By Josh Bosman —

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).