Ex Parte Malvar et al

Board of Patent Appeals and Interferences

Apr 29, 2011

11057069 - (D) (B.P.A.I. Apr. 29, 2011)

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.
11/057,069 02/10/2005 Thomas M. Malvar MONS:122US 2261
73905 7590 05/02/2011
SNR DENTON US LLP
P.O. BOX 061080
CHICAGO, IL 60606-1080
EXAMINER
MEHTA, ASHWIN D
ART UNIT PAPER NUMBER
OPQA
MAIL DATE DELIVERY MODE
05/02/2011 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte THOMAS M. MALVAR, SHIHSHIEH HUANG,
and MICHAEL H. LUETHY
__________

Appeal 2010-010177
Application 11/057,069
Technology Center 1600
__________

Before ERIC GRIMES, LORA M. GREEN, and STEPHEN WALSH,
Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
recombinant DNA construct, transgenic seed, and methods for increasing the
level of lysine or an amino acid in corn seed. The Patent Examiner rejected
the claims on the grounds of lack of enablement, obviousness, and
nonstatutory obviousness-type double patenting. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.
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Application 11/057,069

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STATEMENT OF THE CASE
The Specification states that “[c]ertain plants have low levels of
specific amino acids compared to other plants, e.g. corn has low levels of
lysine, methionine and tryptophan.” (Spec. 1, ll. 18-19.) Earlier patents or
publications are said to have addressed the problem by making transgenic
corn with a bacterial gene coding for dihydropicolinic acid synthase in order
to increase lysine levels. (Id. at ll. 19-25.)
According to the Specification, “[a] concept for even more enhanced
levels of amino acids includes suppression of genes encoding proteins in
amino acid catabolic pathways.” (Id. at ll. 25-26.) The invention is said to
relate to, among other things, transgenic corn having integrated into its
genome a recombinant DNA construct that transcribes an anti-sense-oriented
RNA that suppresses the production of a protein in an amino acid catabolic
pathway. (Id. at 4, ll. 5-8.)
Claims 2-5, 9, 10, 12-15, and 19-21, which are all the pending claims,
are on appeal. Claims 9 and 2 are representative and read as follows:
9. A recombinant DNA construct for producing in a plant a loop of anti-
sense-oriented RNA for gene suppression, wherein said construct comprises
in 5' to 3' order a seed specific promoter element operably linked to an anti-
sense-oriented DNA element and sense-oriented DNA element that is not
more than one-quarter the length of the anti-sense-oriented DNA element,
wherein sense-oriented RNA transcribed by the sense-oriented DNA
element is complementary to at least a part of the anti-sense-oriented RNA
transcribed by the anti-sense oriented DNA element, wherein said DNA
elements are transcribed as RNA that forms into a loop of anti-sense-
oriented RNA for suppressing the expression of at least one gene; and
wherein the at least one gene targeted for suppression expresses lysine
ketoglutarate reductase.

2. Seed for producing a transgenic corn with enhanced amino acid
content having integrated into its genome a first recombinant DNA construct
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which transcribes anti-sense-oriented RNA that suppresses the production of
a protein in an amino acid catabolic pathway, further having integrated into
its genome a second recombinant DNA which expresses a bacterial gene
encoding dihydrodipicolinic acid (DHDP) synthase which is substantially
resistant to feedback inhibition, wherein the first and second recombinant
DNAs comprise a seed specific promoter operably linked to DNA that is
transcribed to said RNA, wherein said seed has an elevated amino acid
content as compared to progeny seed from control corn plants in which
production of said protein in an amino acid catabolic pathway is not
suppressed, wherein said DNA that is transcribed to said RNA comprises an
anti-sense-oriented DNA element and a sense-oriented DNA element that is
not more than one-quarter the length of the anti-sense-oriented DNA
element, wherein sense-oriented RNA transcribed by the sense-oriented
DNA is complementary to at least a part of the 5'-most end of anti-sense-
oriented RNA transcribed by the anti-sense oriented DNA element, and
wherein said transcribed RNA forms into a loop of anti-sense-oriented RNA
for suppressing said protein in an amino acid catabolic pathway.

The Examiner rejected the claims as follows:
• claims 2-5, 9, 10, 12-15, and 19-21 on the ground of nonstatutory
obviousness-type double patenting over claims 1, 4, 5, 8, 11, 12, and 17 of
then copending Application No. 11/057,0621 in view of Falco;2
• claims 2-5, 10, and 12-15 under 35 U.S.C. § 112, ¶ 1, because the
Specification enables seeds and methods with a dihydrodipicolinic acid
synthase [DHDPS] gene operably linked to a chloroplast transit sequence,
but not seeds and methods without an operable linkage between a DHDPS
gene and a chloroplast transit sequence; and
• claims 2-5, 9, 10, 12-15, and 19-21 under 35 U.S.C. § 103(a) as
unpatentable over Falco and Agrawal.3

1 Application No. 11/057,062 issued on Dec. 21, 2010 as US Patent No.
7,855,323 B2, to Shihshieh Huang et al.
2 Saverio Carl Falco et al., US 6,459,019 B1, issued Oct. 1, 2002.
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NONSTATUTORY OBVIOUSNESS-TYPE DOUBLE PATENTING
The Issue
Appellants contend that the rejection is “premature and speculative,”
and request deferring consideration of the rejection until allowable subject
matter is indicated. (App. Br. 7(a).)
Findings of Fact
1. The rejection cited claim 1 in then copending Application No.
11/057,062 as directed to a recombinant DNA construct having
certain sense- and anti-sense-oriented features, and claim 17 as
directed to the construct wherein the sense-oriented DNA element is
not more than about one-quarter the length of the anti-sense-oriented
DNA element.
2. Formerly copending Application No. 11/057,062, issued as Patent No.
7,855,323 B2 on Dec. 21, 2010, with five claims.
3. Claim 1 of the ‘323 patent is directed to a recombinant DNA construct
having certain sense- and anti-sense oriented features, and claim 5
reads as follows, incorporating the language of claim 1, from which it
depends:
5. [A recombinant DNA construct for suppression of at
least two target genes which comprises in 5’ to 3’ order a
promoter element operably linked to an anti-sense-oriented
DNA element from at least two target genes and a sense-
oriented DNA element comprising at least 50 nucleotides,
wherein the sense-oriented DNA element is not more than
about one-half of the length of the anti-sense oriented DNA
element, and sense oriented RNA transcribed by the sense-
oriented DNA is complementary to the 5’-most end of the anti-

3 Sudhir Agrawal et al., WO 94/01550, published Jan. 20, 1994.
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sense-oriented RNA transcribed by the anti-sense-oriented
DNA element, wherein said transcribed RNA forms a loop of
anti-sense-oriented RNA for suppressing said at least two target
genes], wherein said sense-oriented DNA element is not more
than about one-quarter the length of the anti-sense-oriented
DNA element.

Analysis
Appellants have raised no substantive arguments concerning the
rejection. It appears that the copending subject matter upon which the
rejection was based remains the subject of the renumbered claims in the now
issued application, Patent No. US 7,855,323 B2. (Compare Answer 4-6 with
FF 3.) Although the claim numbers have changed, we agree with the
Examiner’s analysis and affirm the rejection.

ENABLEMENT
The Issue
The Examiner’s position is that a bacterial DHDPS gene must be
operably linked to a chloroplast transit sequence in order to function in a
corn plant. Citing the Specification’s disclosure that the DHDPS enzyme
“must” be localized near other synthetic enzymes in the chloroplast, the
Examiner reasoned that it would require undue experimentation to make and
used the invention without a chloroplast transit sequence. (Ans. 8-9.)
Appellants contend that the rejection is “tantamount to requiring
claims to be limited to examples, a principle that has been consistently
rejected by the Court.” (App. Br. 7(b).)
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The issue with respect to this rejection is whether the weight of the
evidence supports a conclusion that undue experimentation would be
required to make and use the claimed construct, seeds, and method.
Further Findings of Fact
4. The Specification states:
One such gene for producing enhanced levels of corn is a
bacterial dihydropicolinic acid synthase as disclosed in U.S.
Patents . . . 6,459,019 (Falco et al.) . . . each of which is
incorporated herein by reference in their entirety.

(Spec. 1, ll. 21-25.)
5. The Specification states:
In the first place, the bacterial DHDP synthase gene must be
modified in vitro to include regulatory signals required for gene
expression in plant cells. Because the lysine biosynthetic
pathway in plants is reported to be sequestered in the
chloroplasts, the bacterial gene is preferably modified to add
sequences encoding an amino-terminal chloroplast transit
peptide sequence, in order to direct the gene product to these
organelles.

(Spec. 6, as amended April 3, 2009.)
6. Falco states:
DNA sequences coding for intracellular localization
sequences may be added to the lysC and dapA coding sequence
if required for the proper expression of the proteins to
accomplish the invention. Plant amino acid biosynthetic
enzymes are known to be localized in the chloroplasts and
therefore are synthesized with a chloroplast targeting signal.
Bacterial proteins such as DHDPS and AKIII have no such
signal. A chloroplast transit sequence could, therefore, be fused
to the dapA and lysC coding sequences. Preferred chloroplast
transit sequences are those of the small subunit of ribulose 1,5-
bisphosphate carboxylase, e.g. from soybean [Berry-Lowe et al.
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(1982) J. Mol. Appl. Genet. 1:483-498] for use in
dicotyledonous plants and from corn [Lebrun et al. (1987)
Nucleic Acids Res. 15:4360] for use in monocotyledonous
plants.

(Falco, col. 20, ll. 17-31.)
Principles of Law
The first paragraph of 35 U.S.C. § 112 requires that the specification
teach persons skilled in the art to make and use the invention without undue
experimentation. In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). A lack
of enablement rejection is appropriate where the written description fails to
teach those in the art to make and use the invention as broadly as claimed
without undue experimentation. In re Cortright, 165 F.3d 1353, 1356 (Fed.
Cir. 1999). “The PTO cannot make this kind of rejection, however, unless it
has reason to doubt the objective truth of the statements contained in the
written description.” Id., 165 F.3d at 1357.
Analysis
We agree with the Examiner’s position and adopt the findings and
reasoning set out in the Answer. (See Ans. 6-9 and 13-14.)
Appellants’ arguments fail to come to grips with the pertinent
evidence and complete explanation in the rejection. (Ans. 6-9.) The
Specification explained the need for a chloroplast transit sequence. (FF5.)
Rather than address the identified facts, Appellants divert to an argument
that the rejection improperly limits the claims to the working examples.
(App. Br. 7(b), quoting LizardTech, Inc. v. Earth Resource Mapping, Inc.,
424 F.3d 1336, 1345 (Fed. Cir. 2005).) Conclusions about enablement are
based on the particular facts in a case. The facts here support the rejection,
because the evidence is that constructs without the sequence coding for a
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chloroplast transit peptide will not work. This result is not contrary to
LizardTech and other cases stating that a claim will not be invalidated
“simply” because embodiments of the specification do not contain examples
explicitly covering the full scope of the claim language. LizardTech, 424
F.3d at 1345. The rejection thoroughly explained why constructs lacking a
sequence coding for a chloroplast transit peptide will not work in the seeds
and methods. (Ans. 6-9.) The rejection was not based “simply” on the lack
of a working example.
Appellants also pose the question “Why would it be harder to make
and use a simpler DNA construct?” (App. Br. 7(b).) In our review of the
Specification, we found no indication that a simpler construct, lacking a
chloroplast transit sequence, could be used, nor did Appellants point to a
statement in the Specification that a simpler construct could be used. To the
contrary, in our review, we found that the Specification also includes, via
incorporation by reference (FF 4), another explanation by Falco that a
chloroplast transit peptide is needed (FF 6). Even assuming that original
claims failing to recite the chloroplast transit sequence might be interpreted
as an assertion that a simpler construct could be used, the objective evidence
is that the assertion is factually mistaken. See Cortright, 165 F.3d at 1357.
If the Specification did disclose an enabled use for a construct, seeds, and
method lacking the chloroplast transit peptide sequence, Appellants have not
identified it, nor have Appellants produced evidence from other sources that
a simpler construct could be used.
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OBVIOUSNESS
The Issue
The Examiner found that Falco disclosed production of seeds from
transgenic corn plants, with a genome that included a sequence encoding
plant lysine ketoglutarate reductase (a protein in an amino acid catabolic
pathway) in an antisense orientation, and a sequence encoding a bacterial
dihydropicolinic acid synthase (DHDPS) insensitive to lysine feedback
inhibition, both sequences operably linked to seed specific promoters, and
the DHDPS operably linked to a chloroplast transit sequence. (Ans. 10.)
The Examiner found that Agrawal taught that self-stabilized antisense
oligonucleotides have increased resistance to degradation. According to the
Examiner, Agrawal taught oligonucleotides comprising a target region and a
self-complementary region, taught applying the principle to plant cells,
taught that the target hybridizing region is preferably from about 8 to about
50 nucleotides in length, and taught that the self-complementary region
generally has about 4 or more base-pairs to maintain the double-stranded
structure. (Id. at 10-11.)
The Examiner concluded “it would have been obvious and within the
scope of one of ordinary skill in the art to modify the method of Falco et al.
by expressing the antisense LKR RNA sequence as a hairpin loop, following
the design of Agrawal et al. It would have been obvious to design the
antisense LKR RNA in this manner, as Agrawal et al. teach that such a
design is resistant to nucleolytic degradation.” (Id. at 11.) The Examiner
further concluded “[i]t would also have been obvious to make the sense-
oriented DNA sequence to be no more than one-quarter the length of the
anti-sense oriented DNA element, as Agrawal et al. teach that the target
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hybridizing region may preferably be up to about 50 nucleotides in length,
and the self-complementary region may be about 4 base pairs in length. In
the case where the claimed ranges overlap or lie inside ranges disclosed by
the prior art a prima facie case of obviousness exists.” (Id. at 12.)
Appellants contend that Agrawal does not supplement Falco’s
deficiency. (App. Br. 7(c).) According to Appellants, Agrawal disclosed
“stabilizing an anti-sense oligonucleotide by hairpin at either the 5’ end or
the 3’ end or across the entire length,” but Agrawal did not teach or suggest
“anti-sense RNA molecule stabilized by double stranded RNA at the 5’ end
of the anti-sense segment and having a large anti-sense loop,” and did not
suggest suppressing production of a protein in an amino acid catabolic
pathway. (Id.) Appellants contend that “a hairpin loop is not the structure
required by Appellants’ claims.” (Id.) According to Appellants, the
rejection is “not only incorrect . . . it is remotely hypothecated only by
blatant hindsight reconstruction using the details of Appellants’ claims as a
template.” (Id.) “At best Agrawal describes a ‘general approach’ of
forming hairpin oligonucleotides. . . . Agrawal provides ‘little or no
guidance as to the particular form of the invention or how to achieve it.”
(Id.)
Further Findings of Fact
7. We adopt the Examiner’s findings of fact concerning the prior art.
(See Ans. 10-12 and 15-18.)
Principles of Law
A rejection for obviousness must include “articulated reasoning with
some rational underpinning to support the legal conclusion.” KSR Int’l Co.
v. Teleflex Inc., 550 U.S. 398, 418 (2007), quoting In re Kahn, 441 F.3d 977,
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988 (Fed. Cir. 2006). “[I]f a technique has been used to improve one device,
and a person of ordinary skill in the art would recognize that it would
improve similar devices in the same way, using the technique is obvious
unless its actual application is beyond his or her skill.” KSR, 550 U.S. at
417. “One of the ways in which a patent’s subject matter can be proved
obvious is by noting that there existed at the time of invention a known
problem for which there was an obvious solution encompassed by the
patent’s claims.” Id. at 419-420; see also Princeton Biochemicals, Inc. v.
Beckman Coulter, Inc., 411 F.3d 1332, 1338-1339 (Fed. Cir. 2005)
(affirming obviousness where motivation was found in the knowledge of
those skilled in the art at the time, and where the nature of the problem also
supplied a motivation) (“In other words, the nature of the problem called for
exactly the solutions in the prior art.”). Princeton Biochemicals, 411 F.3d at
1339; accord, DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H.
Patrick Co., 464 F.3d 1356, 1366 (Fed. Cir. 2006) (“the ‘evidence’ of
motive will likely consist of an explanation of the well-known principle or
problem-solving strategy to be applied”).
“[T]he discovery of an optimum value of a variable in a known
process is usually obvious.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348,
1368 (Fed. Cir. 2007). The rationale for determining the optimal parameters
for prior art result effective variables “flows from the ‘normal desire of
scientists or artisans to improve upon what is already generally known.’” Id.
(quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)).
Accordingly, “a prima facie case of obviousness exists when the claimed
range and the prior art range do not overlap but are close enough such that
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one skilled in the art would have expected them to have the same
properties.” Peterson, 315 F.3d at 1329.
Analysis
We have considered the evidence and reasoning advanced by the
Examiner and by Appellants. On this record, we conclude that the evidence
supports a conclusion of obviousness for the reasons given by the Examiner.
We find Appellants’ arguments about Agrawal’s purported failure to
suggest a “large” hairpin loop unpersuasive because a large hairpin is not a
feature of the claims. The evidence supports the Examiner’s analysis on this
point. We disagree that impermissible hindsight was used. Instead,
Agrawal explicitly taught that antisense oligonucleotides would be more
resistant to degradation in the form Agrawal taught. The motivation to make
changes to Falco’s antisense approach, directed to a protein in an amino acid
catabolic pathway, is not hindsight but the desire to apply a known solution
to a known problem. Although Appellants argue that Agrawal provided
little guidance, Appellants have not provided any objective evidence to show
that the Examiner erred in finding it within the skill in the art to adjust the
length of the antisense oligonucleotide.

SUMMARY
We affirm the rejection of claims 2-5, 9, 10, 12-15, and 19-21 on the
ground of nonstatutory obviousness-type double patenting over claims in
copending Application No. 11/057,062, now Patent No. US 7,855,323 B2, in
view of Falco.
We affirm the rejection of claims 2-5, 10, and 12-15 under 35 U.S.C.
§ 112, ¶ 1, for lack of enablement.
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We affirm the rejection of claims 2-5, 9, 10, 12-15, and 19-21 under
35 U.S.C. § 103(a) as unpatentable over Falco and Agrawal.

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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