Anti-psgl-1 antibodies and uses thereof

Abstract

Provided herein, in one aspect, are antibodies that immunospecifically bind to PSGL-1, polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to PSGL-1, as well as methods of treating a disorder or disease caused by or associated with increased proliferation and/or numbers of activated T cells using the antibodies described herein.

1 .- 16 . (canceled) 
     
     
         17 . A method for treating an inflammatory disorder, the method comprising administering to a subject in need thereof a therapeutically effective amount of a monoclonal antibody which immunospecifically binds to human PSGL-1, the monoclonal antibody comprising:
 (i) a variable light (“VL”) chain region comprising the amino acid sequence of SEQ ID NO: 3;   (ii) a heavy chain comprising variable heavy (“VH”) chain region comprising the amino acid sequence of SEQ ID NO: 4; and   (iii) a human IgG4 constant region which contains a Serine to Proline substitution at amino acid 228 of the heavy chain numbered according to the EU index.   
     
     
         18 . The method of  claim 17 , wherein the monoclonal antibody comprises:
 (i) a light chain comprising the amino acid sequence of SEQ ID NO: 1; and   (ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 2.   
     
     
         19 . The method of  claim 18 , wherein the monoclonal antibody comprises:
 (i) a light chain consisting of the amino acid sequence of SEQ ID NO: 1; and   (ii) a heavy chain consisting of the amino acid sequence of SEQ ID NO: 2.   
     
     
         20 . The method of  claim 17 , wherein the monoclonal antibody is purified. 
     
     
         21 . The method of  claim 17 , wherein the inflammatory disorder is an autoimmune disease. 
     
     
         22 . The method of  claim 17 , wherein the inflammatory disorder is: psoriasis, plaque psoriasis, chronic plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, or diabetes. 
     
     
         23 . The method of  claim 18 , wherein the monoclonal antibody is purified. 
     
     
         24 . The method of  claim 18 , wherein the inflammatory disorder is an autoimmune disease. 
     
     
         25 . The method of  claim 18 , wherein the inflammatory disorder is: psoriasis, plaque psoriasis, chronic plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, or diabetes. 
     
     
         26 . A method for treating an inflammatory disorder, the method comprising administering to a subject in need thereof a therapeutically effective amount of A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a monoclonal antibody which immunospecifically binds to human PSGL-1, the monoclonal antibody comprising:
 (i) a variable light (“VL”) chain region comprising the amino acid sequence of SEQ ID NO: 3;   (ii) a heavy chain comprising variable heavy (“VH”) chain region comprising the amino acid sequence of SEQ ID NO: 4; and   (iii) a human IgG4 constant region which contains a Serine to Proline substitution at amino acid 228 of the heavy chain numbered according to the EU index.   
     
     
         27 . The method of  claim 26 , wherein the monoclonal antibody comprises:
 (i) a light chain comprising the amino acid sequence of SEQ ID NO: 1; and   (ii) a heavy chain comprising the amino acid sequence of SEQ ID NO: 2.   
     
     
         28 . The method of  claim 27 , wherein the monoclonal antibody comprises:
 (i) a light chain consisting of the amino acid sequence of SEQ ID NO: 1; and   (ii) a heavy chain consisting of the amino acid sequence of SEQ ID NO: 2.   
     
     
         29 . The method of  claim 26 , wherein the monoclonal antibody is purified. 
     
     
         30 . The method of  claim 26 , wherein the inflammatory disorder is an autoimmune disease. 
     
     
         31 . The method of  claim 26 , wherein the inflammatory disorder is: psoriasis, plaque psoriasis, chronic plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, or diabetes. 
     
     
         32 . The method of  claim 27 , wherein the monoclonal antibody is purified. 
     
     
         33 . The method of  claim 27 , wherein the inflammatory disorder is an autoimmune disease. 
     
     
         34 . The method of  claim 27 , wherein the inflammatory disorder is: psoriasis, plaque psoriasis, chronic plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, psoriatic arthritis, rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, or diabetes.