Anti aqp3 monoclonal antibody specifically binding to extracellular domain of aquaporin 3 (aqp3) and use thereof

Abstract

A subject of the present invention is to provide an anti AQP3 antibody specifically recognizing the extracellular domain of aquaporin 3 (AQP3), which is one type of a water channel protein. By selecting a monoclonal antibody which specifically binds to an oligopeptide included in loop C as one of the extracellular domains of AQP3, an anti AQP3 antibody that is desired in the present invention is provided. An anti AQP3 monoclonal antibody of the present invention can directly bind, from the outside of a cell, to AQP3 present in a cell membrane. Furthermore, as an anti AQP3 monoclonal antibody of the present invention can have an inhibitory activity, the function of permeating a low molecular weight molecule or the like, which is carried by AQP3, can be suppressed.

1 . An anti AQP3 antibody or a functional fragment thereof that specifically binds to (i) an oligopeptide whose amino acid sequence consists of ATYPSGHLDM (SEQ ID NO:1) or (ii) the extracellular domain of human AQP3 and/or the extracellular domain of mouse AQP3. 
     
     
         2 - 5 . (canceled) 
     
     
         6 . The antibody or functional fragment thereof according to  claim 1 , which:
 a) has an inhibitory activity on at least one function of human and/or mouse AQP3;   b) inhibits proliferation of one or more of PAM212 cells, HaCaT cells, and A431 cells;   c) inhibits H 2 O 2  transport;   d) inhibits phosphorylation of p65;   e) inhibits a liver inflammatory response in mice treated with carbon tetrachloride; or   f) comprises a combination of (a) to (e).   
     
     
         7 - 10 . (canceled) 
     
     
         11 . An anti AQP3 antibody or a functional fragment thereof comprising a heavy chain complementarity determining region 1 (HCDR1), a heavy chain complementarity determining region 2 (HCRD2), a heavy chain complementarity determining region 3 (HCDR3), a light chain complementarity determining region 1 (LCDR1), a light chain complementarity determining region 2 (LCDR2), and a light chain complementarity determining region 3 (LCDR3) comprising amino acid sequences selected from the sequences set forth in one of Tables 2A-5E. 
     
     
         12 . The antibody or functional fragment thereof according to  claim 11 , comprising complementarity determining region (CDR) sequences of antibody A, antibody B, antibody C, antibody D, antibody E, antibody F, antibody G, antibody H, antibody J, or antibody K. 
     
     
         13 - 21 . (canceled) 
     
     
         22 . The antibody or functional fragment thereof according to  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         23 . The antibody or functional fragment thereof according to  claim 1 , wherein the antibody or functional fragment thereof is a chimeric antibody or a humanized antibody having a constant region of a human antibody. 
     
     
         24 . The antibody or functional fragment thereof according to  claim 1 , which is an antibody. 
     
     
         25 . The antibody or functional fragment thereof according to  claim 24 , which is a monospecific antibody. 
     
     
         26 . The antibody or functional fragment thereof according to  claim 24 , which is a multispecific antibody. 
     
     
         27 . The antibody or functional fragment thereof according to  claim 1 , which is a functional fragment of an antibody. 
     
     
         28 . The antibody or functional fragment thereof according to  claim 27 , which is a functional fragment selected from F(ab′) 2 , Fab, Fab′ and Fv. 
     
     
         29 - 30 . (canceled) 
     
     
         31 . An antibody drug conjugate (ADC) comprising the antibody or a functional fragment thereof according to  claim 1  conjugated to a cytotoxic agent. 
     
     
         32 - 37 . (canceled) 
     
     
         38 . A composition comprising the monoclonal antibody or functional fragment thereof according to  claim 1  and a pharmaceutically acceptable carrier, wherein the monoclonal antibody or a functional fragment thereof has an inhibitory activity on at least one function of AQP3. 
     
     
         39 - 40 . (canceled) 
     
     
         41 . A method of treating a subject having cancer comprising administering a therapeutically effective amount of the antibody of  claim 1  or a functional fragment thereof to the subject. 
     
     
         42 . The method of  claim 41 , wherein the cancer is colorectal cancer, cervical cancer, liver cancer, lung cancer, esophageal cancer, kidney cancer, stomach cancer, tongue cancer, skin cancer, or breast cancer. 
     
     
         43 . A method of preventing and/or treating a skin disorder in a subject comprising administering a therapeutically effective amount of the antibody of  claim 1  or a functional fragment thereof to the subject. 
     
     
         44 . The method of  claim 43 , wherein the skin disorder is psoriasis, actinic keratosis, ichthyosis, or seborrheic dermatitis. 
     
     
         45 . A method of preventing and/or treating an inflammatory disorder in a subject comprising administering a therapeutically effective amount of the antibody or  claim 1  or a functional fragment thereof to the subject. 
     
     
         46 . The method of  claim 45 , wherein the inflammatory disorder is atopic dermatitis, psoriasis, asthma, chronic obstructive pulmonary disease, or hepatitis. 
     
     
         47 - 51 . (canceled) 
     
     
         52 . A method for generating an anti AQP3 antibody, comprising immunizing a non-human mammal with a combination of (i) a peptide whose amino acid sequence consists of the amino acid sequence of SEQ ID NO:1 and (ii) AQP3 overexpressing cells. 
     
     
         53 - 55 . (canceled)