Kylie Vincent et al.

Patent Trials and Appeals Board

Aug 22, 2019

14349126 - (D) (P.T.A.B. Aug. 22, 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.
14/349,126 04/02/2014 Kylie Vincent 16206.0039FPWO 5729
23552 7590 08/22/2019
MERCHANT & GOULD P.C.
P.O. BOX 2903
MINNEAPOLIS, MN 55402-0903
EXAMINER
SWOPE, SHERIDAN
ART UNIT PAPER NUMBER
1652
NOTIFICATION DATE DELIVERY MODE
08/22/2019 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):
USPTO23552@merchantgould.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte KYLIE VINCENT, LARS LAUTERBACH, and OLIVER LENZ
(APPLICANTS: OXFORD UNIVERSITY INNOVATION LIMITED
and HUMBOLDT-UNIVERSITAT ZU BERLIN)
____________

Appeal 2019-002051
Application 14/349,1261
Technology Center 1600
____________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
JENNIFER MEYER CHAGNON, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
This Appeal under 35 U.S.C. § 134(a) involves claims 1, 2, 11, 21,
and 47 (App. Br. 4).2 Examiner entered rejections under the enablement and

1 Appellants identify “Oxford University Innovation Limited
and Humboldt-Universitat [z]u Berlin” as the real party in interest
(Appellants’ June 13, 2018 Appeal Brief (App. Br.) 2). Note: Appellants’
Appeal Brief is not paginated; therefore, all reference to page numbers of
Appellants’ Appeal Brief refer to Appellants’ Appeal Brief as it was
numbered consecutively starting with the first page.
2 Pending claims 3–10, 12–18, 23–41, 43–46, and 48–63 stand withdrawn
from consideration (App. Br. 4).
Appeal 2019-002051
Application 14/349,126

2
written description provisions of 35 U.S.C. § 112, first paragraph. We have
jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.
STATEMENT OF THE CASE
Appellants’ disclosure “relates to a cofactor regeneration system,
components and uses thereof, products comprising said cofactor
regeneration system and components thereof, as well as methods for cofactor
generation and regeneration” (Spec. 1: 6–9). Appellants’ claim 1 is
representative and reproduced below:
1. A cofactor regeneration system comprising:
i) a first electron transfer component selected from one or
more polypeptides comprising a NADH:acceptor oxido-
reductase or a NADPH:acceptor oxido-reductase,
ii) a second electron transfer component selected from a
hydrogenase moiety and/or non-biological nanoparticles; and,
iii) an electronically conducting surface wherein said
electronically conducting surface is a carbon particle;
wherein the first and second electron transfer components are
immobilised on the carbon particle, wherein the first and
second electron transfer components do not occur together in
nature as an enzyme complex, and wherein the cofactor
regeneration system is configured so that in use, electrons flow:
from the first electron transfer component via the carbon
particle to the second electron transfer component; or
from the second electron transfer component via the
carbon particle to the first electron transfer component.
(Claims App’x3 2.)

3 Appellants’ Claims Appendix filed with Appellants’ July 25, 2018
Supplemental Brief on Appeal. Because this document is not paginated, we
refer to page numbers as if the document was paginated consecutively
beginning with the first page.
Appeal 2019-002051
Application 14/349,126

3
Grounds of rejection before this Panel for review:
Claims 1, 2, 11, 21, and 47 stand rejected under the enablement
provision of 35 U.S.C. § 112, first paragraph.
Claims 1, 2, 11, 21, and 47 stand rejected under the written
description provision of 35 U.S.C. § 112, first paragraph.

Enablement:
ISSUE
Does the evidence of record support Examiner’s conclusion that
undue experimentation would be required to practice the claimed invention?
ANALYSIS
Examiner states that Appellants’
elected invention is directed to a cofactor regeneration system
comprising:
i) the first electron transfer component being the
diaphorase consisting of SEQ ID NO: 1 and 2,
ii) the second electron transfer component being the
E. coli hydrogenase 2, consisting of the subunits SEQ ID NO:
33 and 34,
iii) the electronically conducting surface being carbon
black,
iv) the cofactor NAD+,
wherein the oxido-reductase and hydrogenase are
immobilized on the carbon particle surface, and wherein the
cofactor regeneration system does not further comprise a
second oxido-reductase and is not in a kit.
(Final Act.4 2.) Examiner finds that Appellants’ “[S]pecification is enabling
for regenerating NADH from NAD+ using the [R. eutropha] diaphorase

4 Examiner’s December 21, 2017 Final Office Action.
Appeal 2019-002051
Application 14/349,126

4
HoxFU (SEQ ID NO: 1+2) and the [E. coli] hydrogenase 2 (SEQ ID NO:
33+34) immobilized on pyrolytic graphite particles . . . as per [Appellants’]
elected invention” (Ans.5 4). In this regard, Examiner finds that Appellants’
“elected invention is allowable” (id. at 6).
Examiner further finds, however, that Appellants’ Specification “does
not enable any person skilled in the art to which it pertains, or with which it
is most nearly connected, to make and use the invention commensurate in
scope with” Appellants’ rejected claims (id. at 5). Examiner finds that
Appellants’
Specification does not reasonably provide enablement for the
following.
Any cofactor regeneration system comprising:
i) any first electron transfer component selected from one
or more polypeptides comprising any NADH:acceptor oxido-
reductase or any NADPH:acceptor oxido-reductase,
ii) any second electron transfer component selected from
any hydrogenase moiety and/or any non-biological
nanoparticle, and,
iii) an electronically conducting surface wherein said
electronically conducting surface is a carbon particle;
wherein the first and second electron transfer components
are immobilized on the carbon particle,
wherein the first and second electron transfer components
do not occur together in nature as an enzyme complex, and
wherein the cofactor regeneration system is configured so
that in use, electrons flow:
from the first electron transfer component via the carbon
particle to the second electron transfer component; or

5 Examiner’s November 14, 2018 Answer.
Appeal 2019-002051
Application 14/349,126

5
from the second electron transfer component via the
carbon particle to the first electron transfer component.
(Id. at 4–5.) Examiner finds that Appellants’ claimed
system for regenerating any cofactor using any first electron
transfer component selected from one or more polypeptides
comprising a NADH:acceptor oxido-reductase or a
NADPH:acceptor oxido-reductase, any second electron transfer
component selected from any hydrogenase and/or any non-
biological nanoparticle wherein said first and second
components are immobilized on any electrically conducting
carbon particle.
(Id. at 5–6; see id. at 7 (Examiner finds that Appellants’ “claims encompass
any naturally occurring or recombinantly mutated protein having any
structure that falls into one of . . . over 40 E.C. categories and has the desired
utility to mediate cofactor regeneration” and “non-biological nanoparticles,
having any structure and having any electron transfer activity”).)
Examiner further finds that “NADH/NADPH oxido-reductases,
hydrogenases and/or non-biological nanoparticles having electron transfer
activity which can be used in combination for regeneration of any cofactor
remained highly unpredictable,” even after Appellants’ filing date (id. at 8
(citing Reeve6); id. at 9 (Examiner finds the “challenges (described 6-7 years
after the effective filing date herein) the use of redox enzymes and/or non-
biological nanoparticles on electronically conducting carbon particles in
order to produce cofactors was an immature art fraught with a myriad of
unpredictable variables at the time of filing of this application”); see also id.

6 Reeve et al., Enzymes as modular catalysts for redox half-reactions in H2-
powered chemical synthesis: from biology to technology, 474 BIOCHEMICAL
JOURNAL 215–230 (2017).
Appeal 2019-002051
Application 14/349,126

6
at 12–13 (citing Guo7)). In addition, Examiner finds that “[t]here was little
expectation that substituting the [R. eutropha] HoxFU (SEQ ID NO: 1 + 2
herein) and the [E. coli] hydrogenase 2 (SEQ ID NO: 33 + 34 herein) with
any other enzymes or non-biological nanoparticle, having any structure,
would be successful” (id. at 9). In this regard, Examiner finds that
Appellants’ “[S]pecification fails to provide . . . guidance as to specific
NADH/NADPH:acceptor oxido-reductases and hydrogenases which, in
combination, can regenerate any cofactor” and “the structural features of
NADH/NADPH:acceptor oxido-reductases and hydrogenases that mediate
electron flow” throughout the full scope of Appellants’ claimed invention
(id. at 10).
With regard to the claimed electronically conducting surface,
Examiner finds that although Appellants’ Specification “provides that the
non-biological nanoparticles may be metal nanoparticles (such as platinum
or palladium nanoparticles), or nanoparticles of a metal oxide, or
nanoparticles of a metal sulphide (such as molybdenum disulfide)”;
Appellants’ Specification “fails to provide any guidance as to which of the
essentially infinite non-biological nanoparticles may be used in combination
with any NADH/NADPH:acceptor oxido-reductase to successfully
regenerate any cofactor” (id.). In this regard, Examiner finds:
Without guidance as to the functional characteristics coupled
with a known or disclosed correlation between function and
structure, these few examples, using only the [R. eutropha]
diaphorase or a specific variant thereof (out of all enzymes
encompassed by over 50 E.C. numbers) and only two
hydrogenase (out of all enzymes encompassed by the 40 E.C.

7 Guo et al., Protein tolerance to random amino acid change, 101 PNAS
9205–9210 (2004).
Appeal 2019-002051
Application 14/349,126

7
numbers) or a single nanoparticle (out of all nanoparticle
having any structure), are not sufficient to enable the skilled
artisan to practice the full scope of the encompassed
regeneration systems.
(Id. at 12). Thus, Examiner finds that a “skilled artisan would be reduced to
[a] trial and error [process of] making and testing the genus of all
hydrogenases and all non-biological nanoparticles” (id. at 11; see also id. at
13–14). We are not persuaded.
As Appellants explain, their Specification discloses “an
electrochemical assay which can be used to determine if the
hydrogenases/non-biological nanoparticles/NAD(P)H:acceptor oxido-
reductases can transfer/receive electrons to/from carbon particles” (Reply
Br. 4 (citing Spec. 11: 26 – 12: 17 and 20: 9 – 21: 2)). In this regard, we
note that Parkin declares that the identification of “an enzyme as a
‘NADH:acceptor oxido-reductase’, ‘hydrogenase’, etc. employs routine
techniques comprised in the skilled person’s common general knowledge
and would not require undue experimentation” (Parkin Decl.8 ¶ 12). Further,
Parkin declares that “electronically conducting ‘carbon particles’ (which
constitute the electronically conducting surface, as recited in [Appellants’]
pending claims) are inherently, both structurally and functionally configured
to allow electron flow, therefore any electronically conducting ‘carbon
particle’ would find utility in [Appellants’] claimed invention” (id.).
In sum, there is no doubt that Appellants’ claimed invention is broad
and encompasses various combinations of a first and second electron
transfer component with an electronically conducting surface (see Claims
App’x 2). Examiner acknowledges, however, “that determining whether a

8 Declaration of Dr. Alison Parkin, signed October 12, 2017.
Appeal 2019-002051
Application 14/349,126

8
single, specific protein has ‘NADH/NADPH:acceptor oxido-reductase’ or
‘hydrogenase’ activity does not represent undue experimentation” (Ans. 21;
see also id. at 27; cf. Ans. 12 (Examiner relies on Guo to emphasize the
scope of proteins encompassed by Appellants’ claimed invention)).
Examiner further does not dispute Parkin’s statement that
“electronically conducting ‘carbon particles’ (which constitute the
electronically conducting surface, as recited in [Appellants’] pending claims)
are inherently, both structurally and functionally configured to allow
electron flow” (Parkin Decl. ¶ 12). Thus, the issue distills down to whether
it would require undue experimentation to test the various combinations of a
first and second electron transfer component with an electronically
conducting surface, consistent with the scope of Appellants’ claimed
invention (see, e.g., Ans. 21).
“The test [for undue experimentation] is not merely quantitative, since
a considerable amount of experimentation is permissible, if it is merely
routine.” Johns Hopkins Univ. v. Cellpro, Inc., 152 F.3d 1342, 1360 (Fed.
Cir. 1998), citing PPG Indus., Inc. v. Guardian Indus. Corp., 75 F.3d 1558,
1564 (Fed. Cir. 1996) (alteration original). On this record, Appellants
disclose “an electrochemical assay which can be used to determine if the
hydrogenases/non-biological nanoparticles/NAD(P)H:acceptor oxido-
reductases can transfer/receive electrons to/from carbon particles” (Reply
Br. 4 (citing Spec. 11: 26 – 12: 17 and 20: 9 – 21: 2)). In addition, Examiner
acknowledges that Appellants’ disclosure exemplifies an electrochemical
assay (see Ans. 11). In this regard, for the reasons provided by Appellants
(see Reply Br. 5–11), we are not persuaded by Examiner’s reliance on Reeve
to suggest that Appellants’ disclosed assay is unpredictable (see, e.g., Ans.
Appeal 2019-002051
Application 14/349,126

9
8–9). Thus, although a considerable amount of experimentation may be
required to test every combination encompassed by the scope of Appellants’
claimed invention, we are not persuaded that such testing is undue, but
instead find that such testing would be routine in this art.
CONCLUSION
The evidence of record fails to support Examiner’s conclusion that
undue experimentation would be required to practice the claimed invention.
The rejection of claims 1, 2, 11, 21, and 47 under the enablement provision
of 35 U.S.C. § 112, first paragraph is reversed.

Written Description:
ISSUE
Does the preponderance of evidence on this record support
Examiner’s finding that Appellants’ Specification fails to provide written
descriptive support for the claimed invention?
ANALYSIS
Examiner finds that Appellants’ claimed invention fails to comply
with the written description provision of 35 U.S.C. § 112, first paragraph
(see Ans. 14–15).
An adequate written description allows those skilled in the art to
visualize or recognize the members of the claimed genus. See Regents of the
University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir.
1997) (description that “does not distinguish the claimed genus from others,
except by function,” is not an adequate written description). In this regard,
Examiner finds that Appellants’ claimed invention encompasses “systems
comprising essentially any protein having any structure and having
Appeal 2019-002051
Application 14/349,126

10
NADH/NADPH oxido-reductase activity, essentially any protein having any
structure and having hydrogenase activity and/or any non-biological
nanoparticle having any structure, and any combination thereof” (Ans. 15).
In the absence of a correlation between structure and function, a
description that defines a claimed genus only by function does not satisfy the
written description provision of 35 U.S.C. § 112. See Lilly, 119 F.3d at
1568; see also In re Wallach, 378 F.3d 1330, 1335 (Fed. Cir. 2004) (A
“functional description can be sufficient only if there is also a structure-
function relationship known to those of ordinary skill in the art.”).
Appellants’ claim 2 depends from and further limits the
NADH:acceptor oxido-reductase or NADPH:acceptor oxido-reductase to a
sequence comprising “an amino acid sequence having at least 20% sequence
identity to the amino acid sequence of Ralstonia eutropha diaphorase HoxF
(SEQ ID NO: 1) and/or an amino acid sequence having at least 20%
sequence identity to the amino acid sequence of Ralstonia eutropha
diaphorase HoxU (SEQ ID NO: 2)” (see Claims App’x 2; see also id. at 11–
12 (Appellants’ claim 47, which requires the hydrogenase moiety of
Appellants’ claim 1 to comprise “two amino acid sequences, a first amino
acid sequence having at least 70% sequence identity to SEQ ID NO:33 and a
second amino acid sequence having at least 70% sequence identity to SEQ
ID NO:34”)). Therefore, we interpret the scope of Appellants’ claimed
invention to encompass variants of known NADH/NADPH:acceptor oxido-
reductases and hydrogenases (see, e.g., Spec. 4: 10–14 (The
NADH/NADPH:acceptor oxido-reductase “comprises or consists of an
amino acid sequence having at least 20% . . . sequence identity to the amino
acid sequence of Ralstonia eutropha diaphorase HoxF (SEQ ID NO: 1)
Appeal 2019-002051
Application 14/349,126

11
. . . ”); see also id. at 4: 14 – 10: 12). We recognize that Parkin declares that
the identification of “an enzyme as a ‘NADH:acceptor oxido-reductase’,
‘hydrogenase’, etc. employs routine techniques comprised in the skilled
person’s common general knowledge and would not require undue
experimentation” (Parkin Decl. ¶ 12). Neither Parkin, nor Appellants’
Specification, however, identify the structural requirements of the proteins
encompassed by Appellants’ claimed invention, which includes proteins
having “at least 20%” sequence identity to known proteins that correlate to
function (see Ans. 34 (discussing the lack of structure-function correlation
with regard to the scope of protein mutants encompassed by Appellants’
claimed invention)). Therefore, the Specification does not describe the
claimed genus adequately to satisfy the written description requirement of
35 U.S.C. § 112. Cf. Univ. of Rochester v G.D. Searle & Co., Inc., 358 F.3d
916, 925 (Fed. Cir. 2004) (“Even with the three-dimensional structures of
enzymes such as COX–1 and COX–2 in hand, it may even now not be
within the ordinary skill in the art to predict what compounds might bind to
and inhibit them”).
To be clear, Appellants’ claimed system depends upon finding an
operable combination of NADH/NADPH:acceptor oxido-reductase and
hydrogenase among those encompassed by the scope of Appellants’ claimed
invention (see App. Br. 18 (“only cofactor regeneration systems capable of
correctly transferring electrons are encompassed, while non-working
embodiments are excluded from the scope of the claims”)). As the
Rochester Court explained,
Regardless whether a compound is claimed per se or a method
is claimed that entails the use of the compound, the inventor
cannot lay claim to that subject matter unless he can provide a
Appeal 2019-002051
Application 14/349,126

12
description of the compound sufficient to distinguish infringing
compounds from non-infringing compounds, or infringing
methods from non-infringing methods. As the district court
observed, “[t]he claimed method depends upon finding a
compound that selectively inhibits PGHS–2 activity. Without
such a compound, it is impossible to practice the claimed
method of treatment.”
Rochester, 358 F.3d at 926 (citing Univ. of Rochester, 249 F.Supp.2d 216,
228 (W.D.N.Y 2003)). On this record, Appellants failed to provide a written
description of the proteins required to practice their claimed invention that is
commensurate in scope with their claims. In this regard, we acknowledge
Appellants’ contentions regarding the listing of NADH/NADPH:acceptor
oxido-reductases and hydrogenases provided in Appellants’ Specification
(see Reply Br. 11–14). For the reasons set forth above, however, this listing
serves only to emphasize the number of variants, including mutated proteins,
encompassed by Appellants’ claimed invention, which are not adequately
described.
Appellants contend that their “Specification clearly provides adequate
written description. For instance, the vast number of NAD(P)H:acceptor
oxidoreductases and hydrogenases, and assays for selecting the same
mentioned in the Specification . . .[, wherein] [t]he assays described in the
Specification can be used for selecting an appropriate NADH:acceptor
oxido-reductase and hydrogenase” (App. Br. 16). Stated differently,
Appellants contend that their Specification makes obvious a screening
method to select functional NADH/NADPH oxido-reductase and
hydrogenase (see id.). We are not persuaded. See Lockwood v. American
Airlines Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (“One shows that one is
‘in possession’ of the invention by describing the invention, with all its
Appeal 2019-002051
Application 14/349,126

13
claimed limitations, not that which makes it obvious. One does that by such
descriptive means as words, structures, figures, diagrams, formulas, etc., that
fully set forth the claimed invention.”) (citation omitted).
CONCLUSION
The preponderance of evidence on this record supports Examiner’s
finding that Appellants’ Specification fails to provide written descriptive
support for the claimed invention. The rejection of claim 1 under the written
description provision of 35 U.S.C. § 112, first paragraph is affirmed.
Claims 2, 11, 21, and 47 are not separately argued and fall with claim 1.

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)(1)(iv).

AFFIRMED