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 . An isolated anti-human chemokine CXCLI monoclonal antibody or an isolated antigen binding fragment thereof, comprising
 a heavy chain variable domain comprising
 a complementary-determining region (CDR) 1 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; and 
 wherein the light chain variable domain comprises at most one amino acid substitution in the CDR1, the CDR2, and/or the CDR3, 
 wherein the antibody or the antigen-binding fragment thereof binds to human chemokine CXCLI protein comprising the amino acid sequence of SEQ ID NO: 5. 
   
     
     
         2 . The antibody or the antigen-binding fragment thereof of  claim 1 , wherein the antibody comprises an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 2 and an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 4. 
     
     
         3 . The antibody or the antigen-binding fragment thereof of  claim 1 , wherein the antibody comprises an immunoglobulin light chain comprising at least one amino acid addition, substitution, insertion, and/or deletion in the amino acid sequence of SEQ ID NO:2. 
     
     
         4 . The antibody or the antigen-binding fragment thereof of  claim 1 , wherein the antibody comprises an immunoglobulin heavy chain comprising at least one amino acid addition, substitution, insertion, and/or deletion in the amino acid sequence of SEQ ID NO:4. 
     
     
         5 . The antibody or the antigen-binding fragment thereof of  claim 1 , wherein the antibody or the antigen-binding fragment thereof is labeled with a toxin. 
     
     
         6 . The antibody or the antigen-binding fragment thereof of  claim 1 , wherein the antibody or the antigen-binding fragment thereof is labeled with a radionucleotide, a fluorescent dye, a fluorescent protein, an enzyme, biotin and/or streptavidin. 
     
     
         7 . The antibody or the antigen-binding fragment thereof of  claim 6 , wherein the antibody or antigen binding fragment thereof is labelled with a radionucleotide. 
     
     
         8 . The antibody or the antigen-binding fragment thereof of  claim 6 , wherein the fluorescent protein is phycoerythrin (PE), allophycocyanin (APC), or green fluorescent protein (GFP). 
     
     
         9 . The antibody or the antigen-binding fragment thereof of  claim 6 , wherein the enzyme is horseradish peroxidase, alkaline phosphatase, or glucose oxidase. 
     
     
         10 . An isolated nucleic acid molecule encoding the antibody or the antigen-binding fragment thereof of  claim 1 . 
     
     
         11 . The nucleic acid molecule of  claim 10 , wherein the nucleic acid molecule encoding an immunoglobulin light chain comprising the amino acid sequence of SEQ ID NO: 2 comprises the nucleotide sequence of SEQ ID NO: 1. 
     
     
         12 . The nucleic acid molecule of  claim 10 , wherein the nucleic acid molecule encoding an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO: 4 comprises the nucleotide sequence of SEQ ID NO: 3. 
     
     
         13 . A vector comprising the nucleic acid molecule of  claim 10 . 
     
     
         14 . A host cell comprising the nucleic acid molecule of  claim 10 . 
     
     
         15 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one active ingredient selected from the group consisting of the antibody and the antigen-binding fragment thereof of  claim 1 . 
     
     
         16 . The antibody or the antigen-binding fragment thereof 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: 13 or 15. 
     
     
         17 . The antibody or the antigen-binding fragment thereof of  claim 1 , comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 14, 16, 17, and 18. 
     
     
         18 . The antibody or the antigen-binding fragment thereof of  claim 1 , wherein the light chain variable domain comprises a signal peptide comprising the amino acid sequence of SEQ ID NO: 19. 
     
     
         19 . The antibody or the antigen-binding fragment thereof of  claim 1 , wherein the heavy chain variable domain comprises a signal peptide comprising the amino acid sequence of SEQ ID NO: 20. 
     
     
         20 . An isolated anti-human chemokine CXCL1 monoclonal antibody or an isolated antigen-binding fragment thereof, wherein the antibody or the antigen-binding fragment thereof binds to human chemokine CXCL1 protein having the amino acid sequence of 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 5) 
                 
                     
                   ASVATELRCQCLQTLQGIHPKNIQSVNVKSPGPHCAQ 
                 
                     
                     
                 
                     
                   TEVIATLKNGRKACLNPASPIVKKIIEKMLNSDKSN.