Thomas C. Dowling

Patent Trials and Appeals Board

Sep 30, 2019

14507391 - (D) (P.T.A.B. Sep. 30, 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.
14/507,391 10/06/2014 Thomas C. DOWLING 0096994-000001 3302
21839 7590 09/30/2019
BUCHANAN, INGERSOLL & ROONEY PC
POST OFFICE BOX 1404
ALEXANDRIA, VA 22313-1404
EXAMINER
PERKINS, STEPHEN A
ART UNIT PAPER NUMBER
1657
NOTIFICATION DATE DELIVERY MODE
09/30/2019 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):
ADIPDOC1@BIPC.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte THOMAS C. DOWLING

Appeal 2018-007814
Application 14/507,391
Technology Center 1600
____________

Before DEBORAH KATZ, JOHN G. NEW, and JOHN E. SCHNEIDER,
Administrative Patent Judges.

SCHNEIDER, Administrative Patent Judge.

DECISION ON APPEAL

Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 8–10, 12, and 13 as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.2

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 the inventor,
Thomas C. Dowling. Appeal Br. 2.
2 We have considered and herein refer to the Specification of Oct. 6, 2014
(“Spec.”); Final Office Action of July 11, 2017 (“Final Act.”); Appeal Brief
of Feb. 5, 2018 (“Appeal Br.”); Examiner’s Answer of May 24, 2018
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STATEMENT OF THE CASE

The invention relates to a method for determining drug interactions to
prevent or reduce renal failure. See Spec. 1–2.
Claims 8–10, 12, and 13 are on appeal.3 Claim 8 is representative of
the rejected claim and reads as follows:
8. A method of determining drug interactions of
pharmaceutical combinations, said method comprising
conducting a metabolite formation study in phase II enzymes in
human HK-2 cells using Para-aminohippuric acid (PAH) and a
first active pharmaceutical ingredient in a control group,
measuring phase II enzyme metabolite formation in said
pharmaceutical control group, exposing said cells to one or
more active pharmaceutical ingredients pharmaceuticals in a
treatment group, measuring phase II enzyme metabolite
formation in said treatment group, comparing phase II enzyme
metabolite formation in said control group and said treatment
group, and determining the drug interactions of said
pharmaceutical combinations.

(“Ans.”); and Reply Brief July 24, 2018 (“Reply Br.”). Oral Arguments
were heard on Sept. 17, 2019.
3 Claims 1–7, 11, and 14–20 are pending in the application but have been
withdrawn from consideration. Final Act. 2.
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The claims have been rejected under 35 U.S.C. § 103(a) as
unpatentable over Carpenter4 in view of Naud5 as evidenced by Colman6
and Geisler.7
DISCUSSION
Issue
The issue before us is whether a preponderance of the evidence
supports the Examiner’s conclusion that the subject matter of claims 8–10,
12, and 13 would have been obvious to one of ordinary skill in the art at the
time the invention was made over Carpenter combined with Naud.
The Examiner finds that claim 8 is directed to a method comprising
the steps of
A. Conducting a metabolite formation study in phase II
enzymes in cells using PAH and a first active pharmaceutical
ingredient in a control group
B. Measuring phase II enzyme metabolite formation in
said pharmaceutical control group
C. Exposing cells to one or more active pharmaceutical
ingredients in a treatment group

4 Carpenter, H.M. & Mudge, G.H. (1980). Uptake and Acetylation of p-
Aminohippurate by Slices of Mouse Kidney Cortex. J. Pharmacol. Exp.
Ther., 213(2), 350–354. (“Carpenter”).
5 Naud, J., Michaud, J., Beauchemin, S., Hébert, M.-J., Roger, M.,
Lefrancois, S., . . ., Pichette, V. (2011). Effects of Chronic Renal Failure on
Kidney Drug Transporters and Cytochrome P450 in Rats. Drug Metabolism
and Disposition, 39(8), 1363–1369. (“Naud”).
6 Colman, E. (2007). Dinitrophenol and obesity: An early twentieth-century
regulatory dilemma. Regulatory Toxicology and Pharmacology, 48(2), 115–
117. (“Colman”).
7 Geisler, J.G., Marosi, K., Halpern, J., & Mattson, M.P. (2017). DNP,
mitochondrial uncoupling, and neuroprotection: A little dab’ll do ya.
Alzheimer’s and Dementia, 13(5), 582–591. (“Geisler”).
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D. Measuring phase II enzyme metabolite formation in
said treatment group
E. Comparing metabolite formation in said control group
and said treatment group
F. Determining the drug interactions of said
pharmaceutical combinations

Final Act. 3.
The Examiner finds that Carpenter teaches a study of metabolite
formation in cells using PAH and a first pharmaceutical in a control group,
thus teaching steps A and B of claim 8. Id. at 4. The Examiner finds that
lactate, acetate, and succinate used with PAH in Carpenter meet the
limitation calling for an “active pharmaceutical ingredient” as the term is
used the present application. Id. at 5.
The Examiner finds that Carpenter teaches steps C and D as Carpenter
teaches exposing a set of cells to active pharmaceutical agent such as p-
aminobenzoate, sulfadiazine, sulfanilamide, and dapsone. Id. The Examiner
finds that Carpenter teaches measuring acetylation or metabolite formation
of the recited compounds. Id.
The Examiner finds that Carpenter teaches steps E and F in that
Carpenter compares the metabolite formation by cells exposed to PAH and
an active pharmaceutical ingredient with the second set of cells exposed to
as p-aminobenzoate, sulfadiazine, sulfanilamide, and dapsone. Id. at 6.
The Examiner finds that while Carpenter does not teach the use of
human HK-2 cells, this element is taught by Naud. Id. at 7.
The Examiner concludes
It would be obvious to one of ordinary skill in the art
before the effective filing date of the claimed invention to
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modify Carpenter’s method by conducting the method of
determining drug interactions of pharmaceutical combinations
as taught by Carpenter within the HK-2 cells taught by Naud.
One would be motivated to do so to determine drug interaction
in a human model. One would expect a reasonable amount of
success due to the similarities Naud demonstrated between a
rodent model and the HK-2 along with the conclusion that para-
aminohippuric acid is a known modulator of drug transporters
responsible for alteration in renal transporters in vivo.

Id. at 8.
Principles of Law
[T]he examiner bears the initial burden, on review of the prior
art or on any other ground, of presenting a prima facie case of
unpatentability. If that burden is met, the burden of coming
forward with evidence or argument shifts to the applicant.
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.

In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
Analysis
We adopt the Examiner’s findings of fact, reasoning on scope and
content of the prior art, and conclusions set out in the Final Action and
Answer regarding this rejection. We find the Examiner has established that
the subject matter of the claims would have been obvious to one of ordinary
skill in the art, at the time the invention was made, over Carpenter combined
with Naud. Appellant has not produced evidence showing, or persuasively
argued, that the Examiner’s determinations on obviousness are incorrect.
Only those arguments made by Appellant in the Briefs have been considered
in this Decision. Arguments not presented in the Briefs are waived. See 37
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C.F.R. § 41.37(c)(1)(iv) (2015). We have identified claim 8 as
representative; therefore, all claims fall with claim 8.8 We address
Appellant’s arguments below.
Appellant contends that the Examiner has improperly concluded that
acetate, lactate, succinate, and 2,4-DNP are active pharmaceutical agents as
the term is used in the claims and the Specification. Appeal Br. 4.
Appellant contends that the evidence of record, including the inventor’s
declaration demonstrate that lactate, succinate, and acetate are inert
ingredients are not used in the medical diagnosis, cure, treatment, or
prevention of disease. Id. at 9–10. With respect to 2,4-DNP, Appellant
contends that one skilled in the art would understand that the compound is
toxic and would not be used as an active pharmaceutical agent. Id. at 11–12.
We have considered Appellant’s argument, and we are not persuaded
that the Examiner erred in finding that the recited compounds are active
pharmaceutical agents. “[D]uring examination proceedings, claims are
given their broadest reasonable interpretation consistent with the
specification.” In re Hyatt, 211 F.3d 1367, 1372 (Fed. Cir. 2000).
The Specification defines the term pharmaceutical or drug to mean “a
pharmaceutical drug or medicinal product or any chemical substance
formulated or compounded as a single active ingredient product intended for
internal, or external or for use in the medical diagnosis, cure, treatment, or

8 In its Reply Brief, Appellant for the first time presents separate arguments
for dependent claims 9, 10, 12, and 13. Reply Br. 14–15. Since Appellant
has not shown good cause why these arguments were not presented in its
Appeal Brief, we decline to consider those arguments. 37 C.F.R.
§ 41.41(b)(2).
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prevention of disease.” Spec. 11. We agree with the Examiner that acetate,
lactate, succinate, and 2,4-DNP are active pharmaceutical agents as the term
is used in the claims. The Specification specifically teaches that sodium
lactate is a pharmaceutical. Spec. 18. The Specification teaches that PAH
“is a diagnostic agent used to measure renal plasma blood flow,” which is an
indicator of kidney disease. Spec. 2 and 5. Carpenter teaches that lactate,
acetate, succinate, and 2,4-DNP affect the uptake and accumulation of PAH,
which in turn affect the production of PAAH. Carpenter, 352. Thus, the
recited compounds act with PAH as a diagnostic and fall within the
definition of a pharmaceutical.
Appellant points to the declaration9 of the inventor, Dr. Dowling as
evidence that acetate, lactate, and succinate are not active pharmaceutical
ingredients but are inactive ingredients. Appeal Br. 9–10, citing Dowling
Decl. 2. Dr. Dowling, citing to Berge,10 testifies that components such as
acetate, lactate, and succinate are anions used to create salts but have no
other active qualities. Dowling Decl. 2 ¶ 18.
We have considered Dr. Dowling’s Declaration and are not persuaded
that acetate, lactate, and succinate are inactive pharmaceutical ingredients.
As noted above, the Specification teaches that sodium lactate is a
pharmaceutical. In addition, Carpenter teaches that acetate, lactate, and
succinate have an effect on the uptake of PAH indicating that the
compounds are active.

9 Second Supplemental Declaration of Thomas C. Dowling, Pharm. D, Ph.D.
Under 37 C.F.R. § 1.132, filed Apr. 6, 2017 Dowling Decl. 2”).
10 Berge S., Bighley, L.D., & Monkhouse, D.C. (1977). Pharmaceutical
Salts. J. Pharm. Sci., 66(1), 1–19. (“Berge”).
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Appellant next argues that acetate, lactate, and succinate are not active
pharmaceutical ingredients as the claims call for the active pharmaceutical
ingredient to produce a phase II enzyme metabolite and there is no evidence
of record that any of the recited compounds produce such a metabolite.
Appeal Br. 11.
We are not persuaded by Appellant’s argument. Claim 8, as written,
merely calls for measuring phase II enzyme metabolite formation, it does not
call for the metabolite to arise from the first active pharmaceutical
ingredient. Appeal Br. Claims App. 1.
Appellant next argues that one skilled in the art would not use 2,4-
DNP as the active pharmaceutical ingredient as it has been found to be toxic
and has not been used in the US since 1938. Appeal Br. 11–12. Again we
are not persuaded by Appellant’s argument.
As the Examiner has pointed out, Geisler teaches that at low doses,
2,4-DNP is useful in treating certain neurological disorders such as
Alzheimer’s and Parkinson’s disease. Ans. 14–15. Moreover, 2,4-DNP is
but one compound taught by Carpenter that effects uptake and use of PAH.
See Carpenter 352. As discussed above, the other compounds, acetate,
lactate and succinate are used in pharmaceuticals and exhibit activity when
combined with PAH. Thus Carpenter teaches that combination of PAH and
an active pharmaceutical ingredient in that it teaches PAH in combination
with acetate, lactate or succinate.
Appellant contends that the Examiner is improperly combining the
teachings of Tables II and III of Carpenter. Appeal Br. 13. Appellant
contends that the tables represent divergent data under differing study
conditions. Id.
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Once again, we are not persuaded by Appellant’s argument. The
Examiner’s rejection is based on not only the data in Tables II and III of
Carpenter, but the discussion of those experiments reflected on page 352 of
Carpenter. Ans. 16. We agree with the Examiner that one skilled in the art
would be led by the teachings of Carpenter to the claimed method. Id. As
the Examiner points out, the active pharmaceutical ingredient used with the
control group does not need to be the same as the one or more active
pharmaceutical ingredients in the treatment group. Id. Additionally, claim 8
does not call for the administration of PAH to the control group.
Appellant also contends that the Examiner did not fully consider the
evidence presented in the declarations by Dr. Dowling. Appeal Br. 14.
Appellant contends that the Examiner failed to present any evidence to
contradict Dr. Dowling’s testimony. Id.
We are not persuaded that the Examiner failed to give Dr. Dowling’s
declarations careful consideration. The first declaration11 of Dr. Dowling
focused almost exclusively on the fact that Naud did not teach a method with
the steps recited in the present claims. Dowling Decl. 1, ¶¶ 21–30. The
Examiner, however, did not rely on Naud for teaching the steps of the
claimed method but only for the teaching of human HK-2 cells. Final Act.
7. Dr. Dowling’s opinion regarding Naud’s failure to teach the steps of the
method did not address the Examiner’s rejection based on Carpenter and
Naud.

11 Declaration of Thomas C. Dowling, Pharm. D., Ph.D. Under 37 C.F.R.
§ 1.132, filed Oct. 5, 2016 (“Dowling Decl. 1”).
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With respect to the second Dowling declaration, the Examiner
explained in detail why the Examiner found the declaration unpersuasive.
Final Act. 11–17. For example, the Examiner discusses how Carpenter
supports the Examiner’s contention that acetate, lactate, and succinate fit the
definition of active pharmaceutical ingredient and that Geisler teaches that
2,4-DNP can be used to treat various neurological conditions. Id. at 13–14.
We conclude that a preponderance of the evidence supports the
Examiner’s conclusion that the subject matter of the claim 8 would have
been obvious over Carpenter combined with Naud. Claims 9, 10, 12, and 13
have not been separately argued and therefore fall with claim 8. 37 C.F.R.
§ 41.37(c)(iv).

CONCLUSION
In summary:
Claims
Rejected
Basis Affirmed Reversed
8–10, 12, and 13 35 U.S.C. § 103(a)
Carpenter and Naud
8–10, 12, and
13

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