Ex Parte Woolf et al

Patent Trial and Appeal Board

May 10, 2017

13800845 (P.T.A.B. May. 10, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
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www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/800,845 03/13/2013 Tod Woolf IVGN 481.9 CON 6618
52059 7590 05/12/2017
LIFE TECHNOLOGIES CORPORATION
Attn: IP Department
5823 Newton Drive
Carlsbad, CA 92008
EXAMINER
MCGARRY, SEAN
ART UNIT PAPER NUMBER
1674
NOTIFICATION DATE DELIVERY MODE
05/12/2017 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):
LSGDocketing@thermofisher.com
pair_thermofisher @ firsttofile. com
LifetechDocket @ system.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TOD WOOLF and MARGARET TAYLOR1
Appeal 2016-003199
Application 13/800,845
Technology Center 1600
Before DEMETRA J. MILLS, TAWEN CHANG, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a composition
of double-stranded oligonucleotides. The Examiner entered final rejections
for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE.
1 Appellants identify the Real Party in Interest as Life Technologies Corp.
App. Br. 1.
Appeal 2016-003199
Application 13/800,845
STATEMENT OF THE CASE
Background
“Antisense and double-stranded RNA oligonucleotides are promising
therapeutic agents and useful research tools for elucidating gene function.
However, it is often difficult to achieve efficient inhibition of protein
synthesis using such compositions.” Spec 1:23—25. The Specification
discloses “double-stranded oligonucleotide compositions that provide
improved inhibition of gene expression.” Id. at 1:32.
The Claims
Claims 43—62 are on appeal.2 App. Br. 16 (Claims App’x.). Claim 43
is illustrative and reads as follows, with the relevant portion italicized:
43. A composition comprising a combination of
double-stranded RNA oligonucleotides, the combination
consisting of three or four different double-stranded RNA
oligonucleotides,
wherein each double-stranded RNA oligonucleotide is
targeted to a different sequence within a single target gene,
each double-stranded RNA oligonucleotide consists of
two separate strands,
each strand is between 20 and 30 nucleomonomers in
length, and
wherein the combination is capable of RNA interference
(RNAi), and wherein at least one of the oligonucleotides
comprises at least one modified intemucleoside linkage.
App. Br. 16 (Claims App’x.).
2 Claims 1—42 are cancelled. App. Br. 16 (Claims App’x.).
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Application 13/800,845
The claims stand rejected as follows:
Claims 43—62 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Tuschl,3 Farese,4 and Branch.5
DISCUSSION
The Examiner has rejected all of the claims on appeal as obvious
based on Tuschl, Farese, and Branch. The Examiner finds that Tuschl
disclose[s] RNA interference compounds and method of their
use [and that] the siRNA compounds of the invention are
desirous over prior art compounds [antisense] due to their
improved efficacy and safety.... the synthesizing of two strands
each having a length from 19—25 nucleotides wherein the RNA
strands are capable of forming a double stranded structure,
wherein preferably at least one strand has a 3 ’ overhang from 1—
5 nucleotides and combining the RNA strands so as to form a
double stranded [ds] molecule, wherein the ds molecule is
capable of mediating target specific nucleic acid modifications
[and] to utilize sugar modifications including 2’-O-methyl
modifications which were known in the art to benefit nucleic acid
based inhibitors in target affinity and nuclease stability. Tuschl
et al asserts that siRNA containing modified nucleotides are
preferred embodiments.
Ans. 3.
The Examiner finds that although Tuschl teaches “the use of at least
one siRNA . . . Tuschl et al do not specifically teach making several
different dsRNA compounds in a composition where 3 or 4 different siRNA
compounds targeted to the same nucleic acid are combined.” Id. The
3 US 2004/0259247 Al; pub. Dec. 23, 2004
4 US 2004/0078836 Al; pub. April 22, 2004
5 Andrea D. Branch, A good antisense molecule is hard to find, TIBS, Vol.
23:45—50, © 1998 Elsevier Science Ltd..
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Application 13/800,845
Examiner finds “the prior art has shown that it was known in the art of
nucleic acid based inhibitors to use several molecules to ensure the
inhibition and specificity of/to a desired target nucleic acid” and turns to
Farese and Branch for their disclosure of combinations of multiple antisense
sequences targeted toward different regions of the targeted site. Id. at 3^4.
The Examiner concludes that:
The invention appears to be an application of known
techniques of antisense to the nascent art of siRNA. One in the
art would surely have looked to the antisense art in the use of
siRNA since it was known at the time of invention that
techniques of gene function analysis and types of modification
could be performed and utilized in siRNA compounds . . . One
in the art would have known to utilize more than one siRNA, for
example, if the one siRNA was not inhibiting to ones desired
inhibition level. . . .
Furthermore it is prima facie obvious to combine known
equivalents. The prior art has shown motivation and evidence of
providing multiple antisense compounds to inhibit a gene[’]s
expression. Tuschl et al have taught that siRNA can be used in
place of antisense and ribozymes, for example. In this case the
equivalents ensure the inhibition of a desired target where it is
clear from the prior art that one siRNA or antisense may not
provide 100% inhibition. Where one in the art would want more
inhibition it would be obvious to use more inhibitors. Clearly
one in the art would have known that different siRNA molecules
targeting the same gene are equivalents that could be combined
and further obvious to optimize the combinations that are most
effective in the inhibition of a target gene.
Id. at 4—5.
Appellants argue that, “Tuschl is the only applied reference
teaching RNAi and double-stranded RNA” but “does not teach or
suggest a composition comprising 3 or 4 different double-stranded
RNAs targeting different regions of the same target, as presently
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Application 13/800,845
claimed.” App. Br. 3. Appellants argue that secondary references
Farese and Branch are “inapplicable because they are directed to a
different field of invention.” Id. at 4. According to Appellants, a
skilled artisan would not look to the field of antisense for guidance in
RNAi because “antisense and RNAi work by very different
mechanisms.” Id. at 5.
In support of their position, Appellants present the Declaration
of Dr. Klimkait (“Klimkait Deck)6 Dr. Klimkait explains that, inter
alia, “it is known that for [inhibition employing] antisense strategies,
stoichiometric amounts of single-stranded nucleic acid
complementary to the messenger RNA for the gene of interest need to
be introduced into the cell. . . antisense is a concentration-dependent
method, often requiring the delivery of large absolute quantities.”
Klimkait Decl. 19. In contrast, Dr. Klimkait states, because inhibition
using RNAi “elicit[s] effective degradation in a catalytic way . . .
‘only a few molecules of dsRNA per cell are sufficient to mount an
RNAi response.’” Id. at^flf 12, 13 (citation omitted).
The Examiner responds:
antisense, ribozymes and siRNA ALL function by different
mechanisms, yet all utilize the same chemical modifications
[since ALL need such modifications to increase nuclease
stability, for example]. It is noted again that ALL of the chemical
modifications and formulations disclosed in Tuschl et al were
known from the antisense and ribozyme art.
6 Declaration of Thomas Klimkait Under 37 C.F.R. § 1.132, signed February
27,2015.
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It is clear that one in the art that wished to endeavor to inhibit a
target nucleic acid at the time of invention could have used an
antisense oligonucleotide, or a ribozyme, or an[] siRNA
compound, or all of the aforementioned together, for example.
Each of antisense, ribozymes and RNAi function to inhibit
nucleic acid expression and each is a small nucleic acid based
inhibitor that can utilize the same chemical modifications and
delivery formulations. . . . [I]f it was not known at the time of
invention, one in the art would surely have been motivated to test
whether this was true since, of course, the prior art has already
shown that providing multiple antisense inhibitors does indeed
provide for increased inhibition.
Ans. 7—8.
In reply, Appellants argue that “the core reason why more inhibitors
are likely to provide benefits in antisense is completely absent from RNAi,
because RNAi is not concentration-dependent, and relies on endogenous
cellular machinery for its mode of action.” Reply Br. 2. In addition,
Appellants argue the Examiner improperly dismisses the Klimkait
Declaration, “rel[ying] on the assertion that because single-stranded
antisense and dsRNA used in RNAi both ‘utilize the same chemical
modifications and delivery formulations’, that antisense and RNAi are
analogous.” Id. at 3.
Under § 103(a), “there must be some articulated reasoning with some
rational underpinning to support the legal conclusion of obviousness.” KSR
Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 418 (2007) (internal quotation marks
and citation omitted).
“The Patent Office has the initial duty of supplying the factual basis
for its rejection. It may not. . . resort to speculation, unfounded assumptions
or hindsight reconstruction to supply deficiencies” in the cited references. In
re Warner, 379 F.2d 1011, 1017 (CCPA 1967). While the analysis under 35
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U.S.C. § 103 allows flexibility in determining whether a claimed invention
would have been obvious, KSR, 550 U.S. at 418, it still requires showing
that “there was an apparent reason to combine the known elements in the
fashion claimed by the patent at issue.” Id. “We must still be careful not to
allow hindsight reconstruction of references to reach the claimed invention
without any explanation as to how or why the references would be combined
to produce the claimed invention.” Innogenetics, N. V. v. Abbott Labs., 512
F.3d 1363, 1374 n.3 (Fed. Cir. 2008).
Appellants persuade us that the evidence does not support the
Examiner’s finding that the skilled artisan would look to the antisense art for
guidance regarding use of RNAi, simply because the techniques of working
with both types of nucleic acids are similar. What is missing is an
articulated reasoning with some rational underpinning to support the legal
conclusion of obviousness. In particular, the Examiner has failed to provide
a reason to make the RNAi and double-stranded RNA taught by Tuschl as
embodiments targeted toward different portions of the same target gene,
when the mechanism of RNAi differs from that of antisense. In particular,
we find unpersuasive the Examiner’s response to issues raised by the
Klimkait Declaration.
Because the Examiner has not provided evidence sufficient to support
a prima facie case of obviousness, we reverse the rejection of claims 43—62
as obvious based on Tuschl, Farese, and Branch.
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SUMMARY
We reverse the rejection of all claims on appeal.
REVERSED
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