Daniell, Henry

Patent Trials and Appeals Board

Aug 30, 2019

13865146 - (D) (P.T.A.B. Aug. 30, 2019)

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.
13/865,146 04/17/2013 Henry Daniell 1070-P05952US00 7243
270 7590 08/30/2019
HOWSON & HOWSON LLP
350 Sentry Parkway
Building 620, Suite 210
Blue Bell, PA 19422
EXAMINER
KUBELIK, ANNE R
ART UNIT PAPER NUMBER
1662
NOTIFICATION DATE DELIVERY MODE
08/30/2019 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):
ckodroff@howsoniplaw.com
docketing@howsoniplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte HENRY DANIELL1
__________

Appeal 2019-003468
Application 13/865,146
Technology Center 1600
__________

Before ERIC B. GRIMES, TAWEN CHANG, and MICHAEL A. VALEK,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to
expression vectors for plastids such as chloroplasts, which have been
rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
“Chloroplast transformation strategies have utilized both endogenous
and foreign regulatory elements to facilitate high levels of foreign gene
expression.” Spec. ¶ 4. One “approach incorporates the native psbA 5′ and 3′

1 Appellant identifies the Real Party in Interest as The Trustees of the
University of Pennsylvania. Appeal Br. 3.
Appeal 2019-003468
Application 13/865,146

2
UTRs [untranslated regions] into transformation constructs.” Id. “[T]he
psbA 5′ UTR [is] an attractive tool to enhance the level of foreign gene
expression in transplastomic lines. The use of endogenous psbA regulatory
elements has facilitated the generation of transplastomic N. tabacum
[tobacco] lines with enhanced expression of a large number of . . . proteins.”
Id.
“However, [the] overwhelming majority of foreign proteins has been
expressed in N. tabacum chloroplasts. In order to advance this field,
chloroplast genomes of several crop species should be transformed.” Id. ¶ 5.
“[T]he invention pertains to a stable plastid transformation and expression
vector which comprises an expression cassette optimized for expression in a
target plant species.” Id. ¶ 15.
Claims 1, 6, 12, 14, and 21 are on appeal. Claim 1 is illustrative and
reads as follows (formatting added):
1. A stable plastid transformation and expression vector
which comprises an expression cassette optimized for
expression of a heterologous polynucleotide sequence of
interest in a target plant species,
the expression cassette comprising a plant chloroplast
promoter sequence operably linked to a chloroplast regulatory
sequence each being endogenous to said target plant species,
said promoter and endogenous regulatory sequence
including a 5′ UTR psbA sequence which are each operably
linked to said heterologous polynucleotide sequence of interest
and a transcription termination sequence functional in said
target plant plastid,
said expression cassette being flanked on each side by
homologous DNA sequences which facilitate homologous
recombination of said expression cassette with homologous
Appeal 2019-003468
Application 13/865,146

3
sequences in a chloroplast genome in a spacer region between
trnI and trnA,
said plant species being selected from the group
consisting of L. sativa, B. rapa, D. carota, G. hirsutum, S.
lycophersicum, G. max, and O. sativa, and said endogenous
chloroplast regulatory sequence consisting of SEQ ID NO: 22,
10, 12, 13, 15, 19, 21, and 29 respectively,
said expression cassette optionally including a
heterologous selectable marker sequence,
wherein endogenous stromal binding proteins
preferentially associate with said 5′ UTR psbA sequence,
thereby protecting a stem loop region within said 5′ UTR from
endonucleolytic cleavage and increasing transcript stability of
said operably linked heterologous polynucleotide sequence of
interest relative to transcript stability observed when
heterologous 5′ UTR psbA sequences to said target plant
species are present in said expression cassette.

The claims stand rejected as follows:
Claims 1, 12, 14, and 21 under 35 U.S.C. § 103(a) as obvious based
on Ruhlman,2 Shi,3 and Zou4 (Ans. 3);

2 Expression of cholera toxin B-proinsulin fusion protein in lettuce and
tobacco chloroplasts – oral administration protects against development of
insulitis in non-obese diabetic mice, 5 Plant Biotechnology Journal 495–510
(2007).
3 Lactuca sativa tRNA-Lys gene, partial sequence; photosystem II D1
protein (psbA) gene, complete cds; and tRNA-His gene, complete sequence;
chloroplast genes for chloroplast products, GenBank AF426317,
http://www.ncbi.nlm.nih.gov/nuccore/16755684.
4 The stem-loop region of the tobacco psbA 5′UTR is an important
determinant of mRNA stability and translation efficiency, 269 Mol. Gen.
Genomics 340–349 (2003).
Appeal 2019-003468
Application 13/865,146

4
Claims 1, 6, and 14 under 35 U.S.C. § 103(a) as obvious based on
Kumar,5 Zou, and Lee6 (Ans. 7); and
Claims 1, 6, 12, 14, and 21, provisionally, for obviousness-type
double patenting based on claims 4, 5, 11, 20, and 26–31 of application
12/059,376, combined with Shi (Ans. 13).
I
The Examiner has rejected claims 1, 12, 14, and 21 as obvious based
on Ruhlman, Shi, and Zou. The Examiner finds that Ruhlman teaches “a
plastid transformation vector comprising an expression cassette comprising
the tobacco Prrn promoter, the T7 5′ UTR, a heterologous nucleic acid
encoding a cholera toxin B subunit (CTB)-human proinsulin fusion protein,
and the tobacco rps16 or psbA 3′ UTR, [w]herein the expression cassette
was flanked by lettuce trnI and trnA plastid sequences.” Ans. 3.
The Examiner finds that Shi teaches “the sequence of the L. sativa
[lettuce] psbA gene, including portions of the genes flanking it. This region
has 100% identity to the instant SEQ ID NO:22.” Id. at 4. The Examiner
finds that Zou teaches that “the tobacco psbA 5′ UTR interacts with trans-
acting factors, and the interaction is very specific, requiring specific primary,
secondary and tertiary structures in the psbA 5′ UTR.” Id. at 5. The
Examiner finds that Zou teaches that “these are important protein binding

5 Stable transformation of the cotton plastid genome and maternal
inheritance of transgenes, 56 Plant Mol. Biol. 203–216 (2004).
6 Gossypium hirsutum cultivar coker 310 FR chloroplast, complete genome,
GenBank DQ345959, https://www.ncbi.nlm.nih.gov/nuccore/DQ345959.
Appeal 2019-003468
Application 13/865,146

5
sites, that they play crucial roles in mRNA stabilization and translation, and
that the function of this stem-loop is sequence dependent.” Id.
The Examiner concludes that it would have been obvious to modify
Ruhlman’s plastid transformation vector by replacing its Prrn promoter and
T7 5′ UTR with the lettuce promoter and psbA 5′ UTR, respectively, taught
by Shi, “because Ruhlman et al indicate that the psbA 5′ UTR was more
efficient at driving expression than the T7 5′ UTR” and “Ruhlman et al
suggest its use in the lettuce plastid transformation vectors to increase the
level of expression of the heterologous protein of interest.” Id.
The Examiner reasons that a skilled artisan would have expected
lettuce regulatory elements to increase expression of a heterologous gene
because Zou teaches that the interaction of the psbA 5′ UTR with protein
factors (“cpRNP”) “is very specific” and one would expect that “the lettuce
psbA 5′ UTR would [have] the best primary, secondary and tertiary
structures for interacting with the lettuce cpRNP.” Id. at 5–6. Thus, “[l]ike
Ruhlman et al, others of ordinary skill in the art would have expected the
lettuce psbA 5′ UTR to result in higher protein production levels than would
use of the tobacco psbA 5′ UTR in lettuce plastid transformants.” Id. at 6.
Finally, the Examiner concludes that the “wherein” clause of claim
1—referring to protecting a stem/loop region from endonucleolytic
cleavage—would be an inherent property of the vector made obvious by the
cited references. Id. at 6–7.
We agree with the Examiner that the vector of claim 1 would have
been obvious to a person of ordinary skill in the art based on Ruhlman, Shi,
and Zou. Ruhlman discloses “[l]ettuce and tobacco chloroplast transgenic
Appeal 2019-003468
Application 13/865,146

6
lines expressing the cholera toxin B subunit-human proinsulin (CTB-Pins)
fusion protein.” Ruhlman 495, Summary.
“The L. sativa long flanking plastid transformation vector (pLS-LF,
Figure 2a) was constructed.” Id. at 497, left col. “The full-length genes for
plastid trnI . . . and trnA . . . were amplified and cloned. The unique PvuII
site was used to insert transformation cassettes into the intergenic spacer
region between the tRNAs.” Id. Ruhlman’s pLS-LF vector thus comprises
an expression cassette flanked by homologous sequences that facilitate
recombination in an L. sativa chloroplast genome in the spacer region
between trnI and trnA, as recited in claim 1.
The expression cassette in Ruhlman’s pLS-LF also includes the CTB-
Pins heterologous polynucleotide sequence operably linked to a plant plastid
(chloroplast) promoter (Prrn, “[t]he tobacco native plastid ribosomal operon
promoter” (id. at 497, left col.)); a 5′ regulatory sequence (G10, “the 5′-
translation control element of bacteriophage T7 gene 10” (id. at 497, right
col.)); and a transcription terminator sequence (Trps16, “3′ UTR[] (rps16)”
(id. at 497, left col.)). See id. at 498, Figure 2a.
Ruhlman discloses that the “CTB-Pins fusion gene was [also] inserted
into chloroplast transformation vector pLD-ctv.” Id. at 496, right col. “The
5CP construct[7] was expressed under the control of the psbA 5′ untranslated
region (UTR)/promoter in order to achieve hyper-expression.” Id. at 496–497.

7 “The construct containing 5′UTR-CTB . . . and human proinsulin was
designated as 5CP. . . . [T]he the fusion gene was ligated into the pLD-ctv
chloroplast transformation vector.” Id. at 506, right col.
Appeal 2019-003468
Application 13/865,146

7
Ruhlman states that
[t]obacco expression of CTB-Pins is driven by the endogenous
psbA 5′ UTR, whereas lettuce expression is regulated by the
inclusion of the translational control region of bacteriophage T7
gene 10. Previous studies have demonstrated that the level of
foreign protein accumulation is lower when these translation
elements are used to drive expression of the same gene, with
psbA 5′ UTR being more efficient.
Id. at 506, left col. “We are developing new transformation constructs
for lettuce for CTB-Pins expression which will employ lettuce
endogenous translation elements, such as psbA 5′ UTR, to further
increase the level of expression.” Id. at 506, left col.
The Examiner finds that Shi discloses “the sequence of the L. sativa
psbA gene, including portions of the genes flanking it,” which is identical to
SEQ ID NO:22. Ans. 4. “Appellants do not dispute that this sequence was in
the public domain as of Appellant[’]s filing date.” Appeal Br. 10–11.
Zou discloses that “RNA stability and mRNA translation efficiency
are mainly mediated via the 5′ and/or 3′ untranslated regions (UTRs) of
chloroplast transcripts.” Zou 340, right col. “[T]he 5′UTRs appear to be of
crucial importance for both mRNA stability and translation efficiency.” Id.
Zou states that a discrepancy between prior findings regarding the
importance of the tobacco psbA 5′UTR “prompted us to undertake a more
detailed analysis of the psbA 5′UTR.” Id. at 341, left col. Zou states that
their analysis “indicates that the stem-loop of the psbA 5′UTR is essential for
both mRNA stability and translation efficiency, and that its function depends
on its correct sequence and secondary conformation.” Id.
Based on the above teachings, it would have been obvious to modify
Ruhlman’s lettuce expression vector (pLS-LF) to replace the tobacco Prrn
Appeal 2019-003468
Application 13/865,146

8
promoter and T7 gene 10 (G10) 5′ regulatory sequence with a lettuce
(L. sativa) promoter and psbA 5′ UTR regulatory sequence. Ruhlman
provides a reason to make the modification, because it states that the authors
themselves were developing constructs for lettuce that included the
endogenous psbA 5′ UTR, with an expectation of increasing expression of
heterologous proteins. See Ruhlman 506, left col. Further reason to make the
modification is provided by Zou, which discloses that the sequence and
secondary conformation (folding pattern) of the psbA 5′ UTR is critical to
mRNA stability and translation efficiency of a downstream transcript.
We agree with the Examiner that, based on Zou, a skilled artisan
would reasonably expect better expression of a gene, in a lettuce cell, using
the lettuce psbA 5′ UTR sequence rather than a non-lettuce sequence,
because the lettuce sequence would be expected to be adapted to interact
correctly with the lettuce proteins involved in translation. See Ans. 16. At a
minimum, a skilled artisan would recognize that the lettuce psbA 5′ UTR,
which was undisputedly known in the prior art, would be functionally
equivalent to Ruhlman’s tobacco psbA 5′ UTR when used in a vector for
chloroplast transformation in lettuce cells. “[W]hen a patent claims a
structure already known in the prior art that is altered by the mere
substitution of one element for another known in the field, the combination
must do more than yield a predictable result.” KSR Int’l Co. v. Teleflex Inc.,
550 U.S. 398, 416 (2007)
The cited references thus disclose all of the elements of claim 1 and
provide a reason to combine them in the manner claimed.
Appeal 2019-003468
Application 13/865,146

9
Appellant argues that those skilled in the art would not have modified
Ruhlman’s vector to increase expression because Ruhlman discloses that
“the expression levels obtained in the lettuce expression system lacking the
endogenous 5′ psbA UTR . . . ‘were sufficient to proceed with animal or
preclinical studies.’” Appeal Br. 10. Appellant argues that,
[i]n stark contrast the present specification provides vectors,
plants and methods of transforming plants to increase
translation efficiency. . . . [I]t logically follows that the
“motivation” . . . has been improperly gleaned from Applicant’s
own specification and that the combination of Ruhlman, Shi
and Zou is an exercise of impermissible hindsight.
Id. at 11.
This argument is unpersuasive. Ruhlman itself expresses a desire to
improve expression levels in its lettuce expression system. See Ruhlman
506, left col. (“[C]onstructs for lettuce . . . will employ lettuce endogenous
translation elements, such as psbA 5′ UTR, to further increase the level of
expression.”). And the fact that something is described as good enough for
some purposes doesn’t mean that people wouldn’t want to improve it. See,
e.g., Dystar Textilfarben Gmbh & Co. Deutschland KG v. C.H. Patrick Co.,
464 F.3d 1356, 1368 (Fed. Cir. 2006) (“[T]he desire to enhance commercial
opportunities by improving a product or process is universal—and even
common-sensical.”).
Appellant argues that the “Examiner has not provided any rationale
supporting that the notion that . . . [the psbA 5′ UTR modifications]
described in Zou would lead the skilled artisan to employ the endogenous
lettuce 5′ psbA UTR 142 bp sequence in lettuce plants.” Appeal Br. 13.
Appellant argues that Zou “note[s] conflicting results and species differences
Appeal 2019-003468
Application 13/865,146

10
regarding the functionality of the 5′ psbA UTR in maintaining mRNA
stability.” Id.
Appellant argues that, based on Zou, “the skilled person might
conclude that the 5′ psbA UTR in tobacco was essential. This disclosure is
silent regarding the utility of this element in other plants.” Id. Appellant
concludes that
[t]here is absolutely no basis for the Examiner’s assertion that
the skilled person would conclude based on this combination of
references that the “lettuce psbA 5′ UTR of SEQ ID NO: 22
would work better in lettuce than would the tobacco 5′ UTR” as
Zou et al teach that this region can be deleted in its entirety
without adverse effects in Chlamydomonas and in in vitro
tobacco based assays.
Id. at 14.
These arguments are unpersuasive. First, Ruhlman itself says that
constructs employing lettuce endogenous translation elements, including the
lettuce psbA 5′ UTR, would be expected to increase expression in lettuce
cells. Ruhlman 506, left col. That disclosure alone provides a reason to make
the proposed modification of Ruhlman’s vector with a reasonable
expectation of success.
In addition, Zou discloses that “the stem-loop of the psbA 5′UTR is
essential for both mRNA stability and translation efficiency, and . . . its
function depends on its correct sequence and secondary conformation.” Zou
341, left col. The Examiner has shown that the relevant psbA sequences
differ in tobacco and lettuce. Ans. 6. Thus, it is reasonable to expect that the
lettuce, not tobacco, psbA 5′ UTR sequence would interact optimally with
the proteins involved in translation in a lettuce cell, and therefore would
Appeal 2019-003468
Application 13/865,146

11
result in more efficient translation of a linked protein-coding sequence.
Appellant has cited no evidence that contradicts this expectation.
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) based on
Ruhlman, Shi, and Zou. Claims 12, 14, and 21 were not argued separately
and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv).
II
The Examiner has rejected claims 1, 6, and 14 as obvious based on
Kumar, Zou, and Lee. The Examiner finds that “Kumar et al [teaches]
transformation of cotton (Gossypium hirsutum) plastids” using a vector
comprising (a) cotton trnI and trnA flanking sequences, (b) “the aphA-6
selectable marker expressed from the tobacco Prrn promoter, the G10 5′ UTR,
and the rps10 3′ UTR,” and (c) “a multicloning site for expression of a gene
[of] interest from the tobacco psbA promoter, 5′ UTR and 3′ UTR.” Ans. 7.
The Examiner finds that “Kumar et al do not teach use of cotton psbA
regulatory sequences in the vectors,” but Zou teaches that “the tobacco psbA
5′ UTR interacts with trans-acting factors, and the interaction is very
specific,” and that these protein-binding sites “play crucial roles in mRNA
stabilization and translation.” Id. at 8. The Examiner finds that Lee teaches
“the sequence of the G. hirsutum chloroplast genome, including the psbA
regulatory sequences,” which are identical to SEQ ID NO:13. Id.
The Examiner concludes that it would have been obvious to “to
modify the cotton plastid transformation vectors taught by Kumar et al to
use the cotton psbA regulatory sequences.” Id. at 11. The Examiner reasons
that Zou teaches that the interaction of the psbA 5′ UTR sequence with
proteins is very sequence specific, and the relevant sequences differ between
Appeal 2019-003468
Application 13/865,146

12
cotton and tobacco, and therefore “one of ordinary skill in the art would
expect that use of the tobacco psbA 5′ UTR in lettuce plastids would result
in reduced RNA levels and translation efficiency compared to what would
be seen with the use of the cotton psbA 5′ UTR in cotton plastids.” Id. at 12.
Thus, “the tobacco psbA promoter and 5′ UTR would be replaced with the
cotton psbA promoter and 5′ UTR to get the higher expression levels Zou et
al teach are conferred by use of 5′ UTRs whose sequences match the
requirements of endogenous” proteins. Id. at 13.
We agree with the Examiner that the vector of claim 1 would have
been obvious based on the cited references. Kumar discloses cotton plastid
transformation vectors. Kumar 205, left col. The vector pKD-Gh-aphA-6
(id., Fig. 1B) includes a multiple cloning site (“MCS”) for inserting a
heterologous polynucleotide sequence; the promoter and 5′ UTR of psbA
(“PpsbAUTR5′”); the psbA 3′ terminator sequence (“TpsbA3′”); and
flanking sequences from the cotton trnI and trnA genes (“trnI,” “trnA”). Id.;
see also id. at 205, right col. (“cotton chloroplast DNA flanking sequences
. . . in the intergenic region between the trnI and trnA genes”).
The Examiner finds that Lee discloses “the sequence of the G.
hirsutum chloroplast genome, including the psbA regulatory sequences,
which have 100% identity to the instant SEQ ID NO:13.” Ans. 8. Appellant
acknowledges that “Lee et al. disclose the entire [chloroplast] genome
sequence of G. hisrsutum [sic] which contains the psbA gene.” Appeal Br.
16–17.
The Examiner relies on Zou for the same teachings discussed above
with regard to the other rejection under 35 U.S.C. § 103(a).
Appeal 2019-003468
Application 13/865,146

13
Based on the above teachings, it would have been obvious to modify
Kumar’s cotton expression vector (pKD-Gh-aphA-6) to replace the tobacco
psbA promoter and 5’ UTR with the homologous cotton psbA promoter and
5’ UTR sequences disclosed by Lee. A skilled artisan would reasonably
expect increased expression of a heterologous gene in cotton plastids from
the resulting vector because Zou discloses that the sequence and secondary
conformation (folding pattern) of the psbA 5′ UTR is critical to mRNA
stability and translation efficiency of a downstream transcript. Zou 341, left
col.
Thus, based on Zou, a skilled artisan would expect a gene to be
translated more efficiently in a cotton plastid when under the control of the
cotton psbA 5′ UTR sequence rather than the tobacco psbA 5′ UTR
sequence in Kumar’s vector. See Ans. 12–13. In addition, a skilled artisan
would recognize that the cotton psbA 5′ UTR, which Appellant
acknowledges was part of the sequence taught by Lee (Appeal Br. 16–17),
would be functionally equivalent to Kumar’s tobacco psbA 5′ UTR for use
in a vector for transforming cotton plastids.
The cited references thus disclose all of the elements of claim 1 and
provide a reason to combine them in the manner claimed.
Appellant argues that
Kumar et al. teach that the T7 gene 10 5′ UTR and rps16
3′ UTR facilitated 74.8% transgene expression in non-green
edible parts. Given the high level of expression reported in
Kumar et al., Applicant submits that the Examiner’s assertion
that the skilled person would be motivated to replace the T7
gene 10 5′ UTR with an endogenous 5′ psbA UTR is misplaced.
Appeal Br. 16.
Appeal 2019-003468
Application 13/865,146

14
This argument is unpersuasive. Appellant does not cite any specific
support for this argument, but it appears to be based on Kumar’s statement
that
[t]he T7 gene 10 5′ UTR and rps16 3′ UTR facilitated 74.8%
transgene expression in non-green edible parts (carrots)
containing chromoplasts (grown under the ground in the dark)
and 48% in proplastids, compared to chloroplasts in leaves
(100%, Kumar et al., 2004). Therefore, it is reasonable to
assume that the aphA-6 gene is expressed in nongreen and
green plastids in the light or dark.
Kumar 213, left col.
This passage, however, does not refer to the work reported in the
Kumar reference, but to earlier work (“Kumar et al., 2004”) using carrots.
Appellant does not explain why the earlier results from carrot experiments
would have deterred a skilled artisan from making the modification to
Kumar’s pKD-Gh-aphA-6 vector that the Examiner proposes. And, as
discussed above with respect to the other § 103 rejection, those skilled in the
art would be motivated to increase expression to levels above 74.8%. See
Dystar, 464 F.3d at 1368 (“[T]he desire to enhance commercial
opportunities by improving a product or process is universal—and even
common-sensical.”).
Appellant argues that “[t]he cotton transformation system
embodiment encompassed by claim 1 . . . is not found in the prior art.”
Appeal Br. 16. “Kumar et al. do not teach use of an endogenous cotton
5′ UTR.” Id. “Plastid transformation expression vectors comprising
5′ regulatory sequences consisting of SEQ ID NOS: 22, 10, 12, 13, 15, and
21 are not disclosed in the combined disclosures of Kumar, Zou and Lee et
al.” Id.
Appeal 2019-003468
Application 13/865,146

15
However, the instant rejection is based on obviousness, not
anticipation. Thus, the relevant question is not whether the claimed
invention is “found in” or “disclosed in” the prior art, or whether Kumar
discloses all of the limitations of claim 1; “[t]he test for obviousness is what
the combined teachings of the references would have suggested to one of
ordinary skill in the art.” In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991)
(emphasis added). For the reasons discussed above, we agree with the
Examiner that a vector within the scope of claim 1 would have been obvious
based on the combined teachings of the references.
Appellant argues that
[t]he Examiner again relies on Zou et al. who disclose that the
tobacco psbA 5′ UTR is an important determinant of mRNA
stability and translation efficiency. . . . As above, the Examiner
has not provided any rationale motivating the skilled person to
substitute the 5′ UTR employed by Kumar with the cotton
5′ psbA UTR of SEQ ID NO: 13 sequence for enhancing
expression of transgenes in cotton plants.
Appeal Br. 17. Appellant argues that “there is absolutely no basis for the
Examiner’s assertion that the skilled person would conclude based on this
combination of references that the ‘cotton psbA 5′ UTR would induce higher
protein production’ as very high protein production was observed in the
system.”
This argument is unpersuasive for the reasons discussed with regard to
the other § 103 rejection: Zou discloses that the sequence and folding pattern
of the psbA 5′ UTR are critical to its efficient functioning; the Examiner has
shown that the psbA 5′ UTR sequences from tobacco and cotton differ (Ans.
12); and, therefore, it is reasonable to expect that the cotton psbA 5′ UTR
sequence would function more efficiently in cotton plastids than would the
Appeal 2019-003468
Application 13/865,146

16
corresponding sequence from tobacco. Appellant has cited no evidence to
the contrary.
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) based on
Kumar, Zou, and Lee. Claims 6 and 14 were not argued separately and
therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv).
III
The Examiner has provisionally rejected all of the claims on appeal
for obviousness-type double patenting based on claims 4, 5, 11, 20, and 26–
31 of application 12/059,376, combined with Shi. The Examiner finds that
the ’376 application claims a plastid vector very similar to that of claim 1,
and including “a L. sativa psbA 5′ UTR,” but “does not claim the specific
sequence of the L. sativa psbA 5′ UTR as being that of SEQ ID NO:22.”
Ans. 13–14.
The Examiner finds that, as discussed above, Shi teaches the sequence
of the L. sativa psbA 5′ UTR (SEQ ID NO:22). Id. at 14. The Examiner
concludes it would have been obvious “to use the L. sativa psbA 5′ UTR
taught by Shi et al in the plastid transformation vector claimed in” the ’376
application. Id. The Examiner reasons that the “selection of one L. sativa
psbA 5′ UTR over another,” including start and stop points, is a design
choice, as is the selection of a specific promoter that would function in a
plastid. Id.
We agree with the Examiner that the cited claims are not patentably
distinct. Claim 4 of the ’376 application reads as follows:
4. A Lactuca sativa homoplasmic plant cell for producing
cholera toxin B subunit-proinsulin (CTB-Pins) comprising
plastids transformed to express CTB-Pins, said plastids
Appeal 2019-003468
Application 13/865,146

17
comprising an expression cassette of the following operably
linked components, a promoter operative in said plastid, a
selectable marker sequence, a psbA 5′ UTR translation element
endogenous to Lactuca sativa, a heterologous polynucleotide
sequence encoding said proinsulin expressed as a fusion protein
conjugated to cholera toxin B subunit (CTB), and a
transcription terminator functional in said plastid, said
expression cassette being flanked by sequences which are
homologous to DNA sequences of the Lactuca sativa plastid
and facilitate homologous recombination of said expression
cassette into said Lactuca sativa plastid genome in the
intergenic region between trnI and trnA genes, said selectable
marker sequence encoding an antibiotic-free selectable marker,
wherein said plant cell produces a lettuce plant producing
cholera toxin B subunit-proinsulin upon propagation.
’376 application, Appeal Brief8 filed March 27, 2018, at 29 (Claims App’x).
The conflicting claims are not identical but we conclude that they are
not patentably distinct from each other, either. Claim 4 of the ’376
application is directed to a lettuce cell, while claim 1 on appeal is directed to
a vector; however, the claimed vector is optimized for expression in a target
plant species, one of which is lettuce, so a lettuce cell containing the vector
and the vector itself are not patentably distinct.
As to the vector itself, both claims recite a selectable marker (optional
in instant claim 1), flanking sequences from the spacer region between trnI
and trnA, a transcription terminator, and a promoter. Claim 4 of the ’376
application recites a generic promoter while claim 1 on appeal requires that
the promoter includes a 5′ UTR psbA sequence, and both claims recite a
5′ UTR psbA sequence from L. sativa. Instant claim 1 requires the 5′ UTR

8 The ’376 application is the subject of Appeal 2018-008360, which will be
decided in due course.
Appeal 2019-003468
Application 13/865,146

18
psbA sequence to be SEQ ID NO: 22, while claim 4 of the ’376 application
does not require a specific sequence. However, SEQ ID NO: 22 is disclosed
by Shi to be a 5′ UTR psbA sequence from L. sativa, so SEQ ID NO: 22 is at
least an obvious species of the genus of 5′ UTR psbA sequences from L.
sativa.
Finally, claim 4 of the ’376 application requires a specific
heterologous polynucleotide sequence, while claim 1 on appeal is open to
inclusion of any heterologous polynucleotide sequence. However, “a later
genus claim limitation is anticipated by, and therefore not patentably distinct
from, an earlier species claim.” Eli Lilly & Co. v. Barr Labs., Inc., 251 F.3d
955, 971 (Fed. Cir. 2001).
We conclude that claim 1 on appeal is an obvious variant of the
invention claimed in the ’376 application.
Appellant argues that “claim 1 recites features not disclosed in the
’376 application and the addition of Shi et al. does not rectify this
deficiency.” Appeal Br. 1.
The Examiner, however, acknowledges that the two claims are not
identical. Ans. 14. Appellant’s argument does not address the issue of why
the acknowledged differences between the claims make them patentably
distinct from each other. The argument therefore is not persuasive.
Appellant also argues that “the constructs encompassed by the claims
of the ’376 contain a unique insulin encoding sequence.” Appeal Br. 18.
This argument is also unpersuasive. As discussed above, the specific
heterologous polynucleotide sequence recited in the ’376 application’s
claims is a species encompassed by the genus recited in instant claim 1, and
Appeal 2019-003468
Application 13/865,146

19
a later generic limitation is not patentably distinct from an earlier limitation
reciting a species within the genus. Eli Lilly, 251 F.3d at 971.
We affirm the provisional obviousness-type double patenting rejection
of claim 1 based on claims 4, 5, 11, 20, and 26–31 of application
12/059,376, combined with Shi. Claims 6, 12, 14, and 21 were not argued
separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv).
SUMMARY
We affirm all of the rejections on appeal.
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