Claims
- 1. A method to reduce liver disease in a chronic HCV-infected mammal comprising administering a therapeutic HCV vaccine composition to said mammal.
- 2. A method to reduce liver fibrosis progression in a chronic HCV-infected mammal comprising administering a therapeutic HCV vaccine composition to said mammal.
- 3. A method to reduce liver fibrosis in a chronic HCV-infected mammal comprising administering a therapeutic HCV vaccine composition to said mammal.
- 4. A method to reduce liver disease by at least 2 points according to the overall Ishak score in a chronic HCV-infected mammal comprising administering a therapeutic HCV vaccine composition to said mammal.
- 5. A method to reduce liver disease by at least 1 point according to the Ishak fibrosis score in a chronic HCV-infected mammal comprising administering a therapeutic HCV vaccine composition to said mammal.
- 6. A method to reduce serum ALT levels in a chronic HCV-infected mammal comprising administering a therapeutic HCV vaccine composition to said mammal.
- 7. A method to reduce steatosis in a chronic HCV-infected mammal comprising administering a therapeutic HCV vaccine composition to said mammal.
- 8. A method to reduce anti-E2 immunoreactivity in the liver of a chronic HCV-infected mammal comprising administering a therapeutic HCV vaccine composition to said mammal.
- 9. A method of treating a chronic HCV-infected mammal comprising a plurality of administrations of a therapeutic HCV vaccine composition to said mammal wherein said administrations are separated by a time interval of 4 weeks or less.
- 10. The method of claim 9 wherein said time interval is 3 weeks.
- 11. The method according to claim 9 wherein said plurality of administrations consists of a first series of at least 5 administrations followed by an administration-free period of at least 12 weeks followed by a second series of at least 3 administrations.
- 12. The method according to any of claims 1 to 9 wherein said therapeutic HCV vaccine composition comprises a HCV antigen and, optionally, a pharmaceutically acceptable adjuvant.
- 13. The method according to claim 12 wherein said HCV antigen is an E1 or E2 antigen, or an immunogenic part of an E1 or E2 antigen.
- 14. The method according to claim 12 wherein said HCV antigen is an E1s antigen.
- 15. The method according to claim 12 wherein said HCV antigen is the E1s antigen as defined by SEQ ID NO:123.
- 16. The method according to claim 12 wherein said pharmaceutically acceptable adjuvant is alum.
- 17. A method to predict changes in liver disease in a chronic HCV-infected mammal comprising
(i) determining the level of serum anti-E1 antibody level prior to therapeutic vaccination with a HCV vaccine composition comprising an E1 antigen; (ii) determining the level of serum anti-E1 antibody level after therapeutic vaccination with a HCV vaccine composition comprising an E1 antigen; (iii) inferring the difference in level of serum anti-E1 antibody level determined in (i) and (ii) and, therefrom, predicting the change in liver disease.
- 18. A therapeutic HCV vaccine composition comprising a therapeutically effective amount of at least one purified HCV single or specific oligomeric recombinant envelope protein selected from the group consisting of an E1 protein, an E2 protein, a part of said E1 and E2 proteins, an E1/E2 protein complex formed from purified HCV single or specific oligomeric recombinant E1 or E2 proteins or parts thereof; and optionally a pharmaceutically acceptable adjuvant.
- 19. A therapeutic HCV vaccine composition comprising a therapeutically effective amount of a combination of at least two purified HCV single or specific oligomeric recombinant envelope proteins selected from the group consisting of E1 proteins derived from different HCV genotypes or subtypes, E2 proteins derived from different HCV genotypes or subtypes, parts of said E1 and E2 proteins, and E1/E2 protein complexes formed from purified HCV single or specific oligomeric recombinant E1 or E2 proteins, or parts thereof, derived from different HCV genotypes or subtypes; and optionally a pharmaceutically acceptable adjuvant.
- 20. A therapeutic HCV vaccine composition comprising a therapeutically effective amount of at least one of the following E1 and E2 peptides:
E1-31 spanning amino acids 181 to 200 of the Core/E1 V1 region (SEQ ID NO:56), E1-33 spanning amino acids 193 to 212 of the E1 region (SEQ ID NO:57), E1-35 spanning amino acids 205 to 224 of the E1 V2 region (SEQ ID NO:58), E1-35A spanning amino acids 208 to 227 of the E1 V2 region (SEQ ID NO:59), 1bE1 spanning amino acids 192 to 228 of E1 regions V1, C1, and V2 regions (SEQ ID NO:53), E1-51 spanning amino acids 301 to 320 of the E1 region (SEQ ID NO:66), E1-53 spanning amino acids 313 to 332 of the E1 C4 region (SEQ ID NO:67), E1-55 spanning amino acids 325 to 344 of the E1 region (SEQ ID NO:68), Env 67 or E2-67 spanning amino acid positions 397 to 418 of the E2 region (SEQ ID NO:72), Env 69 or E2-69 spanning amino acid positions 409 to 428 of the E2 region (SEQ ID NO:73), Env 23 or E2-23 spanning positions 583 to 602 of the E2 region (SEQ ID NO:86), Env 25 or E2-25 spanning positions 595 to 614 of the E2 region (SEQ ID NO:87), Env 27 or E2-27 spanning positions 607 to 626 of the E2 region (SEQ ID NO:88), Env 17B or E2-17B spanning positions 547 to 586 of the E2 region (SEQ ID NO:83), Env 13B or E2-13B spanning positions 523 to 542 of the E2 region (SEQ ID NO:82), IGP 1626 spanning positions 192-211 of the E1 region (SEQ ID NO:112), IGP 1627 spanning positions 204-223 of the E1 region (SEQ ID NO:113), IGP 1628 spanning positions 216-235 of the E1 region (SEQ ID NO:114), IGP 1629 spanning positions 228-247 of the E1 region (SEQ ID NO:115), IGP 1630 spanning positions 240-259 of the E1 region (SEQ ID NO:116), IGP 1631 spanning positions 252-271 of the E1 region (SEQ ID NO:117), IGP 1632 spanning positions 264-283 of the E1 region (SEQ ID NO:118), IGP 1633 spanning positions 276-295 of the E1 region (SEQ ID NO:119), IGP 1634 spanning positions 288-307 of the E1 region (SEQ ID NO:120), IGP 1635 spanning positions 300-319 of the E1 region (SEQ ID NO:121) and IGP 1636 spanning positions 312-331 of the E1 region (SEQ ID NO:122); and, optionally, a pharmaceutically acceptable adjuvant.
- 21. A therapeutic HCV composition comprising a therapeutically effective amount of at least one purified HCV single or specific oligomeric recombinant envelope protein selected from the group consisting of an E1 protein, an E2 protein, a part of said E1 and E2 protein, and an E1/E2 protein complex formed from purified HCV single or specific oligomeric recombinant E1 or E2 proteins or parts thereof, and optionally a pharmaceutically acceptable adjuvant.
- 22. A therapeutic HCV composition comprising a therapeutically effective amount of a combination of at least two purified HCV single or specific oligomeric recombinant envelope proteins selected from the group consisting of E1 proteins derived from different HCV genotypes or subtypes, E2 proteins derived from different HCV genotypes or subtypes, parts of said E1 and E2 proteins, and E1/E2 protein complexes formed from purified HCV single or specific oligomeric recombinant E1 or E2 proteins, or parts thereof, derived from different HCV genotypes or subtypes; and optionally a pharmaceutically acceptable adjuvant.
- 23. A therapeutic HCV composition comprising a therapeutically effective amount of at least one of the following E1 and E2 peptides:
E1-31 spanning amino acids 181 to 200 of the Core/E1 V1 region (SEQ ID NO:56), E1-33 spanning amino acids 193 to 212 of the E1 region (SEQ ID NO:57), E1-35 spanning amino acids 205 to 224 of the E1 V2 region (SEQ ID NO:58), E1-35A spanning amino acids 208 to 227 of the E1 V2 region (SEQ ID NO:59), 1bE1 spanning amino acids 192 to 228 of E1 regions V1, C1, and V2 regions (SEQ ID NO:53), E1-51 spanning amino acids 301 to 320 of the E1 region (SEQ ID NO:66), E1-53 spanning amino acids 313 to 332 of the E1 C4 region (SEQ ID NO:67), E1-55 spanning amino acids 325 to 344 of the E1 region (SEQ ID NO:68), Env 67 or E2-67 spanning amino acid positions 397 to 418 of the E2 region (SEQ ID NO:72), Env 69 or E2-69 spanning amino acid positions 409 to 428 of the E2 region (SEQ ID NO:73), Env 23 or E2-23 spanning positions 583 to 602 of the E2 region (SEQ ID NO:86), Env 25 or E2-25 spanning positions 595 to 614 of the E2 region (SEQ ID NO:87), Env 27 or E2-27 spanning positions 607 to 626 of the E2 region (SEQ ID NO:88), Env 17B or E2-17B spanning positions 547 to 586 of the E2 region (SEQ ID NO:83), Env 13B or E2-13B spanning positions 523 to 542 of the E2 region (SEQ ID NO:82), IGP 1626 spanning positions 192-211 of the E1 region (SEQ ID NO:112), IGP 1627 spanning positions 204-223 of the E1 region (SEQ ID NO:113), IGP 1628 spanning positions 216-235 of the E1 region (SEQ ID NO:114), IGP 1629 spanning positions 228-247 of the E1 region (SEQ ID NO:115), IGP 1630 spanning positions 240-259 of the E1 region (SEQ ID NO:116), IGP 1631 spanning positions 252-271 of the E1 region (SEQ ID NO:117), IGP 1632 spanning positions 264-283 of the E1 region (SEQ ID NO:118), IGP 1633 spanning positions 276-295 of the E1 region (SEQ ID NO:119), IGP 1634 spanning positions 288-307 of the E1 region (SEQ ID NO:120), IGP 1635 spanning positions 300-319 of the E1 region (SEQ ID NO:121) and IGP 1636 spanning positions 312-331 of the E1 region (SEQ ID NO:122); and, optionally, a pharmaceutically acceptable adjuvant.
- 24. The therapeutic HCV composition according to any of claims 18 to 23 which is therapeutically effective in a HCV carrier infected with a HCV genotype different from the HCV genotype or HCV genotypes from which said E1, E2, or E1/E2 protein complexes are derived.
- 25. A composition comprising at least one of the following E1 and E2 peptides:
IGP 1626 spanning positions 192-211 of the E1 region (SEQ ID NO:112), IGP 1627 spanning positions 204-223 of the E1 region (SEQ ID NO:113), IGP 1628 spanning positions 216-235 of the E1 region (SEQ ID NO:114), IGP 1629 spanning positions 228-247 of the E1 region (SEQ ID NO:115), IGP 1630 spanning positions 240-259 of the E1 region (SEQ ID NO:116), IGP 1631 spanning positions 252-271 of the E1 region (SEQ ID NO:117), IGP 1632 spanning positions 264-283 of the E1 region (SEQ ID NO:118), IGP 1633 spanning positions 276-295 of the E1 region (SEQ ID NO:119), IGP 1634 spanning positions 288-307 of the E1 region (SEQ ID NO:120), IGP 1635 spanning positions 300-319 of the E1 region (SEQ ID NO:121) and IGP 1636 spanning positions 312-331 of the E1 region (SEQ ID NO:122); and, optionally, a pharmaceutically acceptable adjuvant.
- 26. The composition according to any of claims 18, 19, 21, or 22 wherein the cysteines of said recombinant HCV envelope proteins are blocked, or according to any of claims 20, 23 and 25 wherein the cysteines of said E1 and E2 peptides are blocked.
- 27. The composition according to any of claims 18, 19, 21, or 22 wherein said recombinant HCV envelope proteins are added as viral-like particles.
- 28. The composition according to any of claims 18, 19, 21, or 22 wherein said recombinant HCV E1 envelope protein is an E1s protein.
- 29. The composition according to claim 28 wherein said E1s protein is defined by SEQ ID NO:123.
- 30. The composition according to any of claims 18, 19, 21, or 22 wherein said recombinant HCV envelope proteins are produced by recombinant mammalian cells, by recombinant yeast cells or by a recombinant virus.
- 31. The composition according to any of claims 20, 23 and 25 wherein said peptides are recombinant peptides or synthetic peptides.
- 32. An immunogenic HCV composition comprising a recombinant virus allowing expression of at least one HCV recombinant envelope protein chosen from an E1 protein and/or an E2 protein, and parts of said E1 and E2 proteins; and, optionally, a pharmaceutically acceptable adjuvant.
- 33. A HCV vaccine composition comprising a recombinant virus allowing expression of at least one HCV recombinant envelope protein chosen from an E1 protein and/or an E2 protein, and parts of said E1 and E2 proteins; and, optionally, a pharmaceutically acceptable adjuvant.
- 34. The composition according to claim 32 or 33 which is effective against a HCV genotype or subtype different from the HCV genotype or subytpe from which said E1 protein and/or E2 protein, or said parts thereof, are derived.
- 35. The composition according to claim 32 or 33 wherein said recombinant virus is a recombinant vaccinia virus, a recombinant avipox virus or a recombinant Ankara Modified Virus.
- 36. A method of treating a mammal infected with HCV comprising administering to said mammal an effective amount of a composition according to any one of claims 18 to 23, 25, 32 and 33.
- 37. The method according to any of claims 1 to 9 and 17 wherein said mammal is a human.
- 38. The method of claim 36 wherein said mammal is a human.
Parent Case Info
[0001] U.S. Provisional Patent Application No. 60/418,358, filed Oct. 16, 2002, and U.S. Patent application Ser. No. 10/020,510 (now 60/___,___), filed Dec. 18, 2001 All references cited herein are incorporated in their entirety by reference.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60418358 |
Oct 2002 |
US |
|
60453708 |
Dec 2001 |
US |