Variant ICOS ligand immunomodulatory protein and related compositions and methods

Abstract

To provide a variant ICOS ligand (ICOSL) polypeptide.SOLUTION: Provided is a variant ICOSL polypeptide that comprises one or more amino acid modifications in an immunoglobulin superfamily domain of an ICOSL polypeptide, the variant ICOSL polypeptide being a truncated extracellular domain comprising: a contiguous sequence of amino acids comprising amino acids 1 to 112; and a C-terminal truncation of at least 25 amino acids, based on the ICOSL extracellular domain sequence represented by a specific sequence.SELECTED DRAWING: Figure 13A

Claims

1. A pharmaceutical composition for parenteral administration for treating an inflammatory or autoimmune disease or condition, comprising a variant ICOS ligand (ICOSL) polypeptide consisting of the amino acid sequence shown in SEQ ID NO: 565, an immunomodulatory ICOSL fusion protein comprising the Fc region of an immunoglobulin containing the amino acid sequence shown in SEQ ID NO: 637, and a pharmaceutically acceptable excipient.

2. The pharmaceutical composition according to claim 1, wherein the variant ICOSL polypeptide and the Fc region are linked via a linker having the amino acid sequence shown in SEQ ID NO:

229.

3. The aforementioned inflammatory or autoimmune diseases or conditions include Addison's disease, allergies, alopecia areata, Alzheimer's disease, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, ankylosing spondylitis, antiphospholipid syndrome (Hughes' syndrome), asthma, atherosclerosis, rheumatoid arthritis, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease, autoimmune lymphoproliferative syndrome, autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, azoospermia, Behçet's disease, Buerger's disease, bullous pemphigoid, cardiomyopathy, cardiovascular disease, celiac disease, chronic fatigue immune dysfunction syndrome (CFIDS), chronic idiopathic polyneuritis, and chronic inflammatory demyelinating polyradicalneuropathy.CIDP, chronic relapsing polyneuropathy (Guillain-Barré syndrome), Churg-Strauss syndrome (CSS), pemphigoid scarring, cold agglutinin disease (CAD), COPD (chronic obstructive pulmonary disease), CREST syndrome, Crohn's disease, herpetic dermatitis (dermatitis herpetiformus), dermatomyositis, diabetes mellitus, discoid lupus, eczema, acquired epidermolysis bullosa, essential mixed cryoglobulinemia. Cryoglobulinemia, Evans syndrome, exopthalmos, fibromyalgia, Goodpasture syndrome, Graves' disease, Hashimoto's thyroiditis, idiopathic pulmonary fibrosis, idiopathic thrombocytopenic purpura (ITP), IgA nephropathy, immunoproliferative disorders or disorders, inflammatory bowel disease (IBD), interstitial lung disease, juvenile arthritis, juvenile idiopathic arthritis (JIA), Kawasaki disease, Lambert-Eaton myasthenia palsy, lichen planus, lupus nephritis, lymphocytic hypophysitis, Meniere's disease, Miller-Fischer syndrome / acute disseminated cerebrospinal radiculopathy Encephalomyeloradiculopathy), mixed connective tissue disease, multiple sclerosis (MS), muscular rheumatoid arthritis, myalgic encephalomyelitis (ME), myasthenia gravis, ocular inflammation, pemphigus foliaceus, pemphigus vulgaris, pernicious anemia, polyarteritis nodosa, polychondritis, polyglandular syndrome (Whitaker's syndrome), polymyalgia rheumatica, polymyositis, primary agammaglobulinemia, primary biliary cirrhosis / autoimmune cholangiopathies, psoriasis, psoriatic arthritis, Raynaud's phenomenon, Reiter's syndrome / reactive arthritis, restenosis, rheumatic fever, rheumatic diseases, sarcomatoid syndrome, Schmidt's syndrome, scleroderma, Sjögren's syndrome The pharmaceutical composition according to claim 1 or 2, wherein the condition is generalized rigidity syndrome, systemic lupus erythematosus (SLE), systemic scleroderma, Takayasu's arteritis, temporal arteritis / giant cell arteritis, thyroiditis, type 1 diabetes mellitus, ulcerative colitis, uveitis, vasculitis, vitiligo, interstitial bowel disease, or Wegener's granulomatosis.

4. The pharmaceutical composition according to claim 3, wherein the inflammatory or autoimmune disease or condition is systemic lupus erythematosus (SLE).

5. The pharmaceutical composition according to claim 4, wherein the inflammatory or autoimmune disease or condition is inflammatory bowel disease (IBD), a disease or disorder related to IBD, interstitial lung disease, graft-versus-host disease (GVHD), psoriatic arthritis (PsA), rheumatoid arthritis, an autoimmune condition related to organ transplantation, or Sjögren's syndrome.

6. The pharmaceutical composition according to claim 5, wherein the graft-versus-host disease (GVHD) is acute graft-versus-host disease (aGVHD).

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