Ex Parte Agan et al

Patent Trial and Appeal Board

Nov 30, 2016

12713554 (P.T.A.B. Nov. 30, 2016)

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.
100353-USl 4955
EXAMINER
KIM, YOUNG J
ART UNIT PAPER NUMBER
1637
MAIL DATE DELIVERY MODE
12/713,554 02/26/2010
26384 7590 12/01/2016
NAVAL RESEARCH LABORATORY
ASSOCIATE COUNSEL (PATENTS)
CODE 1008.2
4555 OVERLOOK AVENUE, S.W.
WASHINGTON, DC 20375-5320
Brian K. Agan
12/01/2016 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 STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BRAIN K. AGAN, ERIC H. HANSON, MICHAEL J. JENKINS,
BAOCHUAN LIN, CHRIS C. OLSEN, ROBB K. ROWLEY,
DAVID A. STENGER, DZUNG C. THACH, CLARK J. TIBBETTS,
ELIZABETH A. WALTER, and JINNY LIN LIU
Appeal 2015-001596
Application 12/713J5541
Technology Center 1600
Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to methods for identifying gene
expression markers for distinguishing between healthy, febrile, or
convalescence subjects exposed to a pathogen. The Examiner rejected the
claims under 35U.S.C. § 101, under 35U.S.C. § 112, first paragraph, and
under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 134. The
Examiner’s decision is affirmed.
1 “The ’554 Application.” The real party in interest listed in the Appeal Brief
is “the Government of the United States of America.” Appeal Br. 2.
Appeal 2015-001596
Application 12/713,554
STATEMENT OF THE CASE
Claims 1—9 stand rejected by the Examiner as follows:
1. Claim 2 under 35 U.S.C. § 101 as directed to non-statutory subject
matter. Ans. 3.
2. Claim 2 under 35 U.S.C. § 112, first paragraph (pre-AIA), as failing
to comply with the written description requirement. Ans. 6.
3. Claims 1—4 under 35 U.S.C. § 103(a) (pre-AIA) as obvious in view
ofEremeeva {Ann. N.Y. Acad. Sci. 2003, vol. 990, pages 468-473) and
Lockhart (WO 97/10365, published March 20, 1997). Ans. 12.
4. Claims 5 and 6 under 35 U.S.C. § 103(a) (pre-AIA) as obvious in
view of Eremeeva, Lockhart, Scherf (US 2005/0170375 Al, published
August 4, 2005; filed Sept. 24, 2004), and GLOBINclear™ Kit manual
(“GLOBINclear”). Ans. 16.
5. Claim 7 under 35 U.S.C. § 103(a) (pre-AIA) as obvious in view of
Eremeeva, Lockhart, Scherf, GLOBINclear, and Conner (U.S. Patent No.
6,506,565 Bl, patented January 14, 2003). Ans. 20.
6. Claim 8 under 35 U.S.C. § 103(a) (pre-AIA) as obvious in view of
Eremeeva, Lockhart, Scherf, GLOBINclear, and Christians (US
2005/0003369 Al, published January 6, 2005, filed October
10,2003). Ans. 21.
7. Claim 9 under 35 U.S.C. § 103(a) (pre-AIA) as obvious in view of
Eremeeva, Lockhart, and Ideker {Journal of Computational Biology 2000,
vol. 7, no. 6, pages 805-817). Ans. 23.
2
Appeal 2015-001596
Application 12/713,554
Claim 1, the only independent claim on appeal, reads as follows:
1. A method for identifying gene expression markers for
distinguishing between healthy, febrile, or convalescence in
reference to one or more infectious pathogens comprising:
acquiring a gene expression profile for a subject that has
been exposed to one or more infectious pathogens and having a
fever of 100.4-F or above;
acquiring a gene expression profile for a subject that has
recovered from exposure to the one or more infectious
pathogens;
acquiring a gene expression profile for a healthy subject
that has not been exposed to the one or more infectious
pathogens;
comparing the gene expression profiles for the exposed
subject, the recovered subject and the healthy subject by a
pairwise comparison;
determining the identity of the nested to minimal set(s) of
genes that classify the subject’s phenotypes as healthy, febrile,
or convalescent by class prediction algorithm based on the
pairwise comparison; and
assigning the classification of healthy, febrile, or
convalescence based on gene expression profile of the minimal
set of genes;
wherein the gene expression profile are acquired by:
collecting biological sample from the subject;
isolating RNA from the sample;
removing DNA contaminants from the sample;
spiking into the sample a normalization control;
synthesizing cDNA from the RNA contained in the
sample;
in vitro transcribing cRNA from the cDNA and labeling
the cRNA;
hybridizing the cRNA to a gene chip followed by
washing, staining, and scanning; and
acquiring the gene expression profile from the gene chip
and analyzing the gene expression profile represented by
the RNA in the sample.
3
Appeal 2015-001596
Application 12/713,554
1. § 101 REJECTION
Claim 2, depends from claim 1, and further requires “classifying the
patient as healthy, febrile, or convalescence” based on the patient’s gene
expression profile. Citing Mayo Collaborative Services v. Prometheus
Laboratories, Inc., 132 S.Ct. 1289 (2012), the Examiner rejected the claim
under 35U.S.C. § 101 as directed to non-statutory subject matter. Office
Action 3.
Since Mayo, a two-step for patent eligibility under Section 101 has
emerged. As set forth in Alice Corp. Pty. Ltd. v. CLS BankInt'l, 134 S.Ct.
2347, 2355 (2014):
First, we determine whether the claims at issue are directed to
one of those patent-ineligible concepts [e.g., a law of nature,
natural phenomenon, or abstract idea]. If so, we then ask, what
else is there in the claims before us? . . . We have described step
two of this analysis as a 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. (alterations, citations, and quotation marks omitted).
With respect to the first step, in Mayo, the Supreme Court considered
method claims that required analysis of a metabolite in the blood of a patient
being treated with a thiopurine drug to determine the likelihood that the
patient could suffer toxic side effects from particular doses of the drug.
Mayo, 132 S.Ct. at 1296—9. The Court concluded that “the claims were
necessarily directed to an underlying law of nature or natural phenomenon,
even if implementation of the method involves substantial human labor and
ingenuity.” Genetic Technologies Ltd. v. MerialL.L.C., 818 F.3d 1369,
1375 (Fed. Cir. 2016). The Court stated:
4
Appeal 2015-001596
Application 12/713,554
While it takes a human action (the administration of a
thiopurine drug) to trigger a manifestation of this relation in a
particular person, the relation itself exists in principle apart
from any human action. The 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.
Mayo, 132 S.Ct. at 1297.
In this case, it is undisputed that a gene expression profile is a “natural
phenomenon” because it is a snapshot of the naturally-occurring genes
expressed by an organism at a given time. The inventors have not done
anything to the profile other than detect it in a biological sample obtained
from the subject. The subsequent “classifying” step is a correlation step
between the gene expression profile and the disease status of the subject.
We conclude that the classifying step is a manifestation of the naturally
occurring gene expression observed in a subject who happens to be healthy,
febrile, or convalescent with respect to an infectious pathogen. While the
discovered gene expression profile might be new, the claim simply
characterizes a “discovered fact about. . . biology” and therefore is a natural
law. Genetic Technologies, 818 F.3d at 1376. As a consequence, we
conclude claim 2 is directed to unpatentable subject matter in accordance
with the first step of the Mayo/Alice test.
The second part of the test asks whether the claims contains an
“inventive concept” sufficient to transform the claimed law of nature into
patent-eligible subject matter. Id.
“The question ... is whether the claims do significantly more
than simply describe [a] natural relation[ ].”, 132 S.Ct. at 1297.
The inventive concept necessary at step two Mayo of the
Mayo/Alice analysis cannot be furnished by the unpatentable
law of nature (or natural phenomenon or abstract idea) itself.
5
Appeal 2015-001596
Application 12/713,554
That is, under the Mayo/Alice framework, a claim directed to a
newly discovered law of nature (or natural phenomenon or
abstract idea) cannot rely on the novelty of that discovery for
the inventive concept necessary for patent eligibility; instead,
the application must provide something inventive, beyond mere
“well-understood, routine, conventional activity.” Mayo, 132
S.Ct. at 1294; see also Myriad, 133 S.Ct. at 2117; Ariosa, 788
F.3d at 1379. “[SJimply 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 patentable.” Mayo, 132 S.Ct. at 1300.
Claims directed to laws of nature are ineligible for patent
protection when, “(apart from the natural laws themselves)
[they] involve well-understood, routine, conventional activity
previously engaged in by researchers in the field.” Mayo, 132
S.Ct. at 1294.
Id.
In this case, we have not been directed to evidence that the steps of
claim 2 in determining the gene expression profile adds anything more to the
routine technology conventionally used to characterize gene expression in an
organism. Appellants contend that the claim is “more limiting than simply
‘applying the law.’” Appeal Br. 3. However, Appellants only pointed to
conventional gene detection steps. Id. As held in Mayo, the claim as a
whole sets forth “laws of nature” because the relationship between the gene
expression levels and the disease state “itself exists in principle apart from
any human action. The relation is a consequence of the ways in which
thiopurine compounds are metabolized by the body—entirely natural
processes.” Mayo at 1297. Accordingly, we conclude that the additional
elements of claim 2 are insufficient to provide the inventive concept
necessary to render the claim patent-eligible.
6
Appeal 2015-001596
Application 12/713,554
2. WRITTEN DESCRIPTION REJECTION
The Examiner found that the inventors were not in possession of a
representative number of gene expression profiles to justify a genus claim
Office Action 7—8 (hereinafter, “Office Act.”, mailed Nov. 1, 2013). The
Examiner found that the inventors described gene expression analysis of
subjects infected with adenovirus, but not “for a reasonable number of
species of pathogens so as to justify the genus embraced by the instant
claims.” Id. at 9. The Examiner stated that “the sets of genes which
Applicants were in possession of were based on a single type of pathogen,
Ad4.” Id. at 10. The Examiner concluded that the ’554 Application lacks a
written description of the genus of pathogens encompassed by the claims,
and rejected the claims under 35 U.S.C § 112. Id. at 11—12.
35 U.S.C. § 112 requires a patentee to provide a written description of
the claimed subject matter that allows a person of skill in the art to recognize
that the patentee invented what is claimed. Ariad Pharms., Inc. v. Eli Lilly
& Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (enbanc).
In this case, Appellants have described a generic invention using gene
expression technology to characterize the gene expression profile of subjects
exposed to a pathogen and classify the subjects as healthy, febrile, or
convalescent based on the profiles. It is not disputed that disease pathogens
are known in the art. The inventor have not asserted to have invented a
pathogen or gene expression profile, but instead assert to have invented a
method of detecting changes in genes expression characteristic of a pathogen
or infection. ’554 Application 10: 12—16.
“[Wjhat is needed to support generic claims to biological subject
matter depends on a variety of factors, such as the existing knowledge in the
7
Appeal 2015-001596
Application 12/713,554
particular field, the extent and content of the prior art, the maturity of the
science or technology, [and] the predictability of the aspect at issue.” Capon
v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005). “[I]t is not necessary that
every permutation within a generally operable invention be effective in order
for an inventor to obtain a generic claim, provided that the effect is
sufficiently demonstrated to characterize a generic invention. See In re
Angstadt, 537 F.2d 498, 504 (CCPA 1976).” Capon, 418 F.3d at 1359. The
inventors are not asserting to have invented a specific expression profile or
pathogen. It is evident from the ’554 Application, and reflected in the claim,
that the invention is a method to determine and classify disease status upon
exposure to a pathogen. Thus, to meet the written description requirement, it
is not necessary for the inventors to have described additional gene
expression profiles associated with different pathogens. The illustrative
gene expression profiles based on adenovirus infection demonstrate how the
claimed method is performed and establish that the inventors had possession
of a generic invention.
The rejection is reversed.
3-7. OBVIOUSNESS REJECTIONS
The Examiner found that Eremeeva describes a method of identifying
gene expression markers for distinguishing between healthy, febrile, or
convalescent pine voles in reference to one or more infectious pathogens.
Office Act. 14. The Examiner identified where each step in the claimed
method could be found in Eremeeva. Id. The Examiner stated that
Eremeeva does not teach that the identified gene expression markers are
used to classify subjects as required by the claims. Id. However, the
8
Appeal 2015-001596
Application 12/713,554
Examiner found that Lockhart described such a step. Id. at 15—16. The
Examiner determined it would have been obvious to apply Lockhart’s
techniques to Eremeeva for the advantages described by Lockhart. Id. at 16.
Appellants contend that neither Eremeeva nor Lockhart describe the
recited step of “determining the identity of the nested to minimal set(s) of
genes that classify the subjects’ phenotypes as healthy, febrile, or
convalescent.” Appeal Br. 5. Appellants contend that the Examiner did not
provide a rationale to have arrived at this limitation. Id. at 6.
We do not agree. The Examiner found that, while the skilled worker
would begin by assaying for a plurality of genes expressed during the
various disease and non-disease states, the skilled worker would have been
motivated to identify a minimal set of genes in order to arrive at a gene
signature which is indicative of a particular phenotype. Office Act. 19.
Thus, the Examiner provided a clear reason as to why a minimal set of genes
would be selected by one of ordinary skill in the art at the time of the
invention.
The Examiner further explained:
A typical gene expression study involves sampling a
patient/subject population with a particular phenotype (e.g.,
disease) and identifying a set of genes which are similarly
expressed in the population. Once such genes are identified, a
test subject's sample is analyzed for the same set of genes to see
if there is a similar expression pattern between the two for
diagnosis.
Therefore, based on the teachings of Eremeeva et al. who
demonstrated the difference in gene expression levels from
subjects undergoing various stages of infections (e.g., healthy,
infection, and convalescent), one of ordinary skill in the art
would have been motivated to arrive at a set of genes which are
9
Appeal 2015-001596
Application 12/713,554
able to classify a subject's health status and then classify a test
subject's health status by comparison.
Ans. 32.
The Examiner’s logic is that there would be motivation to identify the
recited set of minimal genes to classify a subject’s health status because such
set would enable the skilled worker to distinguish between the various stages
of infection. Id. Appellants did not persuasively identify an error in the
Examiner’s reasoning. Rather, Appellants argue that Eremeeva does not
identify a minimal gene set, but instead looks at the same enzyme genes.
Reply Br. 2. However, this statement ignores the fact that rejection is based
on the obviousness of applying Lockhart’s method of conducting gene
expression assays for distinguishing between healthy patients and patients
with disease as the motivation to pick minimal sets of differentially
expressed genes. Office Act. 18—20.
In addition to this, Appellants have not provided a definition of
“minimal set of genes” as recited in claim 1 which would distinguish the set
of enzyme genes utilized in the Eremeeva publication to characterize the
infectious state of the pine voles.
For the foregoing reasons, the obviousness rejection of claim 1 is
affirmed. Appellants did not argue the dependent claims separately, or
Rejections 3—7. Consequently, the rejections of claims 2—9 are affirmed for
the reasons set forth by the Examiner. See 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
1. The § 101 of claim 2 is affirmed.
2. The § 112, first paragraph rejection of claim 2 is reversed.
3. Obviousness rejections 3—7 of claims 1—9 are affirmed.
10
Appeal 2015-001596
Application 12/713,554
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l)(iv).
AFFIRMED
11