Use of binding molecule specifically binding to precursor of brain-derived neurotrophic factor

Abstract

Disclosed herein is use of a binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor (proBDNF). The binding molecule for proBDNF, especially a monoclonal antibody against proBDNF, can be used to prevent, mitigate or treat autoimmune diseases.

What is claimed is: 
     
         1 . A method for preventing, mitigating or treating an autoimmune disease comprising administering to a subject in need thereof a binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor. 
     
     
         2 . The method according to  claim 1 , wherein the binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor is a monoclonal antibody comprising a heavy chain variable region having a CDR1 region as shown in SEQ ID NO: 1, a CDR2 region as shown in SEQ ID NO: 2 and a CDR3 region as shown in SEQ ID NO: 3; and a light chain variable region having a CDR1 region as shown in SEQ ID NO: 4, a CDR2 region as shown in SEQ ID NO: 5 and a CDR3 region as shown in SEQ ID NO: 6. 
     
     
         3 . The method according to  claim 2 , wherein the heavy chain variable region of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 7; and the light chain variable region of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 8. 
     
     
         4 . The method according to  claim 3 , wherein the heavy chain variable region of the monoclonal antibody has a nucleotide sequence as shown in SEQ ID NO: 11; or the light chain variable region of the monoclonal antibody has a nucleotide sequence as shown in SEQ ID NO: 12. 
     
     
         5 . The method according to  claim 2 , wherein the heavy chain of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 9; or the light chain of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 10. 
     
     
         6 . The method according to  claim 5 , wherein the heavy chain of the monoclonal antibody has a nucleotide sequence as shown in SEQ ID NO: 13; or the light chain of the monoclonal antibody has a nucleotide sequence as shown in SEQ ID NO: 14. 
     
     
         7 . The method according to  claim 1 , wherein the binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor is a polyclonal antibody. 
     
     
         8 . The method according to  claim 7 , wherein the polyclonal antibody is produced by immunizing an animal with a precursor of brain-derived neurotrophic factor, or a protein fragment thereof, preferably, a fragment comprising an amino acid sequence as shown in SEQ ID NO: 37. 
     
     
         9 . The method according to  claim 1 , wherein the autoimmune disease includes rheumatoid arthritis, ankylosing spondylitis, psoriasis, systemic lupus erythematosus, insulin-dependent diabetes mellitus, multiple sclerosis, aplastic anemia, cryoglobulinemia, or a combination thereof. 
     
     
         10 . The method according to  claim 1 , wherein the binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor mitigates neurologic impairment; inhibits inflammatory cytokine infiltration in the central nervous system; alleviates myelin sheath loss in the spinal white matter; or reduces the expression of IL-1, IL-6, IL-17, IFN-γ or TNF-α. 
     
     
         11 . The method according to  claim 1 , wherein the binding molecule is administered to the subject at an amount in the range of 0.1-100 mg/kg body weight, or 0.5-15 mg/kg body weight. 
     
     
         12 . A method for inhibiting an interleukin (IL) production, comprising administering to a subject in need thereof a binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor. 
     
     
         13 . The method according to  claim 12 , wherein the interleukin is selected from one or more of IL-1, IL6, and IL-17. 
     
     
         14 . The method according to  claim 12 , wherein the binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor is a monoclonal antibody comprising a heavy chain variable region having a CDR1 region as shown in SEQ ID NO: 1, a CDR2 region as shown in SEQ ID NO: 2 and a CDR3 region as shown in SEQ ID NO: 3; and a light chain variable region having a CDR1 region as shown in SEQ ID NO: 4, a CDR2 region as shown in SEQ ID NO: 5 and a CDR3 region as shown in SEQ ID NO: 6. 
     
     
         15 . The method according to  claim 12 , wherein the heavy chain variable region of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 7; and the light chain variable region of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 8. 
     
     
         17 . The method according to  claim 15 , wherein the heavy chain of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 9; or the light chain of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 10. 
     
     
         18 . The method according to  claim 12 , wherein the binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor is a polyclonal antibody. 
     
     
         19 . The method according to  claim 18 , wherein the polyclonal antibody is produced by immunizing an animal with a precursor of brain-derived neurotrophic factor, or a protein fragment thereof, preferably, a fragment comprising an amino acid sequence as shown in SEQ ID NO: 37. 
     
     
         20 . The method according to  claim 12 , wherein the binding molecule is administered to the subject at an amount in the range of 0.1-100 mg/kg body weight, or 0.5-15 mg/kg body weight. 
     
     
         21 . A method for inhibiting an interferon (IFN) or a tumor necrosis factor production, comprising administering to a subject in need thereof a binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor. 
     
     
         22 . The method according to  claim 21 , wherein the interferon comprises IFN-γ. 
     
     
         23 . The method according to  claim 21 , wherein the binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor is a monoclonal antibody comprising a heavy chain variable region having a CDR1 region as shown in SEQ ID NO: 1, a CDR2 region as shown in SEQ ID NO: 2 and a CDR3 region as shown in SEQ ID NO: 3; and a light chain variable region having a CDR1 region as shown in SEQ ID NO: 4, a CDR2 region as shown in SEQ ID NO: 5 and a CDR3 region as shown in SEQ ID NO: 6. 
     
     
         24 . The method according to  claim 23 , wherein the heavy chain variable region of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 7; and the light chain variable region of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 8. 
     
     
         25 . The method according to  claim 23 , wherein the heavy chain of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 9; or the light chain of the monoclonal antibody has an amino acid sequence as shown in SEQ ID NO: 10. 
     
     
         26 . The method according to  claim 22 , wherein the binding molecule which specifically binds to a precursor of brain-derived neurotrophic factor is a polyclonal antibody. 
     
     
         27 . The method according to  claim 26 , wherein the polyclonal antibody is produced by immunizing an animal with a precursor of brain-derived neurotrophic factor, or a protein fragment thereof, preferably, a fragment comprising an amino acid sequence as shown in SEQ ID NO: 37. 
     
     
         28 . The method according to  claim 22 , wherein the binding molecule is administered to the subject at an amount in the range of 0.1-100 mg/kg body weight, or 0.5-15 mg/kg body weight. 
     
     
         29 . A pharmaceutical composition for treating an autoimmune disease, comprising at least one binding molecule of  claim 1 . 
     
     
         30 . A kit comprising at least one binding molecule of  claim 1 , which specifically binds to a precursor of brain-derived neurotrophic factor and an instruction for treating a subject suffering from an autoimmune disease with the kit.