Ex Parte Schröder et al

Patent Trial and Appeal Board

Aug 22, 2018

13516034 (P.T.A.B. Aug. 22, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/516,034 06/14/2012
123223 7590 09/18/2018
Drinker Biddle & Reath LLP (WM)
222 Delaware A venue, Ste. 1410
Wilmington, DE 19801-1621
FIRST NAMED INVENTOR
Hartwig Schroder
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
074008-1412-US (286259) 1095
EXAMINER
RAMIREZ, DELIA M
ART UNIT PAPER NUMBER
1652
NOTIFICATION DATE DELIVERY MODE
09/18/2018 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):
IPDocketWM@dbr.com
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HARTWIG SCHRODER, WEOL KYU JEONG,
ANNEGRET SERWE, and OSKAR ZELDER
Appeal2017-007193
Application 13/516,034
Technology Center 1600
Before JEFFREY N. FRED MAN, RICHARD J. SMITH, and
DAVID COTTA, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134 involving claims to a
recombinant Corynebacterium. The Examiner rejected the claims as
obvious under 35 U.S.C. § 103(a) and on the grounds ofnonstatutory double
patenting. We have jurisdiction under 35 U.S.C. § 6(b ). We affirm.
1 Appellants identify the Real Party in Interest as BASF SE (see App. Br. 1 ).
2 We have considered and herein refer to the Specification of June 14, 2012
("Spec."); Final Office Action of Sept. 10, 2015 ("Final Action"); Appeal
Brief of Sept. 12, 2016 ("App. Br."); and Examiner's Answer of Jan. 19,
2017 ("Answer").
Appeal2017-007193
Application 13/516,034
Statement of the Case
Background
"[T]he present invention provides a microorganism which has an
intracellular lysine decarboxylase activity and an enhanced lysine import
activity" and produces cadaverine (Spec. 1 :30-31, 35). The microorganism
has "no or a decreased acetylcadaverine-forming activity" (Spec. 2:14). The
"preferred ... species" of the microorganism is "Corynebacterium
glutamicum" (Spec. 8:21 ).
The Claims
Claims 1, 2, 5, 8-10, 12, 14--16, 18, 20, 24, and 25 are on appeal.
Claim 1 is representative and reads as follows:
1. A recombinant Corynebacterium comprising no or a
decreased acetylcadaverine-forming activity, an intracellular
lysine decarboxylase activity, and an enhanced lysine import
activity as compared to a naturally-occurring Corynebacterium
from which said recombinant Corynebacterium is derived,
wherein the acetylcadaverine-forming activity is decreased due
to insertions or deletions within a gene encoding an
acetylcadaverine-forming polypeptide comprising an amino
acid sequence being at least 95% identical to SEQ ID NO: 11,
and wherein the lysine import activity is enhanced due to
insertions or deletions within a gene encoding a lysine exporter
polypeptide comprising an amino acid sequence which has at
least 95% sequence identity to SEQ ID NO: 3.
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Application 13/516,034
The Rejections3
A. The Examiner rejected4 claims 1, 2, 5, 8-10, 14--16, 20, 24, and
25 under 35 U.S.C. § 103(a) as obvious over Zelder, 5 Mimitsuka, 6
Mimizuka 17, Mimizuka 28, Kikuchi9, Meng 10, Mateos 11, and Vrljic 12 (Ans.
2-7).
B. The Examiner rejected claims 12 and 18 under 35 U.S.C.
§ 103(a) as obvious over Zelder, Mimitsuka, Mimizuka 1, Mimizuka 2,
3 The Examiner objected to claims 9 and 40 (Final Act. 3). Appellants state
that they "will take appropriate actions to address these objections upon
resolution of the instant Appeal" (App. Br. 5).
4 The rejection heading includes claims 38 and 39; however, these claims are
not on appeal.
5 Zelder et al., WO 2007/113127 Al, published October 11, 2007.
6 Mimitsuka et al., Metabolic Engineering of Corynebacterium glutamicum
for Cadaverine Fermentation, 71(9) BIOSCI. BIOTECHNOL. BIOCHEM., 2130-
2135 (2007).
7 Mimizuka et al., JP 2002-223770 A, published August 13, 2002.
8 Mimizuka et al., JP 2004-222569 A, published August 12, 2004.
9 Kikuchi et al., Characterization of a second lysine decarboxylase isolated
from Escherichia coli, 179(14) J. BACTERIOL., 4486-4492 (1997).
10 Meng et al., Nucleotide Sequence of the Escherichia coli cad Operon:
a System for Neutralization of Low Extracellular pH, 174(8) J. BACTERIOL.,
2659-2669 (1992).
11 Mateos et al., Nucleotide Sequence of the Homoserine Dehydrogenase (thr
A) Gene of Brevibacterium Lactofermentum, 15 NUCLEIC Acrns RES. 10598
(1987).
12 Vrljic et al., A New Type of Transporter with a New Type of Cellular
Function: L-lysine Export from Corynebacterium Glutamicum, 22 MOL.
MICROBIOL., 815-826 (1996).
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Application 13/516,034
Kikuchi, Meng, Mateos, Vrljic, Soksawatmaekhin13 , and Nakagawa 14 (Ans.
7-8).
C. The Examiner rejected 15 claims 1, 2, 5, 8-10, 12, 14--16, 18,
20, 24, and 25 on the grounds of nonstatutory obviousness type double
patenting over claims 1-3 of US 9,745,608 B2 in view of Mimitsuka (Final
Act. 13).
D. The Examiner rejected claims 1, 2, 5, 8-10, 14--16, 20, 24, and
25 on the grounds of nonstatutory obviousness type double patenting over
claims 1-3 and 10-15 of U.S. 8,741,623 B2 in view ofMimitsuka,
Mimizuka 1, Mimizuka 2, Kikuchi, Meng, Mateos, and Vrljic (App. Br. 6).
E. The Examiner rejected claims 12 and 18 on the grounds of
nonstatutory obviousness type double patenting over claims 1-3 and 10-15
of U.S. 8,741,623 B2 in view ofMimitsuka, Mimizuka 1, Mimizuka 2,
Kikuchi, Meng, Mateos, Vrljic, Soksawatmaekhin, and Nakagawa (App. Br.
6).
A andB. Obviousness
Because both of the obviousness rejections tum on the same issue and
rely upon the basic combination of Zelder, Mimitsuka, Mimizuka 1,
13 Soksawatmaekhin et al., Excretion and uptake of cadaverine by CadB and
its physiological functions in Escherichia coli, 51(5) MOL. MICROBIOL.,
1401-1412 (2004).
14 Nakagawa, Corynebacterium glutamicum ATCC 13032 DNA, complete
genome, GenBank accession number BA000036.3, (2004), GenBank
accession number BAC00096, 2002, protein; http://www.ncbi.nlm.nih.gov/
nuccore/42602314?sat=34&satkey=2171562.
15 Copending Application No. 13/985,330 issued as US 9,745,608 B2 on
August 29, 2017. This rejection is therefore no longer provisional.
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Mimizuka 2, Kikuchi, Meng, Mateos, and Vrljic, we will consider them
together.
We begin with claim interpretation. The Specification states that the
"term 'decreased activity' includes the expression of a gene product, e.g. of
a lysine exporter molecule, spermidine synthase, homoserine dehydrogenase
or others, at a lower level than that expressed prior to manipulation of the
microorganism or in a comparable microorganism which has not been
manipulated" (Spec. 15 :7-10). Therefore, consistent with the Specification,
a decreased acetylcadaverine forming activity will be interpreted as any
decrease in the amount of acetylcadaverine as compared to the amount
formed by the naturally-occurring bacterium. Similarly, an enhanced lysine
import activity will be interpreted as any increase in the amount of
intracellular lysine as compared to the naturally-occurring bacterium.
Consistent with the Specification and claims, this increase or decrease is due
to insertions and deletions in the claimed sequences.
The Examiner finds that Zelder teaches:
a process for the production of cadaverine by constructing a C.
glutamicum mutant strain from a lysine producer LUl 1271,
wherein said mutant strain is obtained by genetically modifying
the LUl 1271 strain to (i) introduce a disruption in an
endogenous gene encoding an acetyltransferase responsible for
the formation of acetyl cadaverine ... and [to] (ii) introduce a
plasmid comprising the E. coli cadA and ldcC genes which
encode lysine decarboxylases.
(Ans. 2-3.)
The Examiner finds that the "acetyltransferase of Zelder et al. is
98.4% sequence identical to the polypeptide of SEQ ID NO: 11" (Ans. 3).
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The Examiner finds that Zelder teaches "(a) Mimizuka 1 discloses the
production of cadaverine by introducing a lysine decarboxylase and a
lysine/ cadaverine anti porter into a lysine producing organism, and (b)
Mimizuka 2 teaches the production of cadaverine by culturing a
microorganism that has lysine decarboxylase activity and homoserine
auxotrophy" (Ans. 3).
The Examiner finds that Mimitsuka teaches that "disruption of the
gene encoding homoserine dehydrogenase in C. glutamicum allows C.
glutamicum to produce L-lysine (homoserine auxotrophy) and that L-lysine
is a precursor of cadaverine since L-lysine is converted into cadaverine in a
reaction catalyzed by lysine decarboxylase" (Ans. 4).
The Examiner finds that Vrljic teaches that the sequence of the "C.
glutamicum lysine exporter [is] SEQ ID NO: 3" and that the "lysine exporter
specifically exports L-lysine from the cell" (Ans. 4).
The Examiner finds that a person of ordinary skill in the art would be:
motivated to further modify the C. glutamicum mutant strain of
Zelder et al. as described above for the benefit of improving the
production of cadaverine. As indicated above, Mimitsuka et al.
specifically teach that disruption of the gene encoding
homoserine dehydrogenase in C. glutamicum allows C.
glutamicum to produce L-lysine, which can then be converted
to cadaverine via lysine decarboxylase. A person of ordinary
skill in the art is motivated to disrupt the gene encoding the
lysine exporter of SEQ ID NO: 3 for the benefit of improving
the production of cadaverine since Mimitsuka et al. teach that
L-lysine is a precursor of cadaverine and Vrljic et al. teach that
a functional lysine exporter would direct intracellular L-lysine
to the culture medium. Thus, disruption of the endogenous gene
encoding the lysine exporter of SEQ ID NO: 3 would allow
more lysine to stay in the cell and be available for intracellular
cadaverine production.
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(Ans. 6.)
The issue with respect to these rejections is: Does the evidence of
record support the Examiner's conclusion that the combination of Zelder,
Mimitsuka, Mimizuka 1, Mimizuka 2, Kikuchi, Meng, Mateos, and Vrljic
renders the claims obvious?
Findings of Fact
1. Zelder teaches a "process for the production of cadaverine" by
"the use of recombinant microorganism comprising DNA molecules in a
deregulated form which are essential to produce cadaverine" (Zelder 1:5-7).
"acetylcadaverine-forming activity"
2. Zelder teaches that "a significant portion of the cadaverine
produced in the microorganism according to the inventive process is
acetylated" and "to block this acetylation reaction ... and in order to
increase the yield of cadaverine it is a preferred embodiment of the invention
to deregulate the diamine acetyltransferase ... to decrease its activity, e.g.
by deletion or disruption of the gene" (Zelder 9:20-26).
3. Zelder teaches the details of constructing a mutant C.
glutamicum by disrupting the acetyltransferase gene (Zelder 16-18).
4. Zelder teaches that a mutant C. glutamicum with a disrupted
acetyltransferase gene "showed no accumulation of acetylcadaverine" and
"cadaverine productivity was improved by disruption of the gene resulting in
elimination of acetylcadaverine formation" (Zelder 17: 18-21 ).
5. Zelder provides the sequence for the acetyltransferase gene
(Zelder 17:26-18:6). The Examiner finds this sequence is greater than 95%
identical to SEQ ID NO: 11 (see Ans. 3).
"lysine decarboxylase activity"
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6. Zelder teaches that lysine decarboxylase "catalyzes the
decarboxylation of L-lysine into cadaverine" (Zelder 4:30).
7. Zelder teaches "a lysine decarboxylase activity, is introduced
into a microorganism where the respective gene activity, e.g. the lysine
decarboxylase activity, has not been observed before ... preferably by
means of genetic engineering" (Zelder 4:24--28).
8. Zelder teaches that the mutant includes a lysine decarboxylase
gene (Zelder 14:31, 16-17).
9. Zelder teaches "[i]n the broth cultured with all recombinant
strains containing the lysine decarboxylase genes a significant amount of
cadaverine was accumulated" (Zelder 15:11-12).
10. Mimitsuka teaches a C. glutamicum with a lysine decarboxylase
gene that produces cadaverine from L-lysine (Mimitsuka 2130).
"lysine exporter polypeptide"
11. Mimitsuka teaches: "Cadaverine, the expected raw material of
polyamides, is produced by decarboxylation of L-lysine. If we could
produce cadaverine from the cheapest sugar, and as a renewable resource, it
would be an effective solution against global warming" (Mimitsuka 2130).
12. Mimitsuka teaches "it should be possible to convert L-lysine to
cadaverine completely by allowing the reaction to run for several min, but L-
lysine in the medium was not converted to cadaverine" (Mimitsuka 2134
(col. 2)).
13. Vrljic teaches "identification of lysE, which encodes the
translocator specifically exporting L-lysine from the cell" (Vrljic 815).
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14. Vrljic teaches that a mutant without a lysine exporter is unable
to secrete lysine and will accumulate an "extremely high concentration of'
"intracellular lysine" (Vrljic 820 ( col. 1 )).
15. Vrljic teaches that C. glutamicum 's lysine exporter has a
sequence of SEQ ID NO: 3 (Vrljic 817, Fig. 2).
16. Figure 8 of Vrljic is reproduced below:
Sugar
L-Lysine syn thesis
I \ Hydrolysis
Flux increase Flux increa/e
by artificial by methionine
mutation excess
\ i
Celi"material
L-Lysine
"Fig. 8. The physiological function of the L-lysine exporter in C.
glutamicum. The exporter serves to excrete an excess of L-lysine" (Vrljic
821 (col. 1)).
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17. Figure 2 of Mimitsuka is reproduced below:
"Fig. 2. Strategy of Cadaverine Fermentation by C. glutamicum" showing
that intracellular lysine is a precursor for cadaverine synthesis (Mimitsuka
2131 ( col. 2)).
Principles of Law
A prima facie case for obviousness requires "a reason that would have
prompted a person of ordinary skill in the relevant field to combine the
elements in the way the claimed new invention does" KSR Int 'l Co. v.
Teleflex Inc., 550 U.S. 398, 418 (2007).
Analysis
We adopt the Examiner's findings of fact and conclusions of law (see
Ans. 2-8; FF 1-16) and agree that the cited prior art renders the claims
obvious. We address Appellants' arguments below.
Appellants contend
the Examiner finds the required "reasonable expectation of
success" only in the production of a modified recombinant
Corynebacterium but not whether the cadaverine production
would have been increased as proposed. Thus, it appears that
the alleged "reasonable expectation of success" does not
support the motivation suggested by the Examiner to make the
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necessary modification so to arrive at the claimed subject
matter.
(App. Br. 8.)
We do not find this argument persuasive for two reasons. First, claim
1 does not include a limitation requiring an increase in the amount of
cadaverine production. See In re Self, 671 F.2d 1344, 1348 (CCPA 1982)
("[A]ppellant's arguments fail from the outset because ... they are not based
on limitations appearing in the claims.")
However, more importantly, Zelder specifically suggests production
of cadaverine in a recombinant C. glutamicum (FF 1, 3) and explains that
increased cadaverine levels would result from eliminating a pathway in the
cell that uses cadaverine as a precursor for acetyl cadaverine (FF 2). Zelder
evidences that "cadaverine productivity was improved by disruption of the
gene resulting in elimination of acetylcadaverine formation" (FF 4 ).
Zelder also teaches increasing cadaverine levels by adding an
enzymatic pathway that converts lysine to cadaverine, specifically lysine
decarboxylase (FF 6-7) and teaches that after inserting the lysine
decarboxylase genes "a significant amount of cadaverine was accumulated"
(FF 9).
Lastly, Zelder teaches that lysine is a precursor for cadaverine (FF 11)
and Mimitsuka teaches conversion of lysine into cadaverine in the
cadaverine synthesis pathway (FF 17). Mimitsuka explains that only lysine
in the cell, not in the extracellular medium, is useful for cadaverine synthesis
(FF 12). Based on this teaching, the Examiner notes that increasing
intracellular levels of lysine would have been expected to increase
cadaverine production to some degree by the ordinary artisan based on the
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cadaverine synthesis pathway (see Ans. 35; FF 12, 17). Vrljic teaches that a
mutant without a lysine exporter is unable to secrete lysine and will
accumulate an "extremely high concentration of' "intracellular lysine" (FF
14, 16).
Thus, the Examiner finds it would have been obvious to modify
Zelder' s obvious recombinant C. glutamicum that has active lysine
decarboxylase to produce cadaverine and inactivated acetyltransferase gene
to prevent conversion of the cadaverine to acetylcadaverine to further
inactivate the lysine exporter gene in order to maximize the intracellular
lysine pool and consequent production of cadaverine because "[i]f we could
produce cadaverine from the cheapest sugar, and as a renewable resource, it
would be an effective solution against global warming" (FF 11 ).
To the extent that Appellants directly contest the reasonable
expectation of success in generating a recombinant C. glutamicum that
increases cadaverine levels based on the three enzymatic changes, Zelder
evidences that adding a lysine decarboxylase gene and inactivating the
acetyltransferase gene increase cadaverine levels (FF 4, 9) and Vrljic
evidences that inactivating the lysine exporter gene increases levels of the
cadaverine precursor lysine (FF 14). These teachings provide evidence that
there would have been a reasonable expectation of success in producing a
recombinant C. glutamicum that increases cadaverine levels. "Obviousness
does not require absolute predictability of success ... all that is required is a
reasonable expectation of success." In re Kubin, 561 F.3d 1351, 1360 (Fed.
Cir. 2009).
Appellants contend "experimental data presented in the instant
specification actually support a conclusion that the skilled artisan would not
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have had a reasonable expectation that the production of cadaverine would
have been increased by disrupting an endogenous lysine exporter gene"
(App. Br. 9).
We are not persuaded. Appellants acknowledge that "[ d]eletion of the
lysine exporter (lysE), the strain 'LU14646 delta lysE,' results in a reduced
loss of lysine to the growth medium, but results only in the production of
additional 3.3 g/1 of cadaverine to the final production level of 9.9 g/1 of
cadaverine" (App. Br. 9). Thus, Appellants' own data shows that the level
of cadaverine produced will increase by deleting the lysine exporter.
Whether there would have been expected to be, as Appellants argue, a
"maximal capacity of the lysine decarboxylase or by a maximal level of
cadaverine which can be tolerated by the producing cell" (App. Br. 9) does
not rebut the Examiner's reasonable expectation of some degree of increase
in cadaverine levels due to reduced export of lysine (see Ans. 36). The
Examiner did not find that all the lysine would be used to produce
cadaverine, but merely that it would be "reasonable to expect some increase
in cadaverine production as a result of an increase in intracellular lysine due
to the reduction/elimination of lysine export to the medium" (Ans. 35).
Appellants contend that according to the Examiner's logic, "one ...
would ... expect an increase in acetyl-cadaverine production" in the strain
with higher cadaverine, because the strain "would not only produce the
normal level of acetyl-cadaverine, but also use the additional cadaverine
produced by the higher supply of intracellular lysine" and that an increase in
acetyl-cadaverine did not occur (App. Br. 9--10).
We find this argument unpersuasive because the Examiner "has made
no proposition as to how acetylcadaverine synthesis is impacted by deletion
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of the endogenous lysine exporter gene because the cell of Zelder et al.
already lacks acetylcadaverine synthesis ability due to the deletion of the
acetyltransferase gene" (Ans. 36 (emphasis omitted)). That is, there would
only have been an expectation of an increase in acetylcadaverine if the
acetyltransferase gene was present in the cell (FF 3). However, Zelder
teaches that deletion of this gene abolishes acetylcadaverine synthesis (FF 4)
and, therefore, the ordinary artisan would not have expected
acetylcadaverine synthesis to impact production of cadaverine in a cell
containing all three alterations.
Appellants contend
one skilled in the art would not have been motivated to combine
these two mutations (i.e. deletion of cadaverine
acetyltransferase and lysine exporter) in one strain because he
or she would not have had a reasonable expectation of success
that a higher level of cadaverine production could have been
achieved.
(App. Br. 10.) Appellants contend "the results shown by the recombinant
Corynebacterium recited in the present claims are rather unexpected and
surprising, which further evidences the nonobviousness nature of the
claimed subject matter" (App. Br. 10).
We find these arguments unpersuasive. Zelder teaches that two of the
mutations result in increased cadaverine levels (FF 4, 9). Mimitsuka teaches
"it should be possible to convert L-lysine to cadaverine" but that lysine
exported to the extracellular medium will not be converted (FF 12), so that
inactivation of the export would have been expected to result in increased
conversion of lysine to cadaverine (FF 16-17). Thus, we agree with the
Examiner that there would have been a reasonable expectation of success
because "there is absolutely no evidence to show that 10.2 g/L of cadaverine
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is near a toxicity threshold level, or that higher concentrations of cadaverine
cannot be tolerated by the lysine decarboxylase" (Ans. 37 (emphasis
omitted)).
We find the unexpected and surprising results argument unpersuasive
because Appellants do not identify any specific teaching in the Specification
or other evidence of record that identifies the results as surprising or
unexpected. "It is well settled that unexpected results must be established by
factual evidence. Mere argument or conclusory statements ... [do] not
suffice." In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995). Nor is there any
evidence that the results of the particular strains disclosed in the examples
are commensurate in scope with the breadth of claim 1 encompassing any
lysine decarboxylase gene and inactivation of any gene 95% identical to
SEQ ID NOs: 3 and 11 (see claim 1 ). Unexpected results must be
"commensurate in scope with the degree of protection sought by the claimed
subject matter." In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005).
Appellants contend that
other than asserting that the motivation to combine the
references is the production of more cadaverine, the Examiner
has not identified any particular reason that would have
prompted the skilled artisan to specifically pick and choose
these two mutations, i.e., deletion of cadaverine
acetyltransferase and deletion of lysine exporter gene, and
combine them in the way the present application does.
(App. Br. 11.) Appellants further contend that "it is clear that the
Examiner's finding of obviousness is based on the knowledge gleaned only
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from Appellants' disclosure, which constitutes an impermissible hindsight
reconstruction of the claimed invention" (App. Br. 11 ).
We do not find the Appellants' picking and choosing argument
persuasive because Zelder specifically teaches to produce cadaverine (FF 1 ),
teaches that disrupting the acetyltransferase gene increased cadaverine
production (FF 3--4), and teaches that inserting a lysine decarboxylase gene
increased cadaverine production (FF 8-9). Mimitsuka teaches that lysine
transport to the medium results in reduced cadaverine production (FF 12)
and Vrljic teaches that lysine transport to the medium can be abolished by
inactivating the lysine transporter gene (FF 14). Moreover, simply because
the prior art "discloses a multitude of effective combinations does not render
any particular formulation less obvious." Merck & Co. v. Biocraft Labs.,
Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). In Corkill, an obviousness
rejection was affirmed in light of prior art teachings that "hydrated zeolites
will work" in detergent formulations, even though "the inventors selected
the zeolites of the claims from among 'thousands' of compounds." In re
Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985).
We also find the hindsight argument unpersuasive. While we are fully
aware that hindsight bias may plague determinations of obviousness,
Graham v. John Deere Co., 383 U.S. 1, 36 (1966), we are also mindful that
the Supreme Court has clearly stated that the "combination of familiar
elements according to known methods is likely to be obvious when it does
no more than yield predictable results." KSR, 550 U.S. at 416.
Here, the Examiner has provided specific reasons based on evidence
to combine the three genetic modifications to produce a recombinant C.
glutamicum that increases cadaverine production levels (see Ans. 6). These
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reasons include Zelder's specific desire to produce cadaverine (FF 1) and
Mimitsuka's teaching that if "we could produce cadaverine from the
cheapest sugar, and as a renewable resource, it would be an effective
solution against global warming" (FF 11 ).
Appellants argue that the lysine/cadaverine and lysine exporter have
different functions, and it is unclear why upregulating one in Mimitsuka
would motivate one of ordinary skill in the art to downregulate another
(App. Br. 12). Appellants contend "[i]t is further unclear as to why one
skilled person, in view of the art disclosing the upregulation of a
lysine/cadaverine antiporter which transports lysine into a cell, would have
been motivated to down-regulate a lysine exporter which transports lysine
out of the cell" (App. Br. 12). Appellants then argue that it is unclear why a
skilled artisan "'would have been highly motivated to further reduce the
production of acetylcadaverine by disrupting the gene encoding a lysine
exporter"' (App. Br. 12).
We find these arguments unpersuasive for the reasons discussed at
length above. To briefly reiterate, Zelder expressly teaches to inactivate
acetylcadaverine synthesis to improve cadaverine production (FF 2--4).
Mimitsuka teaches that only lysine in the cell, not in the extracellular
medium, is converted to cadaverine (FF 12), thus, suggesting that it is
desirable to retain lysine in the cell for cadaverine synthesis. Vrljic teaches
that a mutant without a lysine exporter is unable to secrete lysine and will
accumulate an "extremely high concentration of' "intracellular lysine" (FF
14). The ordinary artisan would have recognized that higher levels of the
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intracellular lysine precursor would allow for higher levels of formation of
the product, cadaverine, as desired by Zelder and Mimitsuka (FF 1, 11 ).
Conclusion of Law
The evidence of record supports the Examiner's conclusion that the
combination of Zelder, Mimitsuka, Mimizuka 1, Mimizuka 2, Kikuchi,
Meng, Mateos, and Vrljic renders the claims obvious.
C. Nonstatutory Obviousness Type Double Patenting over '608 patent
Appellants do not dispute the rejection of the claims under
obviousness-type double patenting over claims 1-3 of U.S. Patent No.
9,745,608 B2 in view of Mimitsuka on the merits (see App. Br. 5). We,
therefore, summarily affirm the obviousness-type double patenting rejection
over U.S. Patent No. 9,745,608 B2. See Manual of Patent Examining
Procedure§ 1205.02 ("If a ground of rejection stated by the examiner is not
addressed in the appellant's brief, ... that ground of rejection" will be
summarily sustained by the Board.).
D. and E. Nonstatutory Obviousness Type Double Patenting
over '623 patent
U.S. Patent No. 8,741,623 B2 corresponds to Zelder (App. Br. 13).
For the reasons given above in the analysis of the obviousness rejection, we
find that that the combination of the claims of U.S. Patent No. 8,741,623 B2
in combination with Mimitsuka, Mimizuka 1, Mimizuka 2, Kikuchi, Meng,
Mateos, and Vrljic renders claim 1, 2, 5, 8-10, 14--16, 20, 24, and 25
obvious and that the combination of Mimitsuka, Mimizuka 1, Mimizuka 2,
Kikuchi, Meng, Mateos, Vrljic, Soksawatmaekhin, and Nakagawa renders
claims 12 and 18 obvious.
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Appeal2017-007193
Application 13/516,034
SUMMARY
In summary, we affirm the obviousness and obviousness-type double
patenting rejections.
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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