Earlier this month, the U.S. Patent and Trademark Office issued U.S. Patent No. 8,409,819, entitled "Methods to predict risk for celiac disease by detecting anti-flagellin antibody levels." The '819 patent is assigned to Nestec S.A. of Vevey, Switzerland, a research and testing subsidiary of Nestlé. (Interestingly, the application from which the '819 patent issued was originally assigned to Prometheus Laboratories Inc., which then assigned the application to Nestec.)
Celiac disease is a relatively common disease with an estimated prevalence of approximately 0.5%-1% resulting from both environmental factors (e.g., exposure to gluten), and genetic factors (e.g., HLA-DQ2/8 genotypes). Currently, the only effective treatment for celiac disease is a life-long strict gluten free diet. The inventors demonstrated that a subset of at risk patients had elevated anti-CBir1 antibodies and that this correlated with HLA-DQ2.5 and HLA-DQ8 genotypes.
The patent has two independent claims (claims 1 and 9) reciting two methods to aid in predicting whether a patient (who either has a relative with celiac disease or is EMA positive) is at risk of developing celiac disease. Claim 1 recites:
1. A method for aiding in the prediction of whether an individual having a relative with celiac disease (CD) is at risk of developing CD, the method comprising:
(a) contacting a sample from the individual with a CBir1 flagellin antigen under conditions suitable to form a complex of the CBir1 flagellin antigen and an anti-CBir1 flagellin antibody, wherein the CBir1 flagellin antigen comprises the amino terminal conserved region (amino acid residues 1-147) of the sequence set forth in SEQ ID NO:1;
(b) contacting the complex with a labeled antibody to form a labeled complex;
(c) detecting the level of the labeled complex with a detection device, thereby determining a level of anti-CBir1 flagellin antibodies in the sample; and
(d) associating an elevated level of anti-CBir1 flagellin antibodies in the sample relative to a control with a high risk of developing CD, thereby aiding in the prediction of whether an individual having a relative with CD is at risk of developing CD.
Both claimed methods use the CBir1 flagellin antigen, specifically the N-terminal residues 1-147, to determine whether or not a sample from an at-risk patient contains anti-CBir1 flagellin antibodies. Flagellin is a component of bacterial flagella, the molecular apparatus responsible for a propeller like motion in bacteria. As billions of bacteria make up the intestinal microbiota, the theory is that individuals at risk for celiac disease may have an aggressive immune response to resident bacterial proteins, in this case flagellin. There are a number of highly specific and sensitive serological tests that can be used in diagnosing celiac disease; however the gold standard for diagnosis is histological examination of a biopsy acquired by endoscopic evaluation. As some patients may wish to avoid an endoscopic procedure, or at least have additional confirmatory diagnostics before doing so, the methods claimed here may help clinicians in making a diagnosis. The '819 patent also notes that the method may be useful for identifying groups of patients at risk of developing celiac disease before showing any symptoms, which could help in the development of preventative interventions or other alternatives to a strict gluten free diet (e.g., enzyme supplements).