US2011008289A1PendingUtilityA1

Hyperglycosylated polypeptide variants and methods of use

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Assignee: ALIOS BIOPHARMA INCPriority: Aug 9, 2004Filed: Aug 17, 2009Published: Jan 13, 2011
Est. expiryAug 9, 2024(expired)· nominal 20-yr term from priority
Inventors:Lawrence M. BlattScott D. SeiwertJin Hong
A61P 37/00A61P 31/12A61P 35/00A61P 25/00A61P 21/00C07K 14/56C07K 14/565C07K 14/555A61K 38/00C07K 14/57Y02A50/30
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Claims

Abstract

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.

Claims

exact text as granted — not AI-modified
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 α (IFN α), interferon β (IFN β), interferon κ(IFN κ), interferon ω (IFN ω), and interferon τ (IFN τ), 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, K31N, D102N, S102N, T102N, R102N, I102N, D108N, E108N, K108N, E138T, G138T, and I138T. 
     
     
         2 . The hyperglycosylated Type 1 interferon variant of  claim 1 , further comprising the amino acid substitution P33T. 
     
     
         3 . The hyperglycosylated Type 1 interferon variant of  claim 1 , further comprising the amino acid substitution S104T. 
     
     
         4 . The hyperglycosylated Type 1 interferon variant of  claim 1 , further comprising the amino acid substitution S110T. 
     
     
         5 . The hyperglycosylated Type 1 interferon variant of  claim 1 , wherein the parent Type 1 interferon is an interferon α (IFN α); wherein the interferon α (IFN α) is selected from the group consisting of interferon α2a, interferon α2b, interferon α1, interferon α4a, interferon α4b, interferon α5, interferon α6, interferon α7, interferon α8, interferon α10, interferon α13, interferon α14, interferon α16, interferon α17, interferon α21, interferon αH, interferon αI, interferon αJ1, recombinant interferon alpha-2b, recombinant interferon alpha-2a, recombinant interferon alpha-2C, interferon alpha-n1, interferon alpha-n3, interferon alfacon-1, IFN-con2, and IFN-con3. 
     
     
         6 . The hyperglycosylated Type 1 interferon variant of  claim 5 , wherein the parent Type 1 interferon is interferon α2a. 
     
     
         7 . The hyperglycosylated Type 1 interferon variant of  claim 6 , wherein the hyperglycosylated Type 1 interferon variant is interferon α2a comprising at least the amino acid substitution D31N. 
     
     
         8 . The hyperglycosylated Type 1 interferon variant of  claim 7 , further comprising the amino acid substitution P33T. 
     
     
         9 . The hyperglycosylated Type 1 interferon variant of  claim 6 , wherein the hyperglycosylated Type 1 interferon variant is interferon α2a comprising at least the amino acid substitution D102N. 
     
     
         10 . The hyperglycosylated Type 1 interferon variant of  claim 9 , further comprising the amino acid substitution S104T. 
     
     
         11 . The hyperglycosylated Type 1 interferon variant of  claim 6 , wherein the hyperglycosylated Type 1 interferon variant is interferon α2a comprising at least the amino acid substitution D108N. 
     
     
         12 . The hyperglycosylated Type 1 interferon variant of  claim 6 , wherein the hyperglycosylated Type 1 interferon variant is interferon α2a comprising at least the amino acid substitutions D31N and D102N. 
     
     
         13 . The hyperglycosylated Type 1 interferon variant of  claim 6 , wherein the hyperglycosylated Type 1 interferon variant is interferon α2a comprising at least the amino acid substitutions D31N and D108N. 
     
     
         14 . The hyperglycosylated Type 1 interferon variant of  claim 6 , wherein the hyperglycosylated Type 1 interferon variant is interferon α2a comprising at least the amino acid substitutions D102N and D108N. 
     
     
         15 . The hyperglycosylated Type 1 interferon variant of  claim 6 , wherein the hyperglycosylated Type 1 interferon variant is interferon α2a comprising at least the amino acid substitutions D31N, D102N, and D108N. 
     
     
         16 . The hyperglycosylated Type 1 interferon variant of  claim 15 , further comprising the amino acid substitution P33T. 
     
     
         17 . The hyperglycosylated Type 1 interferon variant of  claim 6 , wherein the hyperglycosylated Type 1 interferon variant is SEQ ID NO:1433. 
     
     
         18 . The hyperglycosylated Type 1 interferon variant of  claim 5 , wherein the parent Type 1 interferon is interferon α2b. 
     
     
         19 . The hyperglycosylated Type 1 interferon variant of  claim 18 , wherein the hyperglycosylated Type 1 intefron variant is interferon α2b comprising at least the amino acid substitution D31N. 
     
     
         20 . The hyperglycosylated Type 1 interferon variant of  claim 19 , further comprising the amino acid substitution P33T. 
     
     
         21 . The hyperglycosylated Type 1 interferon variant of  claim 18 , wherein the hyperglycosylated Type 1 intefron variant is interferon α2b comprising at least the amino acid substitution D102N. 
     
     
         22 . The hyperglycosylated Type 1 interferon variant of  claim 21 , further comprising the amino acid substitution S104T. 
     
     
         23 . The hyperglycosylated Type 1 interferon variant of  claim 18 , wherein the hyperglycosylated Type 1 intefron variant is interferon α2b comprising at least the amino acid substitution D108N. 
     
     
         24 . The hyperglycosylated Type 1 interferon variant of  claim 18 , wherein the hyperglycosylated Type 1 intefron variant is interferon α2b comprising at least the amino acid substitutions D31N and D102N. 
     
     
         25 . The hyperglycosylated Type 1 interferon variant of  claim 18 , wherein the hyperglycosylated Type 1 intefron variant is interferon α2b comprising at least the amino acid substitutions D31N and D108N. 
     
     
         26 . The hyperglycosylated Type 1 interferon variant of  claim 18 , wherein the hyperglycosylated Type 1 intefron variant is interferon α2b comprising at least the amino acid substitution D102N and D108N. 
     
     
         27 . The hyperglycosylated Type 1 interferon variant of  claim 18 , wherein the hyperglycosylated Type 1 intefron variant is interferon α2a comprising at least the amino acid substitutions D31N, D102N, and D108N. 
     
     
         28 . The hyperglycosylated Type 1 interferon variant of  claim 27 , further comprising the amino acid substitution P33T. 
     
     
         29 . The hyperglycosylated Type 1 interferon variant of  claim 18 , wherein the hyperglycosylated Type 1 interferon variant is SEQ ID NO:1449. 
     
     
         30 . A pharmaceutical composition comprising the hyperglycosylated Type 1 interferon variant of  claim 1 ; and a pharmaceutically acceptable excipient. 
     
     
         31 . The composition of  claim 30 , wherein the pharmaceutically-acceptable excipient is suitable for oral delivery. 
     
     
         32 . The composition of  claim 30 , wherein the pharmaceutically-acceptable excipient is suitable for parenteral delivery.

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