By Kevin E. Noonan —

On December 3rd, the
biotechnology, chemical, and pharmaceuticals (BCP) technology groups at the
U.S. Patent and Trademark Office held their most recent quarterly customer
partnership meeting.  During one of six presentations, Kathleen Bragdon, a
Quality Assurance Specialist from Technology Center 1600, presented "A Look at
Personalized Medicine."  In prior
years, this talk may have been anticipated to be a prospective look at a
developing technology area, or represent the Office's attempt to open a dialog
with applicants and their representatives.  But these have not been normal times, and the presentation
contained a few unpleasant but not entirely unexpected surprises.

The majority of the
presentation was a competent, but by no means comprehensive, review of
personalized medicine (referencing scientific journal articles and Wikipedia)
and pharmacogenetics.  Warfarin,
and the use of genetic screening of single nucleotide polymorphisms (SNPs) to
determine patients for whom warfarin treatment may be contraindicated, was used
as a case study.  Ms. Bragdon also
reviewed FDA approval of genetic testing of two human genes (VKORC1 and CYP2C9) having SNPs predictive for warfarin sensitivity.

The talk featured
several examples of how these relationships between genotype and drug treatment
could be claimed, including the following:

3. A method for determining whether a
human subject having breast cancer will be effectively treated with "breast
cancer drug X", said method comprising:
a) considering
data in a database comprising genetic patient information about the ERBB2
gene at position 101 of SEQ ID NO:1; and
b) correlating
the presence of a cytosine at position 101 of SEQ ID NO:1 with effective
treatment of the human subject with "breast cancer drug X".

This is an invalid
claim, according to Ms. Bragdon, for failing to qualify as statutory subject
matter under the Bilski decision,
because it is neither tied to a machine or apparatus nor performs a
transformation (see ".  The following
claim, on the other hand, would be statutory subject matter:

4. A method for treating a human subject
having breast cancer, said method comprising:
a) obtaining
a nucleic acid sample from said human subject;
b) subjecting
the sample to PCR and identifying the nucleotide present at position 101 of SEQ
ID NO:1; and
c) treating
the human subject with "breast cancer drug X" when a cytosine is detected at
position 101 of SEQ ID NO:1.

A comparison
between these claims illustrates the Office's solution to how Bilski (or whatever form a future LabCorp decision may take regarding
these kinds of claims) may be applied to biotechnology (or more specifically,
molecular diagnostic) claims (see "The Relevance of In re Bilski to the Patentability of the Metabolite Claim").  By
casting the claim as a method of treatment, and tying the step of identifying
patients bearing a diagnostic SNP to a treatment step, the policy and
philosophical problems presented by the LabCorp
case are apparently solved.  While
the identification step can still be interpreted to be either a "mental step" or a mere recitation of a natural principle, treatment methods are clearly
statutory subject matter (in the U.S.).

One difficulty with
this solution, however, is that it may frequently be the case that the actor
who performs the diagnostic step of determining whether a patient bears a
diagnostically-relevant SNP is a different actor than the one who performs the
method of treatment step.  This
dichotomy of action then directly implicates the principle enunciates in the Muniauction case, that a claim cannot be
infringed by joint tortfeasors unless there is one actor exercising direction
and control over the others (see "Adequate Method Claiming Requirements:  Muniauction, Inc v. Thomson Corp.").  This situation
may frequently be the case in the practice of claims such as claim 4 in the
presentation.  However, there may
be instances when it is not the case.  In these cases, the Office's solution to the LabCorp problem will be unavailing.  The introduction of method of treatment claims in this
regard is also problematical insofar as it implicates the infringement
exemption embodied in 35 U.S.C. § 287(c) for physicians and other medical
personnel.

The presentation
also discusses the Office's interpretation of how the enablement requirement
may be implicated in personalized medicine claims.  In this regards, Ms. Bragdon discussed the following claim:

5. A
method for treating a human subject having breast cancer, said method
comprising:
a) obtaining
a nucleic acid sample from said human subject;
b) subjecting
the sample to PCR and identifying the nucleotide present at position 101 of SEQ
ID NO:1; and
c) treating
the human subject with "breast cancer drug X" when a cytosine is detected at
position 101 of SEQ ID NO:1.

The presentation
supplies the (putative) disclosure from the specification supporting this
claim, that SEQ ID NO:1 is a variant of the ERBB2 gene having an A
(adenine) to C (cytosine) mutation at position 101 (A101>C).  This mutation (A101>C) is typically found
in breast cancer patients, according to the hypothetical, and it correlates
with a significantly better response to treatment with "breast cancer drug X" versus placebo (i.e., without the mutation, breast cancer drug X is ineffective).  Finally, the hypothetical specification
does not distinguish among patient populations tested, but teaches that variability
in treatment responses among patient populations may be an unpredictable (emphasis in
original) factor in SNP correlation studies (presumably, this factor in the
analysis could also be something within the skill of one having ordinary skill
in the art).

The enablement
issue arises under this hypothetical because post-filing data establishes that
there is a patient population that does not show the claimed correlation
between the mutation in the ERBB2 gene and responsiveness vel non to breast cancer drug X.  Ms. Bragdon did
not assert that under these circumstances the claim would necessarily be invalid for lack of enablement, but suggested that "[t]he
appropriateness of making any enablement rejection should be considered based on the
foregoing facts."

While it is
certainly the case that post-filing evidence can be used to show that a claim
is not enabled, here it seems that the more appropriate question would be
whether the specification provided sufficient guidance to enable the skilled
worker to determine whether a particular patient (as opposed to a patient
population) would bear a predictive SNP, and whether the practice of the
claimed invention with a particular patient having a particular SNP to predict
drug sensitivity would require undue experimentation.  Perhaps Ms. Bragdon was performing her analysis in view of
the Federal Circuit's Monsanto Co. v. Syngenta
Seed, Inc. case, where the Court found invalid claims reciting genetic
transformation of plant cells where certain plant cells (monocots) could not be
transformed at the time the application was filed, and the specification
provided neither any teaching regarding how to transform monocot cells nor
disclaimer or limitation to transformable dicot cells.  However, the Office appears to be
suggesting that claims like claim 5 may be per
se unpatentable in the face of after-filing evidence that not all patients
fall within the scope of the claim.  This seems an unnecessary conclusion and extension of the requirements
for enablement under 35 U.S.C. § 112, first paragraph.

A copy of Ms. Bragdon's presentation can be obtained here.

Additional BCP
presentations will be discussed in future posts.  For information regarding other BCP posts, please see:

• "USPTO Implements New Program to Teach Examiners How to Read and Understand Case Law," December 4, 2008.