COMPOSITIONS AND METHODS FOR INHIBITING INTERLEUKIN PATHWAYS

• US 20110052585A1
• Filed: 03/25/2010
• Published: 03/03/2011
• Est. Priority Date: 09/25/2007
• Status: Active Grant

• Current Assignee: Genzyme Corporation (Sanofi )
• Original Assignee: Genzyme Corporation (Sanofi )
• Inventors: White, Gary, Scaria, Abraham
• Granted Patent: US 10,822,391 B2
• Time in Patent Office: Days
• US Class Current: 424/134.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/7155 for interleukins [IL]
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C12N 2750/14143 viral genome or elements thereof as genetic vector

Abstract

Fusion proteins including an IL-17 receptor with a multimerization domain, or an IL-23 receptor and a multimerization domain, and recombinant viral vectors encoding such fusions, are described. The fusion proteins and vectors encoding such fusions, alone or in combination, can be used in methods for modulating the IL-17 and IL-23 signaling pathways and for treating or preventing diseases mediated by interleukin-17 and interleukin-23, such as immune-related and inflammatory diseases.

Claims

1-39. -39. (canceled)

40. A fusion protein comprising:

(a) an interleukin receptor or a portion thereof, wherein said interleukin receptor is selected from the group consisting of an IL-17 receptor and an IL-23 receptor which lacks an IL-12 receptor component; and

(b) an immunoglobulin constant region multimerization domain, which is linked to the interleukin receptor or a portion thereof via a 5-25 amino acid residue linker.

41. The fusion protein of claim 40, wherein the linker is selected from the group consisting of Gly₉(SEQ ID NO:

9), Glu₉ (SEQ ID NO;

10), Ser₉ (SEQ ID NO;

11), Gly₅-Cys-Pro₂-Cys (SEQ ID NO;

12), (Gly₄-Ser)₃(SEQ ID NO;

13), Ser-Cys-Val-Pro-Leu-Met-Arg-Cys-Gly-Gly-Cys-Cys-Asn (SEQ ID NO;

14), Pro-Ser-Cys-Val-Pro-Leu-Met-Arg-Cys-Gly-Gly-Cys-Cys-Asn (SEQ ID NO;

     15), Gly-Asp-Leu-Ile-Tyr-Arg-Asn-Gln-Lys (SEQ ID NO;

16), and Gly₉-Pro-Ser-Cys-Val-Pro-Leu-Met-Arg-Cys-Gly-Gly-Cys-Cys-Asn (SEQ ID NO;

17).

42. The fusion protein of claim 40, wherein the multimerization domain comprises the CH3 domain of an IgG heavy chain molecule, or an Fc portion of an antibody molecule.

43. The fusion protein of claim 40, wherein the interleukin receptor is a soluble interleukin receptor.

44. The fusion protein of claim 40, comprising the amino acid sequence of FIG. 5B (SEQ ID NO:

6) or FIG. 6B (SEQ ID NO;

8), or an active variant thereof having at least 90% sequence identity to the sequence of FIG. 5B (SEQ ID NO;

6) or FIG. 6B (SEQ ID NO;

8).

45. A polynucleotide encoding a fusion protein of claim 40 or 44.

46. The polynucleotide of claim 45, wherein said polynucleotide is a recombinant virus.

47. The recombinant virus of claim 46, wherein the recombinant virus is a recombinant adenovirus or a recombinant adeno-associated virus.

48. A method of inhibiting an interleukin pathway selected from the group consisting of an IL-23 pathway and an IL-17 pathway, said method comprising administering the polynucleotide of claim 45 to a cell to transduce the cell.

49. The method of claim 48, wherein the polynucleotide is administered in vitro to transduce cells.

50. The method of claim 49, wherein the polynucleotide is a recombinant adenovirus or a recombinant adeno-associated virus.

51. The method of claim 49, wherein cells so transdused are administered to a subject in need thereof.

52. The method of claim 49, wherein the polynucleotide is administered to cells in vivo in a subject in need thereof.

53. The method of claim 52, wherein the polynucleotide is a recombinant adenovirus or a recombinant adeno-associated virus.

54. Cells transduced with the polynucleotide of claim 45.

55. A method of inhibiting an interleukin pathway selected from the group consisting of an IL-23 pathway and an IL-17 pathway, said method comprising administering the fusion protein of claim 40 to a subject in need thereof.