Anti-stem cell factor antibodies and methods of use thereof

Abstract

The disclosure relates to antibodies and antigen-binding fragments thereof that bind to Stem Cell Factor (SCF). The antibodies and antigen-binding fragments thereof specifically bind to SCF248. The disclosure further relates to methods for making the antibodies, and to methods of use of the antibodies including methods of treatment for inflammatory and/or fibrotic diseases and disorders.

1 . An isolated nucleic acid molecule encoding an antibody or fragment thereof that specifically binds to stem cell factor (SCF), wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 1, 2, and 3, respectively; and a light chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 4, 5, and 6, respectively. 
     
     
         2 . An expression vector comprising the nucleic acid molecule of  claim 1 . 
     
     
         3 . A recombinant host cell comprising the expression vector of  claim 2 . 
     
     
         4 . A method for making an antibody or fragment thereof comprising a heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 1, 2, and 3, respectively; and a light chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 4, 5, and 6, respectively, wherein the antibody or fragment thereof specifically binds to stem cell factor isoform 248 (SCF248), the method comprising immunizing a host animal with a peptide comprising SEQ ID NO: 30 or a fragment thereof, and obtaining the antibody or fragment thereof from the immunized host animal. 
     
     
         5 . The method of  claim 4 , wherein the peptide comprises at least 5 amino acids and wherein the N-terminal amino acid of the peptide is the alanine at position 1 of SEQ ID NO: 30. 
     
     
         6 . A method for treating a chronic inflammatory disease or a fibrotic disease in a subject in need thereof, the method comprising administering to the subject an antibody or fragment thereof that specifically binds to stem cell factor (SCF), wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 1, 2, and 3, respectively; and a light chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 4, 5, and 6, respectively. 
     
     
         7 . The method of  claim 6 , wherein the chronic inflammatory disease or fibrotic disease is selected from the group consisting of urticaria, atopic dermatitis, non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis, pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), cystic fibrosis, peribronchial fibrosis, hypersentitivity pneumonitis, asthma, bleomycin lung, scleroderma, liver cirrhosis, endomyocardial fibrosis, fibromyalgia, and eosinophilic esophagitis. 
     
     
         8 . The method of  claim 7 , wherein the chronic inflammatory disease or fibrotic disease is pulmonary fibrosis. 
     
     
         9 . The method of  claim 8 , wherein the pulmonary fibrosis is idiopathic pulmonary fibrosis or scleroderma lung fibrosis. 
     
     
         10 . The method of  claim 6 , wherein the method further comprises administering an additional therapeutic agent to the subject. 
     
     
         11 . A method for inhibiting the activation of immune cells, comprising contacting the immune cells with an antibody or fragment thereof that specifically binds to stem cell factor (SCF), wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 1, 2, and 3, respectively; and a light chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 4, 5, and 6, respectively. 
     
     
         12 . The method of  claim 11 , wherein the immune cells are selected from the group consisting of mast cells, eosinophils, and innate lymphoid cells 2, and innate lymphoid cells 3. 
     
     
         13 . A method for inhibiting inflammation, fibrosis, or both in a subject in need thereof, the method comprising administering to the subject an antibody or fragment thereof that specifically binds to stem cell factor (SCF), wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 1, 2, and 3, respectively; and a light chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 4, 5, and 6, respectively. 
     
     
         14 . A method for treating an inflammatory disease or disorder, a fibrotic disease, or both in a subject in need thereof, the method comprising administering to the subject an antibody or fragment thereof that specifically binds to stem cell factor (SCF), wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 1, 2, and 3, respectively; and a light chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 4, 5, and 6, respectively. 
     
     
         15 . The method of  claim 14 , comprising treating an inflammatory disease or disorder. 
     
     
         16 . The method of  claim 15 , wherein the inflammatory disease or disorder is a chronic inflammatory disease or disorder. 
     
     
         17 . The method of  claim 14 , comprising treating a fibrotic disease. 
     
     
         18 . The method of  claim 14 , wherein the inflammatory disease or disorder or the fibrotic disease is selected from the group consisting of urticaria, atopic dermatitis, non-alcoholic steatohepatitis (NASH), primary sclerosing cholangitis, pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), cystic fibrosis, peribronchial fibrosis, hypersensitivity pneumonitis, asthma, bleomycin lung, scleroderma, liver cirrhosis, endomyocardial fibrosis, fibromyalgia, and eosinophilic esophagitis. 
     
     
         19 . A method for inhibiting chronic inflammation, fibrosis, or both in a subject in need thereof, the method comprising administering to the subject an antibody or fragment thereof that specifically binds to stem cell factor (SCF), wherein the antibody or fragment thereof comprises a heavy chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 1, 2, and 3, respectively; and a light chain CDR1, CDR2, and CDR3 comprising SEQ ID NOs: 4, 5, and 6, respectively.