Antibodies, uses & methods

Abstract

The present invention relates to anti-human OX40L antibodies, new medical uses and methods.

1 - 30 . (canceled) 
     
     
         31 . An anti-OX40L antibody or antibody fragment comprising:
 (a) a HCDR1 amino acid sequence of SEQ ID NO: 36 or 42;   (b) a HCDR2 amino acid sequence of SEQ ID NO: 38 or 44;   (c) a HCDR3 amino acid sequence of SEQ ID NO: 40 or 46;   (d) a LCDR1 amino acid sequence of SEQ ID NO: 50 or 56;   (e) a LCDR2 amino acid sequence of SEQ ID NO: 52 or 58; and   (f) a LCDR3 amino acid sequence of SEQ ID NO: 54 or 60.   
     
     
         32 . The anti-OX40L antibody or antibody fragment of  claim 31 , having:
 (a) a V H  amino acid sequence of SEQ ID NO: 34; and   (b) a V L  amino acid sequence of SEQ ID NO: 48.   
     
     
         33 . The anti-OX40L antibody or antibody fragment of  claim 31  or  claim 32 , wherein the anti-OX40L antibody or antibody fragment further comprises a heavy chain constant region, wherein the heavy chain constant region is IgG4-PE. 
     
     
         34 . The anti-OX40L antibody or antibody fragment of  claim 31  or  claim 32 , wherein the heavy chain constant region has the amino acid sequence of SEQ ID NO: 128. 
     
     
         35 . The anti-OX40L antibody or antibody fragment of  claim 31 , having:
 (a) a heavy chain amino acid sequence of SEQ ID NO: 62; and   (b) a light chain amino acid sequence of SEQ ID NO: 64.   
     
     
         36 . A pharmaceutical composition comprising the anti-OX40L antibody of any one of  claims 31 - 35  and a pharmaceutically acceptable carrier. 
     
     
         37 . The pharmaceutical composition of  claim 36 , further comprising a therapeutic agent. 
     
     
         38 . The pharmaceutical composition of  claim 37 , wherein the therapeutic agent is selected from the group consisting of rapamycin (sirolimus), tacrolimus, ciclosporin, corticosteroids (e.g. methylprednisolone), methotrexate, mycophenolate mofetil, anti-CD28 antibodies, anti-IL12/IL-23 antibodies (e.g. ustekinumab), anti-CD20 antibodies (e.g. rituximab), anti-CD30 antibodies (e.g. brentuximab), CTLA4-Fc molecules (e.g. abatacept), CCR5 receptor antagonists (e.g. maraviroc), anti-CD40L antibodies, anti-VLA4 antibodies (e.g. natalizumab), anti-LFA1 antibodies, fludarabine, anti-CD52 antibodies (e.g. alemtuzumab), anti-CD45 antibodies, cyclophosphamide, anti-thymocyte globulins, anti-complement C5 antibodies (e.g. eculizumab), anti-a4b7 integrin antibodies (e.g. vedolizumab), anti-IL6 antibodies (e.g. tocilizumab), anti-IL2R antibodies (e.g. basilixumab), anti-CD25 antibodies (e.g. daclizumab), anti-TNFa/TNFa-Fc molecules (e.g. etanercept, adalimumab, infliximab, golimumab or certolizumab pegol) and Vorinostat. 
     
     
         39 . A method of treating a subject having or at risk of inflammatory bowel disease (IBD), Crohn's disease, rheumatoid arthritis, transplant rejection, allogenic transplant rejection, graft-versus-host disease (GvHD), ulcerative colitis, systemic lupus erythematosus (SLE), diabetes, dermatitis, uveitis, ankylosing spondylitis, contact hypersensitivity, multiple sclerosis, or atherosclerosis, the method comprising administering to the subject the pharmaceutical composition of  claim 36  or  claim 37 . 
     
     
         40 . A nucleotide sequence encoding the anti-OX40L antibody or antibody fragment of any one of  claims 31 - 35 . 
     
     
         41 . The nucleotide sequence of  claim 40 , comprising:
 (a) a HCDR1 nucleotide sequence of SEQ ID NO: 35 or 41;   (b) a HCDR2 nucleotide sequence of SEQ ID NO: 37 or 43;   (c) a HCDR3 nucleotide sequence of SEQ ID NO: 39 or 45;   (d) a LCDR1 nucleotide sequence of SEQ ID NO: 49 or 55;   (e) a LCDR2 nucleotide sequence of SEQ ID NO: 51 or 57; and   (f) a LCDR3 nucleotide sequence of SEQ ID NO: 53 or 59.   
     
     
         42 . The nucleotide sequence of  claim 40 , having:
 (a) a V H  nucleotide sequence of SEQ ID NO: 33; and   (b) a V L  nucleotide sequence of SEQ ID NO: 47.   
     
     
         43 . The nucleotide sequence of  claim 40 , having:
 (a) a heavy chain nucleotide sequence of SEQ ID NO: 61; and   (b) a light chain nucleotide sequence of SEQ ID NO: 63.