereby. 25. A method for improving the shelf life of Type I interferon, comprising storing said interferon in the form of a complex in accordance with any one of claims 1 to 8.