Otto O. Yang et al.

Patent Trials and Appeals Board

Feb 13, 2020

14131159 - (D) (P.T.A.B. Feb. 13, 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.
14/131,159 03/11/2014 Otto O. Yang G&C 30435.251-US-WO 7077
22462 7590 02/13/2020
GATES & COOPER LLP (General)
HOWARD HUGHES CENTER
6060 CENTER DRIVE
SUITE 830
LOS ANGELES, CA 90045
EXAMINER
GOTFREDSON, GAREN
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
02/13/2020 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):
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gates-cooper@blackhillsip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte OTTO O. YANG, YUNFENG LU, CHENG JI, MING YAN, and
YANG LIU
Appeal 2018-006733
Application 14/131,159
Technology Center 1600
BEFORE ULRIKE W. JENKS, JENNIFER MEYER CHAGNON, and
ELIZABETH A. LAVIER, Administrative Patent Judges.
LAVIER, Administrative Patent Judge.
DECISION ON APPEAL
STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1–8 and 21–30. 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 Regents of the
University of California. Appeal Br. 2.
Appeal 2018-006733
Application 14/131,159
2
CLAIMED SUBJECT MATTER
The claims are directed to methods for decreasing an individual’s
ethanol concentration. Claim 1, reproduced below, is illustrative:
1. A method of decreasing the concentration of ethanol in an
individual comprising the steps of:
(a) administering a multiple-enzyme nanocomplex system to the
individual, wherein the multiple-enzyme nanocomplex system
comprises:
an alcohol oxidase enzyme that generates hydrogen
peroxide in a first enzymatic reaction with ethanol;
a catalase enzyme that converts the hydrogen peroxide
into water in a second enzymatic reaction; and
a polymeric network configured to form a shell that
encapsulates the alcohol oxidase and the catalase,
wherein:
the shell is formed in situ on a complex comprising the
alcohol oxidase enzyme coupled to the catalase enzyme so
as to encapsulate the alcohol oxidase enzyme together
with the catalase enzyme;
the polymeric network encapsulates the alcohol oxidase
and the catalase in a manner that inhibits degradation of
the alcohol oxidase and the catalase when the multiple-
enzyme nanocomplex is disposed in an in vivo
environment;
the polymeric network exhibits a permeability sufficient to
allow the ethanol to diffuse from an external environment
outside of the shell to the alcohol oxidase so that the
hydrogen peroxide is generated;
the polymeric network exhibits a permeability sufficient to
allow the hydrogen peroxide to diffuse away from the
alcohol oxidase and to the catalase so that the water is
generated; and
the alcohol oxidase is coupled to the catalase; or
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the polymeric network is coupled to the alcohol oxidase or
the catalase; and
(b) allowing the alcohol oxidase and the catalase in the multiple-
enzyme nanocomplex system to react with ethanol in the
individual and generate hydrogen peroxide and water;
so that the concentration of ethanol in the individual is decreased.
Appeal Br. 10 (Claims Appendix).
REFERENCES
The Examiner relies on the following references:
Name Reference Date
Hopkins US 4,450,153 May 22, 1984
Somberg et al. US 2009/0060894 A1 Mar. 5, 2009
Lu et al. (“Lu ’873”) App. No. 14/130,873,
published as US
2014/0134700 A1
May 15, 2014
Hnaien et al., A rapid and sensitive alcohol oxidase/catalase
conductometric biosensor for alcohol determination, 81 TALANTA
222−27 (2009)
Bäumler et al., Coupled Enzyme Reactions in Multicompartment
Microparticles, BIOMACROMOLECULES, Vol. 11, No. 6, 1480−87 (2010)
Niemeyer et al., DNA-Directed Assembly of Bioenzymic Complexes from
In Vivo Biotinylated NAD(P)H:FMN Oxidoreductase and Luciferase, 02-
03 CHEMBIOCHEM 242−45 (2002)
Wang et al. Semi-permeable nanocapsules of konjac glucomannan-
chitosan for enzyme immobilization, 364 INT’L J. PHARMACEUTICS
102−07 (2008)
REJECTIONS
1. Claims 1, 3–6, and 30 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Hopkins, Hnaien, and Bäumler. Final Action 3.
2. Claims 2 and 7 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Hopkins, Hnaien, Bäumler, and Somberg. Final
Action 7.
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3. Claim 8 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Hopkins, Hnaien, Bäumler, and Niemeyer. Final Action 9.
4. Claims 21–27 and 29 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Hopkins, Hnaien, Bäumler, and Wang. Final
Action 10.
5. Claim 28 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Hopkins, Hnaien, Bäumler, Wang, and Niemeyer. Final
Action 11.
6. Claims 1–8 and 21–30 stand provisionally rejected on the ground
of nonstatutory double patenting over the claims of Lu ’873, in
view of Hopkins, Hnaien, Bäumler, Wang, and/or Somberg. Final
Action 16.
OPINION
Obviousness
Appellant addresses the independent claims (i.e., claims 1, 21, and 30)
together (see Appeal Br. 4–8), and does not present additional arguments
regarding the dependent claims (see id. at 8–9). Accordingly, we treat claim
1 as representative. See 37 C.F.R. § 41.37(c)(1)(iv).
In rejecting claim 1, the Examiner begins with Hopkins, which
teaches administering alcohol oxidase to decrease the alcohol content of
human blood. Final Action 3 (citing Hopkins claim 1). Although Hopkins
provides for a microencapsulating the alcohol oxidase in a semipermeable
membrane (see Hopkins 7:11–16, claim 13; see also Ans. 4–5), Hopkins
does not teach also using a catalase. For the coupling of alcohol oxidase and
catalase, as well as the claimed permeability characteristics, the Examiner
turns to Hnaien. See Final Action 4–5. Hnaien describes a bi-enzymatic
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biosensor for quantitating alcohol in a sample, by immobilizing alcohol
oxidase and catalase in a polymeric coating on an electrode. See Hnaien
222–23. Hnaien describes the utility of co-immobilizing alcohol oxide and
catalase:
Catalase . . . catalyzes both the decomposition of hydrogen
peroxide into water and oxygen and the degradation of ethanol
in the presence of H2O2 . . . . The first advantage of the bi-
enzymatic system proposed is that ethanol acts as a substrate for
both enzymes. In addition, hydrogen peroxide, produced by the
alcohol oxidation at the outer membrane of the biosensor
(alcohol oxidase membrane), is used as a co-substrate in the inner
membrane containing catalase and regenerates oxygen, required
for [the oxidization of alcohol by alcohol oxidase]. In addition,
H2O2 consumption by catalase can help to improve [alcohol
oxidase] stability.
Hnaien 223. Also with respect to claim 1, the Examiner cites Bäumler, as
teaching coupling together enzymatic reactions to form a chain reaction. See
Final Action 5 (discussing Bäumler Abstract, 1481).
Appellant offers two arguments: (1) modifying the multicompartment
microparticles taught in Bäumler would render them unsatisfactory for their
intended purpose, and (2) Hnaien teaches away from encapsulating the
enzymes. See Appeal Br. 5, 7; see also Reply Br. 5–7. We are not
persuaded by either argument.
First, Appellant is correct that in Bäumler’s microparticles, the
enzymes are separated into different compartments, and that this separation
(and resultant spacing) controls the reaction kinetics. See Appeal Br. 5–6
(discussing Bäumler 1485). But “[t]he test for obviousness is not whether
the features of a secondary reference may be bodily incorporated into the
structure of the primary reference . . . . Rather, the test is what the combined
teachings of those references would have suggested to those of ordinary skill
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in the art.” In re Keller, 642 F.2d 413, 425 (CCPA 1981). In rejecting claim
1, the Examiner does not cite Bäumler for the internal structure of its
microparticles, or the identity of its enzymes. Rather, the Examiner relies on
Bäumler for its teaching of coupling enzymes inside a complete polymeric
shell. See Ans. 5. Furthermore, as the above-quoted passage from Hnaien
makes clear, co-immobilizing alcohol oxidase and catalase is advantageous
insofar as alcohol is a substrate for both enzymes, and also because the
hydrogen peroxide produced in the alcohol oxidase reaction serves as a
substrate for the catalase reaction (the consumption of which, in turn,
improves alcohol oxidase stability). See Hnaien 223. As the Examiner
explains:
The Examiner notes that the structural configuration of the
Hnaien biosensor does not in any way separate into individual
compartments the oxidase and catalase that are immobilized
inside the polymeric covering, yet Hnaien discloses that the bi-
enzymatic system described therein nevertheless successfully
acts in concert to degrade ethanol. Therefore, the skilled artisan
reading Hnaien would have recognized that while the enzymes
could indeed be separated into different compartments as taught
by Baumler, no such separation is necessary in order to couple
the oxidase and catalase together; otherwise, the Hnaien
configuration could not function as a biosensor that quantitates
ethanol levels.
Ans. 4. In contrast, Bäumler uses different enzymes (with different reaction
kinetics), for which it is helpful to separate those enzymes into different
compartments. Accordingly, Appellant’s argument regarding Bäumler is not
persuasive.
Appellant’s second argument, regarding Hnaien, is also unpersuasive
because it focuses on aspects of Hnaien not relied on the by Examiner in
formulating the rejection. Here, Appellant asserts that “Hnaien teaches
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away from the encapsulation of enzymes because the bienzymatic
biosensor of Hnaien requires contact between the enzymes and the
electroactive surface of the electrodes in the biosensor (contact that cannot
occur if the alcohol oxidase and catalase were encapsulated by a polymeric
shell).” Appeal Br. 7. Such incomplete encapsulation may well be
necessary for electrodes, but not for formulating a composition (i.e., a
“multiple-enzyme nanocomplex system” as recited in claim 1) for
administration. As the Examiner explains:
this argument is not persuasive because the rejection does not
propose to modify the Hnaien biosensor by encapsulating the
glucose oxidase and catalase together within a polymer shell.
Hnaien is merely a secondary reference used to modify the
method of the primary reference Hopkins (which does not
involve the use of an electrode) by providing a motivation to
couple the oxidase with a catalase inside a polymeric membrane
as taught by Hnaien. Consequently, the method of the prior art
as combined in the rejection does not even comprise an electrode
that would be rendered useless if the enzymes were fully
encapsulated as argued by Appellant.
Ans. 6. We agree. Accordingly, we are not persuaded that Hnaien teaches
away from claim 1.
Having considered Appellant’s two arguments, we are not convinced
of any reversible error by the Examiner in rejecting claim 1. Accordingly,
we affirm the rejection of claim 1. Claims 3–6 and 30 fall with claim 1. The
rejections of the remaining claims (i.e., the rejections of claims 2, 7, 8, and
21–29) rely on the same combination of Hopkins, Hnaien, and Bäumler, in
addition to other references. See generally Final Action 7–14. Appellant
offers no separate arguments regarding these other rejections and claims.
See Appeal Br. 8–9. For the same reasons that we affirm the rejection of
claim 1, we likewise affirm the rejections of claims 2, 7, 8, and 21–29.
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Nonstatutory Double Patenting
Appellant does not argue the provisional nonstatutory double
patenting rejection. See Appeal Br. 4. Accordingly, we summarily affirm
this rejection. See 37 C.F.R. § 41.37(c)(1)(iv); Hyatt v. Dudas, 551 F.3d
1307, 1314 (Fed. Cir. 2008); MPEP § 1205.02 (“If a ground of rejection
stated by the examiner is not addressed in the appellant’s brief, appellant has
waived any challenge to that ground of rejection and the Board may
summarily sustain it.”).
CONCLUSION
The Examiner’s rejections are affirmed.
DECISION SUMMARY
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 3–6, 30 103 Hopkins, Hnaien,
Bäumler
1, 3–6, 30
2, 7 103 Hopkins, Hnaien,
Bäumler, Somberg
2, 7
8 103 Hopkins, Hnaien,
Bäumler,
Niemeyer
8
21–27, 29 103 Hopkins, Hnaien,
Bäumler, Wang
21–27, 29
28 103 Hopkins, Hnaien,
Bäumler, Wang,
Niemeyer
28
1–8, 21–30 nonstatutory
double patenting
1–8, 21–30
Overall
Outcome
1–8, 21–30

Appeal 2018-006733
Application 14/131,159
9
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