Ian Harding et al.

Patent Trials and Appeals Board

Jan 28, 2020

13557372 - (D) (P.T.A.B. Jan. 28, 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.
13/557,372 07/25/2012 Ian Harding AGAM.P-073 9310
57381 7590 01/28/2020
Larson & Anderson, LLC
P.O. BOX 4928
DILLON, CO 80435
EXAMINER
KAUR, GURPREET
ART UNIT PAPER NUMBER
1795
MAIL DATE DELIVERY MODE
01/28/2020 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte IAN HARDING, MARY Y. LEE, and SANDIE TAN
Appeal 2018-005558
Application 13/557,372
Technology Center 1700
Before CATHERINE Q. TIMM, JEFFREY R. SNAY, and
MICHAEL G. McMANUS, Administrative Patent Judges.
TIMM, 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, 5, 6, 8–11, 15–18, 22–24, 27–32, and
37.2 We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42. Appellant identifies the real party in interest as Agamatrix, Inc.
Appeal Br. 1.
2 Claims 12, 13, 19, 20, 38, and 39 have been allowed. Ans. 12.
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CLAIMED SUBJECT MATTER
The rejected claims are directed to a dry reagent composition (see,
e.g., claim 1), a test strip using the dry reagent composition (see, e.g., claim
27), a method for testing for an analyte in a liquid sample using the test strip
(see, e.g., claim 30), and a method for forming a dry shelf-stable
electrochemical test reagent for use in detection of an analyte (see, e.g.,
claim 32). All of the claims require the formation or use of a dry reagent
composition including an active redox enzyme and tris-
tetramethylammonium ferricyanide. Claim 1, reproduced below, is
illustrative of dry reagent composition of the claims:
1. A dry reagent composition comprising:
(a) an active redox enzyme that oxidizes an analyte as a
specific substrate to produce an inactive reduced form of the
enzyme; and
(b) tris-tetramethylammonium ferricyanide.
Appeal Br. 15 (Claims Appendix).
REFERENCES
The prior art relied upon by the Examiner is:
Name Reference Date
Yaginuma US 5,008,078 Apr. 16, 1991
Harding ’0353 US 2005/0258035 A1 Nov. 24, 2005
Lau US 2006/0096859 A1 May 11, 2006
Harding US 2007/0295616 A1 Dec. 27, 2007
Martin US 2009/0295616 A1 Dec. 3, 2009

3 The Examiner discusses Harding’035 when rejecting claims 28 and 29
(Final Act. 8; Ans. 9), but does not include Harding’035 in the statement of
the rejection and, thus, the Examiner did not properly inform Appellant of
the reliance on this reference. This was error, but harmless given that we are
reversing on other grounds.
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Bertin4 US 2010/0003710 A1 Jan. 7, 2010
Pei US 2010/0270175 A1 Oct. 28, 2010
Carrington US 2013/0092536 A1 Apr. 18, 2013
Cheng Determination of stepwise stability
constants for aqueous
hexacyanoferrate-
tetramethylammonium ions pairs by
cyclic voltammetry, Analytic
Chimica Acta, 251 (1991) 35–38
1991

REJECTIONS
Due to the entry of the After-Final Amendment of May 25, 2017
(Advisory Action of July, 3, 2017), the status of the claims has changed and
is reflected in the Answer, which indicates the following rejections are
maintained:
A. The rejection of claims 1, 5, 6, 8–10, 27–32, and 37 under 35
U.S.C. § 103(a) as obvious over Harding, Lau, and Cheng;5
B. The rejection of claims 11 and 18 under 35 U.S.C. § 103(a) as
obvious over Harding, Lau, Cheng, and further in view of
Carrington and Yaginuma; and

4 The Examiner cites Bertin for the first time in the Answer to support the
determination that Appellant’s unexpected result showing is not
commensurate in scope with the claims. Ans. 15. Appellant recognizes the
Examiner’s new reliance on Bertin. Reply Br. 2. Given Appellant recognized
the Examiner was relying on Bertin and we reverse on other grounds, any
error was harmless.
5 In the Answer, the Examiner added Lau to the statement of rejection of
claim 32. Compare Ans. 4, with Final Act. 3. Lau had previously been
mentioned only in the body of the rejection. Final Act. 3.
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C. The rejection of claims 15–17 and 22–24 under 35 U.S.C. § 103(a)
as obvious over Harding, Lau,6 Cheng, and further in view of Pei
and Martin.7

OPINION
After reviewing the evidence of record, we determine a preponderance
of the evidence supports Appellant’s contention that the Examiner reversibly
erred in weighing the evidence of unexpected results.
As a first matter, we consider the evidence of what was known in the
prior art as that evidence is important in our weighing of the evidence of
unexpected results.
Harding and Lau both provide evidence of what was known in the art
of reagents used for detecting analytes such as glucose. Harding ¶ 2; Lau
¶¶ 1–2. As evidenced by Harding and Lau, it was known in the art to pair an
active redox enzyme and a mediator such that a redox reaction occurs that
produces a measurable current representative of the concentration of an
analyte such as glucose. Harding ¶ 3; Lau ¶¶ 2–13. The redox enzyme
maybe, e.g., glucose oxidase, which oxidizes glucose, to produce an inactive
reduced form of the enzyme in a redox reaction. Harding ¶ 2; Lau ¶ 2.
Various mediators were known in the art including ferricyanide anion-
based [(Fe(CN)6]3- mediators. Harding ¶ 4; Lau ¶¶ 20, 29. Harding does not

6 Although the Examiner omits Lau, we treat the rejection as including Lau
given the statement in the rejection “as applied to claim 11 and 18 above.”
The rejection of claims 11 and 18 included Lau. Given the disposition of the
issues on appeal, the error was harmless.
7 The Examiner refers to US 2009/0295616 to Martin as “Marfurt.”
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discuss pairing the ferricyanide anion with any cation, much less Appellant’s
tetramethylammonium cations.
Harding discloses that there are several factors considered when
selecting the mediator. Harding ¶ 4. For example, to detect glucose, one
selects a mediator with a redox potential that will quickly oxidize the
enzyme to regenerate it from its reduced state, i.e., a mediator that has fast
kinetics. Id. The problem is that, frequently, mediators with the desired
redox potential and fast kinetics are poorly soluble in aqueous solutions,
such as blood. Id. Poor solubility limits the maximum concentration of
mediator and, as a result, limits the maximum amount of signal that can be
generated. Id.
Harding discloses that the mediator is an electron transfer agent.
Harding ¶ 5. Harding tackles the solubility problem by adding another
electron transfer agent, which Harding calls a shuttle. Id. The shuttle
interacts with the electrodes and, optionally, the mediator, and serves as a
major source of current. Id. As acknowledged by Appellant, in some
embodiments of Harding, the ferricyanide anion performs the role of the
shuttle because of its solubility, but it can also function as a mediator as in
the prior art of Figure 1 when a more effective mediator is not present.
Appeal Br. 4; Harding ¶¶ 4, 51, 77.
As pointed out by Appellant, Harding is silent on the stability of
reagents in a dry test strip. Appeal Br. 4. Lau, however, discloses that
mediators can be unstable and tend to undergo autoxidation. Lau ¶ 14. Lau
solves the stability problem by a different method than Appellant. Lau uses a
ferricyanide mediator selective for hydrogen peroxide. Lau ¶ 16. Lau’s
general formula of ferricyanides (X3Fe(CN)6) encompasses Appellant’s tris-
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tetramethylammonium ferricyanide, however, Lau specifically requires the
ferricyanide mediator have more carbon atoms so the compound is insoluble,
which Lau discloses is an advantage. Lau ¶¶ 20–25. Lau specifically limits
the genus to species where at least one of the quaternary ammonium ions
contains at least four carbon atoms. Lau ¶ 24. Thus, Lau does not include the
more soluble tris-tetramethylammonium ferricyanide of Appellant’s claims.
To summarize, Harding indicates that, generally, ferricyanides were
known for use as mediators and shuttles and Lau indicates that quaternary
ammonium ferricyanides with higher numbers of carbons than Appellant’s
tris-tetramethylammonium ferricyanide were known mediators in dry
reagent compositions selective for hydrogen peroxide.
The Examiner, recognizing that Harding does not explicitly teach that
the shuttle compound is tris-tetramethylammonium ferricyanide, turns to
Cheng. Ans. 6–7.
Cheng is a research paper that studies ion pairing between aqueous
hexacyanoferrate (ferricyanide/ferrocyanide) and tetramethylammonium
ions (TMA+). Cheng, Abs. Cheng creates aqueous solutions including 10
mM potassium hexacyanoferrate(II) in two solutions, one containing 0.146
M tetramethylammonium chloride (TMACl) and one containing 3.494 M
TMACl. Cheng, Experimental. Cheng measures a redox shift that Cheng
attributes to the association of tetramethylammonium (TMA+) ions with
ferricyanide ions [(Fe(CN)6]3-. Cheng, Results and Discussion. Based on the
experiments, Cheng determines that (TMA)3Fe(CN)6 (tris-
tetramethylammonium ferricyanide) predominates at high
tetramethylammonium ion activity. Cheng, Abs. and Results and Discussion
last paragraph.
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Cheng’s research paper was published in 1990. Cheng indicates that,
at that time, tetraalkylammonium (TAA) hexacyanoferrate salts were
“commonly employed as oxidizing agents in a variety of synthetic schemes
that include the oxidation of phenols and proteins.” Cheng, first paragraph.
Cheng further conveys that, at that time, very little systematic work had been
done on the role of TAA ionic activity on hexacyanoferrate redox potentials.
Id. Cheng suggests that bioelectrochemical sensors based on enzymes are a
likely application of (TMA)3Fe(CN)6, i.e., tris-tetramethylammonium
ferricyanide, and that the kinetics of electron transfer from glucose oxidase
to Fe(CN)63-, i.e., ferricyanide, “is currently being examined.” Cheng,
Applications.
Although Cheng does not state that tris-tetramethylammonium
ferricyanide was, in 1990, used in enzyme-based sensors, Lau discloses the
use of other tetraalkylammonium ferricyanides in enzyme-based sensors that
detect hydrogen peroxide, and Harding discloses using ferricyanides as
mediators and shuttles in sensors that operate without hydrogen peroxide
detection. Appellant’s Specification indicates that it was known to use
potassium, sodium, lithium, magnesium, etc. as the cation paired with the
ferricyanide anion. Spec. 2. Potassium ferricyanide has been used in various
commercial test strips. Spec. 30. Together the prior art provides a suggestion
of using tris-tetramethylammonium ferricyanide as a mediator or shuttle
with a reasonable expectation that it would have the necessary redox
potential required by Harding.
That being said, based on the evidence discussed above, there is little
reason to suspect that the tris-tetramethylammonium cation would provide
results significantly different than other cations. However, Appellant’s
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results indicate the results are, in fact, significantly different. According to
Appellant, the use of tris-tetramethylammonium ferricyanide
((TMA)3Fe(CN)6) in place of potassium ferricyanide (K3Fe(CN)6) or other
salts of ferricyanide results in a substantial and unpredictable increase in the
shelf-stability of test strips. Appeal Br. 7. Appellant points to Figures 4–6 as
showing this unexpected stability. Appeal Br. 8–10. We agree with
Appellant that Figure 6 shows a substantial improvement in the stability of
the baseline current. Appeal Br. 8. Figure 6 shows that the baseline current
of ferricyanide paired with tris-tetramethylammonium cation (TMA)
changes much less than the baseline of ferricyanides paired with other
cations (Cs, Na, K, Rb) when aged at 50°C for 14 days. A comparison of
Figures 4 (containing potassium) and 5 (containing TMA) shows that
baseline current stability translates to stability of the current in test strips
containing glucose oxidase enzyme and buffers.
The Examiner finds that the results are not commensurate in scope
with the claims because Appellant reports results for only test strips
containing glucose oxidase, but the claims encompass test strips containing
any active redox enzyme. Ans. 15.
Appellant contends that it is the change in cation that causes the
stability increase and not the composition of the enzyme, thus, comparison
with test strips including other enzymes is not necessary. Appeal Br. 11;
Reply Br. 2.
The Specification supports Appellant’s contention. Figure 6 shows
that the difference arises from the change in cation. Figures 4 and 5 show
how that change effects the current stability. The Specification explains the
stability increase in terms of the cation difference. Spec. 31.
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In response to Appellant’s argument, the Examiner points out that the
claimed genus encompasses oxidoreductase enzymes other than glucose
oxidase (Ans. 15), which is true, but does not address Appellant’s contention
that the identity of the enzyme is not important to the showing because it is
the cation that provides the unexpected result. The Examiner offers no
persuasive technical reasoning or evidence countering the evidence
supporting Appellant’s argument.
The Examiner also suggests that Lau is the closest prior art and
Appellant should compare their TMA ferricyanide-based test strip to Lau’s
quaternary alkylammonium ion-based ferricyanide salts. Ans. 16–17.
However, we agree with Appellant that, although there is a superficial
structural similarity between the longer chain alkylammonium cations of
Lau and Appellant’s methylammonium cations, Lau’s teaching of using
insoluble cations make Lau’s cations less closely related than the soluble
cations of Appellant’s tests. Reply Br. 3–4.
After weighing the evidence relied on by the Examiner and Appellant
in this appeal, we determine that Appellant has identified a reversible error
in the Examiner’s evaluation of the showing of unexpected results, which
affected all the rejections. Thus, we do not sustain the rejections.
CONCLUSION
The Examiner’s rejections are reversed.
More specifically,
A. we do not sustain the rejection of claims 1, 5, 6, 8–10, 27–32, and
37 under 35 U.S.C. § 103(a) as obvious over Harding, Lau, and
Cheng;
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B. we do not sustain the rejection of claims 11 and 18 under 35 U.S.C.
§ 103(a) as obvious over Harding, Lau, Cheng, and further in view
of Carrington and Yaginuma; and
C. we do not sustain the rejection of claims 15–17 and 22–24 under 35
U.S.C. § 103(a) as obvious over Harding, Lau, Cheng, and further
in view of Pei and Martin.
DECISION SUMMARY
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 5, 6, 8–
10, 27–32,
37
103(a) Harding, Lau,
Cheng
1, 5, 6, 8–
10, 27–32,
37
11, 18 103(a) Harding, Lau,
Cheng, Carrington,
Yaginuma
11, 18
15–17, 22–
24
103(a) Harding, Lau,
Cheng, Pei, Martin
15–17, 22–
24
Overall
Outcome
1, 5, 6, 8–
11, 15–18,
22–24, 27–
32, 37

REVERSED