Ex Parte Khvorova et al

Patent Trial and Appeal Board

Jul 30, 2018

10940892 (P.T.A.B. Jul. 30, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
10/940,892 09/14/2004
105841 7590 07/31/2018
Dorf & Nelson LLP
The International Coporate Center
555 Theodore Fremd A venue
Rye, NY 10580
FIRST NAMED INVENTOR
Anastasia Khvorova
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.
DHARMA 2100-US 7436
EXAMINER
BRUSCA, JOHNS
ART UNIT PAPER NUMBER
1631
MAIL DATE DELIVERY MODE
07/31/2018 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 STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANASTASIA KHVOROV A, ANGELA REYNOLDS,
DEVIN LEAKE, WILLIAM MARSHALL,
STEVEN READ, and STEPHEN SCARINGE
Appeal2017-006246
Application 10/940,892
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
JACQUELINE T. HARLOW, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134 involving claims to a
method for obtaining a siRNA sequence for a target gene, wherein said
siRNA sequence comprises 19-30 nucleotide bases. The Examiner rejected
the claims under 35 U.S.C § 101 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 Thermo Fisher Scientific
Inc. (see App. Br. 1 ).
2 We note that there was a prior decision affirming the Examiner, Appeal
2012-010359.
Appeal2017-006246
Application 10/940,892
Statement of the Case
Background
"[R]esearchers observed that double stranded RNA ('dsRNA') could
be used to inhibit protein expression. This ability to silence a gene has broad
potential for treating human diseases, and many researchers and commercial
entities are currently investing considerable resources in developing
therapies based on this technology" (Spec. 1 :21-25). "More recently it has
been shown that when short (18-30 bp) RNA duplexes are introduced into
mammalian cells in culture, sequence-specific inhibition of target mRNA
can be realized without inducing an interferon response" (id. at 2:6-8).
"Successful siRNA-dependent gene silencing depends on a number of
factors. One of the most contentious issues in RN Ai is the question of the
necessity of siRNA design, i.e., considering the sequence of the siRNA
used" (id. at 3: 15-17). "Unfortunately, none of the reported methods have
provided a satisfactory scheme for reliably selecting siRNA with acceptable
levels of functionality" (id. at 3:33 to 4:1). "Accordingly, there is a need to
develop rational criteria by which to select siRNA with an acceptable level
of functionality, and to identify siRNA that have this improved level of
functionality, as well as to identify siRNAs that are hyper functional" (id. at
4: 1--4).
The Claims
Claims 67-69, 73-78, 90 and 91 3 are on appeal. Independent claim
90 is representative and reads as follows:
3 We note that while claims 67----69, 73-79, 81-85, and 89-91 were
rejected in the Final Rejection (See Final Act.5/5/2016 at 2), only
claims 67----69, 73-78, and 90-91 were appealed (see App. Br. 6).
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90. A method for selecting and generating a hyperfunctional
siRNA for a target gene, said method comprising the steps:
(a) selecting a target gene;
(b) generating a set of candidate siRNA sequences that
are between 19 and 3 0 bases in length, and that comprises a
plurality of candidate siRNA sequences, wherein each
candidate siRNA sequence comprises a sense region of 19-30
bases, wherein said sense region comprises a sense sequence of
19 bases that is at least 79% similar to a region of the target
gene;
( c) determining a functionality score for each candidate
siRNA sequence within the set of candidate siRNA sequences,
wherein said functionality score is determined by applying
selection criteria, wherein the selection criteria comprise at least
four non-target specific criteria and wherein the functionality
score for an siRNA corresponds to its relative predicted
functionality;
( d) selecting fewer than all candidate siRNA sequences
in said set of candidate siRNA sequences to form a set of
selected siRNA sequences, wherein said selecting is based on
said functionality scores of each candidate siRNA sequence;
( e) for each siRNA sequence within the set of selected
siRNA sequences, introducing an siRNA molecule that
corresponds to the selected siRN A sequence into a test eel 1 of a
test cell line;
(f) assessing the ability of each siRNA molecule in vitro
to degrade the target mRNA, wherein an siRNA molecule that
induces 80% silencing or greater at subnanomolar
concentrations for greater than 120 hours is a hyperfunctional
siRNA; and
(g) generating the hyperfunctional siRNA in vitro or in
vivo.
The Issue
The Examiner rejected claims 67----69, 73-78, 90 and 91 under 35
U.S.C. § 101 as being directed to non-statutory subject matter (Final Act. 2-
4).
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The Examiner finds that the claims are directed to "an abstract idea"
and a "law of nature describing the relationship between siRNA sequence
data and gene silencing" (Final Act. 3). The Examiner also finds that the
claims "are directed to an algorithm for generating data of an siRNA
sequence that will function to silence expression of a target gene, which is
similar to the abstract idea of organizing information through mathematical
correlations at issue in Digitech Image Techs., LLC v. Electronics for
Imaging, Inc. 758 F.3d 1344 (Fed. Cir. 2014)" (Ans. 2) (italics added).
The Examiner also finds the claims "have additional elements that
constitute conventional steps appended to the judicial exception" (Final Act.
3). The Examiner supports this position by relying on Elbashir, 4 who
teaches
a conventional process of designing siRNA molecules with a
likelihood of inhibiting gene expression at pages 200-202. In
vitro assay of siRNA degradation of mRNA is shown on page
200 and pages 203-209. The commercial availability of prior
art custom synthesis of siRNA molecules that target a desired
mRNA are shown on pages 202-203. The additional elements
do not comprise an inventive concept when considered
individually or as an ordered combination that transforms the
claimed judicial exception into a patent-eligible application of
the judicial exception.
(Final Act. 4).
The Examiner reached these conclusions by applying the test set out
in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S.
4 Elbashir et al., Analysis of gene function in somatic mammalian cells
using small interfering RNAs, 26 Methods 199-213 (2002).
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66 (2012) (Final Act. 2---6) based on the two-step Alice framework. Alice
Corp. Pty. Ltd. v. CLS Bank Int'!, 134 S. Ct. 2347, 2355 (2014).
Analysis
To determine whether a claim is invalid under§ 101, we employ the
two-step Alice framework. In Alice step one, we ask whether the claims are
directed to a patent ineligible concept, such as an abstract idea or law of
nature. Alice, 134 S.Ct. at 2355; Mayo, 566 U.S. at 75-77; Ariosa
Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1375 (Fed. Cir. 2015).
While method claims are generally eligible subject matter, method claims
that are directed only to abstract ideas and/or natural phenomena are directed
to a patent ineligible concept. Ariosa, 788 F.3d at 1376. In Alice step two,
we examine the elements of the claims to determine whether they contain an
inventive concept sufficient to transform the claimed naturally occurring
phenomena into a patent-eligible application. Mayo, 566 U.S. at 71-72
( quoting Alice, 134 S.Ct. at 2355).
Alice Step One
Claims 67 and 90 of the instant application are directed to methods for
obtaining a siRNA sequence for a target gene, wherein said siRNA sequence
comprises 19-30 nucleotide bases. That process is directed to both a law of
nature and an abstract idea. In particular, the law of nature/natural
phenomenon is the correlation between siRNA sequences and gene
silencing. Appellants' claims purport to apply natural laws describing the
relationship between siRNA sequence data and gene silencing to predict the
likelihood that a particular siRNA sequence will result in gene silencing. Cf
Mayo, 566 U.S. at 77 ("[L]aws of nature-namely, relationships between
concentrations of certain metabolites in the blood and the likelihood that a
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dosage of a thiopurine drug will prove ineffective or cause harm"). That the
relationship is obtained by accessing a generic computer and causing the
computer to apply a computer program does not change the fact that the
relationship between siRNA sequence data and gene silencing "exists in
principle apart from any human action" Mayo, 566 U.S. at 77.
In addition, the recited steps of "accessing a computer and causing
said computer to apply a computer program product being embodied in a
computer readable storage medium", "determining a predicted relative
functionality of at least two siRNA sequences within said set of candidate
siRNA sequences ... algorithm", and "generating an output comprising said
siRNA sequence for gene silencing that is selected ... siRNA sequence for
gene silencing" all involve categorizing and/or analyzing information. The
Federal Circuit has explained that "[i]nformation as such is an intangible"
and "that collecting information, including when limited to particular
content (which does not change its character as information)," analyzing it,
and presenting the results of the collection and analysis are patent ineligible
abstract concepts. See, e.g, Electric Power Group, LLC v. Alstom S.A., 830
F.3d 1350, 1353-54 (Fed. Cir. 2016).
This case is similar to Digitech Image Technologies, LLC v.
Electronics for Imaging, Inc., 758 F.3d 1344 (Fed. Cir. 2014).
There, the claims of the challenged patent were directed to the
abstract idea of organizing information through mathematical
correlations. Id. at 13 50-51. . . . A process that started with
data, added an algorithm, and ended with a new form of data
was directed to an abstract idea. Id.
RecogniCorp LLC v. Nintendo Co., Ltd, 855 F.3d 1322, 1327 (Fed. Cir.
2017). Additionally, in Digitech, the Federal Circuit stated that "[w]ithout
additional limitations, a process that employs mathematical algorithms to
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manipulate existing information to generate additional information is not
patent eligible. 'If a claim is directed essentially to a method of calculating,
using a mathematical formula, even if the solution is for a specific purpose,
the claimed method is nonstatutory'" Digitech Image Technologies, LLC v.
Electronics for Imaging, Inc., 758 F.3d 1344, 1351 (Fed. Cir. 2014). Here,
the process employs mathematical algorithms to manipulate existing
information to generate additional information, here an siRNA sequence,
and therefore is not patent eligible.
Additionally, the steps of selecting a target gene and generating a set
of candidate siRNA sequences can be performed mentally and therefore are
abstract ideas. As the Federal Circuit explained, "methods which can be
performed mentally, or which are the equivalent of human mental work, are
unpatentable abstract ideas--the 'basic tools of scientific and technological
work' that are open to all"' CyberSource Corp. v. Retail Decisions, Inc., 654
F.3d 1361, 1372, (Fed. Cir. 2011) (citing Gottschalkv. Benson, 409 U.S. 63
(1972)).
Because the claims are directed to an abstract idea/natural law, we
tum to the second step of the Alice framework.
Alice Step Two
In Alice step two, we examine the elements of the claims to determine
whether they contain an inventive concept sufficient to transform the
claimed naturally occurring phenomena into a patent-eligible application.
Mayo, 566 U.S. at 71-72 (quoting Alice, 134 S.Ct. at 2355). We must
consider the elements of the claims both individually and as an ordered
combination to determine whether the additional elements transform the
nature of the claims into a patent-eligible concept. Ariosa, 788 F.3d at 1375.
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The Specification acknowledges that it was known that inserting
"short (18-30 bp) RNA duplexes" into mammalian cells causes "sequence-
specific inhibition of target mRNA" (Spec. 2:6-8).
The Examiner finds, and Appellants do not dispute, that Elbashir
shows "a conventional process of designing siRNA molecules with a
likelihood of inhibiting gene expression", and that "custom synthesis of
siRNA molecules that target a desired mRNA" was "commercially
available" (Ans. 4; cf Elbashir 202 "selection of siRNA sequences" and
"siRNAs are obtained from commercial RNA oligonucleotide synthesis
suppliers"). Moreover, Elbashir performs an in vitro assay of siRNA
degradation of mRNA (Ans. 4; cf Elbashir 207 "Detection of siRNA-
mediated specific gene silencing"). Elbashir also gives criteria for selecting
the target gene and generating a set of siRNA sequences (Elbashir 199, Fig.
2, 201-202). Additionally, Elbashir teaches that siRNA sequences should be
less than 30 bp and teaches synthesizing sense siRNA sequences that are 21-
24 bp long (e.g. AA(N19)UU or 5'-(N19)TT) using the target sequence (id.).
Therefore, Elbashir teaches that the sense region comprises a sense sequence
of 19 bases that is at least 79% similar to a region of the target gene, because
one selects sense sequences from the target gene that meets the criteria ( e.g.
AA(N19)UU or 5'-(N19)TT) of Elbashir.
Therefore, the instant facts are similar to those confronted in Electric
Power, where the court held that "[n]othing in the claims, understood in
light of the specification, requires anything other than off-the-shelf,
conventional computer, network, and display technology for gathering,
sending, and presenting the desired information" Electric Power Group,
LLC v. Alstom S.A., 830 F.3d 1350, 1355 (Fed. Cir. 2016). Here, the step of
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generating an output requires nothing other than "off-the-shelf, conventional
computer, network, and display technology for gathering, sending, and
presenting the desired information".
The Examiner finds that "additional elements do not comprise an
inventive concept when considered individually or as an ordered
combination that transforms the claimed judicial exception into a patent-
eligible application of the judicial exception" (Ans. 3). Appellants provide
no evidence rebutting this position (see App. Br. 10-11).
In sum, the evidence of record supports the Examiner's position that
the claims do not add something "significantly more" to the abstract idea
and/or law of nature. Instead, each of the steps in the "claims (e.g., selecting
the target gene, generating a set of siRNA sequences, and generating an
output) are conventional, routine, and well-known. The generating step
involves the normal, basic functions of a computer" Versata Development
Group, Inc. v. SAP America, Inc., 793 F.3d 1306, 1335 (Fed. Cir. 2015). "In
order for the addition of a machine to impose a meaningful limit on the
scope of a claim, it must play a significant part in permitting the claimed
method to be performed, rather than function solely as an obvious
mechanism for permitting a solution to be achieved more quickly, i.e.,
through the utilization of a computer for performing calculations" SiRF
Tech., Inc. v. Int 'l Trade Comm 'n, 601 F.3d 1319, 1333 (Fed. Cir. 2010).
We conclude that the method claims does not result in an inventive
concept that transforms the abstract idea/natural phenomena described above
into a patentable invention. Mayo and Ariosa make clear that transforming
claims that are directed to a law of nature requires more than simply stating
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the law of nature while adding the words "apply it." Mayo, 566 U.S. at 72;
Ariosa, 788 F.3d at 1377.
Appellants argue that in the prior decision, the "PT AB emphasized the
following elements as being absent from appealed claim 85: (1) the claim
provided no particular coefficient for the algorithm; and (2) the claim
provided no specific metric by which to identify improved gene silencing"
(App. Br. 8). Appellants contend that the "PT AB implied that the presence
of either of these features could provide the basis for a determination of
patentable subject matter" and that these issues are addressed in the current
claims (id.).
We are not persuaded. We stated:
Claim 85 does not recite a specific algorithm, and preempts any
algorithm for designing siRNA sequences. The claim limitation
recited by Appellants regarding the four asserted "variables"
can simply represents the presence or absence of the four
alternative bases possible in siRNA, adenine, guanine, cytosine,
and uracil (FF 5). The claim requires no particular coefficient
for the algorithm, nor does the claim impose any specific metric
to identify improved gene silencing. Ariosa notes that "patent
claims should not prevent the use of the basic building blocks
of technology-abstract ideas, naturally occurring phenomena,
and natural laws." Ariosa at 7. Instant claim 85, by failing to
recite any specific elements of the claimed algorithm,
specifically attempts to fully preempt any process for designing
siRNA.
(Ex parte Khvorova, 2015 WL 4267897 at *5 (PTAB 2015)). While
preemption is the concern underlying the judicial exceptions, it is not a
stand-alone test for determining eligibility. Rapid Litig. Mgmt. v.
CellzDirect, Inc., 827 F.3d 1042, 1052, (Fed. Cir. 2016). Simply reducing
concerns regarding preemption does not render the claims patent eligible.
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We find Appellants' reliance on McRO, Inc. v. Bandai Namco Games
America Inc., 837 F.3d 1299 (Fed. Cir. 2016) unavailing (see App. Br. 8-9).
Appellants contend that the claims in McRO were "'limited to rules with
specific characteristics', and they required one to apply those rules to sub-
sequences" (id. at 9). Appellants further contend that "claim 67 recites
specific rules in step ( c) and applies those rules to determine a predicted
relative functionality in step ( d)" (id. at 9).
The claims in McRO were drawn to improvements in the operation of
a computer itself at a task, rather than applying a computer to perform
known tasks. See McRO, 837 F.3d at 1314. Here, Appellants have not
demonstrated such an improvement in the operation of the computer itself,
but at best suggest an improvement in the application of an algorithm for
siRNA design. Therefore, McRO does not persuades us that Appellants'
claims relying on correlations using known computer components and
known prior art mathematical algorithms as discussed above are patentable
subject matter.
Appellants contend that:
In Mayo, the Court emphasized that the critical focus should be
on whether the process contains an inventive concept sufficient
to ensure that the patent in practice amounts to significantly
more than a patent upon life itself. In Mayo, the purported
invention was the recognition of the precise correlation between
metabolic levels of 6-TG and 6-MMP with the likelihood that a
particular dosage of a thiopurine drug would cause harm or be
ineffective. Significantly, scientists already knew that the
levels of certain metabolites were correlated with effectiveness
and deleterious effects; the only things that they did not know
were the precise correlations. By contrast, with respect to the
applicant's claim 67, there is no suggestion that at the time of
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the applicant's invention, there was recognition of either: (1)
the fact that the examination of a plurality non-target specific
criteria that are each determined based on the presence or
absence of a base at a position would be helpful in predicting
functionality; or (2) that different criteria could be weighted
differently. Therefore, the presently claimed invention is not
directed to a law of nature under Mayo.
(App. Br. 9-lO)(intemal citations omitted).
We find this argument unpersuasive. Mayo explicitly states "the steps
in the claimed processes (apart from the natural laws themselves) involve
well-understood, routine, conventional activity previously engaged in by
researchers in the field", thereby indicating that the law of nature does not
have to be known in order for it to be a law of nature. Mayo Collaborative
Services v. Prometheus Labs, Inc., 132 S.C.C. 1289, 1294 (2012). The issue
is not whether the abstract idea or law of nature itself is in the prior art, but
rather whether the claim as a whole is drawn to a patent eligible application
of the abstract idea or law of nature. Here, for the reasons already given, we
conclude that the claimed method is not.
Appellants content that
[ w ]ith respect to the issue of whether claim 67 is directed to a
law of nature, Rapid Litigation Management Ltd. v. Cellz
Direct, Inc., 827 F.3d 1042 (Fed. Cir. 2016) is instructive. In
that case, the CAFC contrasted the claimed invention, which
was directed to a method of preserving hepatocytes, with a
hypothetical method that merely detected or observed the
ability of hepatocytes to survive multiple freeze-thaw cycles.
The CAFC emphasized that the inventors had achieved a better
way of preserving the hepatocytes. Id. Similarly, in the present
case, the applicant achieved a better way of discriminating
among candidate siRNA and did not claim a method that
merely observes that different siRNA may be differentiated
based on functionality.
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(App. Br. 10).
We are also not persuaded by these arguments. The claims in Rapid
Litigation Management were directed to a method with specific laboratory
steps for processing and cryopreserving hepatocytes (Rapid Litigation
Management, 827 F.3d at 1046) and did not contain steps that were laws of
nature or abstract ideas. Here, the inquiry is different as the claims contain
abstract ideas (such as using a generic computer to computing an algorithm,
determining, and selecting) as well as a law of nature (the relationship
between siRNA sequence data and gene silencing) (see Claims 67, 90).
Appellants contend that "contained within the methods of claims 90
and 91 is a two-step screening process, first by a bioinformatics technique
( steps (a) ---( c) of claim 90), and then by empirical testing under a specific
metric ( steps ( e )---(g) of claim 90)" and that we stated that "the presence of a
specific metric [is] suggestive of patentable subject matter" (App. Br. 10).
We are also not persuaded by these arguments, because, as explained
above, our prior decision stated that by failing to recite any specific elements
of the claimed algorithm, the claim specifically attempts to fully preempt any
process for designing siRNA. We did not state that the presence of a specific
metric is suggestive of patentable subject matter. While preemption is the
concern underlying the judicial exceptions, it is not a stand alone test for
determining eligibility. Rapid Litig. Mgmt, 827 F.3d at 1052. Simply
eliminating concerns regarding preemption does not render the claims patent
eligible.
We are also not persuaded by these arguments, because steps (a), (c),
( d), and ( e) can be performed mentally and are therefore abstract ideas. As
the Federal Circuit explained, "methods which can be performed mentally,
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or which are the equivalent of human mental work, are unpatentable abstract
ideas--the 'basic tools of scientific and technological work' that are open to
all" CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1361, 1372, (Fed.
Cir. 2011) (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673
(1972)). Moreover, Elbashir shows that steps (b), (f), and (g) are routine and
conventional (see Elbashir 199-203, 207) as discussed above.
Finally, Appellants contend that steps ( e }-(g) are post-solution steps
that are not insignificant, because the steps are "critical for moving from the
set of candidate siRN A that are predicted to be functional to a subset that is
hyperfunctional", "are concrete steps that apply a specific standard in order
to determine which candidate siRNAs are able to effect a desired level of
functionality" and "improve on ... the earlier steps" (App. Br. 10-11).
However, as explained above, Elbashir demonstrates, and Appellants do not
rebut with evidence, that these steps are routine and conventional. Thus, we
are not persuaded by Appellants' arguments.
We therefore conclude that all of the claims on appeal are directed to
patent-ineligible subject matter.
SUMMARY
In summary, we affirm the rejection of claims 67----69, 73-78, 90, and
91 under 35 U.S.C. § 101, as being directed to non-statutory subject matter.
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
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