Hyperglycosylated polypeptide variants and methods of use
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-038/19
A61K-038/21
C07K-014/555
C07K-014/435
C07K-014/56
출원번호
UP-0351163
(2006-02-08)
등록번호
US-7597884
(2009-10-20)
발명자
/ 주소
Blatt, Lawrence M.
Seiwert, Scott D.
Hong, Jin
출원인 / 주소
Alios BioPharma, Inc.
대리인 / 주소
Knobbe Martens Olson & Bear LLP
인용정보
피인용 횟수 :
5인용 특허 :
162
초록▼
The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites. The present invention provides synthetic Type I interferon recepto
The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites. The present invention provides synthetic Type I interferon receptor polypeptide agonists comprising consensus or hybrid Type I interferon receptor polypeptide agonists, containing one or more native or non-native glycosylation sites, as well as erythropoietin and darbepoetin alfa, each of which are linked to a penetrating peptide that facilitates translocation of a substance across a biological barrier as well as pharmaceutical compositions, including oral formulations, of the same. The present invention further provides oral formulations of hyperglycosylated or protease-resistant, hyperglycosylated polypeptide variants, which polypeptide variants lack at least one protease cleavage site found in a parent polypeptide, and thus exhibit increased protease resistance compared to the parent polypeptide, which polypeptide variants further include (1) a carbohydrate moiety covalently linked to at least one non-native glycosylation site not found in the parent protein therapeutic or (2) a carbohydrate moiety covalently linked to at least one native glycosylation site found but not glycosylated in the parent protein therapeutic. The present invention further provides compositions, including oral pharmaceutical compositions, comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides containers, devices, and kits comprising the synthetic Type I interferon receptor polypeptide agonist, the hyperglycosylated polypeptide variant, or the hyperglycosylated, protease-resistant polypeptide variant. The present invention further provides therapeutic methods involving administering an effective amount of an oral pharmaceutical composition comprising a synthetic Type I interferon receptor polypeptide agonist, a hyperglycosylated polypeptide variant, or a hyperglycosylated, protease-resistant polypeptide variant to an individual in need thereof.
대표청구항▼
What is claimed is: 1. A hyperglycosylated Type 1 interferon variant of a parent Type 1 interferon, wherein the parent Type 1 interferon is selected from the group consisting of interferon alfacon-1 and interferon α14, wherein the hyperglycosylated Type 1 interferon variant is the parent Type
What is claimed is: 1. A hyperglycosylated Type 1 interferon variant of a parent Type 1 interferon, wherein the parent Type 1 interferon is selected from the group consisting of interferon alfacon-1 and interferon α14, wherein the hyperglycosylated Type 1 interferon variant is the parent Type 1 interferon that has been modified to include at least three additional glycosylation sites, wherein at least one of the additional glycosylation sites is introduced by an amino acid substitution selected from the group consisting of D31N, D102N, D108N, and E138T. 2. The hyperglycosylated Type 1 interferon variant of claim 1, wherein the parent Type 1 interferon is interferon alfacon-1. 3. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitution D102N. 4. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitution D108N. 5. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitution E138T. 6. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D102N and D108N. 7. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D102N and E138T. 8. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D108N and E138T. 9. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D102N, D108N, and E138T. 10. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is selected from the group consisting of an amino acid sequence set forth in SEQ ID NOS: 1769-1773. 11. The hyperglycosylated Type 1 interferon variant of claim 1, wherein the parent Type 1 interferon is interferon α14. 12. The hyperglycosylated Type 1 interferon variant of claim 11, wherein the hyperglycosylated Type 1 interferon variant is interferon α 14 comprising at least the amino acid substitution D108N. 13. The hyperglycosylated Type 1 interferon variant of claim 11, wherein the hyperglycosylated Type 1 interferon variant is interferon α 14 comprising at least the amino acid substitution E138T. 14. The hyperglycosylated Type 1 interferon variant of claim 11, wherein the hyperglycosylated Type 1 interferon variant is interferon α 14 comprising at least the amino acid substitution D108N and E138T. 15. A pharmaceutical composition comprising the hyperglycosylated Type 1 interferon variant of claim 1; and a pharmaceutically acceptable excipient. 16. The composition of claim 15, wherein the pharmaceutically-acceptable excipient is suitable for oral delivery. 17. The composition of claim 15, wherein the pharmaceutically-acceptable excipient is suitable for parenteral delivery. 18. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D31N and D102N. 19. The hyperglycosylated Type 1 interferon variant of claim 3, further comprising the amino acid substitution S104T. 20. The hyperglycosylated Type 1 interferon variant of claim 1, further comprising the amino acid substitution S104T. 21. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitution D31N. 22. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D31N and D108N. 23. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D31N and E138T. 24. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D31N, D102N, and D108N. 25. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D31N, D102N, and E138T. 26. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D31N, D108N, and E138T. 27. The hyperglycosylated Type 1 interferon variant of claim 2, wherein the hyperglycosylated Type 1 interferon variant is interferon alfacon-1 comprising at least the amino acid substitutions D31N, D102N, D108N, and E138T.
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