Ex Parte Doudna Cate et al

Patent Trials and Appeals Board

Jan 29, 2019

13982248 - (D) (P.T.A.B. Jan. 29, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/982,248 10/23/2013 James H. Doudna Cate
23379 7590 01/31/2019
RICHARD ARON OSMAN
530 Lawrence Expy # 332
Sunnyvale, CA 94085
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.
Bll-097-3US 2850
EXAMINER
EKSTROM, RICHARD C
ART UNIT PAPER NUMBER
1652
NOTIFICATION DATE DELIVERY MODE
01/31/2019 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):
richard@sci-tech.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JAMES H. DOUDNA CATE, YONG-SU JIN,
JONATHAN M. GALAZKA, and SUK-JIN HA 1
Appeal 2017-011527
Application 13/982,248
Technology Center 1600
Before TA WEN CHANG, RYAN H. FLAX, and DAVID COTTA,
Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to a fungal host cell comprising a recombinant Major
Facilitator Superfamily (MPS) cellodextrin transporter and a recombinant
cellodextrin phosphorylase. Claims 286-301 and 304--314 are on appeal as
rejected under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C.
§ 6(b).
We affirm.
1 Appellants identify the Real Parties in Interest as "The Regents of the
University of California, and The Board of Trustees of the University of
Illinois." Appeal Br. 1.
Appeal2017-011527
Application 13/982,248
STATEMENT OF THE CASE
The Specification states:
The engineering of microorganisms to perform the conversion of
lignocellulosic biomass to ethanol efficiently remains a major
goal of the biofuels field. Much research has been focused on
genetically manipulating microorganisms that naturally ferment
simple sugars to alcohol to express cellulases and other enzymes
that would allow them to degrade lignocellulosic biomass
polymers and generate ethanol within one cell, a process known
as consolidated bioprocessing (CBP).
Spec. ,r 4. The Specification further states that "Saccharomyces cerevisiae,
also known as baker's yeast, has been used for bioconversion of simple
hexose sugars into ethanol for thousands of years," "[i]t has a well-studied
genetic and physiological background," but "does not naturally degrade and
ferment the more complex biomass polymers, such as cellulose." Id. ,r,r 5---6.
The Specification describes a yeast cell host having genes whose expression
transports cellodextrin past the cell membrane for metabolizing. Id. ,r 71.
Claim 286 is representative and is reproduced below:
286. A fungal host cell comprising a recombinant Major
Facilitator Superfamily (MPS) cellodextrin transporter, and a
recombinant cellodextrin phosphorylase.
Appeal Br. 22.
2
Appeal2017-011527
Application 13/982,248
The following rejections are appealed (numbering added to
correspond to Appellants' briefing): 2
1. Claims 286-298, 300, 307, 313, and 314 stand rejected under
35 U.S.C. § I03(a) over Blanchard,3 Thompson, 4 and GenBank XP. 5 Final
Action 4--5.
2. Claims 286-298, 300, 307, 309, 310, 313, and 314 stand rejected
under 35 U.S.C. § I03(a) over Blanchard, Thompson, GenBank XP,
Strobel, 6 and GenBank AAA91282.1. 7 Id. at 6-7.
3. Claims 286-298, 300, 307, and 311-314 stand rejected under
35 U.S.C. § I03(a) over Blanchard, Thompson, GenBank XP, Strobel, and
GenBank AAA34698.1. 8 Id. at 8.
2 Rejections under 35 U.S.C. § 112 for lack of written description and
indefiniteness were withdrawn by the Examiner. Answer 9.
3 US 2010/0028966 Al (published Feb. 4, 2010) ("Blanchard").
4 US 2011/0081683 Al (published Apr. 7, 2011) ("Thompson").
5 NCBI Reference Sequence: XP _963801.1, hypothetical protein NCU00801
[Neurospora crassa OR7 4A] (2008), accessed at
https://www.ncbi.nlm.nih.gov/protein/85111152?sat=21 &satkey=3077027,
visited Nov. 13, 2016 ("GenBank XP").
6 H.J. Strobel et al., Carbohydrate Transport by the Anaerobic Thermophile
Clostridium thermocellum LQR!, 61(11) APPL. AND ENVIRON. MICROBIO.
4012-15 (1995) ("Strobel").
7 NCBI Reference Sequence: GenBank: AAA9I282.I,phosphoglucomutase
[Saccharomyces cerevisiae] (1996), accessed at
http://www.ncbi.nlm.nih.gov/protein/AAA91282.1, visited June 25, 2015
("GenBank AAA91281.1 ").
8 NCBI Reference Sequence: GenBankAAA34698.1, hexokinase (HXKJ)
[Saccharomyces cerevisiae] (1993), accessed at
http://www.ncbi.nhn.nih.gov/protein/ AAA34698.1, visited June 25, 2015
("GenBank AAA34698.1 ").
3
Appeal2017-011527
Application 13/982,248
4. Claims 286-298, 300, 307, 308, 313, and 314 stand rejected under
35 U.S.C. § 103(a) over Blanchard, Thompson, GenBank XP, and Brat. 9 Id.
at 9.
5. Claims 286-302, 305, 307, 313, and 314 stand rejected under
35 U.S.C. § 103(a) over Blanchard, Thompson, GenBank XP, and GenBank
BAB. 10 Id. at 10.
6. Claims 286-298, 300, 301, 303, 304, 306, 307, 313, and 314 stand
rejected under 35 U.S.C. § 103(a) over Blanchard, Thompson, GenBank XP,
and GenBank ABD. 11 Id. at 11.
DISCUSSION
"[T]he examiner bears the initial burden, on review of the prior art or
on any other ground, of presenting aprimafacie case ofunpatentability. If
that burden is met, the burden of coming forward with evidence or argument
shifts to the applicant." In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
Arguments made by Appellants in the Appeal Brief and properly presented
in the Reply Brief have been considered; arguments not so presented in the
Briefs are waived. See 37 C.F.R. § 4I.37(c)(l)(iv) (2015); see also Ex parte
Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) ("Any bases for
9 US 8,986,948 B2 (issued Mar. 24, 2015) ("Brat").
10 NCBI Reference Sequence: GenBank: BAB71818.1, cellodextrin
phosphorylase [Ruminiclostridium thermocellum] (2001 ), accessed at
https://www.ncbi.nlm.nih.gov/protein/16797805?report=genbank&log$=pro
talign&blast ... , visited Nov. 13, 2016 ("GenBank BAB").
11 NCBI Reference Sequence: Genbank: ABD80580.1, cellobiose
phosphorylase [Saccharophagus degradans 2-40], accessed at
https://www.ncbi.nlm.nih.gov/protein/89950565?sat= 14&satkey=5430048,
visited Nov. 13, 2016 ("GenBank ABD").
4
Appeal2017-011527
Application 13/982,248
asserting error, whether factual or legal, that are not raised in the principal
brief are waived.").
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "[W]hen a patent
claims a structure [ or method] already known in the prior art that is altered
by the mere substitution of one element [ or step] for another known in the
field, the combination must do more than yield a predictable result." Id.
(citing United States v. Adams, 383 U.S. 39, 50-51 (1966)). "In determining
whether the subject matter of a patent claim is obvious, neither the particular
motivation nor the avowed purpose of the patentee controls. What matters is
the objective reach of the claim. If the claim extends to what is obvious, it is
invalid under§ 103." Id. at 419. "[T]he question is whether there is
something in the prior art as a whole to suggest the desirability, and thus the
obviousness, of making the combination, not whether there is something in
the prior art as a whole to suggest that the combination is the most desirable
combination available." In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004)
( citation omitted).
"[I]f a technique has been used to improve one device, and a person of
ordinary skill in the art would recognize that it would improve similar
devices in the same way, using the technique is obvious unless its actual
application is beyond his or her skill." KSR, 550 U.S. at 417. "[F]amiliar
items may have obvious uses beyond their primary purposes, and in many
cases a person of ordinary skill will be able to fit the teachings of multiple
patents together like pieces of a puzzle." Id. at 420.
5
Appeal2017-011527
Application 13/982,248
"[C]ase law is clear that obviousness cannot be avoided simply by a
showing of some degree of unpredictability in the art so long as there was a
reasonable probability of success." Pfizer, Inc. v. Apotex, Inc., 480 F.3d
1348, 1364 (Fed. Cir. 2007) (citing In re Corkill, 771 F.2d 1496, 1500 (Fed.
Cir. 1985) ). "[A] presumption arises that both the claimed and unclaimed
disclosures in a prior art patent are enabled." Amgen, Inc. v. Hoechst
Marion Roussel, Inc., 314 F.3d 1313, 1355 (Fed. Cir. 2003).
Findings of Fact
We adopt the Examiner's findings of fact and rationale on
obviousness as set forth in the Final Action and Answer. Final Action 4--13
and Answer 2-22 (collectively citing Blanchard Abstract, ,r,r 105, 134, Table
18, ,r 252 (Example 7); Thompson Abstract, ,r,r 13, 17, 31; GenBank XP
generally; Strobel Figure 5; GenBank AAA91282.1 generally; GenBank
AAA34698.1 generally; Brat Abstract, 6:45---62; GenBank BAB generally;
and GenBank ABD generally). The following findings of fact highlight
certain evidence:
FF 1. Blanchard discloses methods and compositions for
improving the production of fuel products such as ethanol by
microorganisms utilizing genes identified in bacteria, for example
Clostridium phytofermentans, those genes ( of interest) encoding for
combinations ofhydrolases, ATP-binding cassette (ABC)
transporters, and transcriptional regulators. Blanchard Abstract, ,r,r 4,
6-9, 11, 74, 76.
FF2. Further to the preceding finding of fact, Blanchard
discloses transforming a microorganism host cell with a nucleic acid
6
Appeal2017-011527
Application 13/982,248
including some combination of the genes of interest. Blanchard ,r,r 3 2,
76, 110.
FF3. Blanchard discloses the "[ a ]dvantages to utilizing nucleic
acids encoding ABC-transporters include increasing the capacity of
trans/ ormed organisms to transport compounds into the organism
and utilize such compounds in the biochemical pathways to produce
fuel, and thus improve fuel production." Blanchard ,r 101-102
( emphasis added). Thus, Blanchard teaches and suggests it is
advantageous to genetically enhance the transport of compounds, e.g.,
sugars and amino acids, important to fermentation production of
ethanol.
FF4. Blanchard discloses that"[ c ]ertain embodiments include
predicted ABC-transporters that transport cellobiose, for example,
predicted ABC-transporters encoded by Cphy2464, Cphy2465, and
Cphy2466," i.e., transport systems with permease and periplasmic
components encoded by genes from C. phytofermentans. Blanchard
,r,r 103-105 (Table 7), 118 (Table 9) ( emphasis added).
FF5. Blanchard suggests that transporters for the disaccharides
lactose and cellobiose are the same or similar. Id. ,r 104.
FF6. Further to the preceding findings of fact, Blanchard
discloses:
Cellobiose Utilization
Some embodiments described herein relate to
polynucleotides, polynucleotide cassettes, expression cassettes,
expression vectors, and microorganisms comprising nucleic
acids identified in C. phytofermentans encoding enzymes/
protein domains involved in cellobiose utilization. Other
7
Appeal2017-011527
Application 13/982,248
embodiments relate to methods for producing fuel utilizing the
polynucleotides, polynucleotide cassettes, expression cassettes,
expression vectors, and microorganisms including nucleic acids
identified in C. phytofermentans encoding enzymes/protein
domains involved in cellobiose utilization. Cellobiose is a
disaccharide derived from the condensation of two glucose
molecules linked in a B(l ----+4) bond. Examples of genes
identified as upregulated during growth on cellobiose include
Cphy0430, Cphy2464, Cphy2465, Cphy2466, and Cphy2467
(see FIG. 17).
Blanchard ,r 134; see also id. ,r 221, Table 18 (listing genes for, inter
alia, extracellular solute-binding protein and cellobiosidase ).
FF7. Further to the preceding findings of fact, Blanchard
discloses:
Some embodiments relate to microorganisms containing
any of the polynucleotides, polynucleotide cassettes, expression
cassettes, or expression vectors described herein. Host cells can
include, but are not limited to, eukaryotic cells, such as animal
cells, insect cells,fungal cells, and yeasts, and prokaryotic cells,
such as bacteria. In some embodiments, the host is C.
phytofermentans. In some embodiments, a potential host
organism can comprise a recombinant organism.
Blanchard ,r 17 6-178 ( emphasis added). Specifically, Blanchard
discloses a variety of examples of yeasts for host organisms, including
Saccharomyces cerevisiae. Id.; see also Spec. ,r 94 ( disclosing the
same example species of yeast as a host organism); see also claim 307
(reciting Saccharomyces as a host yeast). Blanchard suggests that
engineering a yeast cell as a host for bacteria genes of interest would
be successful.
8
Appeal2017-011527
Application 13/982,248
FF8. Blanchard discloses a successful example where
E.coli are engineered to utilize cellobiose by expression of
Cphy2464-2466, encoding an ABC transporter and Cphy0430,
encoding a cellobiose phosphorylase that converts cellobiose
into glucose and glucose-I-phosphate. The Cphy2464-2466 and
Cphy0430 genes are expressed from a constitutive promoter on
a plasmid. The signal sequence of Cphy2466 is replaced with
the signal sequence of an endogenous E. coli ABC transporter
periplasmic binding protein to direct expression of the protein in
the periplasm. The engineered E. coli are able to grow using
cellobiose as a sole carbon source.
Blanchard ,r 252 (Example 7).
FF9. Thompson, similar to Blanchard, is directed to
A genetically modified organism comprising: at least one
nucleic acid sequence and/or at least one recombinant nucleic
acid isolated from Alicyclobacillus acidocaldarius and encoding
a polypeptide involved in at least partially degrading ... [and]
transporting . . . cellulose . . . [ and] sugars, sugar oligomers,
carbohydrates, [or] complex carbohydrates ... ; and at least one
nucleic acid sequence and/or at least one recombinant nucleic
acid encoding a polypeptide involved in fermenting sugar
molecules to a product.
Thompson Abstract, ,r,r 7-8, 13 (emphasis added). One of the sugars
specifically identified by Thompson is cellobiose, to be hydrolyzed by
Cellobiose phosphorylases. Id. ,r 13.
FF 10. Thompson is directed to the fermentation of ethanol.
Thompson ,r 1 7.
FFl 1. Similar to Blanchard, Thompson discloses isolating
genes of interest from various species of Clostridium. Thompson ,r,r
30.
9
Appeal2017-011527
Application 13/982,248
FF12. Similar to Blanchard, Thompson discloses incorporating
isolated genes for expression in various host species of Clostridium,
as well as species of Saccharomyces, Zymomonas, Candida, and E.
coli, specifically Saccharomyces cerevisiae (yeast). Thompson ,r,r 31,
48. Thompson, like Blanchard, suggests that engineering a yeast cell
as a host for bacteria genes of interest would be successful.
FF 13. GenBank XP discloses a hypothetical protein sequence of
Neurospora crassa, a filamentous fungus; the protein being the
product of the NCU00801 gene with an amino acid sequence identical
to SEQ ID NO: 9. GenBank XP; see also Spec. ,r,r 16, 106 (Tables 1
and 2), and Final Action 5.
FF14. GenBank XP discloses its sequenced protein is "similar
to MPS lactose permease." GenBank XP; see also supra FF5
(suggesting transporters for lactose are also suitable transporters for
cellobiose ).
FF15. Strobel discloses the carbohydrate, e.g., cellobiose and
glucose, uptake/transport system of Clostridium thermocellum,
investigated in view of ethanol production from fibrous biomass.
Strobel 4012.
FF16. Further to the preceding finding of fact, Strobel discloses
observing "[h ]igh levels of phosphoglucomutase activity [] in the
cytosol fraction, while no activity was found in the membrane," which
"confirmed that the membrane fraction was essentially free of
contamination by cytosolic enzymes." Strobel 4014.
10
Appeal2017-011527
Application 13/982,248
FF17. Strobel discloses that cellobiose and larger cellodextrins
are transported intact across the cell membrane to then be subjected to
phosphorylytic cleavage within the cell. Strobel 4014.
FF18. Strobel includes the following figure:
ADJ>
+A
Cellob!O&
"'"""'!--91
(i-. l ~P + Glucose
PGM PGII Hit ATP
o.e .. p
01ucosc
HK ATP
FlO. 5. S.:-hematk model of carbohydrat.e uptake and phosphoryJat.ion by C
dterme>cd.lum~ G--1 ... p7 g!ucose-l-phosphate; G-6,.P7 glucose-6,..phosphate; Pi~ £n ..
organic phosphate; CB Pase. cellobiose phosphol)'J ase; CD Pa-;e~ celfodestrln
phosphorylase; HK. b.exokinue; PGM, phospbogluoomuta.se.
Strobel 4015 (Figure 5). Strobel Figure 5 (above) illustrates the
transport of cellodextrin, cellobiose, and glucose across the cell
membrane of Clostridium thermocellum, and shows that cellobiose,
once so-transported, is metabolized with phosphoglucomutase (PGM)
and hexokinase (HK), and that glucose, once transported is
metabolized with hexokinase (HK). Id. Strobel suggests that, inter
alia, sufficient levels of phosphoglucomutase and hexokinase are
11
Appeal2017-011527
Application 13/982,248
required for the metabolism of cellobiose and glucose to produce
ethanol.
FF 19. Further to the preceding findings of fact, Strobel states,
"[ s ]uch information may be useful in developing rational schemes ( or
manipulating the physiology of cellulolytic thermophiles and
optimizing fermentation technology." Strobel 4015. Strobel suggests
engineering microorganisms to ensure the presence of sufficient
phosphoglucomutase and hexokinase.
FF20. Further to the preceding findings of fact, GenBank
AAA912 82 .1 discloses the amino acid sequence of
phosphoglucomutase of Saccharomyces cerevisiae (baker's yeast).
GenBank AAA91282.1; see also Strobel Figure 5 (PGM).
FF21. Further to the preceding findings of fact, GenBank
AAA34698.1 discloses the amino acid sequence ofhexokinase
(HXKl) of Saccharomyces cerevisiae (baker's yeast). GenBank
AAA34698.1; see also Strobel Figure 5 (HK).
FF22. Brat discloses fermentation yeasts genetically engineered
to include genes from Clostridium phytofermentans to enhance the
fermentation of ethanol. Brat Abstract. Brat suggests engineering a
yeast cell as a host for bacteria genes of interest would be successful.
FF23. Brat discloses that ordinary baker's yeast,
Saccharomyces cerevisiae, has been used for fermentation for
centuries, and discloses engineering yeast cells by introducing genes
from bacteria ( Clostridium phytofermentans) that, when expressed,
12
Appeal2017-011527
Application 13/982,248
allowed the yeast to "efficiently metabolize xylose." Brat 1 :36-39,
3:17-28, 4:16-22.
FF24. Further to the preceding finding of fact, Brat discloses
that the engineered yeast cells can include host cells selected from
Saccharomyces, Kluyveromyces, Candida, Pichia,
Schizosaccharomyces, Hansenula, Kloeckera, Schwanniomyces,
Arxula and Yarrowia," and filamentous cells selected from
Aspergillus, Trichoderma, Humicola, Acremonium, Fusarium and
Penicillium. Brat 5:50-6:62.
FF25. GenBank BAB discloses the amino acid sequence of
cellodextrin phosphorylase of Ruminiclostridium thermocellum.
GenBank BAB.
FF26. GenBank ABD discloses the amino acid sequence of
cellobiose phosphorylase of Saccharophagus degradans 2--40.
GenBankABD.
Analysis
1. Rejection of Claims 286-298, 300, 307, 313, and 314 over
Blanchard, Thompson, and GenBank XP
The Examiner determined that claim 286 would have been obvious
over the Blanchard-Thompson-GenBank XP combination. Final Action 4--
6; see also supra Findings of Fact. The Examiner cites Blanchard as
disclosing using genes from bacteria, e.g., Clostridium phytofermentens,
that, when expressed, promote the transport across the cell membrane and
metabolism of cellobiose. Id. The Examiner points to an exemplary host
cell being E. coli; however, Blanchard discloses a variety of host cells,
including yeast cells. Id.; see also FF7, FF8 ( disclosing using yeast cells as
13
Appeal2017-011527
Application 13/982,248
hosts and suggesting the interchangeability of bacterial and yeast cells as
hosts). The Examiner cites Thompson as additional, direct support that yeast
cells would have been engineered as hosts for genes from bacterial cells
relating to the transporting and metabolizing of cellobiose. Final Action 5-
6; see also FF9-FF12. GenBank XP discloses a protein sequence identified
as an MPS lactose permease and Blanchard suggests that such a protein
would also be useful for transporting cellobiose; the Examiner cited
GenBank XP as disclosing SEQ ID NO: 9, which is within the scope of the
appealed claims. Final Action 5---6; see also FF13-FF14. The Examiner
determined that it would have been obvious to combine the teachings of
Blanchard, Thompson, and GenBank XP to improve ethanol production by
applying the genetic engineering elements and steps disclosed by these
references in the fashion taught by the references. Final Action 6. We
discern no error in the Examiner's determinations.
Appellants argue that the Examiner's determination that
[i]t would have been obvious to one of ordinary skill in the art at
the time the invention was made to have incorporated the
recombinant ABC transporter and the recombinant cellobiose
phosphorylase gene described by Blanchard et al., or to have
incorporated the GenBank MPS permease, in the Saccharomyces
cerevisiae or Candida shehatae host cells described by
Thompson et al. because Thompson et al. generically describe
the use of any transporter or carbohydrate metabolizing enzymes
in Saccharomyces cerevisiae or Candida shehatae host cells to
produce fermentation products such as ethanol and the enzymes
described by Blanchard et al. and GenBank Accession No.
XP _963801.1 are merely alternatives within the generic
teachings of Thompson et al.
14
Appeal2017-011527
Application 13/982,248
(Final Action 6), is incorrect because bacteria ( e.g., Clostridium
phytofermentens) and yeast (e.g., Saccharomyces cerevisiae) are so different
("widely diverged") that the skilled artisan would expect that transferring
components (genes) between them would not work. Appeal Br. 3--4.
Appellants argue that only their research discovered that such a transfer,
particularly for MPS transporters, could work; arguing that only improper
hindsight on the part of the Examiner could have led to combining the cited
prior arts' teachings. Id. at 4--5 ( citing Cate Declaration). 12 In the Reply
Brief, Appellants argue that the Examiner's case for obviousness has
changed in that the rejection "seeks now to spotlight Thompson." Reply Br.
2. The Reply Brief also states "Blanchard and Thompson both teach away
from our invention," but offers no persuasive supporting evidence for the
statement. Id. at 4.
These arguments are not persuasive. Appellants' primary argument,
that the skilled artisan would not have engineered a host yeast cell with
genes from a bacterial cell, is not supported by a preponderance of the
evidence. Appellants' Cate Declaration concludes that "because such
bacterial and fungal host cells [ disclosed by Blanchard and Thompson] are
so widely diverged [] persons skilled in the art would reasonably expect that
transferring the components would not work"; however, this statement is not
supported by data or any other evidence, but amounts to only the Professor's
opinion. See Cate Declaration ,r 2. This point is mirrored in Appellants'
12 Declaration of James H. Doudna Cate, dated Dec. 7, 2016 ("Cate
Declaration").
15
Appeal2017-011527
Application 13/982,248
arguments in the Appeal Brief (for each rejection). See, e.g., Appeal Br. 4,
5, 7, 8, 10, 12, 14, 15, 17-20.
This conclusory statement and argument is not persuasive in the face
of the Blanchard and Thompson references' disclosures and suggestions that
it is possible, and would have been obvious, to transfer the claimed
components between bacteria and yeast cells. See supra FF1-FF12; see also
FF22-FF24 (Brat, cited by the Examiner in other obviousness rejections,
also suggests that this is a known technique). The mere suggestion of
unpredictability cannot overcome this evidence suggesting a reasonable
expectation of success.
Appellants' arguments that the Examiner's focus shifted from
Blanchard to Thompson in the Answer, and that these references teach away
from the invention, are also not persuasive. Thompson was always a part of
the prior art combination cited by the Examiner in the final rejection; there
was no error in the Examiner's further explaining its relevance. Further,
Appellants do not identify where or how Blanchard or Thompson teach
away from the claims, as contended.
Regarding claim 297, Appellants argue, similarly, that absent their
discovery that bacterial genes could work effectively in fungal cells, there
would have been no motivation to combine the cited references and employ
a mutated transporter, as claimed. Appeal Br. 5.
As discussed above, Blanchard and Thompson both suggest
engineering yeast cells with genes from bacteria that are useful with respect
to transporting and metabolizing cellobiose. Appellants do not argue the
16
Appeal2017-011527
Application 13/982,248
Examiner's understanding of the claimed "mutant" is incorrect. See Appeal
Br. 5; Reply Br. 5. Appellants' argument is not persuasive.
2. Rejection of Claims 286-298, 300, 307, 309, 310, 313, and 314
over Blanchard, Thompson, GenBank XP, Strobel, and GenBank
AAA91282.l
The Examiner determined that the Blanchard-Thompson-GenBank
XP-Strobel-GenBank AAA91282.1 combination would have rendered the
claims obvious. Final Action 6-7. Blanchard, Thompson, and GenBank XP
were cited by the Examiner here, and in each obviousness rejection
( discussed below), for the same reasons as set forth above for the first (1)
obviousness rejection. The Examiner cited Strobel as teaching the
importance of phosphoglucomutase in metabolizing cellobiose and glucose
once these molecules are transported into the cell. Id. at 7; see also FF15-
FF 19. The Examiner cited GenBank AAA912 82 .1 as disclosing the amino
acid sequence of phosphoglucomutase of Saccharomyces cerevisiae (baker's
yeast). Final Action at 7; see also FF20. We discern no error in the
Examiner's determinations.
Appellants present the same arguments over this rejection as
presented over Rejection 1 and discussed above. Appeal Br. 6-8. These
arguments remain unpersuasive.
Regarding claims 309 and 310, Appellants argue that without their
discovery that phosphoglucomutase, required for glucose conversion, can be
downregulated during glycolytic growth or otherwise effected by other
cellular conditions, there would have been no motivation to express the
recited recombinant phosphoglucomutase. Appeal Br. 8-9.
17
Appeal2017-011527
Application 13/982,248
This argument is not persuasive. Strobel teaches the importance of
phosphoglucomutase ( and hexokinase) in metabolizing cellobiose ( and
glucose) and suggests using this knowledge when engineering
microorganisms to perform this function. FF 15-FF 19. Therefore, even
without Appellants' disclosure, the claimed invention would have been
obvious.
3. Rejection of Claims 286-298, 300, 307, and 311-314 over
Blanchard, Thompson, GenBank XP, Strobel, and GenBank
AAA34698.l
The Examiner determined that the Blanchard-Thompson-GenBank
XP-Strobel-GenBank AAA34698.1 combination would have rendered the
claims obvious. Final Action 8-9. Blanchard, Thompson, and GenBank
XP, and Strobel were cited by the Examiner here for the same reasons as set
forth above for the previous obviousness rejections (1 and 2). The Examiner
cited Strobel as teaching the importance ofhexokinase, in particular. Id. at
8; see also FF15-FF19. The Examiner cited GenBank AAA34698.1 as
disclosing the amino acid sequence of hexokinase of Saccharomyces
cerevisiae (baker's yeast). Final Action at 8; see also FF2I. We discern no
error in the Examiner's determinations.
Appellants present the same arguments over this rejection as
presented over Rejection 1 and discussed above. Appeal Br. 9-12. These
arguments remain unpersuasive.
Regarding claims 311 and 312, Appellants argue that without their
discoveries that hexokinase, required for glucose conversion, may not be
sufficiently expressed and that its expression may be effected by other
18
Appeal2017-011527
Application 13/982,248
cellular conditions, there would have been no motivation to express the
recited recombinant hexokinase. Appeal Br. 12.
As with the prior rejection (2) and for the same reasons discussed
above, this argument is not persuasive.
4. Rejection of Claims 286-298, 300,307,308, 313, and 314 over
Blanchard, Thompson, GenBank XP, and Brat
The Examiner determined that the claims would have been obvious
over the Blanchard-Thompson-GenBank XP-Brat combination, citing the
Blanchard, Thompson, and GenBank XP references for the same teachings
as discussed above. The Examiner cited Brat as teaching engineering
filamentous fungal cells as hosts in the manner taught by Blanchard and
Thompson. Final Action 9-10; see also FF22-FF24. We discern no error in
the Examiner's determinations.
Appellants present the same arguments over this rejection as
presented over Rejection 1 and discussed above. Appeal Br. 12-15. These
arguments remain unpersuasive.
5. Rejection of Claims 286-302, 305, 307, 313, and 314 over
Blanchard, Thompson, GenBank XP, and GenBank BAB
The Examiner determined that the claims would have been obvious
over the Blanchard-Thompson-GenBank XP-GenBank BAB combination,
citing the Blanchard, Thompson, and GenBank XP references for the same
teachings as discussed above. The Examiner cited GenBank BAB as
teaching the amino acid sequence of SEQ ID NO: 184, which is within the
scope of the claims. Final Action 10-11; see also FF25. We discern no
error in the Examiner's determinations.
19
Appeal2017-011527
Application 13/982,248
Appellants present the same arguments over this rejection as
presented over Rejection 1 and discussed above. Appeal Br. 15-18. These
arguments remain unpersuasive.
6. Rejection of Claims 286-298, 300, 301, 303, 304, 306, 307,
313, and 314 stand rejected under 35 USC§ 103(a) over Blanchard,
Thompson, GenBank XP, and GenBank ABD
The Examiner determined that the claims would have been obvious
over the Blanchard-Thompson-GenBank XP-GenBank ABD combination,
citing the Blanchard, Thompson, and GenBank XP references for the same
teachings as discussed above. The Examiner cited GenBank ABD as
teaching the amino acid sequence of SEQ ID NOs: 158 or 12, which are
within the scope of the claims. Final Action 11; see also FF26. We discern
no error in the Examiner's determinations.
Appellants present the same arguments over this rejection as
presented over Rejection 1 and discussed above. Appeal Br. 18-21. These
arguments remain unpersuasive.
SUMMARY
The obviousness rejections are each affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l )(iv).
AFFIRMED
20