Ex Parte Niewczas et al

Patent Trial and Appeal Board

Mar 16, 2017

13130711 (P.T.A.B. Mar. 16, 2017)

United States Patent and Trademark Office
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/130,711 08/09/2011 Monika A. Niewczas JDP-131US 1023
35859 7590
Pierce Atwood LLP
100 Summer Street
Suite 2250
Boston, MA 02110
EXAMINER
HIBBERT, CATHERINE S
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
03/20/2017 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):
Patent @pierceatwood. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MONIKA A. NIEWCZAS and
ANDRZEJ S. KROLEWSKI1
Appeal 2015-001681
Application 13/130,711
Technology Center 1600
Before JOHN G. NEW, JOHN E. SCHNEIDER and
TIMOTHY G. MAJORS, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
SUMMARY
1 Appellants state the real party-in-interest is Joslin Diabetes Center, Inc.
App. Br. 3.
Appeal 2015-001681
Application 13/130,711
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Non-Final Rejection of claims 17—20 which stand rejected as
unpatentable under 35 U.S.C. §101 as being directed to unpatentable
subject matter.
Claims 17—20 also stand rejected as unpatentable under 35 U.S.C.
§103 (a) as being obvious over the combination of C. Keller et al.,
Association of Kidney Function with Inflammatory and Procoagulant
Markers in a Diverse Cohort: A Cross-sectional Analysis from the Multi-
Ethnic Study of Atherosclerosis (MESA), 9:9 BMK Nephrology 1—8
(2008) (“Keller”), E.L. Knight et al., Kidney Dysfunction, Inflammation,
and Coronary Events: A Prospective Study, 15 J. Am. Soc. Nephrol.,
1897—1903 (2004) (“Knight”), and M. Tonelli et al., Biomarkers of
Inflammation and Progression of Chronic Kidney Disease, 68 Kidney
Int’l 237-45 (2005) (“Tonelli”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CFAIMED INVENTION
Appellants’ invention is directed to methods of diagnosing and
predicting renal disease, using one, two, or more biomarkers, including
sTNFR-I, sTNFR-II, sFAS, TNF, and IL-6. Abstract.
GROUPING OF CLAIMS
Claim 17 is representative and recites:
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17. A method of determining whether a human subject
has an increased risk of developing chronic kidney disease
(CKD), or end stage renal disease (ESRD), or both, the method
comprising: obtaining a sample from a human subject who has
proteinuria; measuring the level of soluble TNF receptor type I
(sTNFRI) in the subject sample; comparing the subject levels of
sTNFRI with reference levels of sTNFRI; and determining
whether the subject has an increased risk of developing CKD or
ESRD, or both, based on the comparison of the subject levels
with the reference levels
App. Br. 18-19.
ISSUE AND ANALYSIS
We agree with, and adopt, the Examiner’s reasoning and conclusion
that the claims are both directed to nonstatutory subject matter and obvious
over the cited prior art references. We address Appellants’ arguments
below.
A. Rejection of the claims as being directed to nonstatutory subject matter
Issue
Appellants argue that the Examiner erred in finding that the claims
are directed to nonstatutory subject matter under 35U.S.C. § 101. App. Br.
6.
Analysis
Appellants argue the Examiner has failed to analyze the claims “as a
whole” by including each and every element of the invention including the
element(s) directed to the alleged “law of nature,” as required by the
Supreme Court in Mayo Collaborative Services v. Prometheus
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Application 13/130,711
Laboratories, Inc., 566 U.S. 66, 90 (2012). App. Br. 8—9. According to
Appellants, the alleged “natural law” must be considered in combination
with the other elements of the claimed invention when determining whether
a claimed invention is directed towards patent-eligible subject matter. Id. at
9.
Appellants contend the allegedly non-patent eligible subject matter
was excluded by the Examiner from the analysis and the remaining
elements of the invention were considered separately, with little
consideration given to an analysis of the claim “as a whole.” App. Br. 9.
According to Appellants, the standards employed by the Examiner in the
rejection were overly stringent and go well beyond the criteria that the
Supreme Court’s holding in Prometheus established. Id. Appellants argue
that the claims, when taken as a whole, provide a patent-eligible method to
determine the likelihood of a subject having, or being susceptible to,
developing chronic kidney disease (“CKD”) or end-stage renal disease
(“ESRD”). Id. at 10.
Appellants argue the claimed method combines several elements into
what constitutes a significant advance beyond the elements when taken
separately. App. Br. 10. Appellants assert that the recognition and use of
the level of soluble TNF receptor type I (“sTNFRI”) in a subject is effective
for determining a specific medical condition is analogous to the use of an
algorithm effective for determining when to adjust molding temperature, as
in Diamond v. Diehr, 450 U.S. 175 (1981). Id. Appellants contend the
added elements of the present invention, when taken as a whole in
combination with the alleged natural law, provide, as in Diehr, that “the
process as a whole does not thereby become unpatentable subject matter,”
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merely for containing an alleged law of nature. Id. (quoting Diehr, 450
U.S. at 187). Appellants assert that, as was the case in Diehr, they do not
seek to patent a level of sTNFRI in a subject, nor the relationship of the
level of sTNFRI to a medical condition. Id. (quoting Diehr, 450 U.S. at
187). Rather, Appellants assert that they seek to patent a method of
determining the likelihood of a subject of having an “increased risk of
developing CKD, or ESRD, or both. Id.
Appellants argue further that the Supreme Court’s Prometheus
analysis drew a distinction between claims that were overly preemptive
versus claims that were not overly preemptive in a given field, with the
latter being claims that are more likely drawn to patent eligible subject
matter. App. Br. 10—11. Appellants argue that their claims on appeal, like
the claims in Diehr, are not overly preemptive and are therefore drawn to
patent eligible-subject matter and that they seek only to “foreclose from
others the use of that [relationship] in conjunction with the other steps in the
claimed process.” Id. at 10 (quoting Diehr, 450 U.S. at 187). Appellants
assert further that, rather than being preemptive, the pending claims provide
a teaching to the public that will facilitate research, further investigation,
and further invention with regards to the discovery of new treatments and
the discovery of novel drugs and their use. Id.
Finally Appellants argue that their invention adds matter “significant
beyond the sum of their parts taken separately” because the contribution of
function of the presently claimed invention when taken “as a whole” was
not considered. App. Br. 11. According to Appellants, when the functional
aspects of the claimed invention are considered, it should be evident that the
claimed invention provides a functionally significant difference beyond
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merely reciting a law of nature and, therefore, is drawn to patent eligible
subject matter. Id. at 11—12.
We are not persuaded. When performing an analysis of whether the
claims are directed to patent-eligible subject matter, we perform a two-step
analysis as reflected in the Supreme Court’s Alice and Mayo precedents,2
and as set forth by the Director in the 2014 Interim Guidance on Patent
Subject Matter Eligibility, December 10, 2014 (79(241) Fed Reg. 74618—
33 (December 16, 2014)) (the “Interim Guidance) for claims involving
phenomenon of nature and subsequently updated in 2015 and 2016 (the
“Interim Guidance”).
We agree with the Examiner that the limitations of the claims on
appeal, as exemplified by claim 17, are analogous to the claims at issue in
Mayo and, consequently, dictate the same outcome. See Non-Final Act. 3.
In performing the analysis, we first determine whether the claims on appeal
are directed to a statutory category. See Interim Guidance 76422. In this
instance, we conclude that they are: the claims are explicitly directed to a
method or process of determining whether a human subject has an increased
risk of developing CKD or ESRD, or both. See claim 17.
Next, we determine whether the claims are directed to a judicially-
created exception, in this instance, a natural law or phenomenon of nature.
See Interim Guidance 76422—23. Although the claims require a non-novel
(and unspecified) assay to determine the phenomenon, the phenomenon
itself, the relationship between levels of sTNFRI and the likelihood of
2 Alice Corp. Pty. Ltd. v. CLSBankInt’l, 134 S.Ct. 2347, 2355 (2014);
Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S.Ct. 1289, 1297
(2012).
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Application 13/130,711
developing CKD and ESRD, occurs naturally within the body, whether
detected or not. See Spec. 5—6. Consequently we find that the claims are
directed to a phenomenon of nature and therefore falls within one of the
judicially-created exceptions. See Alice, 134 S.Ct. at 2355; Mayo, 132 S.Ct.
at 1293.
Having determined that the claims are directed to a phenomenon of
nature, we next look to the claim as a whole to determine whether any
element, or combination of elements, is sufficient to ensure that the claim
amounts to significantly more than the exception. See Interim Guidance
76423-23.
The claims are directed to a specific audience, i.e., physicians
treating patients for their likelihood of developing CKD or ESRD, and
directs them to “measure[e] the level of soluble TNF receptor type I
(sTNFRI) in the subject sample; and compar[e] the subject levels of
sTNFRI with reference levels of sTNFRI.” See claim 17.
It has been well settled by our reviewing court that claim steps that
require “assaying” and “comparing” do not add significantly more to a
claim than the recitation of the phenomenon of nature:
In recent cases, we found claims “directed to” a patent-ineligible
concept when they amounted to nothing more than observing or
identifying the ineligible concept itself. For example, in Genetic
Technologies, the claim recited methods for detecting a coding
region of DNA based on its relationship to non-coding regions.
Genetic Techs., Ltd. v. MerialL.L.C., 818 F.3d at 1369, 1373—74
(Fed. Cir. 2016). Because the relationship between coding and
non-coding sequences was a law of nature, the claim amounted
to nothing other than identifying “information about a patient’s
natural genetic makeup.” Id. at 1375. Fikewise in Ariosa, the
claims recited methods for detecting paternally inherited cffDNA
in the blood or serum of a pregnant female. Ariosa Diagnostics,
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Inc. v. Sequenom, Inc., 788 F.3d 1371, 1373—74 (Fed. Cir. 2015),
cert, denied, No. 15—1102,----- U.S.-------- , 136 S.Ct. 2511,-----
L.Ed.2d------- , 2016 WL 1117246 (June 27, 2016). The existence
and location of cffDNA is a natural phenomenon; identifying its
presence was merely claiming the natural phenomena itself. Id.
at 1376. And in In re BRCA, the claims recited methods for
screening human germline for an altered BRCA1 gene by
comparing the target DNA sequence with wild-type sequence. In
re BRCA1— & BRCA2—Based Hereditary Cancer Test Patent
Litig., 774 F.3d 755, 761—62 (Fed. Cir. 2014). But comparing
two sequences to detect alterations is a patent-ineligible “abstract
mental process.” Id. at 763. Although the claims in each of these
cases employed method steps, the end result of the process, the
essence of the whole, was a patent-ineligible concept. See also
Genetic Techs. Ltd. v. Merial L.L.C., 818 F.3d 1369 (Fed. Cir.
2016).
Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042, 1048 (Fed. Cir.
2016) (emphasis added).
Similarly, in this case the recited steps of the claims require
determining the level of sTNFRI in a subject and comparing it to reference
levels. As such, these “functional” steps consist of nothing more than
“observing or identifying” the ineligible concept (i.e., the relationship
between sTNFRI and “comparing” them with a reference to determine the
likelihood of developing CKD or ESRD. These steps, therefore, when
viewed as a whole, add nothing significant beyond the sum of their parts
taken separately. The claims therefore do not amount to significantly more
than the natural law itself.
Appellants may have discovered the relationship between sTNFRI
levels and the likelihood of developing CKD and/or ESRD, but the
discovery of a phenomenon of nature is not, by itself, an invention, and is
consequently not directed to patentable subject matter. See Association for
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Molecular Pathology v. Myriad Genetics, Inc., 133 S.Ct. 2107, 2117 (2013)
(“Groundbreaking, innovative, or even brilliant discovery does not by itself
satisfy the § 101 inquiry.”); Mayo, 132 S.Ct. at 1293 (‘“Phenomena of
nature, though just discovered, mental processes, and abstract intellectual
concepts are not patentable.’”) (quoting Gottschalk v. Benson, 409 U.S. 63,
67 (1972)) (emphasis added). We therefore affirm the Examiner’s rejection
of the claims on this ground.
B. Rejection of the claims as obvious under 35 U.S.C. $ 103(a)
Issue
Appellants argue that the Examiner erred in: (1) not identifying in the
cited prior art all of the elements of the claimed invention; (2) not showing
why a person of ordinary skill in the art would have combined the teachings
of the prior art without the benefit of the teachings of the present invention;
and (3) not showing that a person of ordinary skill would have reasonably
expected to succeed in combining the teachings of the cited prior art to
arrive at Appellants’ claimed invention. App. Br. 14.
Analysis
Appellants argue Keller neither teaches nor suggests proteinuria and
does not specifically identify which, if any, of the subjects taught therein
may have had proteinuria. App. Br. 15. According to Appellants,
proteinuria is determined in the art by measuring either total protein in urine
or albumin in protein, neither of which is taught by Keller. Id. Appellants
assert Keller teaches a correlation between cystatin C and TNF-aRl,
however, Appellants argue, cystatin C levels and proteinuria (total protein
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levels) are not the same. Id. Appellants therefore argue that Keller fails to
teach determining if a significantly higher level of sTNFRI in subjects with
proteinuria have an increased risk of developing chronic kidney disease. Id.
Appellants argue Knight, which teaches that “kidney dysfunction is
associated with increased risk of coronary events and inflammation, as
assessed by the levels of higher sTNFRI and sTNFRII which may be
correlated to the increased risk.” App. Br, 15 (quoting Non-Final Act. 6).
Appellants assert Knight concludes “kidney dysfunction is associated with
an increased odds of coronary events, and inflammation, as assessed by
higher sTNFRI and II levels, may mediate some of this risk.” Id. (quoting
Knight, Abstr.). However, Appellants argue, Knight teaches no association
or prediction at all about the levels of sTNFRI and the risk of progression to
CKD/ESRD. Id.
Appellants argue that Tonelli is cited as teaching biomarkers of
inflammation and progression of chronic kidney disease, and explicitly
correlates a relationship between sTNFR-II and the rate of kidney function
loss. App. Br. 15—16. However, Appellants argue, Tonelli only presents
teachings with respect to sTNFRII and not sTNFRI. Id. at 16.
The Examiner responds that Keller teaches that the measurement of
albumin in the urine, as proteinuria, was well known in the art. Ans. 12
(citing Keller 8) (“The participants in the MESA study were more likely ...
to have diabetes and a higher urine albumin to creatinine ratio,” which the
Examiner asserts is known in the art as proteinuria). The Examiner finds
Keller also teaches obtaining a serum sample from a human subject having
proteinuria and measuring the level of differential gene expression
compared to a reference control level to determine if the subject has an
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increased risk of developing chronic kidney disease (CKD), where
significantly higher sTNFRI levels indicate the increased risk. Id. at 12—13
(citing Keller Table 2).
The Examiner finds Knight teaches that kidney dysfunction is
associated with increased risk of coronary events and inflammation, as
assessed by the levels of higher sTNFRI and sTNFRII which may be
correlated to the increased risk. Non-Final Act. 6. The Examiner finds the
increased levels of inflammation biomarkers, and specifically the markers:
hs-CRP, IL-6, and sTNFR-I and sTNFR-II are significantly correlated with
coronary events. Id.
The Examiner next finds Tonelli teaches biomarkers of inflammation
and progression of chronic kidney disease and explicitly correlates TNFRII
and the rate of kidney function loss. Non-Final Act. 7. The Examiner finds
Tonelli teaches that serum TNF-a levels are associated with the severity of
proteinuria in diabetic nephropathy. Id.
The Examiner concludes that a person of ordinary skill in the art
would realize from the teachings of the cited references that assays showing
levels of sTNFRI in serum samples from patients having proteinuria, and
particularly Type II diabetes, would correlate with an increased risk of
chronic kidney disease, including end stage renal failure. Non-Final Act. 7.
The Examiner further concludes it would have been obvious in view of the
cited references because the TNFRII marker was already known to be
associated with chronic kidney disease, including end stage renal failure
and soluble TNFR biomarkers were already known to be associated with
decreased renal function in patients with Type II diabetes having
proteinuria. Id.
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We are not persuaded by Appellants’ arguments. Keller teaches:
“After adjustment for age, sex, ethnicity, and BMI, cystatin C had
statistically significant partial correlations with all six biomarkers in
participants both with and without CKD (Table 2, p <0.01 for all).
However, the associations with TNF-aRl and fibrinogen were significantly
stronger among participants with CKD.” Keller 3. Keller concludes that:
While the strong association between kidney function and TNF-
aRl levels may be simply attributable to renal clearance of TNF-
aRl, TNF-a itself may also play a more complex role in the
mediation of kidney damage. A future study should evaluate
whether TNF-a and its soluble receptors predict the longitudinal
progression of kidney disease.
Keller 5 (emphasis added). Keller thus teaches the likelihood that soluble
TNF1 may play an important role in kidney disease and suggests its use as a
predictive marker of kidney disease, providing explicit motivation for a
person of ordinary skill in the art to pursue this course.
Moreover, Knight teaches:
Reduced kidney function may result from and cause a state of
chronic inflammation, and inflammation may lead to coronary
artery disease. In terms of the relation between kidney function
and inflammatory biomarkers, our results are consistent with
previous reports that CRP, IL-6, and sTNFR levels are higher in
individuals with reduced kidney function. These levels may be
higher because of increased production in individuals with
kidney disease.
Knight 1901 (emphasis added, internal references omitted). Knight thus
teaches that it was known in the art that elevated levels of sTNFR are
indicative of reduced kidney function.
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Finally, Tonelli is directed to the association between pravastatin use,
levels of C-reactive protein (CRP), soluble tumor necrosis factor receptor II
(sTNFrll), and the rate of kidney function loss. Tonelli, Abstr. Tonelli
teaches:
Tumor necrosis factor-a (TNF-a) is a central proinflammatory
agonist mediator that is generated in a wide variety of innate and
adaptive immune responses, including some forms of chronic
kidney disease. TNF-a binds to cell surface receptors on target
cells and induces expression of adhesion molecules, chemokines
for leukocytes, and apoptosis in susceptible cells. Soluble TNF
receptors are elevated in the setting of inflammation and chronic
kidney disease. TNF-a also appears to have multiple roles that
could mediate progressive renal injury, and both soluble TNF
receptor II (sTNFrll) and CRP may be used as markers of
inflammation.
Tonelli 237—38 (emphases added). Tonelli thus explicitly teaches that
sTNFs are indicators of chronic kidney disease.
We agree with the Examiner that the combined cited prior art
references teach that elevated levels sTNFRs were known in the art to be
associated with chronic kidney disease and that, in view of the prior art, it
would have been obvious to a person of ordinary skill to use an assay for
sTNFRs as an indicator of CKD.
Appellants also argue that the Examiner failed to provide prima facie
findings and conclusions as to why a person of ordinary skill in the art
would have combined the teachings of the prior art without the benefit of
the teachings of the present invention or why a person of ordinary skill
would have reasonably expected to succeed in combining the teachings of
the cited prior art to arrive at Appellants’ claimed invention. See App. Br.
14. However, Appellants have presented no arguments, nor adduced any
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evidence, to support these arguments or to show that the Examiner must
have relied upon impermissible hindsight reasoning. As such, these
arguments amount to little more than attorney argument and we
consequently accord them little weight. See In re De Blauwe, 736 F.2d 699,
705 (Fed. Cir. 1984) (Arguments and conclusions unsupported by factual
evidence carry no evidentiary weight). We therefore affirm the Examiner’s
rejection of claims 17—20 on this ground.
DECISION
The Examiner’s rejection of claims 17—20 under 35 U.S.C. § 101 is
affirmed.
The Examiner’s rejection of claims 17—20 under 35 U.S.C. § 103(a)
is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(l)(iv).
AFFIRMED
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