METHOD FOR PRODUCING MONOCLONAL IgA ANTIBODY

Abstract

The present invention provides a component having effects in vivo of improving or optimizing the intestinal environment, suppressing intestinal putrefaction, or suppressing alternation of intestinal bacterial growth and/or pathological changes of intestinal bacterial growth in gut microbiota. The invention also provides an active ingredient suitably used for treating intestinal diseases. The invention provides a monoclonal IgA antibody that binds to amino acids 11 to 333 of serine hydroxymethyltransferase.

1 .- 26 . (canceled) 
     
     
         27 . A method for treating an intestinal disease in a human subject in need thereof, comprising administering to the subject an effective amount of a monoclonal antibody, wherein the monoclonal antibody is capable of binding to serine hydroxymethyltransferase. 
     
     
         28 . The method according to  claim 27 , wherein the monoclonal antibody is orally or enterally administered. 
     
     
         29 . The method according to  claim 27 , wherein the monoclonal antibody binds to serine hydroxymethyltransferase represented by SEQ ID NO: 74. 
     
     
         30 . The method according to  claim 27 , wherein the monoclonal antibody binds to amino acids 11 to 333 of serine hydroxymethyltransferase represented by SEQ ID NO: 74. 
     
     
         31 . The method according to  claim 27 , wherein the monoclonal antibody binds to an epitope comprising amino acids 26 to 28 of serine hydroxymethyltransferase represented by SEQ ID NO: 74. 
     
     
         32 . The method according to  claim 27 , wherein the monoclonal antibody has a structure selected from the group consisting of F(ab′)2, Fab, Fv, scFv, scFv-Fc, and mini body. 
     
     
         33 . The method according to  claim 27 , wherein the monoclonal antibody is IgA. 
     
     
         34 . The method according to  claim 33 , wherein the monoclonal antibody is IgA1 or IgA2. 
     
     
         35 . The method according to  claim 34 , wherein the monoclonal antibody is a J chain-containing polymer. 
     
     
         36 . The method according to  claim 34 , wherein the monoclonal antibody comprises a secretory component. 
     
     
         37 . The method according to  claim 27 , wherein the monoclonal antibody comprises:
 (1) a heavy chain variable region comprising CDR 1 consisting of the amino acid sequence represented by SEQ ID NO: 3, CDR 2 consisting of the amino add sequence represented by SEQ ID NO: 4, and CDR 3 consisting of the amino add sequence represented by SEQ ID NO: 5, and   a light chain variable region comprising CDR 1 consisting of the amino acid sequence represented by SEQ ID NO: 8, CDR 2 consisting of the amino acid sequence represented by SEQ ID NO: 9, and CDR 3 consisting of the amino acid sequence represented by SEQ ID NO: 10;   (2) a heavy chain variable region comprising CDR 1 consisting of the amino acid sequence represented by SEQ ID NO: 13, CDR 2 consisting of the amino add sequence represented by SEQ ID NO: 14, and CDR 3 consisting of the amino add sequence represented by SEQ ID NO: 15, and   a light chain variable region comprising CDR 1 consisting of the amino add sequence represented by SEQ ID NO: 18, CDR 2 consisting of the amino acid sequence represented by SEQ ID NO: 19, and CDR 3 consisting of the amino add sequence represented by SEQ ID NO: 20;   (3) a heavy chain variable region comprising CDR 1 consisting of the amino acid sequence represented by SEQ ID NO: 23, CDR 2 consisting of the amino add sequence represented by SEQ ID NO: 24, and CDR 3 consisting of the amino add sequence represented by SEQ ID NO: 25, and   a light chain variable region comprising CDR 1 consisting of the amino acid sequence represented by SEQ ID NO: 28, CDR 2 consisting of the amino acid sequence represented by SEQ ID NO: 29, and CDR 3 consisting of the amino acid sequence represented by SEQ ID NO: 30;   (4) a heavy chain variable region comprising CDR 1 consisting of the amino acid sequence represented by SEQ ID NO: 33, CDR 2 consisting of the amino acid sequence represented by SEQ ID NO: 34, and CDR 3 consisting of the amino acid sequence represented by SEQ ID NO: 35, and   a light chain variable region comprising CDR 1 consisting of the amino acid sequence represented by SEQ ID NO: 38, CDR 2 consisting of the amino acid sequence represented by SEQ ID NO: 39, and CDR 3 consisting of the amino acid sequence represented by SEQ ID NO: 40; or   (5) a heavy chain variable region comprising CDR 1 consisting of the amino acid sequence represented by SEQ ID NO: 43, CDR 2 consisting of the amino acid sequence represented by SEQ ID NO: 44, and CDR 3 consisting of the amino acid sequence represented by SEQ ID NO: 45, and   a light chain variable region comprising CDR 1 consisting of the amino acid sequence represented by SEQ ID NO: 48, CDR 2 consisting of the amino acid sequence represented by SEQ ID NO: 49, and CDR 3 consisting of the amino acid sequence represented by SEQ ID NO: 50.   
     
     
         38 . The method according to  claim 27 , wherein the monoclonal antibody comprises:
 (I) a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 2, and a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 7;   (II) a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 12, and a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 17;   (III) a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 22, and a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 27;   (IV) a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 32, and a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 37; or   (V) a heavy chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 42, and a light chain variable region consisting of the amino acid sequence represented by SEQ ID NO: 47.   
     
     
         39 . The method according to  claim 27 , wherein the monoclonal antibody comprises:
 (a) a heavy chain consisting of the amino acid sequence represented by SEQ ID NO: 1, and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 6;   (b) a heavy chain consisting of the amino acid sequence represented by SEQ ID NO: 11, and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 16;   (c) a heavy chain consisting of the amino acid sequence represented by SEQ ID NO: 21, and a light chain consisting of the amino add sequence represented by SEQ ID NO: 26;   (d) a heavy chain consisting of the amino acid sequence represented by SEQ ID NO: 31, and a light chain consisting of the amino add sequence represented by SEQ ID NO: 36; or   (e) a heavy chain consisting of the amino acid sequence represented by SEQ ID NO: 41, and a light chain consisting of the amino acid sequence represented by SEQ ID NO: 46.   
     
     
         40 . The method according to  claim 37 , wherein the monoclonal antibody binds to at least one kind of intestinal bacteria selected from the group consisting of:
   Eubacterium rectale,        Lactobacillus murinus,        Escherichia coli,        Staphylococcus aureus,        Enterococcus faecalis,        Pseudomonas fulva,  and     Enterorhabdus mucosicola.      
     
     
         41 . The method according to  claim 27 , wherein the monoclonal antibody binds to at least two kinds of intestinal bacteria selected from the group consisting of:
   Eubacterium rectale,        Lactobacillus murinus,        Escherichia coli,        Staphylococcus aureus,        Enterococcus faecalis,        Pseudomonas fulva,  and     Enterorhabdus mucosicola.      
     
     
         42 . The method according to  claim 41 , wherein the monoclonal antibody fails to bind to at least one kind of intestinal bacteria selected from the group consisting of:
   Blautia coccoides,        Coprococcus eutactus,        Megamonas hypermegale,        Lactobacillus casei,  and     Bifidobacterium bifidum.      
     
     
         43 . The method according to  claim 27 , wherein the monoclonal antibody is a humanized antibody or a chimeric antibody. 
     
     
         44 . The method according to  claim 27 , wherein the intestinal disease is an inflammatory bowel disease. 
     
     
         45 . The method according to  claim 44 , wherein the inflammatory bowel disease is Crohn's disease. 
     
     
         46 . The method according to  claim 44 , wherein the inflammatory bowel disease is ulcerative colitis.