Compositions and methods for treatment of diseases involving cxcl1 function

Abstract

The present disclosure relates to antibodies, for example monoclonal antibodies, and their use in clinical patient evaluation and therapy. The present disclosure further relates to a method for modulating the activity of human CXCL-1 protein (hereinafter, referred to as CXCL1). In an aspect, antibodies described herein are capable of being used as a medicament for the prevention and/or treatment of diseases involving CXCL1 function, for example, pathological angiogenesis and inflammatory diseases.

What is claimed is: 
     
         1 . A method of treating a patent who has cancer, comprising administering to the patient an antibody comprising
 a heavy chain variable domain comprising
 CDR1 comprising the amino acid sequence of SEQ ID NO: 6, 
 CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and 
 CDR3 comprising the amino acid sequence of SEQ ID NO: 8, 
 wherein the heavy chain variable domain comprises at most one amino acid substitution in the CDR1, the CDR2, and/or the CDR3, and 
   a light chain variable domain comprising
 CDR1 comprising the amino acid sequence of SEQ ID NO: 9, 
 CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and 
 CDR3 comprising the amino acid sequence of SEQ ID NO: 11, 
 wherein the light chain variable domain comprises at most one amino acid substitution in the CDR1, the CDR2, and/or the CDR3, 
 wherein the cancer expresses human chemokine CXCLI protein comprising the amino acid sequence of SEQ ID NO: 5. 
   
     
     
         2 . The method of  claim 1 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 12 and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 14 or 18. 
     
     
         3 . The method of  claim 1 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 28 and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 30 or 32. 
     
     
         4 . The method of  claim 1 , wherein the light chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 12, and the heavy chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 14 or 18. 
     
     
         5 . The method of  claim 1 , wherein the light chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 28, and the heavy chain variable domain comprises CDR regions CDR1, CDR2, and CDR3 of the amino acid sequence of SEQ ID NO: 30 or 32. 
     
     
         6 . The method of  claim 1 , wherein
 the heavy chain variable domain comprises
 CDR1 consisting of the amino acid sequence of SEQ ID NO: 6, 
 CDR2 consisting of the amino acid sequence of SEQ ID NO: 7, and 
 CDR3 consisting of the amino acid sequence of SEQ ID NO: 8, and 
   the light chain variable domain comprises
 CDR1 consisting of the amino acid sequence of SEQ ID NO: 9, 
 CDR2 consisting of the amino acid sequence of SEQ ID NO: 10, and 
 CDR3 consisting of the amino acid sequence of SEQ ID NO: 11. 
   
     
     
         7 . The method of  claim 1 , wherein the antibody comprises the amino acid sequence of SEQ ID NO: 16, 20, 22, or 24. 
     
     
         8 . The method of  claim 1 , wherein the light chain variable domain comprises a signal peptide comprising the amino acid sequence of SEQ ID NO: 26 and the heavy chain variable domain comprises a signal peptide comprising the amino acid sequence of SEQ ID NO: 27. 
     
     
         9 . The method of  claim 1 , wherein the cancer is bladder cancer or prostate cancer. 
     
     
         10 . The method of  claim 1 , wherein the antibody is in the form of a composition comprising an adjuvant, and optionally, a pharmaceutically acceptable carrier, and optionally, pharmaceutically acceptable excipients and/or stabilizers. 
     
     
         11 . The method of  claim 10 , wherein the adjuvant is selected from the group consisting of anti-CD40 antibody, imiquimod, resiquimod, GM-CSF, cyclophosphamide, sunitinib, bevacizumab, interferon-alpha, interferon-beta, CpG oligonucleotides and derivatives, poly-(I:C) and derivatives, RNA, sildenafil, particulate formulations with poly(lactide co-glycolide) (PLG), virosomes, interleukin (IL)-1, IL-2, IL-4, IL-7, IL-12, IL-13, IL-15, IL-21, and IL-23. 
     
     
         12 . The method of  claim 1 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 12, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 14. 
     
     
         13 . The method of  claim 1 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 12, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 18. 
     
     
         14 . The method of  claim 1 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 28, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 30. 
     
     
         15 . The method of  claim 1 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 28, and the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 32. 
     
     
         16 . The method of  claim 1 , wherein the antibody comprises the amino acid sequence of SEQ ID NO: 16. 
     
     
         17 . The method of  claim 1 , wherein the antibody comprises the amino acid sequence of SEQ ID NO: 20. 
     
     
         18 . The method of  claim 1 , wherein the antibody comprises the amino acid sequence of SEQ ID NO: 22. 
     
     
         19 . The method of  claim 1 , wherein the antibody comprises the amino acid sequence of SEQ ID NO: 24. 
     
     
         20 . The method of  claim 1 , wherein the antibody binds to a human chemokine CXCL1 protein comprising the amino acid sequence of SEQ ID NO: 5.