Ex Parte Kuhn et al

Patent Trial and Appeal Board

Feb 27, 2017

13393028 (P.T.A.B. Feb. 27, 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
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/393,028 02/28/2012 Josef Martin Kuhn 074021-0171-US-286748 6289
123223 7590 03/01/2017
Drinker Biddle & Reath LLP (WM)
222 Delaware Avenue, Ste. 1410
Wilmington, DE 19801-1621
EXAMINER
BURAN, ASHLEY KATE
ART UNIT PAPER NUMBER
1662
NOTIFICATION DATE DELIVERY MODE
03/01/2017 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOSEF MARTIN KUHN, LINDA PATRICIA LOYALL,
MALTE SIEBERT, and ELKE DUWENIG1
Appeal 2016-001138
Application 13/393,028
Technology Center 1600
Before ELIZABETH A. LaVIER, RYAN H. FLAX, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to a method
for production of a high expression constitutive plant promoter, a
recombinant expression construct, and a transgenic plant cell, which have
been rejected as failing to comply with the written description requirement.
We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the Real Party in Interest as BASF Plant Science
Company GmbH of Ludwigshafen, Germany. (Appeal Br. 1.)
Appeal 2016-001138
Application 13/393,028
STATEMENT OF THE CASE
“Expression of transgenes in plants is strongly affected by various
external and internal factors resulting in a variable and unpredictable level of
transgene expression.” (Spec. 1.) “Strong promoters can partially overcome
these challenges. However, availability of suitable promoters showing
strong expression with the desired specificity is often limited.” (Id.)
“[S]ome introns have been recognized as genetic elements with a strong
potential for improving gene expression.” (Id.) “The increase of gene
expression observed upon functionally linking intrans to promoters is called
intron mediated enhancement (IME) of gene expression and has been shown
in various monocotyledonous . . . and dicotyledonous plants.” (Id.)
However, “studies also show that combination of introns with heterologous
promoters can have strong negative impacts on strength and/or specificity of
gene expression.” (Id. at 2.) “[S]ome documents show enhanced expression
of a nucleic acid by IME without affecting the tissue specificity of the
respective promoter.” (Id.) Appellants’ Specification provides “further
nucleic acid molecules . . . that enhance the expression of said promoters
without affecting their specificity upon fimctional[] linkage to constitutive
promoters.” (Id.)
Claims 1—20 and 22 are on appeal. Claim 1 is representative and
reads as follows:
1. A method for production of a high expression constitutive plant
promoter, comprising functionally linking to a constitutive promoter
one or more nucleic acid expression enhancing nucleic acid (NEENA)
molecule heterologous to said promoter, wherein said NEENA
comprises:
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i) a nucleic acid molecule comprising the nucleic acid
sequence of SEQ ID NO: 2; or
ii) a nucleic acid molecule having at least 98% sequence
identity to the nucleic acid sequence of SEQ ID NO: 2,
and wherein said high expression constitutive plant promoter
has higher constitutive expression activity as compared to the
constitutive promoter without said one or more NEENA.
(Appeal Br. Appx. A-l.)
The following ground of rejection by the Examiner is before us on
review:
Claims 1—20 and 22 under 35 U.S.C. § 112, first paragraph, as failing
to comply with the written description requirement.
DISCUSSION
The Examiner finds that the essential feature of the claims is a
chimeric promoter that drives high constitutive expression comprising SEQ
ID NO: 2 or a variant of that sequence that shares at least 98% identity to it.
(Ans. 2; Final Action 10; Advisory Action 2—3.) The Examiner finds that:
(a) “[t]he specification describes generating a plant transformation constmct
comprising the constitutive AtNitl promoter operably linked to SEQ ID
NO: 2 and the luciferase reporter gene (see Table 5, page 32),”
(b) “generating transgenic monocot and dicot plants expressing the
constmct,” and (c) SEQ ID NO: 2 operably linked to the promoter enhanced
expression. (Ans. 2—3.) The Examiner finds, though, that while the
Specification describes SEQ ID NO: 2, it does not describe any variants of
it, or any domains or regions of the sequence that “are necessary and
sufficient for increasing constitutive expression;” nor does the specification
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describe “which nucleotides of SEQ ID NO: 2 should be conserved and
which can tolerate mutations and still maintain the function of increasing
expression driven by a constitutive promoter.” (Ans. 7—8.)
In addition, the Examiner finds that “[i]t was unknown in the art how
to modify SEQ ID NO: 2 and retain the function of increasing constitutive
expression of an operably linked heterologous promoter.” (Final Action 11.)
And the Examiner further finds that prior art, such as Wilmink,2 *discloses
that “introns isolated from constitutive promoters can have a negative or
positive effect on expression level in plants.” (Id.)
The Examiner further finds that the Specification indicates that not all
sequences identified as NEENA candidate molecules turned out to have the
function of enhancing the expression driven by an operably linked
constitutive promoter; some even had negative effects. (Ans. 9.) Of the
nineteen NEENA candidates tested, the Examiner finds only nine were
determined to have at least a ‘“2-fold increase in reporter gene expression’,”
but none of the nine “share any substantial structural features with one
another that are responsible for function.” (Id.)
The Examiner further finds that the claimed 98% sequence identity to
SEQ ID NO: 2 “encompasses as many as 410 (1.05e6) molecules.” (Ans. 3.)
The Examiner concludes in light of all of the foregoing that “the
specification does not describe how to distinguish sequences sharing 98%
identity to SEQ ID NO: 2 and having the recited function from those that do
not have the function.” (Ans. 9.) Moreover, the Examiner finds that one of
2 Wilmink et al., Activity of Constitutive Promoters in Various Species from
the Liliaceae, 28 Plant Molecular Biology 949-55, (1995).
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skill in the art would not recognize that Appellants were in possession of the
genus of sequences that have the claimed increase in constitutive expression
in a plant recited by the claims. (Final Action 12; Advisory Action 3; Ans.
10-11.)
We agree with the Examiner’s factual findings and conclusion that the
claimed subject matter has not been adequately described by the
Specification.
Appellants argue the Examiner’s rejection is in error because the
disclosure is sufficient to “put one in possession of the genus of NEENA
sequences recited in the present claims” in light of: (1) the actual reduction
to practice of SEQ ID NO: 2, (2) the fact that the prior art teaches how to
determine sequence identity between variants and initial sequences, and (3)
the fact that screening and testing NEENA variants of SEQ ID NO: 2 for
their ability to enhance constitutive expression activity of a functionally
linked constitutive promoter would be routine to one of ordinary skill in the
art. (Appeal Br. 8.) We do not find this argument persuasive.
Whether or not one of ordinary skill in the art could identify a
sequence that is 98% identical to SEQ ID NO: 2 and then test the sequence
for activity is immaterial to whether the description requirement is met. See
AriadPharms., Inc. v. EliLilly & Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010)
(en banc) (citing Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d
1559, 1568 (Fed. Cir. 1997) (“The description requirement of the patent
statute requires a description of an invention, not an indication of a result
that one might achieve if one made that invention.”). “One needs to show
that one has truly invented the genus, i.e., that one has conceived and
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described sufficient representative species encompassing the breadth of the
genus. Otherwise, one has only a research plan, leaving it to others to
explore the unknown contours of the claimed genus.” AbbVie Deutschland
GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 1300 (Fed. Cir. 2014).
Appellants further argue that because they have actually reduced SEQ
ID NO: 2 to practice and have demonstrated that the molecule is capable of
enhancing the expression claimed that they have sufficiently established they
were in possession of the claimed invention. (Appeal Br. 13—14.) We do
not find this argument persuasive for the reasons noted by the Examiner.
(See, e.g., Ans. 7—11.) Namely, while the Specification has identified a
structure, SEQ ID NO: 2 that achieves the claimed function, Appellants have
not established that there is a known or disclosed correlation between the
function and a specific structure of SEQ ID NO: 2 other than the entire
sequence. That is, the Specification does not provide any specific variants
of SEQ ID NO: 2, much less ones that are capable of increasing constitutive
expression. The Specification also does not identify the domains or regions
of SEQ ID NO: 2 that are necessary for increasing constitutive expression,
or any structural motifs that are necessary, nor which nucleotides should be
conserved and which can tolerate mutations and still maintain the function of
increasing constitutive expression driven by a constitutive promoter.
Moreover, as the Examiner noted (Ans. 8), and Appellants do not
contest, there are no bioinformatics tools readily available that one can use
to identify putative consensus sequences for enhancer and intron sequences.3
3 As the Board noted in Ex parte Heck, 2008-2875, 2008 WL 426620 (BPAI
2008), cited by Appellants (Appeal Br. 8—9), “the determination of what is
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Furthermore, as the Examiner noted (Ans. 9), and Appellants do not contest,
the other sequences that Appellants’ Specification identifies as having the
function of increasing constitutive expression driven by a constitutive
promoter “do not share any substantial structural features with one another
that are responsible for function.”
The evidence of record, as identified by the Examiner, reasonably
suggests that one of ordinary skill in the art could not predict the operability
of undisclosed species. (Final Action 11—12; Ans. 7—9.) As just discussed,
neither the art, nor Appellants’ Specification identifies a particular necessary
structure that is responsible for the enhancing function. That fact, coupled
with Wilmink’s disclosure “that introns isolated from constitutive promoters
when operably linked to a heterologous constitutive promoter can increase
or decrease the expression level of an operably linked sequence in plants”
(Final Action 6), reasonably supports a conclusion that one skilled in the art
would not be able to predict whether a change in a known enhancing intron
sequence would continue to have an enhancing function. It is beside the
point that Wilmink does not test SEQ ID NO: 2 or sequences with 98%
needed to support generic claims to biological subject matter depends on a
variety of factors, such as the existing knowledge in the particular field, the
extent and content of the prior art, the maturity of the science or technology,
the predictability of the aspect at issue, and other considerations appropriate
to the subject matter.” Ex parte Heck, 2008 WL 426620, *3. While the
extent of the factual basis for the Board’s decision in Heck is not
immediately appreciable from the decision, at least because the knowledge
in the art regarding bioinformatics concerning the claims at issue in Heck
and the claims at issue here is significantly different, we agree with the
Examiner that the decision in Heck is not dispositive here.
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identity thereto or that Wilmink’s tested introns are all monocot introns and
not dicots like SEQ ID NO: 2 (see Reply Br. 2). Wilmink supports that there
is unpredictability generally in this field, and Appellants have not provided
any evidence, in the Specification or otherwise, to dispel this evidence of
unpredictability.
Additionally, as Appellants note (Reply Br. 3), they identified all
nineteen NEENA “candidate molecules” as having “the potential to enhance
expression of an operably linked constitutive promoter.” We find the fact
that Appellants identified nineteen candidates as having potential and only
found nine to be NEENA molecules, and that those nine do not share any
substantial structural features with one another, supports the Examiner’s
conclusion that one skilled in the art, based on Appellants’ disclosure and
the absence of any known necessary structure that achieves the claimed
function, would not be able to predict whether a change in a known
enhancing intron sequence would continue to have an enhancing function.
For the foregoing reasons, Appellants do not persuade us that the
Examiner erred in rejecting claim 1 as not being adequately described by
Appellants’ Specification.
Claims 2—20 and 22 have not been argued separately and therefore fall
with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We affirm the rejection of claims 1—20 and 22 under 35 U.S.C. § 112,
first paragraph, as failing to comply with the written description
requirement.
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TIME PERIOD FOR RESPONSE
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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