Strongbridge Dublin Limited

Patent Trials and Appeals Board

Oct 19, 2021

2021003550 (P.T.A.B. Oct. 19, 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.
16/535,704 08/08/2019 Fredric Jay COHEN STRG0001-201TD1-US 6969
159061 7590 10/19/2021
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
10/19/2021 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 2021-003550
Application 16/535,704
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, 24, and 31 (Appeal Br. 5). We have jurisdiction
under 35 U.S.C. § 6(b). We AFFIRM. Because our rationale differs from
Examiner, we designate the affirmance as a New Ground of Rejection.

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 November 13, 2020, 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.). Claim 1 is
reproduced below:
1. A method for administering the organic anion transporter-1
(OAT1) inhibitor dichlorphenamide to a patient in need thereof,
wherein the subject is being administered an [] OAT1 substrate
methotrexate to treat a disease or disorder, the method
comprising:
discontinuing administration of the methotrexate, prior to
administering the OAT1 inhibitor dichlorphenamide, thus
avoiding concomitant administration of said methotrexate and
said dichlorphenamide and avoiding adverse plasma exposure
of the methotrexate, the inhibitor property of dichlorphenamide
having been determined, to avoid adverse drug-drug
interactions between the dichlorphenamide and the
methotrexate, by in vitro experiments in accordance with the
FDA draft guidance documents for Drug Interaction Studies
(FDA 2017), and
initiating administration to the subject of said
dichlorphenamide in an amount of 25 mg to 200 mg daily to
treat primary hyperkalemic periodic paralysis or primary
hypokalemic periodic paralysis.
(Appeal Br. 17.) Appellant’s claims 24 and 31 depend directly from
Appellant’s claim 1 (see id. at 17–18).

2 Appellant’s August 8, 2019, Specification.
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Grounds of rejection before this Panel for review:
I. Claims 1, 24, and 31 stand rejected under 35 U.S.C. § 112(b).
II. Claims 1, 24, and 31 stand rejected under the written
description provision of 35 U.S.C. § 112(a).
III. Claims 1, 24, and 31 stand rejected under the enablement
provision of 35 U.S.C. § 112(a).
IV. Claims 1, 24, and 31 stand rejected under 35 U.S.C. § 103 as
unpatentable over the combination of Keyevis3 and
Methotrexate.4

Rejection I:
ISSUE
Does the preponderance of evidence support Examiner’s conclusion
that Appellant’s claims are indefinite?
ANALYSIS
The method of Appellant’s claim 1 relates to the administration of the
OAT1 inhibitor, dichlorphenamide, to a subject being administered the
OAT1 substrate, methotrexate (see Spec. ¶ 87 (Appellant’s Specification
discloses that methotrexate is an OAT1 substrate); see also International

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.
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Transporter Consortium5 218: Table 1 (International Transporter
Consortium discloses that methotrexate is an OAT1 substrate)).6
The method of Appellant’s claim 1 requires: (1) that the
administration of methotrexate is discontinued prior to administration of
dichlorphenamide and (2) administration of dichlorphenamide in an amount
of 25 mg to 200 mg daily to treat primary hyperkalemic periodic paralysis or
primary hypokalemic periodic paralysis. The method of Appellant’s claim 1
further provides, inter alia, that by avoiding concomitant administration of
methotrexate and dichlorphenamide adverse drug-drug interactions between
the dichlorphenamide and the methotrexate are avoided.
For the foregoing reasons, we are not persuaded by Examiner’s
assertions regarding whether methotrexate is an OAT1 substrate (see Ans.
3–4; cf. Appeal Br. 7–8; Reply Br. 2–7). Further, as discussed above,
Appellant’s claimed method relates to the administration of
dichlorphenamide to a patient who is being administered methotrexate and
the requirement that methotrexate administration be stopped prior to
administration of dichlorphenamide. Therefore, we are not persuaded by
Examiner’s assertions relating to the reason why a subject is being treated
with methotrexate, which is not relevant to Appellant’s claimed method (see
Ans. 4–6; cf. Appeal Br. 8–10).

5 International Transporter Consortium, Membrane transporters in drug
development, 9 Nat. Rev. Drug Discov. 215–236 (2010).
6 We acknowledge the dispute on this record as to whether International
Transporter Consortium, and other documents, were properly presented by
Appellant and reviewed by Examiner (see, e.g., Examiner’s March 25, 2021,
Answer (Ans.) 18; Appeal Br. 7–8; Appellant’s April 15, 2021, Reply Brief
(Reply Br.) 2–7). Upon further prosecution, we encourage Appellant and
Examiner to work cooperatively to resolve this dispute.
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CONCLUSION
The preponderance of evidence fails to support Examiner’s conclusion
that Appellant’s claims are indefinite.
Rejection I: The rejection of claim 1, 24, and 31 under 35 U.S.C.
§ 112(b) is reversed.

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
For the reasons discussed above, with regard to definiteness, we are
not persuaded by Examiner’s interpretation of Appellant’s claimed invention
as it relates to methotrexate (see Ans. 6–7; see also Appeal Br. 10 (Appellant
directs attention to its contentions regarding “the indefiniteness rejection and
incorporates those arguments herein”)). In addition, as discussed above,
Appellant’s Specification and the prior art recognize that methotrexate is an
OAT1 substrate. Appellant’s Specification further discloses:
In certain embodiments, the method further comprises reducing
the dose and/or frequency of the OAT1 substrate administered
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
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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 (emphasis added).)
For the foregoing reasons, we are not persuaded by Examiner’s
assertion that because “there is no mention of the treatment of any disease
with methotrexate, much less such a specific dose regimen like the one that
is now being claimed with recitation of ‘discontinuing the administration of
methotrexate ---, and initiating the administration [to] the subject of
said . . . dichlorphenamide ---’” (Ans. 7; cf. Appeal Br. 10).
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, 24, and 31 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
Examiner finds that although Appellant’s Specification provides an
enabling disclosure “for the treatment of psoriasis and rheumatoid arthritis
comprising the administration of methotrexate” Appellant’s Specification
“does not reasonably provide enablement for the treatment of any other
disease comprising the administration of methotrexate” (Ans. 7–9). In this
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regard, Examiner finds that Appellant’s “claims recite the treatment of ‘a
disease or disorder’ with methotrexate, without specifying any disease or
disorder,” and “[t]here is no evidence that methotrexate can treat any other
disease than psoriasis and rheumatoid arthritis” (id. at 10; see generally id. at
7–12). Because, as discussed above, Examiner’s rejection is based on an
incorrect interpretation of Appellant’s claimed invention, we are not
persuaded by Examiner’s conclusion that Appellant’s Specification fails to
provide an enabling disclosure of Appellant’s claimed invention.
As discussed above, and in contrast to Examiner’s interpretation of
Appellant’s claimed invention, Appellant’s claimed method limits the scope
of the patient population, to those who are being administered methotrexate.
The reason patients in this population are being administered methotrexate is
irrelevant to Appellant’s claimed method. Stated differently, the patient
population of Appellant’s claimed method is satisfied if the patient is
administered methotrexate for any reason. Appellant’s claimed method
further requires, as a first step, that administration of methotrexate is
stopped, i.e. discontinued. Then, after stopping the administration of
methotrexate, Appellant’s claimed method requires the administration of
dichlorphenamide in an amount of 25 mg to 200 mg daily to treat primary
hyperkalemic periodic paralysis or primary hypokalemic periodic paralysis.
In sum, we agree with Appellant’s contention that its
claims expressly recite that methotrexate is not to be
administered if dichlorphenamide is being administered for the
treatment of primary hyperkalemic periodic paralysis or
primary hypokalemic periodic paralysis. The claims are thus
specific as to the disease being treated, i.e., primary
hyperkalemic periodic paralysis or primary hypokalemic
periodic paralysis. The claims are also specific as to the dosage
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of methotrexate, i.e., no amount of methotrexate should be
administered.
(Appeal Br. 11 (emphasis omitted).)
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, 24, and 31 under the
enablement provision of 35 U.S.C. § 112(a) is reversed.

Rejection IV:
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. “Methotrexate (formerly Amethopterin) is an antimetabolite used in
the treatment of certain neoplastic diseases, severe psoriasis, and adult
rheumatoid arthritis” (Methotrexate § Description).
FF 2. Methotrexate discloses:
Methotrexate has the potential for serious toxicity. (See Boxed
WARNINGS.) Toxic effects may be related in frequency and
severity to dose or frequency of administration but have been
seen at all doses. Because they can occur at any time during
therapy, it is necessary to follow patients on methotrexate
closely. Most adverse reactions are reversible if detected early.
When such reactions do occur, the drug should be reduced in
dosage or discontinued and appropriate corrective measures
should be taken.
(Methotrexate § Precautions: General; see generally Ans. 13.)
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FF 3. Methotrexate discloses that “[m]ethotrexate is partially bound to
serum albumin, and toxicity may be increased because of displacement by
certain drugs, such as . . . sulfonamides” (Methotrexate § Drug Interactions;
see also Methotrexate § Pharmacokinetics: Distribution (Methotrexate
discloses that “[m]ethotrexate in serum is approximately 50% protein
bound” and that methotrexate “may be displaced from plasma albumin by
various compounds including sulfonamides”).
FF 4. Examiner finds that Methotrexate does not disclose the
administration of dichlorphenamide (Ans. 13).
FF 5. Keyevis discloses prescribing information for dichlorphenamide
tablets, for oral use (see Keyevis).
FF 6. Keyevis discloses that dichlorphenamide “is an oral carbonic
anhydrase inhibitor indicated for the treatment of primary hyperkalemic
periodic paralysis, primary hypokalemic periodic paralysis, and related
variants” (Keyevis § Indications and Usage; see also Ans. 13).
FF 7. Keyevis discloses that dichlorphenamide is administered at an initial
dosage of “50 mg twice daily,” wherein the dose can be titrated “based on
individual response” and “[t]he maximum recommended dose is 200 mg
daily” (Keyevis § Dosage and Administration; see also Ans. 13).
FF 8. Keyevis discloses that dichlorphenamide “is contraindicated in . . .
[h]ypersensitivity to dichlorphenamide or other sulfonamides” (Keyevis
§ Full Prescribing Information: 4. Contraindications).
ANALYSIS
The evidence on this record supports a finding that dichlorphenamide
is contraindicated for patients who are sensitive to dichlorphenamide or
other sulfonamides (see FF 8). The evidence on this record further supports
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a finding that patients receiving methotrexate may experience a toxic side
effect if co-administered a sulfonamide (see FF 3). Thus, based on the
combination of Keyevis and Methotrexate, it would have been prima facie
obvious to a person of ordinary skill in this art, before the effective filing
date of Appellant’s claimed invention, that the toxic side effect cause by co-
administering methotrexate and dichlorphenamide can be avoided by
stopping methotrexate administration prior to administering
dichlorphenamide to the patient (see FF 1–8; see generally Ans. 14
(Examiner concludes that it would have been prima facie obvious, before the
effective filing date of Appellant’s claimed invention, “to discontinue the
administration of methotrexate due to its side effects, and then start . . . the
administration of dichlorphenamide” (emphasis omitted))). In addition, it
would have been prima facie obvious to a person of ordinary skill in the art,
before the effective filing date of Appellant’s claimed invention, to
administer dichlorphenamide at a dosage of between 50 mg to 200 mg daily
to treat primary hyperkalemic periodic paralysis or primary hypokalemic
periodic paralysis (see FF 5–7; see also FF 7 (Keyevis discloses titrating the
dichlorphenamide dosage base on the individual response of a patient to the
drug, thereby suggesting variability among patient dosages)). See In re
Geisler, 116 F.3d 1465, 1468 (Fed. Cir. 1997) (Overlapping ranges support a
prima facie case of obviousness.).
As discussed above, prior to the effective filing date of Appellant’s
claimed invention, the prior art recognized a toxic side effect resulting from
the co-administration of methotrexate and a sulfonamide, such as
dichlorphenamide (see FF 1–8). Appellant’s characterization of
methotrexate as an OAT1 substrate and the sulfonamide, dichlorphenamide,
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as an OAT1 inhibitor does not change the art recognized contraindication
associated with the co-administration of these two drugs (see id.).
Therefore, we are not persuaded by Appellant’s contention that “the
interaction of dichlorphenamide with an OAT1 substrate such as
methotrexate was not known” (Appeal Br. 15).
For the foregoing reasons, we are not persuaded by Appellant’s
intimation that the claimed invention results in an unexpected result (see id.
at 14 (Appellant refers to “the unexpected nature of the benefits associated
with the claimed method”)).
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness.
Rejection IV: The rejection of claim 1 under 35 U.S.C. § 103 as
unpatentable over the combination of Keyevis and Methotrexate is affirmed.
Claims 24 and 31 are not separately argued and fall with claim 21.
DECISION SUMMARY
In summary:
Claims
Rejected
35
U.S.C. §
Reference(s)/Basis Affirmed Reversed New
Ground
1, 24, 31 112(b) Indefiniteness 1, 24, 31
1, 24, 31 112(a) Written
Description
1, 24, 31
1, 24, 31 112(a) Enablement 1, 24, 31
1, 24, 31 103 Keyevis,
Methotrexate
1, 24, 31 1, 24, 31
Overall
Outcome
1, 24, 31 1, 24, 31

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TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to 37
C.F.R. § 41.50(b) (effective September 13, 2004, 69 Fed. Reg. 49960
(August 12, 2004), 1286 Off. Gaz. Pat. Office 21 (September 7, 2004)).
37 C.F.R. § 41.50(b) provides “[a] new ground of rejection pursuant to this
paragraph shall not be considered final for judicial review.”
37 C.F.R. § 41.50(b) also provides that the appellant, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
the following two options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the proceeding
will be remanded to the examiner. . . .

(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same record. . . .
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED; 37 C.F.R. § 41.50(b)