Thomas Haas et al.

Patent Trials and Appeals Board

Jan 2, 2020

14367610 - (D) (P.T.A.B. Jan. 2, 2020)

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.
14/367,610 06/20/2014 Thomas Haas 435754US99PCT 8227
22850 7590 01/02/2020
OBLON, MCCLELLAND, MAIER & NEUSTADT, L.L.P.
1940 DUKE STREET
ALEXANDRIA, VA 22314
EXAMINER
RAGHU, GANAPATHIRAM
ART UNIT PAPER NUMBER
1652
NOTIFICATION DATE DELIVERY MODE
01/02/2020 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):
OBLONPAT@OBLON.COM
iahmadi@oblon.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 THOMAS HAAS, OLIVER THUM,
JAN CHRISTOPH PFEFFER, PHILIP ENGEL,
CHRISTIAN GEHRING, and MARKUS POETTER
____________

Appeal 2018-003341
Application 14/367,610
Technology Center 1600
____________

Before DONALD E. ADAMS, ULRIKE W. JENKS, and JOHN G. NEW,
Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims as obvious. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42(a). Appellant identifies the real party in interest as Evonik Degussa
GmbH. Appeal Br. 2.
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STATEMENT OF THE CASE
Claims 1, 5–10, 12–16, 19–22, and 25–28 are on appeal, and can be
found in the Claims Appendix of the Appeal Brief. Claim 1, reproduced
below, is illustrative of the claimed subject matter2:
Claim 1: A prokaryotic microorganism expressing a
recombinant alkane oxidase, wherein:
the expressed recombinant alkane oxidase is AlkB from
Pseudomonas putida GPo1 comprising the sequence of SEQ ID
NO: 1 or a variant thereof having at least 90% identity to SEQ
ID NO: 1;
the prokaryotic microorganism has a reduced fatty acid
degradation capacity compared to its wild type, and the fatty
acid degradation capacity is reduced by deletion, inhibition or
inactivation of a gene encoding an enzyme involved in a β-
oxidation pathway; the enzyme involved in the β-oxidation
pathway is selected from the group consisting of:
a fatty acid importer comprising the sequence
of SEQ ID NO: 2 or a variant thereof having at least
90% identity to SEQ ID NO: 2,
a fatty acid-CoA ligase comprising the
sequence of SEQ ID NO: 3 or a variant thereof
having at least 90% identity to SEQ ID NO: 3,
an acyl-CoA dehydrogenase comprising the
sequence of SEQ ID NO: 4 or a variant thereof
having at least 90% identity to SEQ ID NO: 4,
an enoyl-CoA hydratase comprising the
sequence of SEQ ID NO: 5 or a variant thereof having
at least 90% identity to SEQ ID NO: 5, and
a 3-ketoacyl-CoA thiolase comprising the
sequence of SEQ ID NO: 6 or a variant thereof having
at least 90% identity to SEQ ID NO: 6; and

2 Examiner identifies SEQ ID NOs: 2, 3, 5–13, and 16–19 as being directed
to a non-elected invention. Final Act. 2–3.
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the prokaryotic microorganism is suitable for oxidizing an
alkyl.
Appeal Br. 23–24 (Claims Appendix).
REFERENCES
The prior art relied upon by Examiner is:
Name Reference Date
Sieber et al. (“Sieber”) US 8,841,096 B2 Sept. 23, 2014
Karau et al. (“Karau”) US 9,012,227 B2 April 21, 2015
Jessen et al., (“Jessen”) US 9,090,918 B2 July 28, 2015
Gaertner US 2011/0162259 Al July 7, 2011
Campbell and Cronan Jr., The Enigmatic Escherichia coli fadE Gene Is
yafH, 184 J. BACTERIOLOGY 3759–64 (2002) (“Campbell”)
Handke et al., Application and engineering of fatty acid biosynthesis in
Escherichia coli for advanced fuels and chemicals, 13 METABOLIC
ENGINEERING 28–37 (2011) (“Handke”)
Lennen et al., A Process for Microbial Hydrocarbon Synthesis:
Overproduction of Fatty Acids in Escherichia coli and Catalytic
Conversion to Alkanes, 106 BIOTECHNOLOGY AND BIOENGINEERING 193–
202 (2010) (“Lennen”)
van Beilen and Funhoff, Expanding the alkane oxygenase toolbox: new
enzymes and applications, 16 CURRENT OPINION IN BIOTECHNOLOGY 308–
14 (2005) (“van Beilen”)
REJECTION
Appellant requests review of the rejection of claims 1, 5–10, 12–16,
19–22, and 25–28 under pre-AIA 35 U.S.C. § 103(a) as unpatentable over
Karau, in view of Gaertner, Lennen, Handke, Campbell, Sieber, Jessen, and
van Beilen.
ANALYSIS
Appellant contends that Examiner made a new ground of rejection
adding Gaertner to the previous combination, but never adequately addresses
Appellant’s rebuttal evidence of unexpected results. Appeal Br. 9.
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Appellant [contends that their] rebuttal arguments were
sufficient to overcome the previous rejection over the
combination of Karau, Lennen, Handke, Campbell, Sieber,
Jessen and van Bielen, then these rebuttal arguments also were
sufficient to overcome the rejection when Gaertner was added
as a new secondary reference. This is because when
considering rebuttal arguments based on unexpected results, the
proper comparison is to the closest prior art (Karau). . . .
Instead, the showing of unexpected results compared to Karau
rebuts any case of prima facie obviousness using Karau as a
primary reference.
Id. at 11. Appellant identifies Karau is the closest prior art. Id. at 9.
We are not persuaded by Appellant’s contention that Examiner’s
withdrawal of the prior rejection relying on all but the Gaertner reference
(see Non-Final Act. 3–4) supports the position that Examiner was persuaded
by Appellant’s prior unexpected results argument. Examiner indicated that
the prior rejection “is being withdrawn upon further review and
reconsideration.” Non-Final Act. 4. Although Examiner did not articulate
the underlying reasons for reformulating the rejection, there is no reason to
conclude that Examiner was persuaded by Appellant’s argument of
unexpected result.
We turn to Examiner’s prima facie case. We have reviewed the
record and agree with Examiner’s factual findings and conclusion, as set out
in the Non-Final Action and Answer which we adopt and incorporate herein
by reference. To summarize, Examiner finds that Karau teaches a
recombinant E. coli comprising an alkane oxidase/alkane monooxygenase
having the same sequence as listed in claim 1. Non-Final Act. 7. Examiner
finds that Karau teaches increased production of carboxylic acid esters when
the alkaline oxidase is overexpressed in conjunction with an alcohol
dehydrogenase, an amino acid dehydrogenase, a transaminase, and an
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alanine dehydrogenase. Id. Karau supports increasing the production of
precursors of fatty acids leading to increased fatty acid production.
Examiner acknowledges that Karau does not disclose using a modified E.
coli that has reduced fatty acid degradation capacity. Id.
Examiner finds that Gaertner teaches a recombinant E. coli with
reduced fatty acid degradation capacity. Non-Final Act. 8. Gaertner (as
well as some of the other cited references) supports the position that the
disruption of fatty acid metabolism allows for fatty acid accumulation.
Examiner concludes that it is obvious to combine:
[A] host cell involving enhancing the activities of enzymes that
are involved in the synthesis of precursors/intermediate
products and the enhanced production of final product
carboxylic acid esters [taught in Karau] and disrupting the
activities of enzymes in said host cell that divert the
precursors/intermediate products (fatty acid derivatives)
towards formation other unwanted by-products/i.e., break down
of intermediate fatty acid derivatives [taught in Gaertner (as
well as others)],
Id. at 14. Put another way, Examiner finds it obvious to combine Karau’s
recombinant E. coli mechanism that increases the production of carboxylic
acid esters, precursors in the fatty acid production, with Gaertner’s E. coli
mechanism that reduces the ability of the cells to degrade fatty acids in order
to produce a third organism that incorporates both mechanisms in order to
improve fatty acid accumulation. According to Examiner, “[m]otivation to
generate such a modified microorganism derives from the fact that fatty acid
derivatives and carboxylic acid esters of said fatty acid derivatives are
commercial products of importance and useful in the preparation of fine
chemicals, oil, biofuels and in plastic industry.” Id. We find no error with
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Examiner’s rationale and agree with Examiner’s conclusion that the claims
are obvious.
Because Examiner presents a prima facie case of obviousness, we
consider whether Appellant submits sufficient evidence or argument in
rebuttal. In re Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993); In re Hedges,
783 F.2d 1038, 1039 (Fed. Cir. 1986) (“If a prima facie case is made in the
first instance, and if the applicant comes forward with reasonable rebuttal,
whether buttressed by experiment, prior art references, or argument, the
entire merits of the matter are to be reweighed”). Evidence rebutting a
prima face case of obviousness may include “[e]vidence of unexpected
results.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1369 (Fed. Cir. 2007).
“[W]hen unexpected results are used as evidence of nonobviousness, the
results must be shown to be unexpected compared with the closest prior art.”
In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991). The
unexpected results must be “different in kind and not merely in degree from
the results of the prior art.” In re Applied Materials, Inc., 692 F.3d 1289,
1297 (Fed. Cir. 2012).
Appellant directs us to the Declaration of Dr. Thum3 and the
originally filed Specification. Appeal Br. 8. Appellant contends that the
unexpected results in the Specification show improved phase separation and
lower oxygen consumption. Id. at 14.
The Specification describes “[t]he conversion of lauric acid methyl
ester to ω -amino lauric acid (ALS) methyl ester, via ω-hydroxy lauric acid,
. . . from DASGIP, using strains W3110 ∆FadE [alkB-alaD-TA] and W3110

3 Declaration under 37 C.F.R. § 1.132 by Dr. Oliver Thum signed August
25, 2016 (“Thum Declaration”).
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[alkB-alaD-TA].” Spec. 19:5–7. The Specification describes E. coli strain
W3110 [alkB-alaD-TA] as the wild type (WT). Id. at 18:31–32. Figure 4 of
the Specification compares the production of ω-amino lauric acid methyl
ester over time.

The figure shows the amount ω-amino lauric acid methyl ester product
produced by the two different E. coli strains tested. According to the
Specification, “[t]he amount of product formed by both strains is comparable
(Fig. 4), in fact the yield is slightly better in case the mutant is used.” Spec.
21: 26–27.
The Thum Declaration shows a figure of an E. coli (strain W3110
∆FadE [alkB]) “with knocked-out fatty acid dehydrogenase (∆fadE)
accumulated over 50 % more of 1-dodecanol oxidation products” when
compared E.coli (strainW3110 [alkB]) comprising increased oxidoreductase
AlkB. Thum Dec. ¶¶ 5, 6, 16. The figure, reproduced below, shows sum of
oxidation products of 1-dodecanol.
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Id. ¶ 16.
Providing evidence of allegedly unexpected results, however, does not
necessarily mean that the evidence presented is persuasive. Here,
Examiner’s position is that the results shown in the Thum Declaration,
specifically, the figure reproduced above are expected based on the cited
references. Ans. 29– 32. Examiner explains that
the sum products of oxidation of 1-dodecanol is around ~1.63
fold increase (13/8 = ~1.63 fold) between E.coli comprising
alKB and ∆fadE (deletion) yields -13.0 mg/l and E.coli
comprising alKB alone yields ~8.0 mg/l. This result of the
instant invention i.e. yield of fatty acid derivative a ~1.63 fold
increase in yield is very much expected and predictable based
on the combined teachings [of the references].
Id. at 29 (emphasis removed). Examiner finds that Karau suggests product
yields of 10–10,000 times more than for wild type cells can be expected. Id.
(citing Karau 2:56–65). Examiner finds that Gaertner also teaches increased
production of fatty acid derivatives (in the range of 0.5–50 g/ 100 g glucose).
Id. at 30–31. Contrary to Appellant’s contention, Examiner has not ignored
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Appellant’s unexpected result rebuttal but instead has found that is the
results are not persuasive based on the teachings in the art. See Ans. 29–32.
We have reviewed Appellant’s contentions in light of Examiner’s
rebuttals as set out in the Answer and Non-Final Action and find no error
with Examiner’s position. We further note that the data provided in the
Specification as well as Thum Declaration does not provide a comparison to
E. coli host cells without additions or deletions. For example, both the
Specification and the Thum Declaration use the following modified strains
W3110 ∆FadE [alkB-alaD-TA] and W3110 [alkB-alaD-TA] in their
experiments. Contrary to Appellant’s assertion (see Appeal Br. 14), the
Specification does not recognize that the yield between the two strains is
unexpected. See Spec. 21: 26–27 (“[t]he amount of product formed by both
strains is comparable (Fig. 4), in fact the yield is slightly better in case the
mutant is used.”). Describing something as being “slightly better” does not
persuade us that the results are unexpected, especially when balanced against
the teachings in the prior art. What is missing from the results presented in
the Specification and the Thum Declaration are comparisons to an E. coli
strain that has no modification and a strain that only contains a deletion in
∆FadE. Without such comparison, it is difficult to assess that the
combination of modifications produced anything unexpected rather than
showing the additive effect of incremental improvements by interfering with
fatty acid processing. For these reason, we are not persuaded by Appellant’s
unexpected result argument. Although the record may establish evidence of
secondary considerations which are indicia of nonobviousness, the record
may also establish such a strong case of obviousness that the objective
evidence of nonobviousness is not sufficient to outweigh the evidence of
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obviousness. Newell Cos. v. Kenney Mfg. Co., 864 F.2d 757, 769 (Fed. Cir.
1988), cert. denied, 493 U.S. 814 (1989). Accordingly, we affirm the
rejection of claim 1 as obvious over the cited references.
With respect to claims 5–10, 12–16, 19–22, and 26–28, Appellant
relies on the same argument relied upon with respect to claim 1. Appeal
Br. 15–21. For the reasons discussed above, we find that Examiner has
established a prima facie showing of obviousness with respect to claim 1,
which Appellant has failed to rebut. Accordingly, we affirm the rejection of
claims 5–10, 12–16, 19–22, and 26–28 for the same reasons.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § References/Basis Affirmed Reversed
1, 5–10,
12–16, 19–
22, 25–28
103 Karau, Gaertner,
Lennen, Handke,
Campbell,
Sieber, Jessen,
van Bielen
1, 5–10,
12–16, 19–
22, 25–28

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED