Strongbridge Dublin Limited

Patent Trials and Appeals Board

Oct 27, 2021

2021004633 (P.T.A.B. Oct. 27, 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.
16/201,410 11/27/2018 Fredric Jay COHEN STRG0001-201T-US 8461
159061 7590 10/27/2021
GLOBAL PATENT GROUP - STRG
Global Patent Group LLC
P.O. Box 1636
Canóvanas, PR 00729
EXAMINER
SZNAIDMAN, MARCOS L
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
10/27/2021 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):
admin@globalpatentgroup.com
lwilson@globalpatentgroup.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte FREDRIC JAY COHEN
____________

Appeal 2021-004633
Application 16/201,410
Technology Center 1600
____________

Before DONALD E. ADAMS, ULRIKE W. JENKS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 1 and 38 (Appeal Br. 5). 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. Appellant identifies the real party in interest as “Strongbridge
Dublin Limited . . . a wholly owned subsidiary of Strongbridge Biopharma
plc.” (Appellant’s April 20, 2021, Appeal Brief (Appeal Br.) 3). Appellant
further notes that “[o]ther wholly owned subsidiaries of Strongbridge
Biopharma pk include Strongbridge U.S. Inc. Cortendo AB
and Cortendo Cayman” and that “Avenue Venture Opportunities Fund, L.P.
holds a security interest in the subject patent application” (id.).
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STATEMENT OF THE CASE
Appellant’s disclosure relates to “methods for administering
dichlorphenamide, or a pharmaceutically acceptable salt thereof, to a subject
in need thereof, wherein the subject is also being administered an organic
anion transporter-1 (OAT1) substrate” (Spec.2, Abstr.). Claims 1 and 38 are
reproduced below:
1. A method for initiating administration of an organic anion
transporter-1 (OAT1) inhibitor that is dichlorphenamide, or a
pharmaceutically acceptable salt thereof, to a subject in need of
dichlorphenamide, or a pharmaceutically acceptable salt thereof
to treat a first disease or disorder,
wherein the subject is also being administered an organic
anion transporter-1 (OAT1) substrate wherein the OAT1
substrate is furosemide which is for the prophylactic treatment
of hyperkalemic periodic paralysis and the acute treatment of
muscle paralysis or myotonia, the method comprising:
discontinuing administration of the OAT1 substrate, and
subsequently administering to the subject an initial dose
of dichlorphenamide, or a pharmaceutically acceptable salt
thereof, of 50 mg twice daily.
(Appeal Br. 27.)
38. A method for initiating administration of an organic anion
transporter-1 (OAT1) inhibitor that is dichlorphenamide, or a
pharmaceutically acceptable salt thereof, to a subject in need of
dichlorphenamide, or a pharmaceutically acceptable salt thereof
to treat a first disease or disorder,
wherein the subject is also being administered an organic
anion transporter-1 (OAT1) substrate wherein the OAT1
substrate is furosemide which is for the prophylactic treatment
of hyperkalemic periodic paralysis and the acute treatment of
muscle paralysis or myotonia, the method comprising:

2 Appellant’s November 27, 2018, Specification.
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discontinuing administration of the OATI substrate, and
subsequently administering to the subject an initial dose
of dichlorphenamide, or a pharmaceutically acceptable salt
thereof, of 50 mg once daily.
(Id. at 27–28.)

Grounds of rejection before this Panel for review:
I. Claims 1 and 38 stand rejected under 35 U.S.C. § 112(b).
II. Claims 1 and 38 stand rejected under the written description
provision of 35 U.S.C. § 112(a).
III. Claims 1 and 38 stand rejected under the enablement provision
of 35 U.S.C. § 112(a).
IV. Claims 1 and 38 stand rejected under 35 U.S.C. § 103 as
unpatentable over the combination of Keyevis3 and
Methotrexate.4
V. Claims 1 and 38 stand rejected under 35 U.S.C. § 103 as
unpatentable over the combination of Najarian5 and Imran6

Rejection I:
ISSUE
Does the preponderance of evidence support Examiner’s conclusion
that Appellant’s claimed invention is indefinite?

3 KEVEYISTM, dichlorphenamide tablets, for oral use, Highlights of
Prescribing Information, reference ID: 3803244, revised August 2015.
4 Methotrexate Tablets, USP, Prescribing Information, reference ID:
3879293, revised January 2016.
5 Najarian et al., US 2008/0312163 A1, published Dec. 18, 2008.
6 Imran, US 2014/0074060 A1, published Mar. 13, 2014.
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ANALYSIS
Appellant’s claims 1 and 38 are reproduced above.
The method of Appellant’s claim 1 relates to the administration of the
OAT1 inhibitor, dichlorphenamide or a pharmaceutically acceptable salt
thereof, to a subject in need thereof. Appellant’s Specification discloses,
inter alia, “[m]ethods of treating hyperkalemic periodic paralysis, [and]
hypokalemic periodic paralysis” and that “[d]ichlorphenamide (Keveyis®,
Daranideâ„¢) is . . . approved for treating primary hyperkalemic periodic
paralysis, primary hypokalemic periodic paralysis, and related variants, and
has been used to treat intraocular pressure (IOP)” (Spec. ¶¶ 1, 3).
Appellant’s claim 1 limits the genus of subjects falling within the
scope of its method to those individuals who are being administered the
OAT1 substrate, furosemide. Appellant’s claim 1 requires, therefore, that
the administration of furosemide is discontinued and dichlorphenamide, or a
pharmaceutically acceptable salt thereof, is administered at an initial dose of
50 mg twice daily. Appellant’s claim 38 differs from Appellant’s claim 1 by
requiring that the dichlorphenamide, or a pharmaceutically acceptable salt
thereof, is administered at an initial dose of 50 mg once daily.
For the foregoing reasons, we agree with Appellant’s contention that
its
claims are specific as to:
• The subject being treated, i.e., a person who is being
treated with furosemide for prophylactic treatment of
hyperkalemic periodic paralysis and the acute treatment
of muscle paralysis or myotonia, but also requires
treatment with dichlorphenamide, which as explained in
the specification is used for the treatment of primary
hyperkalemic periodic paralysis, primary hypokalemic
periodic paralysis, and related variants;
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• The method of treatment, i.e., administration of
furosemide, is discontinued prior to administering the
initial dose of dichlorphenamide; and
• The amount of drug being administered, i.e., 50 mg
dichlorphenamide once or twice daily after
administration of the furosemide is discontinued. The
amount of furosemide being administered is not recited
in the claim because the furosemide is not to be
administered at the same time as the dichlorphenamide.
The amount of furosemide administered prior to
administration of dichlorphenamide is thus irrelevant for
purpose of the claims.
Thus, the claims inform, with reasonable certainty, those skilled
in the art about the scope of the invention . . . [and] are definite.
(Appeal Br. 10–11.)
For the foregoing reasons, we are not persuaded by Examiner’s
interpretation of Appellant’s claims 1 and 38 or the conclusions Examiner
drew from the incorrect interpretation of Appellant’s claimed methods (see
Ans.7 3–6).
CONCLUSION
The preponderance of evidence fails to support Examiner’s conclusion
that Appellant’s claimed invention is indefinite.
Rejection I: The rejection of claims 1 and 38 under 35 U.S.C.
§ 112(b) is reversed.

7 Examiner’s July 1, 2021, Answer.
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Rejection II:
ISSUE
Does the preponderance of evidence on this record support
Examiner’s finding that Appellant’s Specification fails to provide written
descriptive support for the claimed invention?
ANALYSIS
As discussed above, Appellant’s Specification discloses, inter alia,
“[m]ethods of treating hyperkalemic periodic paralysis, [and] hypokalemic
periodic paralysis” and that “[d]ichlorphenamide (Keveyis®, Daranide™)
is . . . approved for treating primary hyperkalemic periodic paralysis,
primary hypokalemic periodic paralysis, and related variants, and has been
used to treat intraocular pressure (IOP)” (Spec. ¶¶ 1, 3). Appellant’s
Specification further discloses:
In certain embodiments, there is provided a method for
administering dichlorphenamide, or a pharmaceutically
acceptable salt thereof, to a subject in need thereof, wherein the
subject is also being administered an organic anion transporter-
1 (OAT1) substrate. The method comprises administering to
the subject a therapeutically effective amount of
dichlorphenamide, or a pharmaceutically acceptable salt
thereof, and monitoring the subject for signs and symptoms of
toxicity and clinical response associated with the OAT1
substrate.
In certain embodiments, the OAT1 substrate
is . . . furosemide . . . .
In certain embodiments, the OAT1 substrate
is . . . furosemide. . . . Furosemide . . . [is] frequently used to
prophylactically treat hyperkalemic periodic paralysis and to
acutely treat muscle paralysis or myotonia. . . .
In certain embodiments, the method further comprises reducing
the dose and/or frequency of the OAT1 substrate administered
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to the subject based on the subject's ability to tolerate one or
more exposure-related adverse reactions associated with the
OAT1 substrate. In certain embodiments, the dose of the
OAT1 substrate is decreased, such as by at least about 5%, by
at least about 10%, by at least about 20%, by at least about
30%, by at least about 40%, or by at least about 50%. In certain
embodiments, the frequency of administration of the OAT1
substrate is decreased. In certain embodiments, the method
further comprises discontinuing administration of the OAT1
substrate based on the patient's ability to tolerate one or more
exposure-related adverse reactions.
(Spec. ¶ 97.)
For the foregoing reasons, we are not persuaded by Examiner’s
assertion that Appellant’s Specification fails to provide written descriptive
support for Appellant’s claimed “dose regimen” (Ans. 7; cf. Appeal Br. 11–
14).
CONCLUSION
The preponderance of evidence on this record fails to support
Examiner’s finding that Appellant’s Specification fails to provide written
descriptive support for the claimed invention.
Rejection II: The rejection of claims 1 and 38 under the written
description provision of 35 U.S.C. § 112(a) is reversed.

Rejection III:
ISSUE
Does the evidence of record support Examiner’s conclusion that
undue experimentation would be required to practice the claimed invention?
ANALYSIS
The method of Appellant’s claimed invention limits the scope of the
patient population to those patients who are being administered furosemide
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for the prophylactic treatment of hyperkalemic periodic paralysis and the
acute treatment of muscle paralysis or myotonia. Appellant’s claimed
method further requires, as a first step, that administration of furosemide is
stopped, i.e., discontinued. Then, after stopping the administration of
furosemide, Appellant’s claimed method requires the administration of
dichlorphenamide, or a pharmaceutically acceptable salt thereof, in an initial
dose of 50 mg once (claim 38) or twice (claim 1) daily to treat a first disease
or disorder.
Given the foregoing, Examiner’s focus on whether or not those of
ordinary skill in this art would have recognized that furosemide can
prophylactically treat hyperkalemic periodic paralysis and the acute
treatment of muscle paralysis or myotonia, it is not relevant to Appellant’s
claimed method (see Ans. 7–13). In the context of Appellant’s claimed
invention, all that is relevant with respect to furosemide is that patients in the
patient population encompassed by Appellant’s claimed method (1) are
being administered furosemide for the prophylactic treatment of
hyperkalemic periodic paralysis and the acute treatment of muscle paralysis
or myotonia and (2) that furosemide administration is stopped, i.e.
discontinued, prior to administration of an initial dose of dichlorphenamide,
or a pharmaceutically acceptable salt thereof, of 50 mg once or twice daily.
In sum, we agree with Appellant’s contention that its “claims are
enabled” (Appeal Br. 15; see generally id. at 14–15; Reply Br.8 2–6).

8 Appellant’s July 23, 2021, Reply Brief.
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CONCLUSION
The evidence of record fails to support Examiner’s conclusion that
undue experimentation would be required to practice the claimed invention.
Rejection III: The rejection of claims 1 and 38 under the enablement
provision of 35 U.S.C. § 112(a) is reversed.

Rejections IV–V:
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Appellant discloses that furosemide is “frequently used to
prophylactically treat hyperkalemic periodic paralysis and to acutely treat
muscle paralysis or myotonia” (Spec. ¶ 88).
FF 2. Appellant discloses that “[d]ichlorphenamide . . . is a carbonic
anhydrase inhibitor approved for treating primary hyperkalemic periodic
paralysis, primary hypokalemic periodic paralysis, and related variants”
(Spec. ¶ 3).
FF 3. Najarian “relates generally to methods and pharmaceutical
compositions useful in treating pulmonary hypertension” (Najarian ¶ 1; see
Ans. 14).
FF 4. Najarian discloses that “[a]ny carbonic anhydrase inhibitor may be
advantageously employed in conjunction with the present invention,” for
example, furosemide and dichlorphenamide (Najarian ¶ 21; see Ans. 14).
FF 5. Najarian discloses that an oral daily dose of carbonic anhydrase
inhibitor “effective to treat pulmonary hypertension” is “preferably in the
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range of about 50 mg to about 250 mg,” wherein “[t]he daily dose may be
divided into two to four individual doses” (Najarian ¶ 21; see Ans. 14–15).
FF 6. Imran discloses that “furosemide has a number of adverse side
effects including, for example, electrolyte loss/imbalance, hyperglycemia,
otoxicity, hyperuricemia and resulting gout, and low potassium levels as
well as increased diuresis to name a few” (Imran ¶ 74; see Ans. 14).
ANALYSIS
Rejection IV:
We vacate the rejection over the combination of Keyevis and
Methotrexate as cumulative to Rejection V, the rejection over the
combination of Najarian and Imran, discussed below.

Rejection V:
Appellant’s claim 1, reproduced above, is drawn to a method of
initiating the administration of dichlorphenamide to a subject for the
treatment of a first disease or disorder. Appellant’s claim 1 defines the
patient population as a subject being administered furosemide, for the
prophylactic treatment of hyperkalemic periodic paralysis and the acute
treatment of muscle paralysis or myotonia and requires that the
administration of furosemide be discontinued prior to the administration of
dichlorphenamide at an initial dose of 50 mg twice daily.
Appellant discloses that furosemide is “frequently used to
prophylactically treat hyperkalemic periodic paralysis and to acutely treat
muscle paralysis or myotonia” (FF 1). Appellant also discloses that
dichlorphenamide is “approved for treating primary hyperkalemic periodic
paralysis, primary hypokalemic periodic paralysis, and related variants” (FF
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2). Najarian discloses that furosemide and dichlorphenamide are also useful
for the treatment of pulmonary hypertension (FF 3). Thus, a subject
receiving furosemide for the treatment for primary hyperkalemic periodic
paralysis, primary hypokalemic periodic paralysis, and related variants, who
is in need of treatment of “a first disease or disorder,” such as pulmonary
hypertension, may also be administered furosemide or dichlorphenamide for
the treatment of hypertension.
Imran discloses, however, that “furosemide has a number of adverse
side effects including, for example, electrolyte loss/imbalance,
hyperglycemia, otoxicity, hyperuricemia and resulting gout, and low
potassium levels as well as increased diuresis to name a few” (FF 6). Thus,
we find no error in Examiner’s conclusion that, before the effecting filing
date of Appellant’s claimed invention, it would have been prima facie
obvious to “discontinue the administration of furosemide due to its side
effects and then start . . . administration of dichlorphenamide in a dosage
“range of about 50 mg to about 250 mg,” “divided into two to four
individual doses” (Ans. 15 (emphasis omitted); see FF 1–6). Iron Grip
Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004)
(“[W]here there is a range disclosed in the prior art, and the claimed
invention falls within that range, there is a presumption of obviousness.”).
Therefore, we are not persuaded by Appellant’s contentions regarding
dosage (Reply Br. 7–9).
Appellant’s characterization of furosemide as an OAT1 substrate and
dichlorphenamide as an OAT1 inhibitor does not change the foregoing
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factual findings or conclusions based thereon (see Appeal Br. 16; see
generally Reply Br. 6–7; Guttendorf Decl.9 ¶¶ 9 and 14–17).
A reference disclosure is not limited only to its preferred
embodiments, but is available for all that it discloses and suggests to one of
ordinary skill in the art. In re Lamberti, 545 F.2d 747, 750 (CCPA 1976).
Therefore, we are not persuaded by Appellant’s contention that “Najarian
provides no examples of patients being treated with the carbonic anhydrase
inhibitor dichlorphenamide either alone or in combination with one or more
other medications, such as furosemide” (Appeal Br. 18; cf. FF 3–4).
Imran discloses the adverse side effects associated with the
administration of furosemide to a subject (FF 6). Therefore, we are not
persuaded by Appellant’s contention that “Najarian . . . would not have
taught or reasonably suggested that administration of . . . furosemide must be
discontinued prior to administration of . . . dichlorphenamide,” which fails to
account for Imran’s contribution to the rejection (Appeal Br. 18–19; cf. FF
1–6). Imran’s choice to pursue a different therapeutic treatment does not
discount, or otherwise discredit, Imran’s disclosure of furosemide related
side effects or the use of dichlorphenamide, as taught by Najarian, for the
treatment of pulmonary hypertension. Therefore, we are not persuaded by
Appellant’s contention that although Imran taught “that furosemide has a
number of adverse side effects,” Imran’s solution to that problem is the
intra-cranial administration of the drug to produce a localized effect in the
brain or reduce the duration of a seizure or other event” (Appeal Br. 19).

9 Declaration of Robert J. Guttendorf, RPh, Ph.D.
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For the foregoing reasons, we are not persuaded by Appellant’s
contention that “the cited art does not teach or reasonably suggest that when
a patient is taking an OAT1 substrate to treat a disease or disorder and also is
to be administered dichlorphenamide, the administration of the OAT1
substrate should be discontinued before initiating administration of the
dichlorphenamide” (Appeal Br. 19). For the same reasons, we are not
persuaded by Appellant’s contention that “there was no reason or motivation
to avoid the use of dichlorphenamide in combination with furosemide prior
to Appellant’s discovery” (Reply Br. 6).
CONCLUSION
Rejection IV: The rejection of claims 1 and 38 under 35 U.S.C. § 103
as unpatentable over the combination of Keyevis and Methotrexate is
vacated as cumulative to Rejection V.
Rejection V: The preponderance of evidence relied upon by
Examiner supports a conclusion of obviousness. The rejection of claim 1
under 35 U.S.C. § 103 as unpatentable over the combination of Najarian and
Imran is affirmed. Claim 38 is not separately argued and falls with claim 1.

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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 38 112(b) Indefiniteness 1, 38
1, 38 112(a) Written Description 1, 38
1, 38 112(a) Enablement 1, 38
1, 38 103 Keyevis,
Methotrexate10

1, 38 103 Najarian, Imran 1, 38
Overall
Outcome
1, 38
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

10 We vacate the rejection over the combination of Keyevis and
Methotrexate.