United Therapeutics Corporation

Patent Trials and Appeals Board

Mar 15, 2021

2020005926 (P.T.A.B. Mar. 15, 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.
15/316,914 12/07/2016 Ken PHARES 080618-1695 8791
166905 7590 03/15/2021
Foley & Lardner LLP
3000 K Street N.W.
Suite 600
Washington, DC 20007-5109
EXAMINER
FISHER, MELISSA L
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
03/15/2021 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):
ipdocketing@foley.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte KEN PHARES and COURTNEY CHANG

_________________

Appeal 2020-005926
Application 15/316,914
Technology Center 1600
_________________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and
DAVID COTTA. Administrative Patent Judges.

KATZ, Administrative Patent Judge.
DECISION ON APPEAL

Appeal 2020-005926
Application 15/316,914

2
Appellant1 seeks our review2, under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 1, 3, 4, 8, 11–18, and 21–23. We have
jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.
Appellant’s Specification is directed to compositions of treprostinil, a
drug for the treatment of pulmonary arterial hypertension, and an ion-
exchange resin. (Spec. ¶¶ 3, 16.)
Appellant’s claim 1 recites3:
A composition comprising
a) treprostinil or its pharmaceutically acceptable salt and
b) an cholestyramine anion ion-exchange resin,
wherein the treprostinil or its pharmaceutically acceptable salt
forms an ion complex with the anion ion-exchange resin, and
wherein the composition is an oral pharmaceutical formulation
comprising a) the ion complex and b) a pharmaceutically acceptable
carrier as an aqueous dispersion having a concentration of treprostinil
from 0.1 mg/ml to 100 mg/ml of the aqueous dispersion.

(Appeal Br. 16.)

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party-in-interest as United Therapeutics Corporation.
(Appeal Br. 2.)
2 We consider the Final Office Action issued May 1, 2019 (“Final Act.”), the
Appeal Brief filed April 29, 2020 (“Appeal Br.”), the Examiner’s Answer
issued on June 19, 2020 (“Ans.”), the Reply Brief filed August 17, 2020
(“Reply Br.”) and the oral argument held on March 4, 20221, in reaching our
decision.
3 Claim 1 has been modified by adding indentations to separate elements.
See 37 C.F.R. § 1.75(i).
Appeal 2020-005926
Application 15/316,914

3
The Examiner rejected4 claims 1, 3, 4, 8, 11–18, and 21–23 as being
obvious under 35 U.S.C. § 103(a) over Mehta,5 Zhivkova,6 and Wade.7 (See
Final Office Action 5–9.) Appellant does not argue for the separate
patentability of any of the rejected claims. Accordingly, we focus on claim
1 in our review. See 37 C.F.R. § 41.37(c)(1)(iv).
Findings of Fact
1. Mehta teaches pharmaceutically active compounds that form a
complex with an ion-exchange resin and are safe for ingestion. (Mehta
abstract, ¶ 32.)
2. Mehta teaches that “suitable ion-exchange resins include anion
exchange resins, such as have been described in the art and are commercially
available. These resins are particularly well suited for use with acidic drugs
. . . .” (See Mehta ¶ 37.)
3. Mehta teaches cholestyramine resin as an example of an anion
ion-exchange resin. (See Mehta ¶ 38.)

4 The Examiner also rejected claim 12 under 35 U.S.C. § 112(b) and claim
13 under 35 U.S.C. § 112(d) (see Final Act. 3–4), but these rejections were
rendered moot when Appellant canceled claims 12 and 13 in an Amendment
After Final filed October 29, 2019, which the Examiner entered (see
Advisory Action of November 6, 2019).
5 Mehta and Tu, U.S. Patent Application Publication 2007/0215511 A1,
published September 20, 2007.
6 Zhivkova and Doytchinova, “Prediction of Steady-State volume of
Distribution of Acidic Drugs by Quantitative Structure-Pharmacokinetics
Relationships,” J. PHARM. SCI., 101:1253–66 (2012).
7 Wade et al., U.S. Patent Application Publication 2008/0280986 A1,
published November 13, 2008.
Appeal 2020-005926
Application 15/316,914

4
4. Mehta teaches that the compositions of drug and ion exchange
resin may be liquid preparations and oral compositions. (See Mehta ¶¶ 14,
20.)
5. Mehta does not teach treprostinil. (See Final Act. 6.)
6. Zhivkova teaches that treprostinil is an acidic drug with a
steady state volume distribution. (See Zhivkova abstract, Table 2.)
7. Wade teaches methods for using treprostinil or its derivatives.
(See Wade abstract.)
8. Wade teaches that treprostinil can be administered orally and
may be admixed with a carrier in a liquid formulation. (See Wade ¶¶ 16,
36.)
9. Wade teaches that the FDA has approved dose concentrations
of treprostinil of 1.0 mg/ml, 2.5 mg/ml, 5.0 mg/ml and 10.0 ng/ml by
injection for the treatment of pulomary arteriole hypertension. (See Wade
¶ 30.)
10. Wade teaches that treprostinil can be administered orally, as
well as intravenously, at unit dose formulations of from 0.1 to 100 mg,
typically from 1 to 50 mg. (See Wade ¶¶ 16, 35.)
Analysis
The Examiner finds that Mehta teaches anion exchange resins are
particularly well suited for use with acidic drugs and that Zhivkova teaches
that treprostinil is an acidic drug. (See Final Act. 6–7, citing Mehta ¶ 37,
Zhivkova Table 2.) The Examiner also finds that Wade teaches
formulations of treprostinil in concentrations within the ranges recited in
claim 1, specifically 1.0 mg/ml, 2.5 mg/ml, and 5.0 mg/ml, which fall within
the range of “from 0.1 mg/ml to 100 mg/ml of the aqueous dispersion”
Appeal 2020-005926
Application 15/316,914

5
recited in claim 1. (See Final Act. 7, citing Wade ¶ 30.) The Examiner finds
further that treprostinil can be administered orally and provides exemplary
unit dosages. (See Final Act. 7, citing Wade ¶ 35.) The Examiner
determines that the concentration of an administered drug is a result
effective variable, which is determined based on a variety of factors,
including the age, weight, health, adverse effects, etc., and which is routinely
optimized by the ordinarily skilled artisan. (See Final Act. 7.) From these
findings, the Examiner concludes that it would have been obvious to a
person of ordinary skill in the art to use treprostinil as taught in Zhivkova in
a composition as taught in Mehta, at the concentrations taught in Wade.
(See id.)
Appellant argues that the Examiner erred by failing to explain why
one of ordinary skill in the art would choose treprostinil from other drugs
with any expectation of success. (See Appeal Br. 11–13.) According to
Appellant, nothing in Mehta suggests which acidic drugs would work with
an anion-exchange resin or what factors would influence selection of a
particular anion-exchange resin for a particular drug. (See id. 12.)
Appellant argues that Mehta is directed to use of water-permeable diffusion
barriers to create modified-release formulations, not to particular drug anion-
exchange complexes. (See id.)
We are not persuaded by Appellant’s argument because of the express
teachings of Mehta and Zhivkova, which would indicate to one of ordinary
skill that the acidic nature of treprostinil makes it particularly suitable for
combination with an anion resin, for example cholestyramine. (FF82, FF6).

8 Finding of Fact.
Appeal 2020-005926
Application 15/316,914

6
Because it is acidic, the teaching of Mehta indicates trepostinil is one of the
class of drugs that would have been obvious to try with an anion ion-
exchange resin. “When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable solutions, a
person of ordinary skill has good reason to pursue the known options within
his or her technical grasp.” KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421
(2007). Mehta identifies acidic drugs as being suitable for combination with
anion ion-exchange resins (FF6), which provide benefits such as
programmable release characteristics of drugs in the GI tract. (See Mehta
¶ 10.) Thus, we are persuaded one of skill in the art would have considered
it obvious to pursue a composition of trepostinil with an anion ion-exchange
resin.
Furthermore, Appellant fails to direct us to a teaching in Mehta or
elsewhere that indicates any characteristics other than acidity are important
to combining a drug with an anion-exchange resin. Given the evidence
before us, we are persuaded that one of ordinary skill would have had a
reasonable expectation of success in using the type of drug taught in Mehta
(an acidic drug) with the type of resin (an anionic ion-exchange resin) that is
particularly suited for that type of drug. (See Final Act. 6–7.)
Appellant argues further that the Examiner fails to explain how the
teaching in Wade of a concentration of injectable drug translates to a
concentration of an orally administered pharmaceutical. (See Appeal Br.
13–15.) Appellant argues that the pharmacokinetics of oral versus parenteral
delivery are “wildly different” and that concentrations for parenteral
administration are not indicative of a suitable concentration in an aqueous
dispersion that includes a drug-resin complex. (See id. 14.)
Appeal 2020-005926
Application 15/316,914

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Appellant does not dispute that a useful concentration of treprostinil is
a result effective variable that can be determined by routine optimization.
Nor does Appellant direct us to evidence that optimizing the concentration
of treprostinil in an aqueous dispersion would be beyond the skill of the
ordinary artisan. Appellant argues that the claimed “formulation has unique
challenges as compared to other pharmaceutical compositions” (Reply Br.
5), but fails to explain why or direct us to evidence in support. As stated in
Zhivkova “the optimization of drug pharmacokinetic properties in humans
has become an obligatory step in modern drug discovery process.”
(Zhivkova 1253.) Thus, given that Wade teaches dosages for oral
administration of treprostinil and teaches concentrations for injection we
agree with the Examiner that one of ordinary skill would have considered it
obvious to use routine skill to optimize a concentration of treprostinil for an
aqueous dispersion as claimed.
We are also unpersuaded by Appellant’s argument because
Appellant’s claims are not limited to any specific outcome of administering
the oral pharmaceutical formulation. Appellant claims a composition, not
the use of the composition for treating any disease. Appellant cites to the
decision in IPR2015-01136 denying review because the prior art did not
have a description of using a specific drug to treat a specific disease. (See
Reply Br. 3–4.) In that decision the Board determined that the grounds for
unpatentability were based on only a hope that the drug would be useful for
treating that disease. (See id.) We are not persuaded that even if this
decision is binding on us, which it is not, it is informative given the current
facts.
Appeal 2020-005926
Application 15/316,914

8
The claims in IPR2015-01136 were drawn to a method of treating a
disease. Such treatment could be affected by numerous factors, such as the
nature of the disease, the condition of the patients, pharmacokinetics. The
claims before us are directed to a much more predictable art – formulating a
composition with two components in an oral pharmaceutical formulation.
Appellant fails to direct us to evidence that formulating a composition
suitable for oral pharmaceutical formulation would have either been beyond
the skill of an ordinary artisan or not reasonably expected to be successful,
given the cited prior art and the lack of claimed efficacy of the drug in
treating a disease.
Conclusion
Upon consideration of the record and for the reasons given, we affirm
the Examiner’s rejection.
In summary:
Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 3, 4, 8,
11–18, 21–
23
103 Mehta, Zhivkova,
Wade
1, 3, 4, 8, 11–
18, 21–23

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.

AFFIRMED