Ex Parte Karumanchi et al

Patent Trial and Appeal Board

Jul 26, 2016

12227658 (P.T.A.B. Jul. 26, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/227,658 11124/2008
21559 7590
CLARK & ELBING LLP
101 FEDERAL STREET
BOSTON, MA 02110
07/28/2016
FIRST NAMED INVENTOR
S. Ananth Karumanchi
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
01948-106004 6985
EXAMINER
SZPERKA, MICHAEL EDWARD
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
07/28/2016 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
patentadministrator@clarkelbing.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte S. ANANTH KARUMANCHI, VIKAS P. SUKHATME,
MOURAD TOPORSIAN, and MICHELLE V. LETARTE1
Appeal2015-000426
Application 12/227,658
Technology Center 1600
Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of diagnosing pre-term pre-eclampsia or a predisposition to pre-term pre-
eclampsia and treating the patient based on the diagnosis, which have been
rejected as directed to non-statutory subject matter. We have jurisdiction
under 35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the Real Party in Interest as Beth Israel Deaconess
Medical Center, Inc. and The Hospital for Sick Children. (Br. 2.)
Appeal2015-00426
Application 12/227,658
STATEMENT OF THE CASE
"Pre-eclampsia is a syndrome of hypertension, edema, and
proteinuria." (Spec 1: 10.) While there are no known cures for pre-
eclampsia, there are treatments available, which vary depending on the
severity of the syndrome, and include bed rest, and/or taking blood pressure
medication or anticonvulsant medication. (Spec 1: 19-24.)
"The symptoms of pre-eclampsia typically appear after the 20th week
of pregnancy and are usually detected by routine measuring of the [pregnant]
woman's blood pressure and urine." (Spec. 1:13-14.) "Several [growth]
factors have been reported to have an association with ... pre-eclampsia[,
including] vascular endothelial growth factor (VEGF), soluble Flt-1 [, fms-
like tyrosine kinase,] receptor (sFlt-1 ), and placental growth factor (PIGF)."
(Spec. 2: 11-15.) Appellants' Specification notes that prior art monitoring
methods for pre-eclampsia are ineffective for diagnosis of the syndrome at
an early stage. (Spec. 1: 15-16.) Appellants' claims are directed to a method
for diagnosing pre-eclampsia or a propensity to develop the syndrome that
relies on measuring sFlt-1 and soluble endoglin, a cell membrane
glycoprotein, "shown to be a regulatory component of the TGF-B receptor
complex, which modulates angiogenesis, proliferation, differentiation, and
apoptosis." (Spec. 1 :25-32, 9:5-11.)
Appellants "discovered that levels of soluble endoglin (sEng) are
markedly elevated in placental tissue samples from pregnant women
suffering from pregnancy complications associated with hypertension,
including preeclampsia." (Spec. 3:10-13.) Flt-1 "is highly expressed by
trophoblast cells which contribute to placental formation." (Spec. 2:20-21.)
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Soluble Flt-1, ("sFlt-1 "), lacking the transmembrane and cytoplasmic
domains of the receptor, "was recently identified in a cultured medium of
human umbilical vein endothelial cells and in vivo expression was
subsequently demonstrated in placental tissue." (Spec. 2:27-29.)
Claims 58-66, 69-78, 80, 81, and 88-95 are on appeal. Claim 58 is
representative and read as follows:
58. A method of diagnosing a subject as having, or having a
predisposition to, preterm pre-eclampsia, said method
comprising measuring the level of a soluble endoglin
polypeptide and an sFlt-1 polypeptide from said subject and
calculating the relationship between said levels of soluble
endoglin and sFlt-1 using a [soluble endoglin x sFlt-1] metric,
wherein an increase in the metric value in the subject sample
relative to the metric value in a normal reference sample, is a
diagnostic indicator of, or a propensity to develop, pre-term
pre-eclampsia in said subject, and based on said diagnosis,
treating said subject for said pre-eclampsia.
(Appeal Br. 9.)
The single ground of rejection by the Examiner that is before us on
review 1s:
Claims 58-66, 69-78, 80, 81, and 88-95 under 35 U.S.C. § 101 as
directed to non-statutory subject matter.
DISCUSSION
The Examiner finds that the method recited in claim 58 is "drawn to a
mathematical relationship between polypeptide levels in a patient sample
and the presence of a particular disorder[, which] ... is a law of nature."
(Final Action 6.) In particular, the Examiner finds that claim 58 is "directed
to a method of diagnosing a pregnancy related hypertensive disorder in a
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Application 12/227,658
patient by measuring the concentration of markers present in a patient
sample, calculating a value based upon a relationship between the measured
values, and comparing the calculated patient's value with a value obtained
using samples from a normal reference sample." (Final Action 6.) The
markers "are soluble endoglin and soluble Flt-1." (Id.) The Examiner finds
that these "markers ... were known in the prior art and were even known to
be important for the prediction of pregnancy induced hypertensive disorders,
such as preeclampsia, as evidenced by US 2006/0067937 Al (of record)."
(Final Action 6.)
The Examiner further finds that the claimed measurement and treating
steps are well-understood and/or conventional and routine. (Final Action 6-
8.) Regarding the measurement step, the Examiner points to the statement
on page 43 of the Specification that:
Standard methods may be used to measure levels of soluble
endoglin, free VEGF, free PIGF, sFlt-1, TGF-131, TGF-133,
PG12, or eNOS polypeptide in any bodily fluid, including, but
not limited to, urine, serum, plasma, saliva, amniotic fluid, or
cerebrospinal) fluid. Such methods include immunoassay,
ELISA, western blotting using antibodies, [etc ... ].
(Final Action 6.) Regarding the "treating" step, the Examiner finds not only
is the step "specified at a high level of generality as it encompasses any and
all possible treatments" for pre-eclampsia, but that treating "after making a
diagnosis ... is obvious and routine in the medical arts." (Final Action 8.)
In light of the foregoing, the Examiner concludes that "no matter how
important, unexpected or useful" the discovery that "increased levels of sFlt-
1 and soluble endoglin are correlated with increased risks for preeclampsia
and other pregnancy-related hypertensive disorders" or the determination of
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"the mathematical equation by which they can be combined to achieve a
diagnosis of increased accuracy as compared to the prior art," the additional
measurement and treating steps beyond the mathematical relationship recited
in the claims do not transform the law of nature recited by the claim "into a
patent-eligible application of such a law." (Final Action 7-8.)
We agree with the Examiner's conclusion that representative claim 58
is directed to non-statutory subject matter consistent with controlling
case law. Appellants do not dispute that this claim is directed to a law of
nature, but that the treatment step is "a specific, meaningful additional step
that goes well beyond the correlation itself and is not simply an 'apply it'
statement appended to the recitation of a law of nature as construed by the
courts in Mayo [Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct.
1289, 1294 (2012)]." (Br. 6.) We disagree; we conclude that, as in Mayo,
there is "nothing significantly more [recited in claim 58] than an instruction
to doctors to apply the applicable law[] when treating their patient[]." Mayo,
132 S. Ct. 1298.
As the Examiner noted, claim 58 does not "specify any particular
type of treatment, such as use drug A rather than drug B." (Ans. 4.)
Moreover, as the Examiner also noted, there is nothing in the general
statement to treat after the diagnosis is made that could be deemed an
unconventional step. (Final Action 8 ("treating a patient for a diseases after
making a diagnosis of the same disease in the same patient is obvious and
routine in the medical arts;" Ans. 6 (noting the claims do not recite the use
of any novel product in the claimed "treatment" step).) As the Examiner
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noted, claim 5 8 "preempt[ s] all practical uses of the natural
law/phenomenon/correlation." (Ans. 4.)
We disagree with Appellants that claim 58 "closely aligns to the facts
of Example F" of the "2014 Guidance for Determining Subject Matter
Eligibility of Claims Reciting or Involving Laws of Nature, Natural
Phenomena, & Natural Products" such that the claimed treatment step
should be deemed "a practical application of the natural principle" (Br. 7).
We agree with the Examiner that, important to the analysis of patent
eligibility in Example F, was the fact that the claim made use of a novel
product. (Ans. 6.) No such limitation is provided in the treatment step of
claim 58, or any other step for that matter.
Furthermore, we disagree with Appellants "that treatment based on
the level of soluble endoglin and sFlt-1 together is a specific application of
natural principles" that is not conventional (Br. 6). Appellants do not
dispute that the prior art publication US2006/0067397 A 1 "teaches methods
for diagnosing pregnancy related hypertensive disorder or a predisposition to
a pregnancy related hypertensive disorder, such as preeclampsia, by
measuring soluble endoglin (sEng) in combination with other markers
including soluble Flt-1 (sFlt-1 ), calculating a diagnostic index which adds
sFlt-1 and sEng concentration values, and methods of treating women so
diagnosed." (Ans. 3.) Thus, we agree with the Examiner that the only
"unconventional" element of claim 58 is the recited mathematical equation
correlating gathered data of soluble endoglin and sFlt-1 (Ans. 5), and not the
ability to diagnose prior to "visible symptoms such as high blood pressure,
high levels of protein in the urine, and bodily swelling[] in the late stages of
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pregnancy" based on the level of soluble endoglin and sFlt-1 together, as
asserted by Appellants (Br. 6).
Thus, we agree with the Examiner that neither the measuring steps,
nor the treatment step are sufficient alone or in an ordered combination with
the correlation to transform the unpatentable natural correlation claimed into
patentable applications of it. (Final Action 6-7; Ans. 3--4.)
For the reasons discussed, Appellants do not persuade us that the
Examiner erred in rejecting claims 58 as directed to non-statutory subject
matter. Claims 59-66, 69-78, 80, 81, and 88-95 have not been argued
separately and therefore fall with claim 58. 37 C.F.R. § 41.37( c )(1 )(iv).
SUMMARY
We affirm the rejection of Claims 58-66, 69-78, 80, 81, and 88-95
under 35 U.S.C. § 101 as directed to non-statutory subject matter.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § l.136(a).
AFFIRMED
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