Therapeutic antibodies and uses thereof

Abstract

Provided herein are methods, compositions, and uses relating to inhibitors of stem cell factor. For example, provided herein are antibodies targeting stem cell factor and methods for treating fibrotic and tissue remodeling diseases.

We claim: 
     
         1 . An isolated recombinant monoclonal anti-stem cell factor (SCF) antibody comprising: (a) a light chain variable domain comprising the amino acid sequence of SEQ ID NO:4 or sequences with at least 80% identity to SEQ ID NO:4; and (b) a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:2 or sequences with at least 80% identity to SEQ ID NO:2. 
     
     
         2 . The antibody of  claim 1 , wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:4 or sequences with at least 85% identity to SEQ ID NO:4 and said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:2 or sequences with at least 85% identity to SEQ ID NO:2. 
     
     
         3 . The antibody of  claim 1 , wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:4 or sequences with at least 90% identity to SEQ ID NO:4 and said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:2 or sequences with at least 90% identity to SEQ ID NO:2. 
     
     
         4 . The antibody of  claim 1 , wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:4 or sequences with at least 95% identity to SEQ ID NO:4 and said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:2 or sequences with at least 95% identity to SEQ ID NO:2. 
     
     
         5 . The antibody of  claim 1 , wherein said light chain variable region comprises the amino acid sequence of SEQ ID NO:4 or sequences with at least 98% identity to SEQ ID NO:4 and said heavy chain variable region comprises the amino acid sequence of SEQ ID NO:2 or sequences with at least 98% identity to SEQ ID NO:2. 
     
     
         6 . The antibody of  claim 1 , wherein said light chain variable region has the amino acid sequence of SEQ ID NO:4 and heavy chain variable region has the amino acid sequence of SEQ ID NO:2. 
     
     
         7 . The antibody of  claim 1 , wherein the antibody is monovalent and comprises an Fc region. 
     
     
         8 . The antibody of  claim 1 , wherein the antibody is bivalent. 
     
     
         9 . The antibody of  claim 1 , wherein the antibody is bispecific. 
     
     
         10 . The antibody of  claim 1 , wherein the antibody is an antibody fragment selected from the group consisting of a Fab, a Fab′-SH, an Fv, an scFv, and a (Fab′).sub.2 fragment. 
     
     
         11 . The antibody of  claim 1 , wherein the antibody comprises a single Fab region linked to an Fc region. 
     
     
         12 . A nucleic acid encoding the antibody of  claim 1 . 
     
     
         13 . The nucleic acid of  claim 12 , comprising a nucleic acid encoding a light chain variable region comprising SEQ ID NO:3 or sequences that are at least 80% homologous to SEQ ID NO:3 and a nucleic acid encoding a heavy chain variable region comprising SEQ ID NO:1 or sequences that are at least 80% homologous to SEQ ID NO:1. 
     
     
         14 . The nucleic acid of  claim 13 , wherein said nucleic acid encoding a light chain variable region comprises SEQ ID NO:3 or sequences that are at least 85% homologous to SEQ ID NO:3 and said nucleic acid encoding a heavy chain variable region comprises SEQ ID NO:1 or sequences that are at least 85% homologous to SEQ ID NO:1. 
     
     
         15 . The nucleic acid of  claim 13 , wherein said nucleic acid encoding a light chain variable region comprises SEQ ID NO:3 or sequences that are at least 90% homologous to SEQ ID NO:3 and said nucleic acid encoding a heavy chain variable region comprises SEQ ID NO:1 or sequences that are at least 90% homologous to SEQ ID NO:1. 
     
     
         16 . The nucleic acid of  claim 13 , wherein said nucleic acid encoding a light chain variable region comprises SEQ ID NO:3 or sequences that are at least 95% homologous to SEQ ID NO:3 and said nucleic acid encoding a heavy chain variable region comprises SEQ ID NO:1 or sequences that are at least 95% homologous to SEQ ID NO:1. 
     
     
         17 . The nucleic acid of  claim 13 , wherein said nucleic acid encoding a light chain variable region comprises SEQ ID NO:3 or sequences that are at least 98% homologous to SEQ ID NO:3 and said nucleic acid encoding a heavy chain variable region comprises SEQ ID NO:1 or sequences that are at least 98% homologous to SEQ ID NO:1. 
     
     
         18 . The nucleic acid of  claim 13 , wherein said nucleic acid encoding a light chain variable region comprises SEQ ID NO:3 and said nucleic acid encoding a heavy chain variable region comprises SEQ ID NO:1. 
     
     
         19 . A method of treating a fibrotic or tissue remodeling disease comprising administering a therapeutically effective amount of the pharmaceutical composition of  claim 12  to a subject with or at risk for a fibrotic or tissue remodeling disease. 
     
     
         20 . The method of  claim 19 , wherein the disease is fibrosis, a remodeling disease, or a pulmonary disease.