US2008187541A1PendingUtilityA1

Helicobacter pylori adhesin binding group antigen

52
Assignee: BOREN THOMASPriority: Jun 10, 1996Filed: Jun 13, 2007Published: Aug 7, 2008
Est. expiryJun 10, 2016(expired)· nominal 20-yr term from priority
Inventors:Thomas BorenAnna ArnqvistLennart HammarstromStaffan NormarkDag Ilver
A61P 31/04A61P 43/00A61K 2039/51C07K 14/205A61P 1/04A61K 39/00
52
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

A novel Helicobacter pylori blood group antigen binding (BAB) adhesin protein was isolated and purified, whereby said protein or fractions thereof bind specifically to fucosylated blood group antigens. The protein sequence of said adhesin is disclosed in this application. Simultaneously the DNA sequences for two genes, babA and babB, producing highly similar proteins, are disclosed. Said adhesin and/or DNA is useful for diagnose and therapy and/or prophylaxis directed against H. pylori induced infections, e.g. gastritis and acid peptic disease, i.e. active vaccination. A new immunoglobulin composition, which exhibits specific activity to a Lewis b antigen binding Helicobacter pylori adhesin, or preferably, monoclonal and/or polyclonal antibodies to said adhesin offer a new and more efficient method of treatment and/or prevention of gastrointestinal diseases, caused by Helicobacter pylori or other Helicobacter species, i.e. passive vaccination.

Claims

exact text as granted — not AI-modified
1 . A vaccine comprising a nucleotide sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:6. 
     
     
         2 . A test kit comprising a monospecific antisera that recognizes a BabA antigen and comprises an immunoglobulin that binds said BabA antigen via a variable region, wherein said Bab A adhesin protein is produced using an isolated and purified bacterial blood group antigen binding protein (BabA) from  Helicobacter pylori  species, wherein said BabA protein binds specifically to fucosylated Lewis b  type I and H-1 blood group antigen-glycoconjugates and,
 wherein said BabA protein contains less than 20% bacterial protein impurities, has a molecular weight in the interval of 73 to 75 kDa as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and is not a HopA, HopB, HopC, HopD, or HopE protein.   
     
     
         3 . An isolated monospecific immunoglobulin composition from sera which recognizes a BabA antigen and binds said BabA antigen via a variable region and exhibits specific activity to a BabA adhesion protein from  Helicobacter pylori , wherein said adhesin protein binds Lewis b  and H-1 blood group antigen-glycoconjugates and is not a HopA, HopB, HopC, HopD or HopE protein. 
     
     
         4 . The immunoglobulin composition according to  claim 3 , wherein said BabA adhesin protein has a molecular weight in the interval of about 70 to 77 kDa as determined by SDS-PAGE. 
     
     
         5 . The immunoglobulin composition according to any one of  claims 3  or  4  wherein said BabA adhesin protein comprises the following amino acid sequence: EDDGFYTSVGYQIGEAAQMV (SEQ ID NO:5) or homologues thereof. 
     
     
         6 . An isolated monospecific antibody, which recognizes a BabA antigen and binds said BabA antigen via a variable region and exhibits specific activity to a BabA adhesion protein from  Helicobacter pylori  that binds Lewis b  and H-1 blood group antigen-glycoconjugates and is not a HopA, HopB, HipC, HopD or HopE protein. 
     
     
         7 . The antibody according to  claim 6 , wherein said BabA adhesin protein has a molecular weight in the interval of about 70 to 77 kD as determined by SDS-PAGE. 
     
     
         8 . The antibody according to  claim 6 , wherein said BabA adhesin protein comprises the following amino acid sequence: EDDGFYTSVGYQIGEAAQMV (SEQ ID NO:5) or homologues thereof. 
     
     
         9 . The antibody according to  claim 6 , wherein said antibody is a monoclonal antibody. 
     
     
         10 . A method of manufacturing an immunoglobulin composition according to  claim 3 , comprising the following steps:
 immunizing an animal with Lewis b  binding protein or fractions thereof, expressed by  Helicobacter pylori,      isolating the immunoglobulin fraction from an excretion of said host animal, and   purifying the immunoglobulin preparation to obtain an isolated monospecific immunoglobulin composition.   
     
     
         11 . The method according to  claim 10 , wherein said animal is a cow and the immunoglobulin fraction is isolated from the milk, preferably the colostrum thereof. 
     
     
         12 . The method according to  claim 10 , wherein said animal is a chicken and the immunoglobulin fraction is isolated from the egg yolk thereof. 
     
     
         13 . A method of manufacturing an antibody according to  claim 6 , wherein the method comprises the following steps:
 immunizing an animal with a Lewis b  binding protein (BabA) or fractions thereof, expressed by  Helicobacter pylori , fusing immunised, immunoglobulin producing cells with a neoplastic cell line, selecting and growing cells expressing said antibody, and purifying the antibodies.   
     
     
         14 . The method of  claim 13 , further comprising expressing said antibody by a culture of viable microorganisms in an expression system, where said microorganism or organisms are generally recognized as safe (GRAS) and genetically modified to express said antibody. 
     
     
         15 . The method according to  claim 14 , wherein said microorganism is selected from the group consisting of bacteria of the species  Lactobacillus, Staphylococcus  and  Enteriobacteriacea . 
     
     
         16 . A pharmaceutical preparation for treating an individual having or identified as being at risk of developing  Helicobacter pylori  infection, gastric ulcers or acid peptic disease in humans comprising the immunoglobulin composition according to  claim 3 . 
     
     
         17 . A method of treating an individual having or identified as being at risk of developing gastric ulcers comprising administering to a subject in need thereof the immunoglobulin composition according to  claim 3 . 
     
     
         18 . A method of treating an individual having or identified as being at risk of developing acid peptic disease comprising administering to a subject in need thereof the immunoglobulin composition according to  claim 3 . 
     
     
         19 . A pharmaceutical product for treating an individual having or being identified at risk of developing  Helicobacter pylori  infections, gastric ulcers or acid peptic disease in humans, comprising the antibody according to  claim 6 . 
     
     
         20 . A pharmaceutical product for treating an individual having or being identified at risk of developing gastric ulcers comprising the antibody according to  claim 6 . 
     
     
         21 . A pharmaceutical product for the treating an individual having or being identified at risk of developing peptic disease comprising the antibody according to  claim 6 . 
     
     
         22 . The method according to  claim 18 , wherein said subject is human and said immunoglobulin composition is administered orally. 
     
     
         23 . A method for treating a human having or being identified at risk of developing  Helicobacter pylori  infections, comprising orally administering an effective amount of an antibody according to  claim 6  to said human. 
     
     
         24 . A method of treating a human having or being identified at risk of developing  Helicobacter pylori  infections, said method comprising orally administering an effective amount of a culture of viable microorganisms in an expression system, wherein said microorganism or organisms are generally recognized as safe (GRAS) and genetically modified to express an antibody according to  claim 8  or  9 . 
     
     
         25 . An expression system comprising a culture of viable microorganisms wherein said microorganism or organisms are generally recognized as safe (GRAS) and genetically modified to express an antibody according to  claim 8  or  9 . 
     
     
         26 . A method for treating a human having or being identified at risk of developing  Helicobacter pylori  infections, said method comprising orally administering an effective amount of a culture of viable microorganisms in an expression system, wherein said microorganisms or organisms are generally recognized as safe (GRAS) and genetically modified to express an adhesion protein according to  claim 1 . 
     
     
         27 . The composition according to  claim 4 , wherein the molecular weight of said BabA adhesin protein is in the interval of 73 to 75 kDa. 
     
     
         28 . The composition according to  claim 4 , wherein the molecular weight of said BabA adhesin protein is about 73.5 kDa. 
     
     
         29 . The antibody according to  claim 6 , wherein the molecular weight of said BabA adhesin protein is in the interval of 73 to 75 kDa. 
     
     
         30 . The antibody according to  claim 4 , wherein the molecular weight of said BabA adhesin protein is about 73.5 KDa.

Join the waitlist — get patent alerts

Track US2008187541A1 — get alerts on status changes and closely related new filings.

We store only your email — no account needed. See our privacy policy.