Harrow IP, LLC

Patent Trials and Appeals Board

Jul 29, 2021

2020006020 (P.T.A.B. Jul. 29, 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.
15/383,211 12/19/2016 Dennis Elias Saadeh 109554-670706-0012-02-01 9421
27148 7590 07/29/2021
POLSINELLI PC
900 WEST 48TH PLACE
SUITE 900
KANSAS CITY, MO 64112-1895
EXAMINER
KANTAMNENI, SHOBHA
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
07/29/2021 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):
patentdocketing@polsinelli.com
rendsley@polsinelli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DENNIS ELIAS SAADEH and
JOSEPH S. BITTERMAN
Appeal 2020-006020
Application 15/383,211
Technology Center 1600
Before RICHARD M. LEBOVITZ, ULRIKE W. JENKS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims directed to a pharmaceutical
composition for treating or mitigating kidney stone disease including the
reducing agent tiopronin and at least one urine alkanizing agent in amounts
that a therapeutically effective as being obvious. We have jurisdiction under
35 U.S.C. § 6(b).

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42(a). Appellant identifies the real party in interest as Harrow IP,
LLC. (Appeal Br. 3.) (The Appeal Brief we refer to throughout is
Appellant’s Substitute Appeal Brief filed April 1, 2020.)
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Application 15/383,211

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We AFFIRM.
STATEMENT OF THE CASE
“[K]idney stone disease . . . is a condition characterized by the
appearance of stone-like matter (i.e., renal calculi, also known as
nephroliths) that are formed and deposited in the patient’s kidneys, bladder
or ureter, respectively.” (Spec. ¶ 2.) “The symptoms [of the disease]
include strong intermittent or constant pain (i.e., renal colic), hematuria,
nausea, vomiting, and urinary urgency.” (Id. ¶ 3.) Appellant’s Specification
explains that current non-invasive treatments “are of limited effectiveness in
many patients, particularly for larger stones. In many cases, surgical or
ureteroscopical removal is the only viable option.” (Id. ¶ 4.) “Accordingly,
there exists a need for better methods and compositions for treatment,
mitigation and/or prevention of nephrolithiasis and their symptoms.” (Id.
¶ 5.) Appellant’s invention is directed to composition for treating or
mitigating kidney stone disease. (Id.)
Claims 1, 5–7, 9, 21–24, 26–30, and 32 are before us on appeal.
Claim 1, reproduced below, is illustrative of the claimed subject matter:
1. A pharmaceutical composition for treating or mitigating
kidney stone disease, bladder stone disease or ureter stone
disease, the composition comprising:
(a) a therapeutically effective quantity of a first
component, wherein the first component comprises at least
one pharmaceutically acceptable reducing agent selected
from the group consisting of tiopronin, penicillamine, and
captopril; and
(b) a therapeutically effective quantity of a second
component, wherein the second component comprises a
therapeutically effective quantity of at least one urine
alkanizing agent selected from the group consisting of
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alkali metal salts of citric acid, alkaline-earth metal salts
of citric acid, and sodium bicarbonate,
wherein the first component and the second component form a
homogeneous mixture,
wherein the composition is configured for oral administration in
a form selected from the group consisting of a pill, a tablet, a
capsule, and a troche, and
wherein the first component is present at a concentration between
about 25.0 mass% and 50.0 mass% of the total mass of the pill,
tablet, capsule or troche.
(Appeal Br. 25.)
In response to a restriction and species election requirement,
Appellant elected tiopronin as the species for the reducing agent (a).
(Appeal Br. 13.) Accordingly, as to the appealed obviousness rejections, we
limit our analysis to the patentability of the elected species and the extent to
which the rejected claims read on them. See Ex parte Ohsaka, 2 USPQ2d
1460, 1461 (BPAI 1987).

The prior art relied upon by the Examiner is:
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Name Reference Date
Ward et al. US 2015/0099806 A1 Apr. 9, 2015
Xiang et al. CN1615835 A May 18, 2005
Erik Fjellstedt and Jan-
Oluf Jeppson
A comparison of the
effects of potassium
citrate and sodium
bicarbonate in the
alkalinization of urine
in homozygous
cystinuria, 29 Urol.
Res., 295–302
2001
Orson W. Moe, et al. Pharmacotherapy of
urolithiasis: evidence
from clinical trials, 79
(4) Kidney Int., 385–92
2011

The following grounds of rejection by the Examiner are before us for
review:
Claims 1, 5–7, 21–24, and 32 under 35 U.S.C. § 103(a) as
unpatentable over Moe, Fjellstedt, and Ward.
Claims 9 and 26–30 under 35 U.S.C. 103(a) as unpatentable over
Moe, Fjellstedt, Ward, and Xiang.
DISCUSSION
Claim 1 is Obvious from Moe, Fjellstedt, and Ward
The Examiner found that Moe teaches that tiopronin is used for
treating cystinuria (kidney stones), and that alkali treatment has been widely
used to manage cystinuria. (Final Action 4.) The Examiner also found that
Moe discloses that potassium citrate is known to alkalinize urine. (Id.) The
Examiner also found that Moe teaches in mild cases of cystinuria,
alkalinization and fluids may be sufficient to manage the condition, however
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in severe cases such may not be enough and that a thiol agent such as
tiopronin or penicillamine should be added. (Id.)
The Examiner found that Fjellstedt similarly teaches treating
cystinuria by administering tiopronin and potassium citrate. (Id. at 4–5
(citing Fjellstedt, Abstr., and Tables 1 and 2).) The Examiner noted that
Fjellstedt teaches treatment is two-fold: namely, lowering the concentration
of free cystine and increasing cystine solubility, where tiopronin reduces free
urinary cystine by forming soluble disulfide complexes and the use of an
alkalizing agent increases urinary pH, which increases the solubility of
cystine. (Id. at 4, 6 (citing Fjellstedt 295).)
The Examiner found that Ward teaches a pharmaceutical composition
for slowing growth of kidney stones that includes two separate components,
one component including a pharmaceutically acceptable reducing agent
capable of undergoing thiol-disulfide exchange with cystine to form a mixed
disulfide and a second component including a urine alkalizing agent. (Final
Action 5–6 (citing Ward ¶¶ 4, 30–31, 37, 295, 304, 306, 307).) In addition,
the Examiner found that Ward teaches the first and second components are
mixed with powder or liquid carriers, and thus, “intrinsically [provide a]
homogeneous mixture.” (Id. at 5.)
The Examiner recognized that although Moe suggests the use of
tiopronin and potassium citrate together to treat severe cystinuria, Moe does
not teach a single composition that includes both of those components and
does not teach the claimed concentration of tiopronin. (Id.) The Examiner,
however, found that, in light of the teachings of Ward and Fjellstedt, one of
ordinary skill in the art would have found it obvious to have combined these
two ingredients into a single composition with a reasonable expectation of
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success in treating cystinuria. (Id. at 6–7.) Regarding the effective amount
limitation, the Examiner indicated that such would have been obvious to
optimize “since the optimization of effective amounts of known agents to be
administered, is considered well in the competence level of an ordinary
skilled artisan in pharmaceutical science, involving merely routine skill in
the art.” (Id. at 7.)
We agree with the Examiner’s conclusion of obviousness. Both Moe
and Fjellstedt describe treating cystinuria with a thiol agent such as tiopronin
and an alkalinization agent. (Moe 6; Fjellstedt 296–97.) Moe suggests
using both agents together for those having more than a mild case of
cystinuria (Moe 6) and Fjellstedt teaches that potassium citrate could be used
therapeutically in combination with tiopronin to treat cystinuria (Fjellstedt
298 (Table 2), 300–01). Fjellstedt also teaches that these two compounds
work to treat cystinuria via different mechanisms: (a) potassium citrate by
increasing the solubility of urinary cystine itself and (b) tiopronin by
forming soluble disulfide complexes between cystine and tiopronin.
(Fjellstedt 295.) “It is prima facie obvious to combine two compositions
each of which is taught by the prior art to be useful for the same purpose, in
order to form a third composition which is to be used for the very same
purpose. . . . [T]he idea of combining them flows logically from their having
been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846,
850 (CCPA 1980). Moreover, one of ordinary skill in the art would have
been motivated to combine the two components into a single composition to
assist in patient compliance with taking prescribed medication.
Regarding the requirement of tiopronin being at a particular mass
concentration of the total mass of the dosage form, we agree with the
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Examiner that such would have been obvious as a matter of routine
optimization. Fjellstedt teaches that the therapeutic amounts of potassium
citrate can be varied, as can the amounts of tiopronin. (See Fjellstedt, Tables
1 and 2.) That suggests that therapeutically effective amounts for each
component are known to be result effective and can be varied through
routine practice to determine that which would be therapeutically effective.
Once having determined such an amount, we agree with the Examiner that it
would have involved only routine skill in the art to arrive at a dosage form
having the tiopronin in a mass concentration range based on the total mass of
the dosage form within the claimed range and that such would have been
routine optimization based on the desire to produce a composition with
therapeutically effective amounts. Ward teaches that forming dosage forms,
such as oral dosage forms for combination therapy, and the ingredients, such
as carriers to be used, are well known in the pharmaceutical arts and their
selection is a matter of standard pharmaceutical practice. (See, e.g., Ward
¶¶ 306–07.)
Appellant argues that the Examiner’s rejection is in error because the
prior art does not provide a motivation to determine or optimize the amount
of tiopronin in a composition that includes both tiopronin and an alkalinizing
agent. (Appeal Br. 17; Reply Br. 2.) In particular, Appellant notes that Moe
and Ward are “absolutely silent with regard to use of any concentrations of a
reducing agent selected from the group consisting of tiopronin,
penicillamine, and captopril” and Fjellstedt does not teach that tiopronin is a
result effective variable. (Appeal Br. 17.) Appellant notes that in Fjellstedt,
the 10 patients in the study who received tiopronin and an alkalinizing agent
were those who were on long term treatment with tiopronin, and that those
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patients continued to receive a fixed twice daily dosage of tiopronin while
also being administered the alkalinizing agent. (Id. at 18.) Appellant further
notes that Fjellstedt, although indicating the alkalinizing agent was adjusted
based on urinary pH did not “teach or suggest a correlation between the
amount of tiopronin being administered to the patient and the amount of
alkalizing agent such that one of skill in the art could envision arriving at the
claimed composition with routine experimentation.” (Id.)
We do not find the foregoing arguments persuasive of non-
obviousness. In particular, as the Examiner noted (Ans. 7), Fjellstedt
teaches that patients suffering from cystinuria can be administered different
amounts of tiopronin, (Fjellstedt, Table 1), thus supporting the conclusion
that the amount of tiopronin to treat cystinuria, even when used alone, is a
result-effective variable. Given that it was known that the mechanism of
action of tiopronin and potassium citrate are different in the treatment of
cystinuria, we have not been pointed to any reason by Appellant that one of
ordinary skill in the art would not have expected tiopronin to be a result
effective variable in combination therapy with potassium citrate.
Appellant also argues that Ward discourages use of thiol drugs like
tiopronin because they are inadequate to reduce and solubilize large enough
quantities of L-cystine in the urine based on acceptable dosages (up to 2000
mg/day) and teaches its new compounds provide a new strategy and are
preferable for preventing, inhibiting or slowing the growth of L-cystine
crystallization. (Appeal Br. 18.) We do not find Appellant’s argument
persuasive of non-obviousness. In particular, as already discussed, it was
known that tiopronin and alkalinizing agents work in different ways to aid in
the treatment of cystinuria by solubilizing free cystine as a disulfide complex
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between cystine and tiopronin and to directly increase the solubility of
cystine. Moreover, as taught by Fjellstedt and Moe, both types of
compounds had been taught to be used together to treat cystinuria. That
Ward teaches a different compound to address prevention of L-cystine
crystallization does not teach away from the combination of tiopronin with
potassium citrate suggested by the prior art to be effective in treating
cystinuria. DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d
1314, 1327 (Fed. Cir. 2009) (“A reference does not teach away . . . if it . . .
does not ‘criticize, discredit, or otherwise discourage’ investigation into the
invention claimed.”)
Thus, for the foregoing reasons, we affirm the Examiner’s rejection of
claim 1 as being obvious from Moe, Fjellstedt, and Ward.
Despite providing separate headings to address claims 5, 6, 7, 21, 22,
23, 24, or 32, Appellant does not present different arguments regarding the
rejection of those claims. (See Appeal Br. 20–22.) Consequently, those
claims fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv).

Claim 9 is Obvious from Moe, Fjellstedt, Ward, and Xiang
The Examiner found that Xiang teaches sustained release formulations
of tiopronin that includes material having sustained release properties such
as ethyl cellulose, methyl cellulose, and hydroxypropylmethyl cellulose.
(Final Action 12 (citing Xiang 3).) The Examiner concluded that it would
have been obvious to one having ordinary skill in the art to have included
hydroxypropylmethyl cellulose in the tiopronin and potassium citrate
formulation suggested by Moe, Fjellstedt, and Ward with a reasonable
expectation of success in obtaining a composition with sustained release
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properties. (Id. at 13.) We agree with the Examiner’s conclusion of
obviousness.
In addition to the arguments that we have addressed above, Appellant
argues that the Examiner’s rejection of claim 9 is in error because Xiang is a
formulation for treatment of hepatitis B not kidney stones and is thus in a
different field of endeavor. (Appeal Br. 23.) We do not find this argument
persuasive. Xiang concerns a dosage formulation for tiopronin and indicates
that a number of sustained release materials are compatible with that active
ingredient to provided sustained release properties of that active agent in an
oral formulation. Thus, we conclude that Xiang is reasonably pertinent to
formulation of oral dosage forms of tiopronin that are sustained release,
irrespective of the ultimate treatment for which tiopronin is being
administered. See Scientific Plastic Prods., Inc. v. Biotage AB, 766 F.3d
1355, 1360–61 (affirming PTO finding references directed to resealable
closures for beverage containers that provide fluid tight seals to be
reasonably pertinent to the problem of providing fluid tight seals of a low
pressure liquid chromatographic cartridge while preserving access to the
contents of that cartridge).
Thus, we affirm the Examiner’s rejection of claim 9 as being obvious
from Moe, Fjellstedt, Ward, and Xiang. Despite providing separate
headings to address claims 26–30, Appellant does not present different
arguments regarding the rejection of those claims. (See Appeal Br. 23–24.)
Consequently, those claims fall with claim 9. 37 C.F.R. § 41.37(c)(1)(iv).
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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 5–7, 21–
24, 32
103(a) Moe, Fjellstedt,
Ward
1, 5–7, 21–
24, 32

9, 26–30 103(a) Moe, Fjellstedt,
Ward, Xiang
9, 26–30
Overall
Outcome
1, 5–7, 9,
21–24, 26–
30, 32

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