Ex Parte SCHWARTZ et al

Patent Trial and Appeal Board

Jul 31, 2018

14482950 (P.T.A.B. Jul. 31, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/482,950 09/10/2014
108197 7590 08/02/2018
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
Austin, TX 78746
UNITED ST A TES OF AMERICA
FIRST NAMED INVENTOR
Jacob C. SCHWARTZ
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.
UTSD.P2046US.C2 9206
EXAMINER
ZARA,JANEJ
ART UNIT PAPER NUMBER
1674
NOTIFICATION DATE DELIVERY MODE
08/02/2018 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):
docket@phiplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JACOB C. SCHWARTZ, SCOTT T. YOUNGER,
BETHANY A. JANOWSKI, and DAVID R. COREY
Appeal2017-004975
Application 14/482,950 1
Technology Center 1600
Before ERIC B. GRIMES, KRISTI L. R. SA WERT and DAVID COTTA,
Administrative Patent Judges.
COTT A, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of selectively modulating expression of a target gene in the genome of a
human cell determined to be in need thereof. The Examiner rejected the
claims on appeal under 35 U.S.C. § 101 as not directed to patent eligible
subject matter and as obvious under 35 U.S.C. § 103(a).
We affirm.
1 According to Appellants, the real parties in interest are the Board of
Regents, University of Texas System and MiNA Therapeutics. Br. 3.
Appeal2017-004975
Application 14/482,950
STATEMENT OF THE CASE
The Specification discloses that "[ r ]ecent studies have reported that
duplex RN As complementary to promoter regions can repress or activate
gene expression." Spec. ,r 4 (footnotes omitted). "Other recent work ... has
revealed networks of non-coding transcripts surrounding regions of the
genome that code for mRNA." Id. According to the Specification, the
inventors have "identif[ied] a network of antisense transcripts at the
promoter for progesterone receptor (PR)" and shown that "pdRNAs
[promotor directed RN As] bind antisense transcripts and that activation of
gene expression by pdRNAs requires expression of antisense transcript." Id.
The Specification asserts that "pdRNAs are recognizing previously
undiscovered transcripts that overlap gene promoters, and that we can use
targeted pdRNAs, including antigene RNA [agRNA] and gapmers, to
modulate expression of targeted genes." Id. f 5.
Claims 21--40 are on appeal. Claim 21 is illustrative and reads as
follows:
21. A method [ of] selectively modulating expression of a target
gene in the genome of a human cell determined to be in need
thereof, comprising:
determining the presence of an encoded antisense
transcript overlapping a promoter of the target gene;
contacting the antisense transcript with an exogenous
gapmer or double-stranded agRNA; and
detecting a resultant modulation of expression of the
target gene,
the gapmer comprising a DNA insert complementary to a
sequence in the antisense transcript upstream relative to the
transcription start site of the gene, and the agRNA being 18-28
bases and complementary to a portion of the antisense transcript
2
Appeal2017-004975
Application 14/482,950
upstream to a portion of the antisense transcript upstream
relative to the transcription start site of the gene.
Br. 12.
The claims stand rejected as follows:
Claims 21, 22, and 24--40 stand rejected under 35 U.S.C. § 101 as
directed to patent ineligible subject matter. 2
Claims 21--40 stand rejected under 35 U.S.C. § 103(a) as obvious over
the combination ofWahlestedt, 3 RIKEN, 4 Li, 5 Janowski, 6 and Han. 7
SUBJECT MATTER ELIGIBILITY
In rejecting the pending claims as directed to patent ineligible subject
matter, the Examiner found that the claims were directed to the "abstract
idea of determining the presence of an encoded antisense transcript
2 In the Examiner's Answer, the Examiner withdrew the rejection of claim
23 under 35 U.S.C. § 101. Ans. 1. Accordingly, the rejection of this claim
as directed to patent ineligible subject matter is no longer a part of this
appeal.
3 Wahlestedt, Natural Antisense and Noncoding RNA Transcripts as
Potential Drug Targets, 11(11/12) DRUG DISCOVERY TODAY 503-508
(2 006) ("W ahlestedt").
4 RIKEN, Genome Exploration Research Group and Genome Science
Laboratory, Antisense Transcription in the Mammalian Transcriptome, 309
Science 1564--1567 (2005) ("RIKEN").
5 Li et al., Small dsRNAs Induce Transcriptional Activation in Human Cells,
103(46) PNAS 17337-17342 (2006) ("Li").
6 Janowski et al., Activating Gene Expression in Mammalian Cells with
Promoter-Targeted Duplex RNAs, 3(3) Nature Chemical Biology 166-173
(2007) ("Janowski").
7 Han et al., Promoter-Associated RNA is Required for RNA-Directed
Transcriptional Gene Silencing in Human Cells, 104(30) PNAS 12422-
12427 (2007) ("Han").
3
Appeal2017-004975
Application 14/482,950
overlapping a promoter of a target gene." Ans. 3. The Examiner then
concluded that the additional elements recited in the claims do not add
"significantly more" than this abstract idea because they describe
"conventional techniques that do not add meaningful limits to practicing the
abstract idea." Id.
Appellants argue, inter alia, "the claims do not recite a method of
screening ... [ r ]ather, they contain three active steps that result in the non-
natural manipulation of gene expression using a non-natural molecule." Br.
5. Appellants further argue "[t]he claims are very specific in how to
accomplish the modulation, even if they do not restate the precise molecular
mechanism through [which] the gapmers or agRNAs work." Id.
Determination of subject matter eligibility involves a two-step test.
First, one must determine if the claimed subject matter is directed to a
judicially recognized exception such as a product of nature. Mayo
Collaborative Services, v. Prometheus Labs., Inc., 566 U.S. 66, 78 (2012).
If the claims are not directed to a patent ineligible concept at step one, we
need not address step two of the inquiry. Enfish, LLC v. Microsoft Corp.,
833 F.3d 1327, 1339 (Fed. Cir. 2016). If the claims address a judicially
recognized exception, the next step is to determine if the claims recite
additional elements that transform the nature of the claim. Mayo, 566 U.S.
at 78.
Here, we find that the Examiner erred in finding that the claims were
directed to "the abstract idea of determining the presence of an encoded
antisense transcript overlapping a promoter of a target gene." Ans. 10.
While the claims do require "determining the presence ... " as a step in the
recited method, they are not limited to this step. Considering the claims as a
4
Appeal2017-004975
Application 14/482,950
whole, they are directed not to a method of "determining the presence ... "
but to a method of "selectively modulating expression of a target gene."
See, Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042, 1050 (Fed.
Cir. 2016) ("[I]t is not enough to merely identify a patent-ineligible concept
underlying the claim; we must determine whether that patent-ineligible
concept is what the claim is 'directed to."'); Vanda Pharmaceuticals Inc. v.
West-Ward Pharmaceuticals International Ltd., 887 F.3d 1117, 1134 (Fed.
Cir. 2018) ( accord). Because we disagree with the Examiner's finding that
the claims were directed to the abstract idea of determining the presence of
an encoded antisense transcript overlapping a promoter of a target gene, and
because the Examiner has not identified another applicable judicially
recognized exception, we reverse the Examiner's rejection of claims 21--40
as directed to patent ineligible subject matter.
OBVIOUSNESS
Appellants argue claims 21--40 together. We designate claim 21 as
representative.
The Examiner finds that W ahlestedt teaches "natural antisense and
noncoding RNA transcripts as potential drug targets for siRNA [ small
interfering RNA] silencing." Ans. 6. The Examiner also finds that
Wahlestedt teaches "the knockdown of antisense RNA transcripts by siRNA
or other gene silencing techniques, which knockdown[,] elevates or
decreases expression of the sense gene, depending on the antisense target
gene sequence." Id.
The Examiner finds that RIKEN discloses that "perturbation of
antisense RNA can alter expression of sense messenger RNAs." Id. RIKEN
also discloses "the presence of antisense transcripts, including non-coding
5
Appeal2017-004975
Application 14/482,950
antisense which overlap sense promoter sequences ... and which provide
concordant regulation of sense/antisense pairs." Id. at 6-7.
The Examiner finds that Li teaches "the quantitation of activation of
target gene expression by targeting non-coding regions of gene promoters
with dsRNAs between 18-28 nucleobases in length, which target promoter
sequences are located 200-300 bases 5' to the transcriptional start site of
target genes." Id. at 7.
The Examiner finds that Janowski teaches that "both an increase and a
decrease of progesterone expression comprising administration of dsRNA
which target slightly different regions of the progesterone promoter." Id.
The Examiner finds that Han teaches "modulation of target gene
transcription comprising the administration of siRNA molecules which
target sequences located approximately 200-250 bases 5' to the transcription
start region, and overlap the promoter region of target genes, and which
siRNA bind to antisense sequences and provide a link between RNA,
chromatin and gene expression." Id. at 7-8. Han also teaches the "overlap
of target gene sequence on the promoter using 5 '-RACE/3 '-RACE. Id.
Based on these disclosures, the Examiner concludes:
It would have been obvious to design, test and assess dsRNA or
gapmers, which target promoter sequences, for their ability to
modulate the expression of a target gene, because such
screening assays involving the targeting of promoter sequences
by modulatory oligonucleotides including dsRNA and gapmers
has been done routinely in the prior art, as disclosed by
Wahlestedt, RIKEN, Janowski, Han, and Li. One would have
been motivated to analyze the target gene sequences within the
promoter to which the dsRNA or gapmer molecules bound, in
order to determine the optimal target sites for promoter
regulation, and in order to design and optimize dsRNA
6
Appeal2017-004975
Application 14/482,950
modulators for a given promoter of a given target gene. One
would have been motivated to screen for antisense target
sequences existing upstream from the transcriptional start sites
of genes of interest, and overlapping the promoter because
W ahlestedt and RIKEN taught the existence and antisense
orientation of such natural antisense sequences, and Wahlestedt
provided the motivation to screen for modulation of these
antisense target sequences using inhibitory oligonucleotides,
and identified these antisense target sequences as potential drug
targets.
Id. at 8.
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 4--9, 12-18; Final Act. 8 6-17) and
agree that the claims would have been obvious over Wahlestedt, RIKEN,
Janowski, Han, and Li. We address Appellants' arguments below.
Appellants argue that Wahlestedt and RIKEN "merely disclose that
natural antisense transcripts (NATs) exist." Br. 7. Appellants assert that
"[n]either Wahlestedt nor Riken teaches any NAT that overlaps the
promoter region of a gene" and that the specific exemplars shown to
increase expression of sense RNA, Ddx-39 and rTS-a, do not overlap the
promoter of their target genes. Id. We are not persuaded.
The disclosures of Wahlestedt and RIKEN are not limited to the
existence ofNATs. Wahlested and RIKEN both disclose that antisense
RNA can be used to alter the expression of sense genes. See Wahlestedt
Abstract ("a number of antisense transcripts regulate the expression of their
sense partners, either in a discordant ( antisense knockdown results in sense-
transcript elevation) or concordant (antisense knockdown results in
8 Office Action mailed April 28, 2016 ("Final Act.").
7
Appeal2017-004975
Application 141482,950
concomitant sense-transcript reduction) manner"); id. at 507 ("by using
siRNA, antisense transcript knockdown can result in increases ( discordant
regulation) or decreases ( concordant regulation) of sense transcript
expression. . .. These findings and concepts could form the basis for novel
pharmacological strategies."); RIKEN Abstract ("perturbation of an
antisense RNA can alter the expression of sense messenger RN As").
Further, contrary to Appellants' argument, RIKEN expressly discloses that
NA Ts may overlap with promoter region of a gene. See, e.g., RIKEN 1565
(caption for Table 3) ("Convergent SIAS pairs overlap tail to tail (3'-3'), and
divergent SIAS pairs overlap on the promoter (5'-5' overlap)."); id. at 1564
("For example, the insulin-like growth factor 1 receptor (IGFlR) shows a
very strong antisense CAGE tag overlapping the promoter of the sense
transcript, which provides a parallel to the AIR noncoding RNA (ncRNA) in
the IGF2R loci.").
Appellants argue that "[n]either Li nor Janowski teach anything about
targeting antisense transcripts as the mechanism for action of [progesterone
receptor] gene, so it remains unclear why they are in any way relevant to the
antisense teachings of Wahlestedt or Riken." Br. 7. Similarly, Appellants
contend that Han teaches a "mechanism of gene silencing" and is thus
"solving a different problem than that addressed by the other references."
Id. at 8. We are not persuaded because the combination of Wahlestedt and
RIKEN alone renders claim 21 obvious. In re Bush, 296 F .2d 491, 496
( CCP A 1961) (holding that the Board may rely on fewer than all of the
references relied upon by Examiner). Wahlestedt and RIKEN disclose that
one can increase or decrease the expression of a gene through the
knockdown of antisense transcript RNA. Wahlestedt Abstract, 507; RIKEN
8
Appeal2017-004975
Application 14/482,950
Abstract. The motivation to screen antisense target sequences to identify
candidates for modulation of expression of a target gene, as claimed, is also
found in the combination of Wahlestedt and RIKEN. As the Examiner
explains:
One would have been motivated to screen for antisense target
sequences existing upstream from the transcriptional start sites
of genes of interest, and overlapping the promoter because
W ahlestedt and RIKEN taught the existence and antisense
orientation of such natural antisense sequences, and W ahlestedt
provided the motivation to screen for modulation of these
antisense target sequences using inhibitory oligonucleotides,
and identified these antisense target sequences as potential drug
targets.
Ans. 8. Accordingly, the combination ofWahlestedt and RIKEN alone
renders claim 21 obvious.
Moreover, we do not agree with Appellants that the teachings of Li,
Janowski and Han are irrelevant to "the antisense teaching of Wahlestedt or
Riken." Li and Janowski, like Wahlestedt, disclose the use of dsRNA to
modulate gene expression. Li Abstract; Janowski Abstract. Han teaches "a
role for siRNAs, and specifically antisense-stranded RNAs, in writing the
histone code and the regulation of gene expression." Han 12426 (reference
citation omitted). Accordingly, all three references are within the same field
of endeavor and reasonably pertinent to the problem faced by the inventors. 9
In this regard, we note that the claims encompass modulation of gene
9 We find that the relevant filed of endeavor is the modulation of gene
expression using dsRNA and that the problem faced by the inventors was
identifying RNA targets for modulation of gene expression. See Spec. ,r,r 3-
5; Declaration of Rachel Meyers signed February 24, 2016 ("Meyers Deel.")
,r 5.
9
Appeal2017-004975
Application 14/482,950
expression, which includes both increases and decreases in the expression of
target genes and, more specifically, "gene silencing."
Appellants cite the Meyers Declaration as "objective evidence on the
issue of what the cited art discloses, and how it would be interpreted by the
person of ordinary skill in the art." Br. 9. We have considered the Meyers
Declaration, but do not find it persuasive. We note that the Meyers
Declaration provides principally opinions regarding the disclosures of the
prior art and the non-obviousness of claimed invention. See In re Am. Acad.
of Sci. Tech Ctr., 367 F.3d 1359, 1368 (Fed. Cir. 2004) ("[T]he Board is
entitled to weigh the declarations and conclude that the lack of factual
corroborations warrants discounting the opinions expressed in the
declarations."). Accordingly, we affirm the Examiner's rejection of claim
21 as obvious over the combination of Wahlestedt, RIKEN, Li, Janowski,
and Han. Because they were not argued separately, claims 22--40 fall with
claim 21.
SUMMARY
In summary, for the reasons set forth herein, and those set forth in the
Examiner's Final Office Action and Answer, we affirm the Examiner's
decision to reject claims 21--40 stand rejected under 35 U.S.C. § 103(a) as
obvious over the combination ofWahlestedt, RIKEN, Li, Janowski, and
Han.
For the reasons set forth herein, we reverse the Examiner's decision to
reject claims 21, 22, and 24--40 stand rejected under 35 U.S.C. § 101 as
directed to patent ineligible subject matter.
10
Appeal2017-004975
Application 14/482,950
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R. §
1.136(a)(l )(iv).
AFFIRMED
11