Polypeptides and uses thereof for treatment of autoimmune disorders and infection

Patent metadata

Field	Value
Publication number	US-2016304579-A1
Application number	US-201615055960-A
Country	US
Kind code	A1
Filing date	Feb 29, 2016
Priority date	Jun 30, 2011
Publication date	Oct 20, 2016
Grant date	—

Abstract

This invention relates to C1ORF32 protein and its variants and fragments and fusion proteins thereof, pharmaceutical composition comprising same and methods of use thereof for treatment of immune related disorders and infections.

First claim

1 . An isolated polypeptide, consisting of an amino acid sequence of C1ORF32 IgV domain fragment, set forth in any one of SEQ ID NOs: 30, 41, 44-63, 65-67, 70, 88, 90, with the proviso that the amino acid sequence does not include the complete, exact sequence of SEQ ID NO: 35 or SEQ ID NO:36.

2 . The isolated peptide of claim 1 , wherein the isolated polypeptide has less than 90% identity with SEQ ID NO:35 or SEQ ID NO:36.

3 . The isolated peptide of claim 2 , wherein the isolated peptide has less than 85% identity with SEQ ID NO:35 or SEQ ID NO:36.

4 . The isolated peptide of claim 3 , wherein the isolated peptide has less than 80% identity with SEQ ID NO:35 or SEQ ID NO:36.

5 . (canceled)

6 . A fusion protein comprising the polypeptide according to claim 1 , fused to a heterologous sequence, directly or indirectly via a linker peptide, a polypeptide sequence or a chemical linker.

7 . The fusion protein of claim 6 , wherein the heterologous sequence comprises at least a portion of an immunoglobulin constant domain.

8 . The fusion protein of claim 7 , comprising an immunoglobulin heavy chain constant region corresponding to an antibody isotype selected from the group consisting of an IgG1, IgG2, IgG3, IgG4, IgM, IgE, IgA and IgD.

9 . The fusion protein of 8 , wherein the immunoglobulin constant domain comprises the hinge, CH2 and CH3 regions of a human IgG immunoglobulin, selected from the group consisting of Cγ1, Cγ2, Cγ3 and Cγ4 chain.

10 . The fusion protein of any of claims 6 - 9 , further comprising a domain that mediates dimerization or multimerization of the fusion protein to form homodimers, heterodimers, homomultimers, or heteromultimers; wherein the domain that mediates dimerization or multimerization is selected from the group consisting of one or more cysteines that are capable of forming an intermolecular disulfide bond with a cysteine on the partner fusion protein, a coiled-coil domain, an acid patch, a zinc finger domain, a calcium hand domain, a CHI region, a CL region, a leucine zipper domain, an SH2 (src homology 2) domain, an SH3 (src Homology 3) domain, a PTB (phosphotyrosine binding) domain, a WW domain, a PDZ domain, a 14-3-3 domain, a WD40 domain, an EH domain, a Lim domain, an isoleucine zipper domain, and a dimerization domain of a receptor dimer pair.

11 . (canceled)

12 . The fusion protein of claim 6 , comprising a polypeptide having an amino acid sequence set forth in any one of SEQ ID NOs: 20, 21, 31 or 115.

13 . The fusion protein of claim 12 , wherein said fusion protein comprises the amino acid sequence set forth in anyone of SEQ ID NOs: 30, 41, 44-63, 65-67, 70, 88, 90, fused to human IgG1 Fc set forth in any one of SEQ ID NOs: 20, 21, or 115.

14 . The fusion protein of claim 13 , wherein the amino acid sequence of said fusion protein is set forth in SEQ ID NO: 39, 108-112, 116-190.

15 . (canceled)

16 . (canceled)

17 . A pharmaceutical composition comprising a protein of claim 1 or a fusion protein comprising same, and a pharmaceutically acceptable diluent or carrier, adapted for treatment of any immune related disorder and infectious disorder.

18 . (canceled)

19 . (canceled)

20 . A method for treating an immune related disorder in a subject in need thereof, comprising administering to the subject an effective amount of the polypeptide of claim 1 , or a fusion protein or a pharmaceutical composition comprising same, treatment of immune related disorder without global immunosuppression, and/or wherein the treatment of immune related disorder comprises induction of immune tolerance.

21 . The method of claim 20 , wherein administering an effective amount of the polypeptide of claim 1 , or a fusion protein or a pharmaceutical composition comprising same to the subject inhibits or reduces differentiation of, proliferation of, activity of, and/or cytokine production and/or secretion by an immune cell selected from the group consisting of Th1, Th17, and/or Th22, other cells that secrete, or cells that cause other cells to secrete, inflammatory molecules.

22 . (canceled)

23 . The method of claim 20 , wherein the polypeptide of claim 1 , or a fusion protein or a pharmaceutical composition comprising same is administered in an effective amount to enhance the suppressive or immunomodulatory effect of Tregs and/or Th2 cells on Th1 or Th17 cells.

24 . The method of claim 20 , wherein the polypeptide of claim 1 , or a fusion protein or a pharmaceutical composition comprising same is administered in an effective amount to promote or enhance IL-10 production.

25 . The method of claim 20 , wherein the polypeptide of claim 1 , or a fusion protein or a pharmaceutical composition comprising same is administered in an effective amount to increase cell numbers or increase populations of any of Tregs and/or Th2 cells.

26 . The method of claim 20 , wherein the polypeptide claim 1 , or a fusion protein or a pharmaceutical composition comprising same administered in an effective amount to inhibit the Th1 and/or Th17 pathways and to enhance the activity of Tregs and/or Th2 cells on the Th1 and Th17 pathways and/or to promote or enhance IL-10 secretion.

27 . The method of claim 20 , wherein the polypeptide of claim 1 , or a fusion protein or a pharmaceutical composition comprising same is administered in an effective amount for reducing proinflammatory molecule production in a subject.

28 . (canceled)

29 . The method of claim 20 , wherein the immune related disorder is selected from the group consisting of autoimmune disease and immune disorder associated with graft transplantation rejection.

30 . The method of claim 20 , wherein the immune disorder associated with graft transplantation rejection is selected from the group consisting of acute and chronic rejection of organ transplantation, allogeneic stem cell transplantation, autologous stem cell transplantation, bone marrow transplantation, and graft versus host disease.

31 . The method of claim 20 , wherein the autoimmune disease is selected from the group consisting of multiple sclerosis, rheumatoid arthritis; psoriatic arthritis, discoid lupus erythematosus, systemic lupus erythematosus (SLE); ulcerative colitis; Crohn's disease; benign lymphocytic angiitis, autoimmune lymphoproliferative syndrome, sarcoidosis, autoimmune thrombocytopenic purpura, idiopathic thrombocytopenic purpura, pure red cell aplasia, Sjogren's syndrome, rheumatic disease, polymyalgia rheumatica, mixed connective tissue disease, inflammatory rheumatism, degenerative rheumatism, extra-articular rheumatism, juvenile arthritis, juvenile rheumatoid arthritis, systemic juvenile idiopathic arthritis, arthritis uratica, muscular rheumatism, chronic polyarthritis, reactive arthritis, Reiter's syndrome, rheumatic fever, relapsing polychondritis, Raynaud's phenomenon, vasculitis, cryoglobulinemic vasculitis, ANCA-associated vasculitis, temporal arteritis, giant cell arteritis, Takayasu arteritis, Behcet's disease, antiphospholipid syndrome, myasthenia gravis, autoimmune haemolytic anaemia, Guillain-Barre syndrome, chronic immune polyneuropathy, chronic inflammatory demyelinating polyneuropathy, autoimmune thyroiditis, insulin dependent diabetes mellitus, type I diabetes, Addison's disease, membranous glomerulonephropathy, polyglandular autoimmune synd

Assignees

• Compugen Ltd

Inventors

• Toporik Amir
• Rosenberg Avi Yeshah
• Rotman Galit
• Hecht Iris
• Levine Zurit

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• C07K16/18

  against material from animals or humans · CPC title

• A61K38/00

  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 title

• C07K2319/30

  Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto · CPC title