Ex Parte Vance et al

Patent Trial and Appeal Board

May 15, 2017

13282680 (P.T.A.B. May. 15, 2017)

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
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/282,680 10/27/2011 Viki Bowman Vance USC-164-DIV 7522
22827 7590 05/15/2017
DORITY & MANNING, P.A.
POST OFFICE BOX 1449
GREENVILLE, SC 29602-1449
EXAMINER
KUMAR, VINOD
ART UNIT PAPER NUMBER
1663
MAIL DATE DELIVERY MODE
05/15/2017 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 VIKI BOWMAN VANCE, LEWIS HOWARD BOWMAN,
and ALLISON MALLORY1
Appeal 2016-001272
Application 13/282,680
Technology Center 1600
Before ULRIKE W. JENKS, TIMOTHY G. MAJORS, and RACHEL H.
TOWNSEND, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to a method
for transforming plant cells with designer miRNA precursor constructs,
which have been rejected as obvious. We have jurisdiction under 35 U.S.C.
§ 6(b).
We REVERSE.
1 Appellants identify the Real Party in Interest as The University of South
Carolina. (Br. 1.)
Appeal 2016-001272
Application 13/282,680
STATEMENT OF THE CASE
Appellants’ “invention relates to compositions and methods for
modulating gene expression in plants.” (Spec. 1:12—13.) As the
Specification explains:
MicroRNAs (miRNAs) are small regulatory RNAs that control
gene expression. The miRNA is complementary or partially
complementary to a portion of a target gene or nucleotide
sequence and function to modulate expression of the target
sequence or gene. In this manner, the RNA precursor construct
can be designed to modulate expression of any nucleotide
sequence of interest, either an endogenous plant gene or
alternatively a transgene. The RNA precursor is designed to
produce a transcript that is processed via the miRNA pathway to
produce an miRNA complementary to a portion of RNA, the
target RNA, that corresponds to the target gene.
(Id. at 3:13—21.)
Claims 29-36 are on appeal. Claim 29, the only independent claim, is
illustrative and reads as follows:
29. A method for transforming a plant cell, the method
comprising
(a) replacing an endogenous miRNA sequence of a
nucleotide sequence encoding an isolated plant miRNA
precursor with an exogenous miRNA sequence to form a
designer miRNA precursor, wherein the exogenous miRNA
sequence of the designer miRNA precursor maintains the length
of the endogenous miRNA sequence that is replaced;
(b) modifying additional nucleotides of the nucleotide
sequence encoding the isolated plant miRNA precursor, the
modified nucleotides being opposite the exogenous miRNA
sequence, the modified nucleotides being modified so as to
recreate on the designer miRNA precursor a region of double
strandedness and mismatches that existed on the nucleotide
sequence encoding the isolated plant miRNA precursor prior to
replacement of the endogenous miRNA sequence;
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Application 13/282,680
(c) adjusting the G-C content of the designer miRNA
precursor to levels that are average for the plant cell;
(d) forming an miRNA precursor construct that comprises
the designer miRNA precursor; and
(e) inserting the miRNA precursor construct into the plant
cell.
(Br. 16 (Claims App’x).)
Claims 29-36 stand rejected under 35 U.S.C. § 103(a) over Cullen,2
Llave,3 Reinhart,4 and Baga.5
DISCUSSION
The Examiner finds that “Cullen et al. teach a method of designing an
artificial miRNA precursor (same as designer miRNA precursor) by
modifying a naturally occurring miRNA precursor sequence with an
exogenous miRNA.” (Ans. 6.) According to the Examiner, Cullen further
teaches “substituting stem sequences of [] native miRNA to generate
miRNAs suitable for use in inhibiting expression of any target gene of
interest in any host cell including a plant cell.” (Id.) The Examiner finds
2 Cullen et al., US 2004/0053411 Al, published Mar. 18, 2004 (“Cullen”).
Cullen claims priority to U.S. Provisional Patent Application No.
60/377,224, filed May 3, 2002 (“Cullen Provisional Application” or “Cullen
Prov.”).
3 Llave et al., Endogenous and Silencing-Associated Small RNAs in Plants,
14 The Plant Cell 1605-19 (2002).
4 Reinhart et al., MicroRNAs in plants, 16 Genes & Development 1616—26
(2002).
5 Baga et al., Expression and Regulation of Trans genes for Selection of
Transformants and Modification of Traits in Cereals, in 5 Advances in
Cellular and Molecular Biology of Plants 83-131 (Indra K. Vasil
ed., 1999).
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Application 13/282,680
Cullen “teaches that bulges [i.e., mismatches] may be present in the
sequence.” (Id.) Further, the Examiner finds, Cullen teaches “expressing
. . . artificially designed miRNA precursor from a DNA expression vector in
any host cell.” (Id.)
The Examiner finds that Cullen “do[es] not teach a plant miRNA
precursor” and, thus, the Examiner turns to Llave and Reinhart. According
to the Examiner, “Llave et al. teach a number of plant miRNA precursors
comprising an endogenous miRNA sequence” and that “plant miRNA
precursors contain short and simple stem-loop structures.” (Id. at 7.)
Similarly, the Examiner finds Reinhart teach plant miRNA precursors as
well as the “cloning, sequencing and predicting fold-back secondary
structures (using RNAfold program) of said precursors.” (Id. at 8.)
The Examiner finds Cullen, Llave, and Reinhart “do not teach
adjusting the GC-content of a plant miRNA precursor” and so turns to Baga.
(Id.) The Examiner finds Baga teaches modifying G-C content of gene
sequences for optimal expression in different plant species. (Id. at 8—9.)
The Examiner concludes it would have been obvious “to use the
method of silencing the expression of a desired gene in a cell as taught by
Cullen et al., to silence a desired gene in a plant or plant cell” and “to use a
recombinant DNA encoding a plant miRNA precursor sequence as taught by
Llave et al. or Reinhart et al.” (Id. at 9.) The Examiner reasons:
Given that many native miRNA sequences contain mismatches
or “bulges” ..., it would have been obvious to maintain the size,
and positions of mismatches of the native miRNA secondary
structure in the non-native miRNA sequence of the modified
plant miRNA precursor (same as designer miRNA precursor), to
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Application 13/282,680
avoid any possible problems during processing of the designer
miRNA precursor.
{Id. at 10.) Based on Baga, the Examiner further reasons it would have been
obvious “to have adjusted base composition (e.g. GC content)... for the
purpose of enhancing expression of modified miRNA precursor in diverse
monocot and dicot plant species.” {Id. at 11—12.)
Appellants raise several arguments. Appellants argue “[t]he regular
utility application of Cullen, et al., having a filing date of May 5, 2003, is . . .
not proper prior art under 35 U.S.C. § 102.” (Br. 6.) Appellants argue the
Examiner’s proposed combination of prior art fails to disclose or suggest
elements of independent claim 29 including, for example, the step of:
modifying additional nucleotides . . . opposite the exogenous
miRNA sequence, the modified nucleotides being modified so as
to recreate on the designer miRNA precursor a region of double
strandedness and mismatches that existed on the nucleotide
sequence encoding the isolated plant miRNA precursor prior to
replacement of the endogenous miRNA sequence.
(Br. 16 (claim 29) (emphasis added); id. at 8—10.) Appellants also argue
Cullen teaches away from the method of claim 29 and that the Examiner
improperly relied on hindsight in modifying the prior art. {Id. at 12—15.)
Appellants’ argument that Cullen is not prior art is unpersuasive. The
Cullen Provisional Application, with a filing date of May 3, 2002, predates
the earliest effective filing date of the present application — even assuming
the application on appeal and the appealed claims are entitled to claim
priority to Appellants’ provisional application filed on July 19, 2002. {Id. at
6.) Cullen’s utility application, which published in 2004, is thus § 102(e)
prior art to the extent the relied-upon disclosures are supported in the Cullen
Provisional Application. See, e.g., In re Giacomini, 612 F.3d 1380, 1383
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Application 13/282,680
(Fed. Cir. 2010); Ex parte Yamaguchi, 88 USPQ2d 1606, 1613 (BPAI 2008)
(precedential). Appellants direct us to no material disclosures relied upon by
the Examiner in the Cullen Provisional Application that are absent in the
version of Cullen that published in 2004. For consistency, like the
Appellants and the Examiner, we refer to the disclosures in the Cullen
Provisional Application in addressing the rejection.
Turning to Appellants’ other arguments, we are, however, persuaded
that the cited art neither teaches nor suggests the step of method claim 29
requiring modifying additional nucleotides to recreate the mismatches that
existed on the endogenous miRNA precursor. True, as the Examiner
repeatedly points out, Cullen teaches ‘“bulges’ can be present” on the
miRNA stem. (Cullen Prov. 7:3—4; Ans. 14, 19, 22) But, in context, we
read Cullen as teaching bulges or mismatches are merely tolerable to a
degree. More specifically, Cullen teaches “[wjhile it is preferred that the
stem comprise a perfectly complementary duplex (but for any 3' tail),
‘bulges’ can be present. Advantageously, any such ‘bulges’ are few in
number (e.g., 1, 2 or 3) and are about 3 nucleotides or less in size.” (Cullen
Prov. 7:3—5.) Importantly, Cullen does not teach or suggest that mismatches
should be added, much less that they should be added in a precise pattern to
recreate the mismatches of the native miRNA precursor.6
According to the Examiner it would have been obvious “to maintain
the secondary structure of the modified plant miRNA precursor because it
6 The U.S. published application of Cullen (2004) recites that “‘bulges’ can
be present on either arm of the stem and may be preferred.” (Cullen 122
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was unknown what the effect of removing the secondary structure would
be.” (Ans. 16—17.) The Examiner cites no prior art or other evidentiary basis
for this scientific position. And, as persuasively shown by Appellants, the
Examiner’s reasoning is inconsistent with what is affirmatively taught in
Cullen — where designer miRNA precursors do not maintain the length or
mismatches of the endogenous sequences. (Br. 8—9.) Beyond the general
teachings (such as in Llave and Reinhart) of predicted stem-loop structures
in endogenous miRNA precursors having mismatches and Cullen’s
suggestion that mismatches may be tolerated, the Examiner presents an
insufficient evidentiary basis to support the assertion that skilled persons
would have predictably taken the step of recreating the mismatches in
designer miRNA precursors as required in claim 29.
The Examiner elsewhere responds that “Appellant’s argument is not
persuasive to suggest that maintaining mismatches (bulges)... is absolutely
important for efficient miRNA processing from the artificial miRNA
precursor.” (Ans. 16.) Whether maintaining mismatches is important for
processing purposes, it is a required step of the claims. Moreover, the
Examiner’s suggestion that maintaining mismatches is not important (e.g.,
citing examples in Cullen and other art where miRNA precursor was
efficiently processed without mismatches) weakens the very reasoning
offered by the Examiner for modifying the prior art. {Id. at 15.) That is, if
the art teaches efficient processing without mismatches — and Cullen
teaches that advantageously there should be no mismatches — why would
(emphasis added).) The teaching that bulges “may be preferred” is,
however, notably absent in the Cullen Provisional Application.
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the skilled person think mismatches should be reintroduced “to avoid any
possible problems during processing of the designer miRNA precursor” as
suggested by the Examiner? (Id. at 10; see also id. at 17.)
Finally, we recognize but are not persuaded by the Examiner’s
citation to an earlier decision of the Board concerning a parent (U.S. Appl.
No. 10/623,930) to the present application. (Ans. 16 (citing Ex parte Vance,
No. 2010-011808 (BPAI decided Sept. 1, 2011).) The claims in that prior
appeal were to a product, not the method claims on appeal here. And in the
prior appeal, after determining that the claims were drafted in product-by­
process format, the Board specifically noted “it is the product, not the
claimed process steps that must be found in the prior art.” Vance, No. 2010-
011808, slip op. at 7; see also id. at 11 (“Appellants have not shown with
appropriate evidence that the prior art miRNA precursor product, even if
made by a different process, differs from that claimed”).7 Here, on the other
hand, the steps recited in the method claims must be found in the prior art or
be obvious from it.
For the above reasons, we are unpersuaded the Examiner met the
burden to show that method claim 29 would have been prima facie obvious
over the applied art. We thus reverse the rejection of claim 29 as well as
claims 30-36, which depend from claim 29.
REVERSED
1 Cf. In re Hutchison, 154 F.2d 135, 137 (CCPA 1946) (claims in each
application are examined for patentability on their own merits).
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