Ex Parte Malvar et al

Patent Trial and Appeal Board

Apr 4, 2017

12909466 (P.T.A.B. Apr. 4, 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.
12/909,466 10/21/2010 Thomas M. Malvar MONS:094USD1 5955
73905 7590
DENTONS US LLP
P.O. BOX 061080
CHICAGO, IL 60606-1080
04/06/2017 EXAMINER
DEVEAU ROSEN, JASON
ART UNIT PAPER NUMBER
1662
NOTIFICATION DATE DELIVERY MODE
04/06/2017 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte THOMAS M. MALVAR, SHIHSHIEH HUANG, and
MICHAEL H. LUETHY1
Appeal 2016-001196
Application 12/909,466
Technology Center 1600
Before MELANIE L. McCOLLUM, JOHN G. NEW, 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 com
meal, which have been rejected as obvious. We have jurisdiction under 35
U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
Com “is a grain widely used as animal feed.” (Spec. 2.) There are ten
amino acids that are “deemed essential in a mixed grain feed” including
lysine, methionine, and threonine, and “com is particularly lacking” in those
1 Appellants identify the Real Party in Interest as Monsanto Company, the
parent company of the assignee Monsanto Technology LLC. (Appeal Br. 2.)
Appeal 2016-001196
Application 12/909,466
essential amino acids. (Id.) Thus, feed com is supplemented with these
nutrients. (Id. at 2—3.) Lysine is “often provided by the addition of soybean
meal or synthetic lysine.” (Id. at 3.) Appellants’ Specification indicates that
“[i]t would be of benefit to the art to increase the level of lysine in com seed
as a means of making the seed more nutritious as a food or feed grain.” (Id.)
Appellants’ invention is directed at com meal from transgenic com seed that
has “increased levels of lysine in the seed.” (Id. at 4.)
Claims 39, 42, 48—51, and 53—56 are on appeal. Claim 39 is
representative and reads as follows:
39. Com meal prepared from bulked transgenic com seeds,
said com seeds comprising a heterologous expression cassette
comprising SEQ ID NO: 1 and 4000 ppm to 6500 ppm free
lysine, wherein no lysine is added to said meal, and wherein
said com meal has elevated lysine as compared to a meal
processed in the same manner from com seeds of a control
plant not comprising the heterologous expression cassette.
(Appeal Br. 14.)
The following ground of rejection by the Examiner is before us on
review:
Claims 39, 42, 48—51, and 53—56 under 35 U.S.C. § 103(a) as
unpatentable over Falco ’019,2 Bailey,3 and Falco ’831.4
2 Falco et al., US 6,459,019 Bl, patented Oct. 1, 2002.
3 Bailey et al., US 2005/0255568 Al, published Nov. 17, 2005.
4 Falco et al., WO 98/42831, published Oct. 1, 1998.
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Application 12/909,466
DISCUSSION
The Examiner finds that Falco ’019 teaches that human food and
animal feed derived from com are limited in lysine, which is an important
dietary requirement. (Final Action 5.) According to the Examiner, Falco
’019 teaches it would be desirable to increase the lysine content of com seed
to eliminate the need to supplement mixed grain animal feeds with lysine
produced by fermentation microbes. (Id.; Ans. 10.) The Examiner finds that
Falco ’019 teaches producing com seeds with increased free-lysine. (Final
Action 4.) In particular, the Examiner finds that Falco ’019 teaches co­
expressing lysine insensitive DHDPS and lysine insensitive lysC-M4 gene
(which corresponds to the aspartate kinase (AK) gene) in the com seed
embryo and that this produces com seeds with free lysine levels that are
greater than control seeds that do not express a lysine insensitive DHDPS.
(Id.) According to the Examiner the co-expression of these two genes in the
embryo resulted in an increase in free lysine of 15—27% of free amino acids
compare to the control 1.4% of free amino acids. (Id.)
The Examiner further finds that Falco ’019 teaches that as com
endosperm lysine catabolism is expected to be much greater than in the
embryo, and thus with respect to com endosperm, it is preferable to express
both lysine insensitive DHDPS and lysine insensitive AK and also inhibit
lysine catabolism by reducing the level of FKR. (Id.)
The Examiner finds that Falco ’831 teaches that “FKR is a
bifimctional enzyme that is responsible for the catalysis of the first and
second reaction in the catabolism of lysine,” “and that antisense FKR RNA
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Application 12/909,466
or co-suppression of LKR can be achieved ... to reduce the loss of lysine
due to catabolism.” {Id. at 5—6.)
The Examiner finds in light of the two Falco references that it would
have been obvious to one of ordinary skill in the art to co-transform a com
plant with nucleic acid sequences encoding a DHDPS and an AK gene as
taught by Falco ’019 and a nucleic acid sequence encoding an RNA
molecule to suppress expression of a FKR gene as taught by Falco ’831 to
achieve further increase in free lysine by reducing the loss of lysine due to
catabolism. {Id. at 7.)
The Examiner further finds that Bailey teaches a DHDPS with
reduced feedback inhibition that has 99% identity to SEQ ID NO: 1 recited
in Appellants’ claim 39. (Final Action 5.) The Examiner further finds that
Bailey teaches that when this is expressed in bacterial strains it results in
increase in the production of amino acids of the aspartic acid family having
reduced feedback inhibition. (Final Action 5.) The Examiner explains that
while the sequence identity is not 100%, the difference is a single
conservative mismatch at base pair position 3, and the DHDPS polypeptide
encoded by that sequence has 100% identity with the lysine insensitive
DHDPS disclosed to be encoded by SEQ ID NO: 1. {Id.; Ans. 9.) The
Examiner, thus, concludes that the sequence encoding DHDPS with reduced
feedback disclosed in Bailey is a functional equivalent to the claimed SEQ
IDNO:l. (Final Action at 6.)
In light of Bailey’s teaching, the Examiner further concludes that it
would have been obvious to one of ordinary skill in the art to substitute the
functional equivalent sequence disclosed in Bailey for the DHDPS sequence
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Application 12/909,466
disclosed in Falco ’019 (modified to also include a nucleic acid sequence
encoding an RNA molecule to suppress expression of a LKR gene as taught
by Falco ’831), “because Falco [’019] teach that DHDPS can be isolated
from other sources, and because said method would predictably lead to an
increase in the lysine content of a transgenic com seed.” (Id.)
The Examiner also concludes that one of ordinary skill in the art
would have a reasonable expectation of success in arriving at a com seed
comprising 4000 ppm to 6500 ppm free lysine because the com seed would
have the claimed stmctural features. (Final Action 6—7, 8; Ans. 8, 11—13.)
We agree with the Examiner’s conclusion of obviousness. Falco ’019
and Falco ’831 teach that antisense LKR RNA can be used to reduce the loss
of lysine due to catabolism, and both teach a chimeric gene constmct where
the LKR sequence is linked to genes encoding lysine insensitive DHDPS
and are introduced to plants via transformation simultaneously. (Falco ’019
26; Falco ’831 10, 35, 98.) Both Falco references also teach that preventing
lysine catabolism by reducing or eliminating LKR expression or activity in
the endosperm along with expression of both Corynebacterium DHDPS and
the E.coli AKIII-M4 in the endosperm should “achieve significant lysine
increases in the endosperm.” (Falco ’019 26: 13—15, Falco ’831 31.)
Appellants argue that the prior art does not specify or suggest
transgenic com seeds comprising 4000 to 6500 ppm free lysine, or meal or
product produced therefrom. (Appeal Br. 5.) There is no dispute that the
references do not show transgenic com seeds comprising 4000 to 6500 ppm
free lysine. However, the Examiner’s rejection was based on a combination
of three prior art references that when combined provide for the identical
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Application 12/909,466
structure that Appellants’ Specification teaches achieves the foregoing
production. (Spec. 27—29 (Table 1 (entries 4, 7, 15, and 30).) While the
prior art may not have suggested the combination for the achievement of
precisely the claimed amount of free lysine claimed, “the law does not
require that the references be combined for the reasons contemplated by the
inventor.” In re Beattie, 91A F.2d 1309, 1312 (Fed. Cir. 1992.) We agree
with the Examiner that the prior art provides a reason to make a transgenic
com seed with a reasonable expectation of success that incorporates lysine
insensitive DHDPS, lysine insensitive AK, and mRNA of LKR. Moreover,
such transgenic com seeds would have the stmcture that Appellants’
Specification indicates achieves the claimed amount of free lysine. And, as
the Examiner found, a com meal or product produced therefrom is also
reasonably suggested by the prior art.
Falco ’019 indicates that increases in the “lysine content of. . .
com . . . would reduce or eliminate the need to supplement mixed grain
feeds with lysine produced via fermentation of microbes.” (Falco ’019
1:35—38.) Falco ’019 and ’831 provide a compelling motivation to add a
chimeric gene for antisense LKR to a gene encoding a lysine-insensitive
DHDPS (with or without a lysine-insensitive AKIII) to significantly improve
free lysine.
Falco ’019 indicates that a 27% increase is achievable just by
introducing a lysine-insensitive DHDPS into the embryo. (Falco ’091
(Example 26 and Table 12).) Falco ’019 shows that com seed where the
endosperm was transformed with a lysine-insensitive DHDPS and AKIII-
M4 did not achieve the increase in free amino acid that was achieved with
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com seed where the embryo was transformed with only a lysine-insensitive
DHDPS. However, Falco ’019 specifically teaches that there was lysine
catabolism in the embryo and even higher lysine catabolism is expected in
the endosperm, which “probably prevents the accumulation of increased
levels of lysine in seeds expressing [a lysine-insensitive DHDPS and lysine
insensitive lysC-M4] from the glutelin 2 promoter [in the endosperm].”
(Falco ’019 92 (Example 26).)5 Falco ’831 and Falco ’019 both suggest that
preventing lysine catabolism by reducing or eliminating enzyme function in
the plant gene that encodes LKR should increase accumulation of excess
free lysine that is accomplished by the introduction of lysine insensitive
DHDPS with or without lysine insensitive lysC-M4 introduction to the plant
seed. (Falco ’019 3:47—55, 9:49-65; 26:12-43 (noting that preventing lysine
catabolism is desirable “to accumulate higher levels of free lysine” and that
“to achieve significant lysine increases in the endosperm it is preferable to
5 Appellants’ assertion that “the 130% increase in free lysine seen in com
seeds expressing DHDPS is completely eliminated in seeds expressing
DHDPS and AK” (Reply Br. 5, 6) is not altogether accurate. Notably Table
12 of Falco ’019 demonstrates that the expression of lysine insensitive
DHDPS alone in the endosperm, like the expression of lysine insensitive
DHDPS with AK in the endosperm, also resulted in the failure to accumulate
increased free lysine. What Falco ’019 demonstrates in Table 12 is that the
130% increase in free lysine seen in com seeds whose embryo expressed
lysine insensitive DHDPS is not seen in seeds whose endosperm, but not
embryo, express lysine insensitive DHDPS and AK. Falco ’019 attributes
this observation to a greater lysine catabolism by LKR in the endosperm
where the lysine insensitive DHDPS and AK were expressed rather than to
any combination of expression of lysine insensitive DHDPS and AK as
compared to the expression of lysine insensitive DHDPS alone. (Falco ’019
92:53-61.)
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Application 12/909,466
express both Corynebacterium DHDPS and the E. coli AKTTT-M4 in the
endosperm and to reduce lysine catabolism by reducing the level of lysine
ketoglutarate reductase”); Falco ’831 9-10, 31.) As the Examiner found,
which Appellants’ do not dispute, Falco ’831 teaches “a nucleic acid
sequence having 96% identity to SEQ ID NO: 2 of the instant invention”
(Final Action 5), which “encodes a lysine ketoglutarate reductase” that can
be used to design inhibitory RNA’s (Spec. 5.) Moreover, Falco ’019 and
’831 teach one of ordinary skill in the art how to use such sequences to
create a chimeric gene designed to express antisense RNA for all or a part of
the LKR gene to down-regulate the LKR activity. (Falco ’019 75, Falco
’831 98.)
Endosperm-specific promoters were known. (Falco ’019 19:28-40
(referencing the known 10 kD, 27 kD and 19 kD zein storage proteins).)
And Falco ’019 teaches that using such endosperm-specific promoters, one
can obtain expression of protein in the endosperm. (Falco ’019 Example 26
and Table 12 (last entry, noting glutelin 2 promoter expressed lysine
insensitive DHDPS and lysine insensitive lysC/AKIII-M4 in the
endosperm).) Thus, one of ordinary skill in the art would reasonably expect
from the teachings of Falco ’019 and ’831 that an antisense LKR could be
expressed in com endosperm along with lysine insensitive DHDPS and
lysine insensitive lysC/AKIII-M4, which, as suggested by Falco ’019, would
allow for the increased accumulation of lysine promoted by the expression
of lysine insensitive DHDPS and lysine insensitive lysC/AKIII-M4 in the
endosperm to remain without being catabolized.
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Application 12/909,466
With respect to the claimed SEQ ID NO: 1, which encodes lysine
insensitive DHDPS (Spec. 5), we agree with the Examiner that it would have
been obvious to provide the functional variant taught by Bailey (having 99%
identity with SEQ ID NO: 1 but 100% amino acid identity (compare Bailey
Table 16 (SEQ ID NO: 126) with SEQ ID NO: 7) as the sequence encoding
lysine insensitive DHDPS. Bailey teaches that homologous nucleotide
sequences that are not identical but are functional variants are embodied
within the scope of the sequences taught. (See Bailey Tflf 209, 213.)
Consequently, while Appellants are correct that Bailey does not literally
disclose SEQ ID NO: 1 (Appeal Br. 7; Reply Br. 5—6), the difference of the
single conservative mismatch at base pair position 3 is not a critical
difference for the reason the Examiner expressed, i.e., the encoded amino
acid sequence is 100 % identical. And Bailey contemplates a functional
variant of the disclosed DNA sequence that results in the identical amino
acid sequence that SEQ ID NO: 1 encodes.
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable
results.” KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
Appellants argue that the achievement of free lysine in the range of 4000
ppm to 6500 ppm is a “surprising result[]” because it represents “more than
an order of magnitude greater lysine levels in seeds than the 130% increase
in seed lysine values shown by Falco (’019).” (Appeal Br. 10, 12 (citing
Declaration by Dr. Huang dated 2014); Reply Br. 4.) We do not find this
argument persuasive. “To be particularly probative, evidence of unexpected
results must establish that there is a difference between the results obtained
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Application 12/909,466
and those of the closest prior art, and that the difference would not have been
expected by one of ordinary skill in the art at the time of the invention.”
Bristol-Myers Squibb Co. v. leva Pharms. USA, Inc., 752 F.3d 967, 977
(Fed. Cir. 2014). While Falco ’019 exemplifies transgenic com seed that
includes lysine insensitive DHDPS in the embryo, Falco ’019 and Falco
’831 describe transforming com via introduction of “a chimeric gene for
cosuppression of LKR or antisense LKR” along with either “a chimeric gene
encoding substantially lysine-insensitive DHDPS” (Falco ’831 35), or
“chimeric genes encoding substantially lysine-insensitive DHDPS and AK”
(Falco ’019 9:42—67 and 28:1—9), the cosuppression or antisense LKR gene
could be linked to the chimeric gene(s) encoding substantially lysine-
insensitive DHDPS or lysine-insensitive DHDPS and AK (Falco ’831 35;
Falco ’019 28:1—9). The comparison Appellants and Appellants’ Declarant
rely on is the transgenic com seed that that includes lysine insensitive
DHDPS in the embryo or lysine insensitive DHDPS and AK in the
endosperm demonstrated in Table 12 of Falco ’019 (Appeal Br. 11—12;
Appeal Br. Ex. D19), and not the described com transformed via
introduction of “a chimeric gene for cosuppression of LKR or antisense
LKR” along with “chimeric genes encoding substantially lysine-insensitive
DHDPS and AK” (Falco ’019 9:42—67 and 28:1—9). Consequently, neither
Appellants nor Appellants’ Declarant have compared the claimed invention
to the closest prior art.
For the foregoing reasons, Appellants do not persuade us that the
Examiner erred in rejecting claim 39 for obviousness over Falco ’019,
Bailey, and Falco ’831.
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Claims 42, 48—51, and 53—56 have not been argued separately and
therefore fall with claim 39. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We affirm the rejection of claims 39, 42, 48—51, and 53—56 under 35
U.S.C. § 103(a) as unpatentable over Falco ’019, Bailey, and Falco ’831.
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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