Ex Parte Nagy

Patent Trial and Appeal Board

Jul 30, 2018

14233113 (P.T.A.B. Jul. 30, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/233,113 04/28/2014
110 7590 07/30/2018
DANN, DORFMAN, HERRELL & SKILLMAN
1601 MARKET STREET
SUITE 2400
PHILADELPHIA, PA 19103-2307
Zsuzsanna Nagy
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.
1194-P05918USOO 2905
EXAMINER
HANEY, AMANDA MARIE
ART UNIT PAPER NUMBER
1634
MAIL DATE DELIVERY MODE
07/30/2018 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED ST ATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ZSUZSANNA NAGY
Appeal2017-008793
Application 14/233,113 1
Technology Center 1600
Before DONALD E. ADAMS, ULRIKE W. JENKS, and
CHRISTOPHER G. P AULRAJ, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
Opinion Dissenting by Administrative Patent Judge Paulraj.
DECISION ON APPEAL
This Appeal under 35 U.S.C. § 134(a) involves claims 2, 4, 16-18, 20, 27,
29, and 31 (Final Act. 2 1). Examiner entered a rejection under 35 U.S.C.
§ 101. We have jurisdiction under35 U.S.C. §6(b).
We AFFIRM.
1 Appellant identifies "University of Birmingham, Edgbaston, Birmingham,
United Kingdom" as the real party in interest (Br. 1 ).
2 Office Action mailed May 25, 2016.
Appeal 2017-008793
Application 14/233, 113
STATEMENT OF THE CASE
Appellant's disclosure
relates to diagnosis and monitoring of Alzheimer's disease in
the live subject. Particularly, although not exclusively, the
invention relates to methods involving the measurement of
differential gene expression in non-neuronal cells taken from
human subjects suspected ofhaving Alzheimer's disease. The
invention also relates to a method by which to monitor mTOR
[ signaling] in a human cell.
(Spec. 1: 5-9.) Claims 2 and 27 are representative and reproduced below:
2. A method of assessing the risk of Alzheimer's disease
progression in a human subject suspected ofhaving
Alzheimer's disease, which method comprises
(i) obtaining lymphocytes from said human subject
suspected of having Alzheimer's disease and from an age-
matched healthy subject with normal cognitive ability;
(ii) inducing cell division in the lymphocytes taken from
the human subject suspected ofhaving Alzheimer's disease;
(iii) separating the dividing lymphocytes of (ii) into two
pools and treating one pool of lymphocytes with rapamycin;
(iv) assaying the level of protein of at least one
interleukin selected from interleukin 1 beta (ILIB), interleukin
2 (IL-2), interleukin 6 (IL-6), or interleukin 10 (IL-I 0) in the
pool of lymphocytes treated with rapamycin and in the
untreated pool;
( v) comparing the level of protein of the at 1 east one
interleukin obtained in (iv) for the pool of rapamycin-treated
lymphocytes and the untreated lymphocyte pool to quantify the
change in protein levels in response to rapamycin;
(vi) repeating steps (ii) - (v) using controllymphocytes
taken from the age-matched healthy subject with normal
cognitive ability; and
(vii) determining that said human subject suspected of
having Alzheimer's disease is at increased risk of Alzheimer's
disease progression when (a) the reduction of IL 1 B or IL 10
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Application 14/233, 113
protein levels in response to rapamycin is higher in control
lymphocytes as compared to lymphocytes taken from the
human subject suspected ofhaving Alzheimer's disease; or (b)
the reduction of IL-2 or IL-6 protein levels in response to
rapamycin is lower in control lymphocytes as compared to
lymphocytes taken from the human subject suspected of having
Alzheimer's disease; or (c)the reduction ofILIB or ILIO
protein levels in response to rapamycin is higher in control
lymphocytes as compared to lymphocytes taken from the
human subject suspected ofhaving Alzheimer's disease and the
reduction of IL-2 or IL-6 protein levels in response to
rapamycin is lower in control lymphocytes as compared to
lymphocytes taken from the human subject suspected of having
Alzheimer's disease.
(Br. 10.)
27. A method by which to monitor m TOR signaling in a
human lymphocyte, which method comprises:
(i) isolating lymphocytes from a human subject;
(ii) inducing cell division in said lymphocytes;
(iii) separating the dividing lymphocytes of (ii) into two
pools and treating one pool of lymphocytes with rapamycin;
(iv) assaying the level of protein of at least one
interleukin selected from interleukin I beta (ILIB), interleukin 2
(IL-2), interleukin 6 (IL-6), or interleukin 10 (IL-I 0) in the pool
of lymphocytes treated with rapamycin and in the untreated
pool;
( v) comparing the level of protein of the at least one
interleukin obtained in (iv) for the pool of rapamycin-treated
lymphocytes and the untreated lymphocyte pool to detect a
reduction in protein levels in response to rapamycin;
( vi) determining that m TOR signaling is decreased if
there is a decrease in the protein level of at least one interleukin
1 beta (ILIB), interleukin 2 (IL-2), interleukin 6 (IL-6), or
interleukin 10 (IL- I 0).
(Id. at 11-12.)
3
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Application 14/233, 113
The claims stand rejected as follows:
Claims 2, 4, 16-18, 20, 27, 29, and 31 stand rejected under 35 U.S.C.
§ 101.
ISSUE
Does the evidence of record support Examiner's finding that
Appellants' claimed invention is directed to patent ineligible subject matter?
ANALYSIS
Examiner fmds that Appellant's claimed invention is directed to
patent ineligible subject matter (see Final Act. 3-8). We agree.
The Supreme Court articulated a two-step test for patent eligibility
under§ 101 that "distinguish[ es] patents that claim laws of nature, natural
phenomena, and abstract ideas from those that claim patent-eligible
applications of those concepts." Alice Corp. Pty. Ltd. v. CLSBankint'l, 134
S. Ct. 2347, 2355 (2014) (citing Mayo Collaborative Services v. Prometheus
Laboratories, Inc., 132 S. Ct. at 1296-97). "First," Alice instructs a court to
"determine whether the claims at issue are directed to one of those patent-
ineligible concepts. Id. ( citation and quotations omitted). If the claims are
directed to a patent-ineligible concept then the court must proceed to the
second step of the test - the "search for an inventive concept-i. e., an
element or combination of elements that is sufficient to ensure that the
patent in practice amounts to significantly more than a patent upon the
ineligible concept itself." Id. ( quotations and alterations omitted).
The methods set forth in Appellant's independent claims 2 and 2 7
correlate changes in lymphocyte IL 1 B, IL-2, IL-6 or IL- IO protein levels
resulting from rapamycin exposure to either (a) an increased risk of
Alzheimer's disease progression in a human subject suspected ofhaving
4
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Application 14/233, 113
Alzheimer's disease ( claim 2) or (b) decrease in m TOR signaling ( claim 2 7)
(see Br. 10 and 11-12; id. at 7 ("claim [27] is focused on the process of
determining whethermTORsignaling is decreased in a lymphocyte sample
afterrapamycin treatment"); see also Final Act. 3 and 4). As Appellant
explains, "it is ultimately the differential response to rapamycin observed in
certain human subjects that is informative for the purposes of the presently-
claimed methods, and not the rapamycin response or changes in interleukin
gene expression per se" (Br. 6). Thus, here as in Mayo, the claims are not
directed to a method of treating a disease. To the contrary, Appellant's
claims are similar to those in Mayo, which "were directed to a diagnostic
method based on the 'relationships between concentrations of certain
metabolites in the blood and the likelihood that a dosage of a thiopurine drug
will prove ineffective or cause harm."' VandaPharms., Inc. v. West-Ward
Pharms. Int'lLtd., 887 F.3d 1117, 1134 (Fed. Cir. 2018), quotingMayo, 132
S. Ct. at 1289. "This 'relation is a consequence of the ways in which
thiopurine compounds are metabolized by the body----entirely natural
processes. And so a patent that simply describes that relation sets forth a
natural law."' Id., quoting Mayo, 132 S. Ct. at 1289. Thus, here, as in
Mayo, the relationship between certain interleukin protein levels and either
the risk of Alzheimer's disease progression or the decrease in mTOR
signaling, are entirely natural processes and Appellant's claims do no more
than simply describe that relationship, thereby, setting forth a natural law.
See Final Act. 3-8; Mayo, 132 S. Ct. 1289.
5
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Therefore, with respect to the frrst step of the Alice test, we agree with
Examiner's fmding that Appellant's claim a natural law (see Final Act. 3). 3
For the foregoing reasons, we are not persuaded by Appellant's contentions
to the contrary (see Br. 3-7).
Turning to the second step of the Alice test, the search for an
"inventive concept," we agree with Examiner's fmding that Appellant's
"claims do not include additional elements that are sufficient to amount to
significantly more than the judicial exception" (Final Act. 2). In this regard,
Examiner fmds the additional steps set forth in Appellant's claims "of
3 We also agree with Examiner's fmding that neither Appellant's
Specification nor claims defme the terms "comparing" and "determining," as
set forth in Appellant's claims (Final Act. 3; see also id. at 4; see, e.g., Br.
10 and 11-12). We, therefore, fmdno error in Examiner's interpretation of
the comparing and determining steps of Appellant's claimed invention as
encompassing the mental step of thinking about expression levels and risk,
respectively (id. at 3--4; see also id. at 5 ("The recited steps may[] be
performed mentally or verbally or in writing and do not require the
transformation of a specific article" and "thereby encompass abstract
processes")). Cf In re BRCAJ- and BRCA2-Based Hereditary Cancer Test
Patent Litigation, 774 F.3d 755, 763 (Fed. Cir. 2014) (citation omitted)
('" comparing' and 'analyzing' two gene sequences" is "an abstract mental
process"). In this regard, Examiner fmds that "[ m ]ental activities, data
analysis, and mathematical analysis are all considered to be abstract ideas"
(Final Act. 4). See Fair Warning Ip, LLCv. Iatric Systems, Inc., 839 F.3d
1089, 1093 (Fed. Cir. 2016) ("analyzing information by steps people go
through in their minds, or by mathematical algorithms, without more," are
"essentially mental processes within the abstract-idea category"); Synopsys,
Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1146 (Fed. Cir. 2016)
("Methods which can be performed entirely in the human mind are
unpatentable ... because [they] embody the 'basic tools of scientific and
technological work' that are free to all men and reserved exclusively to
none").
6
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Application 14/233, 113
'obtaining' a lymphocyte sample, 'inducing' cell division, 'separating' the
dividing lymphocytes into two pools, 'treating' one of the pools of
lymphocytes with rapamycin, and 'assaying' the level of protein expression
in the treated pool and the untreated pool," "when considered alone or in
combination are conventional, well understood, and routinely practiced in
the art for just about any protein one cares to detect" ... and "do NOT add
anything significant to the judicial exceptions" (Final Act. 6; see id.
("Nagy[ 4l ... teaches obtaining a sample of lymphocytes from a[n] AD
subject and from age matched healthy controls, treating the samples with
rapamycin, and measuring protein expression (see [Nagy ,rin ... 0011, 0018,
0019, 0025, and 0029)")). We agree.
Nagy qualifies as prior art on this record. Therefore, we are not
persuaded by Appellant's intimation that Nagy, which is Appellant's own
work, is not available as prior art on this record (see Br. 8). We are also not
persuaded by Appellant's contention that because Nagy fails to teach
determining increased risk of Alzheimer's disease progression or a method
of m TOR signal monitoring, Examiner cannot rely upon Nagy to establish
that elements of Appellant's claimed invention are conventional, well
understood, and routine in this art (see id.; cf Final Act. 6 ( citing Nagy
,r,r 0011, 0018, 0019, 0025, and0029)). In addition, in response to
Appellant's contentions regarding Nagy, Examiner provided additional
evidence to support Examiner's fmding of what was well known,
conventional and routine in this art at the time of Appellant's claimed
invention (see Ans. 9; cf Br. 8 ("it cannot reasonably be maintained that a
single prior art document, regardless of its date of publication, establishes, as
4 Nagy, US 2004/0132113,publishedJuly 8, 2004.
7
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Application 14/233, 113
a matter of fact, that the methodology described therein is conventional, well
understood and routinely practiced in the art")). See Berkheimer v. HP Inc.,
881 F.3d 1360, 1369(Fed. Cir. 2018)("[w]hethersomethingis well-
understood, routine, and conventional to a skilled artisan at the time of the
patent is a factual determination"). Appellant does not contest Examiner's
supplemental evidence and findings. Arguments not made are waived.
For the foregoing reasons, we are not persuaded by Appellant's
contention that Appellant's "claims [] include additional elements that are
neither routine nor conventional but rather amount to significantly more than
the alleged judicial exception" (Br. 7). Therefore, we agree with Examiner's
fmding that "appending conventional steps, specified at a high level of
generality, to laws of nature, natural phenomena, and abstract ideas cannot
make those laws, phenomena, and ideas patent-eligible" (Final Act. 6; see
also Ans. 6 and 9).
In sum, when Appellant's claims are considered as a whole, we fmd
no error in Examiner's fmding that Appellant's claimed invention is directed
to patent ineligible subject matter (see, e.g., Final Act. 8).
CONCLUSION
The evidence of record supports Examiner's fmding that Appellant's
claimed invention is directed to patent ineligible subject matter. The
rejection of claims 2 and27 under35 U.S.C. § 101 is affrrmed. Claims 4,
16-18, 20, 29, and 31 are not separately argued and fall with claims 2 and 27
respectively.
8
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Application 14/233, 113
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. § 1.136(a).
AFFIRMED
9
UNITED ST ATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ZSUZSANNA NAGY
Appeal2017-008793
Application 14/233, 113
Technology Center 1600
Before DONALD E. ADAMS, ULRIKE W. JENKS, and
CHRISTOPHER G. P AULRAJ, Administrative Patent Judges.
P AULRAJ, Administrative Patent Judge, dissenting.
I respectfully dissent. I agree with the majority that, under Alice "step
one," the claims on appeal are directed to a judicial exception (law of nature)
insofar as they recite steps of "comparing" levels of certain interleukin
proteins in different pools of lymphocytes and "determining," based on the
comparative protein levels, whether there is either an increased risk of
Alzheimer's disease progression (claim 2) or decreasedmTORsignaling
(claim 27). However, I disagree with the majority's conclusion that the
Examiner has shown, under Alice "step two," that all the additional steps set
forth in Appellant's claims were well-understood, routine, and conventional.
In particular, step (iii) of the claims includes the requirement of
treating one pool of lymphocytes with the drug rapamycin. The Examiner
acknowledges that this step does not recite or describe any recognized
judicial exception (Ans. 6-7), and thus it must be shown to "involve well-
understood, routine, conventional activity previously engaged in by
Appeal 2017-008793
Application 14/233, 113
researchers in the field." Mayo Collaborative Servs. v. Prometheus Labs.,
Inc., 566 U.S. 66, 73 (2012). In Mayo, the Supreme Court noted that the
claim step of "administering a [ thiopurine] drug" to a patient did not
transform the nature of the claims because it "simply refers to the relevant
audience, namely doctors who treat patients with certain diseases with
thiopurine drugs," where "doctors used thiopurine drugs to treat patients
suffering from autoimmune disorders long before anyone asserted these
claims." J d. at 7 8. The Examiner has not made a similar showing with
respect to treating lymphocytes with rapamycin.
The Examiner relies upon prior art references Nagy ( the only
reference identified in the Final Rejection) and Zhou 1 (identified for the frrst
time in the Examiner's Answer) to assert that treatment oflymphocytes with
rapamycin was previously known in the art. Fin. Rej. 6; Ans. 9. Nagy is a
publication of Applicant's own prior work, and describes the use of
rapamycin as a cell division inhibitor in a diagnostic screen for Alzheimer's
disease. See, e.g., Nagy ,r,r 94--96. Zhou likewise describes the use of
rapamycin as a "Gi/S transition blocker" to treat lymphocytes derived from
Alzheimer's disease patients. See Zhou, 321-22. But, other than in the
context of the specific experiments and studies described therein, neither
reference suggests that treatment oflymphocytes with rapamycin was a
well-recognized technique used for the diagnosis of Alzheimer's disease or
any other purpose. "Whether a particular technology is well-understood,
routine, and conventional goes beyond what was simply known in the prior
1 Zhou et al., P53-mediated G 1/S checkpoint dysfunction in lymphocytes
from Alzheimer's disease patients, Neuroscience Letters 468 (2010) 320-
325.
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Application 14/233, 113
art. The mere fact that something is disclosed in a piece of prior art, for
example, does not mean it was well-understood, routine, and conventional."
Berkheimerv. HP Inc., 881 F.3d 1360, 1369 (Fed. Cir. 2018). Accordingly,
in my view, the Examiner's citations to Nagy and Zhou are insufficient to
establish either that "the prior art demonstrated numerous references where
scientists were treating lymphocytes with rapamycin and studying its effects
on gene expression in the context of cancer, lupus, Alzheimer's disease,
etc.," or that "the use of rapamycin in gene expression studies was widely
prevalent." Ans. 9 ( emphasis added).
I, therefore, conclude that the Examiner has not made a prima facie
case of patent ineligibility.
3