High Affinity Fully Human Monoclonal Antibodies To Interleukin-8 And Epitopes For Such Antibodies

Abstract

The present embodiments are related to high-affinity antibodies directed to IL-8, methods of making and characterizing such antibodies and uses of such antibodies. Isolated polynucleotide sequences encoding, and amino acid sequences comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions (FR's) and/or complementarity determining regions (CDR's), are provided.

What is claimed is: 
     
         1 . A human monoclonal antibody or antigen-binding portion thereof that specifically binds to Interleukin-8, wherein the antibody or antigen binding portion binds with a K d  of less than 10 pM. 
     
     
         2 . The monoclonal antibody or antigen-binding portion of  claim 1 , wherein the antibody or antigen binding portion binds with a K d  of less than 1 pM. 
     
     
         3 . The monoclonal antibody or antigen-binding portion of  claim 1 , wherein the antibody or antigen binding portion binds with a K d  of less than 500 fM. 
     
     
         4 . The monoclonal antibody or antigen-binding portion of  claim 1 , wherein the antibody or antigen binding portion binds with a K d  of less than 10 fM as determined through a KinExA equilibrium assay. 
     
     
         5 . An antibody or antigen-binding portion thereof that binds to an epitope of a polypeptide, wherein the epitope comprises the amino acid sequence ELRCQCIKTYSK (SEQ ID NO: 79). 
     
     
         6 . The antibody for antigen-binding portion thereof of  claim 5 , wherein the antibody binds to said epitope with a K d  of less than about 1 pM. 
     
     
         7 . The antibody for antigen-binding portion thereof of  claim 6 , wherein the antibody can bind to said epitope with a K d  of less than about 500 fM. 
     
     
         8 . An antibody or antigen-binding portion thereof that binds to a polypeptide, wherein the polypeptide consists of the amino acid sequence ELRCQCIKTYSK (SEQ ID NO: 79). 
     
     
         9 . The antibody of  claim 8 , wherein the antibody neutralizes a biological activity of human Interleukin-8. 
     
     
         10 . A method for treating a disease comprising administering to a subject an effective amount of an anti-Interleukin-8 antibody, wherein said anti-Interleukin-8 antibody binds to an epitope of a polypeptide, and wherein the epitope comprises the amino acid sequence ELRCQCIKTYSK (SEQ ID NO: 79). 
     
     
         11 . A method for treating a disease comprising administering to a subject an effective amount of an anti-Interleukin-8 antibody, wherein said anti-Interleukin-8 antibody binds to Interleukin-8 with a K d  of less than about 10 pM. 
     
     
         12 . The method of  claim 11 , wherein the K d  is less than about 1 pM. 
     
     
         13 . The method of  claim 11 , wherein the K d  is less than about 0.5 pM. 
     
     
         14 . The method of  claim 11 , wherein the K d  is less than about 0.1 pM. 
     
     
         15 . The method of  claim 11 , wherein the disease is associated with inflammation. 
     
     
         16 . The method of  claim 15 , wherein the subject is a human. 
     
     
         17 . The method of  claim 11 , wherein the disease is selected from the group consisting of a disease associated with Interleukin-8 malignant melanoma, pulmonary disorders, and an inflammatory condition. 
     
     
         18 . The method of  claim 11 , wherein the disease is selected from the group consisting of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis. 
     
     
         19 . The method of  claim 11 , wherein the disease is selected from the group consisting of psoriasis, rheumatoid arthritis, and inflammatory bowel disease. 
     
     
         20 . A therapeutic composition comprising an antibody that immunoreacts with an Interleukin-8 epitope, wherein said Interleukin-8 epitope comprises the amino acid sequence ELRCQCIKTYSK (SEQ ID NO: 79), wherein said antibody prevents inflammation, and wherein the antibody has a K d  that is less than about 10 pM. 
     
     
         21 . Use of a human monoclonal antibody to Interleukin-8 in the preparation of a medicament for the treatment of an Interleukin-8 related disorder, wherein the Interleukin-8 related disorder is selected from the group consisting of: Interleukin-8 malignant melanoma, pulmonary disorders, an inflammatory condition; chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, psoriasis, rheumatoid arthritis, and inflammatory bowel disease, and wherein the human monoclonal antibody has a K d  for Interleukin-8 that is less than about 10 pM. 
     
     
         22 . The use of  claim 21 , wherein the antibody has a K d  that is less than about 1 pM. 
     
     
         23 . Use of the antibody or antigen-binding portion thereof according to  claim 5  in the preparation of a medicament for the treatment of an Interleukin-8 related disorder, wherein the Interleukin-8 related disorder is selected from the group consisting of: Interleukin-8 malignant melanoma, pulmonary disorders, an inflammatory condition; chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, psoriasis, rheumatoid arthritis, and inflammatory bowel disease. 
     
     
         24 . Use of the antibody or antigen-binding portion thereof according to  claim 8  in the preparation of a medicament for the treatment of an Interleukin-8 related disorder, wherein the Interleukin-8 related disorder is selected from the group consisting of: Interleukin-8 malignant melanoma, pulmonary disorders, an inflammatory condition; chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, psoriasis, rheumatoid arthritis, and inflammatory bowel disease.