Anti-ifnar1 antibodies for treating autoimmune diseases

Abstract

Provided are antibodies or fragments thereof having binding specificity to the human interferon alpha and beta receptor subunit 1 (IFNAR1) protein. In various examples, the antibodies or fragments thereof include a VH and VL CDRs as disclosed herein, or variants thereof. Methods of using the antibodies or fragments thereof for treating autoimmune diseases and disorders are also provided.

What is claimed is: 
     
         1 . An antibody or fragment thereof having specificity to a human interferon alpha and beta receptor subunit 1 (IFNAR1) protein, wherein the antibody or fragment thereof comprises a heavy chain variable region comprising heavy chain complementarity determining regions HCDR1, HCDR2, and HCDR3, and a light chain variable region comprising light chain complementarity determining regions LCDR1, LCDR2, and LCDR3, wherein the HCDR1 comprises the amino acid sequence of DYYIH (SEQ ID NO: 92), the HCDR2 comprises the amino acid sequence of RIDPEDGETKYAPKFQG (SEQ ID NO: 93) or RIDPEDAETKYAPKFQG (SEQ ID NO:94), the HCDR3 comprises the amino acid sequence of YHGYWALDY (SEQ ID NO: 95), the LCDR1 comprises the amino acid sequence of KTSQNVGTNVA (SEQ ID NO: 96), the LCDR2 comprises the amino acid sequence of STSYRYS (SEQ ID NO: 97), and the LCDR3 comprises the amino acid sequence of HQYFSYPYT (SEQ ID NO: 98). 
     
     
         2 . The antibody or fragment thereof of  claim 1 , wherein the antibody is a chimeric antibody or a humanized antibody. 
     
     
         3 . The antibody or fragment thereof of  claim 1 , which is humanized and wherein the heavy chain variable region comprises one or more back mutations selected from the group consisting of 20L, 24G, 38K, 48I, 68A, 70I, 72A, 81L, and 97G, according to Kabat numbering, and combinations thereof. 
     
     
         4 . The antibody or fragment thereof of  claim 1 , which is humanized and wherein the light chain variable region comprises one or more back mutations selected from the group consisting of 13T, 21V, 36Y, 46P, 78V, and 104L, according to Kabat numbering, and combinations thereof. 
     
     
         5 . The antibody or fragment thereof of  claim 1 , wherein the heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 73, and 99-102. 
     
     
         6 . The antibody or fragment thereof of  claim 1 , wherein the light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 74, and 103-106. 
     
     
         7 . The antibody or fragment thereof of  claim 1 , wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 100 and the light chain variable region comprises the amino acid sequence of SEQ ID NO: 105. 
     
     
         8 . A bifunctional molecule, comprising a first antigen-binding portion having specificity to a human interferon alpha and beta receptor subunit 1 (IFNAR1) protein and a second portion having specificity to a second protein, wherein the first antigen-binding portion comprises an antibody fragment of  claim 1 . 
     
     
         9 . The bifunctional molecule of  claim 8 , wherein the second portion comprises peptide edratide (hCDR1) or TACI-Ig. 
     
     
         10 . The bifunctional molecule of  claim 8 , wherein the second portion is an antigen-binding fragment having specificity to a protein selected from the group consisting of BAFF, CD20, CD22, CTLA4, IL6, CXCL13 and C5. 
     
     
         11 . One or more polynucleotide encoding the antibody or fragment thereof of  claim 1 . 
     
     
         12 . A method of suppressing an immune response or treating an autoimmune disease or disorder in a patient in need thereof, comprising administering to the patient the antibody or fragment thereof of  claim 1 . 
     
     
         13 . The method of  claim 12 , for treating an autoimmune disease or disorder. 
     
     
         14 . The method of  claim 13 , wherein the autoimmune disease or disorder is selected from the group consisting of type 1 diabetes, rheumatoid arthritis (RA), psoriasis/psoriatic arthritis, multiple sclerosis, systemic lupus erythematosus (lupus), inflammatory bowel disease, Addison's disease, Graves' disease, Sjögren's syndrome, Hashimoto's thyroiditis, myasthenia gravis, vasculitis, pernicious anemia, and celiac disease. 
     
     
         15 . A method of detecting expression of a human interferon alpha and beta receptor subunit 1 (IFNAR1) protein in a sample, comprising contacting the sample with the antibody or fragment thereof of  claim 1 , and detecting the binding which indicates expression of IFNAR1 in the sample.