University Of Cincinnati

Patent Trials and Appeals Board

Mar 23, 2021

2020005139 (P.T.A.B. Mar. 23, 2021)

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.
15/314,414 11/28/2016 Jason C. Heikenfeld UOC-15030US 6526
26875 7590 03/23/2021
WOOD, HERRON & EVANS, LLP
2700 CAREW TOWER
441 VINE STREET
CINCINNATI, OH 45202
EXAMINER
DONOHUE, SEAN R
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
03/23/2021 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):
usptodock@whe-law.com
wjacobs@whe-law.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JASON C. HEIKENFELD1
Appeal 2020-005139
Application 15/314,414
Technology Center 1600
Before ERIC B. GRIMES, RACHEL H. TOWNSEND, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of measuring a drug’s concentration based on sweat sensing, which
have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
STATEMENT OF THE CASE
The Specification discloses that “[t]he concentration in a bodily fluid
of a delivered solute such as a drug administered to an individual is detected

1 Appellant identifies the real party in interest as University of Cincinnati.
Appeal Br. 1. We use the word “Appellant” to refer to “applicant” as defined
in 37 C.F.R. § 1.42.
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Application 15/314,414

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indirectly by co-administering to the patient a known amount of a tracer
compound that predictably emerges in sweat, and is easily detectable.” Spec.
¶ 7. A “‘tracer compound’ or ‘tracer’ means a compound having a known
co-relationship between the tracer compound’s concentration in sweat with
the concentration of a primary drug in blood or an organ.” Id. ¶ 19.
One such candidate tracer compound is the well-known drug
ibuprofen, which has an active and an inactive stereoisomer. . . .
[T]he inactive stereoisomer R-ibuprofen possesses a similar
metabolic path through the liver. . . . It can therefore be co-
administered with the active S-ibuprofen as a tracer compound.
The system could then be used to determine the concentration
of S-ibuprofen indirectly by monitoring the concentration of
R-ibuprofen metabolites.
Id. ¶ 55.
Claims 1–5 and 48–53 are on appeal. Claim 1, reproduced below, is
illustrative:
1. A method comprising:
administering to a patient a known amount of a primary
drug;
administering to the patient a known amount of a tracer;
using a sweat sensing device to take a plurality of
measurements of solutes in sweat at a sampling rate having a
chronological assurance, wherein the solutes include the tracer
or a metabolite of the tracer;
receiving a tracer concentration, wherein the tracer
concentration is a concentration of the tracer in sweat or a
metabolite of the at least one tracer in sweat; and
correlating the tracer concentration with a concentration
of the drug in the patient’s blood or an organ, wherein a sweat
to blood correlation includes one of the following: a time of
administration of the drug, a time of administration of the
tracer, a method of administration of the drug, a method of
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administration of the tracer, and a time of detection of the tracer
concentration.

The claims stand rejected as follows:
Claims 1–5 and 48–52 under 35 U.S.C. § 103 as obvious based on
Hagen,2 Kell,3 and Randloev4 (Final Action5 3);
Claims 1–5 and 48–52 under 35 U.S.C. § 103 as obvious based on
Hagen, Kell, Randloev, and Jamali6 (Final Action 3); and
Claim 53 under 35 U.S.C. § 103 as obvious based on Hagen, Kell,
Randloev, and Roser7 (Final Action 5).
OPINION
All of the claims stand rejected as obvious based on Hagen, Kell, and
Randloev, optionally combined with Jamali or (with respect to claim 53)
Roser. The same issue is dispositive for all of the rejections.
The Examiner finds that Hagen teaches a sweat collection and sensing
system that allows analysis of biomarkers in sweat. Non-Final Action8 4.
The Examiner finds that Hagen claims a method that includes determining
the amounts of first and second chemicals in sweat, and the ratio of the first
chemical to the second chemical, but does not teach administering a primary

2 WO 2013/152087 A2; published Oct. 10, 2013.
3 5,776,783; issued July 7, 1998.
4 US 2014/0073892 A1; published Mar. 13, 2014.
5 Office Action mailed October 1, 2019.
6 Fakhreddin Jamali, Pharmacokinetics of enantiomers of chiral non-
steroidal anti-inflammatory drugs, EUR. J. DRUG METAB. & PHARMACOKIN.
13:1–9 (1988).
7 US 2007/0172424 A1; published July 26, 2007.
8 Office Action mailed June 19, 2019.
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drug and a tracer compound, and correlating the tracer concentration with
the concentration of the primary drug. Id. at 4–5.
The Examiner finds that Kell teaches a method of monitoring
consumption of a therapeutic agent by adding a pharmacologically inert
substance to the drug as a compliance marker, then correlating the amount of
compliance marker in urine to the amount of medication ingested based on
“a simple relationship . . . between oral intake and urine output.” Id. at 5.
The Examiner also finds that Hagen does not teach “a chronologically
assured sampling rate,” id. at 4, but finds that Randloev teaches a glucose
prediction model, where “for identification of a time-series prediction model
one needs chronologically ordered past glucose data with a sufficiently small
sampling rate (sampling interval of 1 to 3 min).” Id. at 5.
The Examiner concludes that it would have been obvious to modify
Hagen’s sweat-sampling method “by using chronologically assured
sampling rate . . . [of] every 1 to 3 min as taught by Hagen et al[.] and
Randloev et al. because it would advantageously enable analyzing drug
concentration over time.” Id. The Examiner also concludes that it would
have been obvious to modify Hagen’s method
by administering a drug combined with at least one tracer
compound and correlating the tracer concentration with the
concentration of primary drug in the patient[’]s blood . . . as
taught by Kell et al. because it would advantageously enable
determining the amount of drug ingested and amount of [drug]
present in blood at the time of sampling based on the known
half-life of the drug.
Id. at 6.
Appellant argues, among other things, that “Hagen, Kell, Randloev,
and Jamali fail to teach a mechanism for correlating a tracer concentration
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with a concentration of the drug in a patient’s blood or an organ.” Appeal
Br. 10 (emphasis omitted). Appellant argues that “Kell describes only that
the compliance markers described in Kell are used to determine if the drug is
ingested, rather than an actual concentration of the drug in the patient’s
blood as recited in claim 1.” Id. at 4. That is, “Kell describes a linear
correlation between compliance marker concentration in urine and
compliance marker dose” but “the relationship described in Kell is between
the concentration of compliance marker in the patient’s urine and the amount
of compliance marker ingested, which is in turn related to the amount of
drug ingested, but not to the amount of drug in the patient’s blood or organ.”
Id. at 5. Appellant argues that Randloev and Jamali fail to cure the
deficiencies of Hagen and Kell. Id. at 12.
We agree with Appellant that the cited references do not support a
prima facie case of unpatentability under 35 U.S.C. § 103. Claim 1 requires
measuring the concentration of a tracer compound in a sweat sample and
“correlating the tracer concentration with a concentration of the drug in the
patient’s blood or an organ.” The Examiner acknowledges that Hagen does
not teach this limitation. See Non-Final Action 4–5 (“Hagen et al. do not
teach correlating the tracer concentration with a concentration of primary
drug.”).
Kell discloses a “method . . . for tracking compliance of patients on
prescription medications (therapeutic agents) by using compliance markers
(quantitative consumption markers) in association with the medications,
which consumption compliance marker concentrations can be accurately
measured in the urine.” Kell 4:47–53. After the compliance marker
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concentration in the urine is determined, “a correlation is made to the
amount of actual medication ingested.” Id. at 4:54–56.
Kell discloses that “quantitative relationships exist between the
amount ingested and the amount appearing in the urine as a function of
physical parameters such as patient weight, lean body mass,” etc. Id. at
4:59–62. Kell does not, however, state that the amount of a compliance
marker in urine has any correlation with the concentration of a drug in a
patient’s blood or organs.
In addition, as Appellant has pointed out, “Kell is directed toward
urine samples and not sweat samples.” Appeal Br. 6. The specific
compliance marker disclosed by Kell is a benzodiazepine. Kell 5:1–4.
“[B]enzodiazepines and their metabolites readily pass through the renal
system into the urine making benzodiazepines and substances with similar
properties especially suitable as compliance markers.” Id. at 5:4–8. Kell
states that “many hepatic metabolites of benzodiazepine[s] . . . are not
significantly further metabolized by the liver. Consequently, simple
relationships exist between oral intake and urine output.” Id. at 7:16–21.
Kell does not, however, state that there is a relationship between oral intake
of a compliance marker and its output in sweat, much less a relationship
between blood concentration and output in sweat.
The Examiner cites Randloev only for its disclosure of a sampling rate
having a chronological assurance. See Non-Final Action 5 (“Randloev et al.
teach . . . chronologically ordered past glucose data with a sufficiently small
sampling rate (sampling interval of 1 to 3 min).”). The Examiner finds that
Jamali would have suggested using the S-enantiomer of ibuprofen as a tracer
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compound. Id. at 6–7. The Examiner does not point to any disclosure in
Randloev or Jamali that makes up for the deficiencies of Kell discussed
above.
The Examiner finds that Roser teaches “a method for measuring the
concentration of a medicament through the introduction of a tracer
compound. The measurement of the blood concentration of the tracer will
yield a result that will enable a prediction of the blood concentration of the
medicament.” Final Action 6. Roser thus teaches correlating the blood
concentration of one compound (a tracer) with the blood concentration of
another compound (a medicament). Roser also fails to make up for the
deficiencies of Kell in failing to teach a method of correlating the
concentration of a compliance marker (or tracer) in urine or sweat with the
concentration of a drug in a patient’s blood or organs.
In summary, the Examiner has not provided adequate evidence to
show that a method meeting all of the limitations of the claims on appeal
would have been obvious based on the cited prior art references. We
therefore reverse all of the rejections on appeal.
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DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–5, 48–52 103 Hagen, Kell, Randloev 1–5, 48–52
1–5, 48–52 103 Hagen, Kell, Randloev,
Jamali
1–5, 48–52
53 103 Hagen, Kell, Randloev,
Roser
53
Overall
Outcome
1–5, 48–53

REVERSED