Ex Parte Srinivasan et al

Patent Trials and Appeals Board

May 28, 2019

11102726 - (D) (P.T.A.B. May. 28, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
11/102,726 04/11/2005
13897 7590 05/30/2019
Abel Schillinger, LLP
8911 N. Capital of Texas Hwy
Bldg 4, Suite 4200
Austin, TX 78759
FIRST NAMED INVENTOR
Viswanathan Srinivasan
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
3205-P27617 6587
EXAMINER
CHANNA V AJJALA, LAKSHMI SARADA
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
05/30/2019 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):
mail@Abel-IP.com
hmuensterer@abel-ip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Exparte VISWANATHAN SRINIVASAN, JUAN CARLOS MENENDEZ,
VENKA TESH BALASUBRAMANIAN,
SOMPHET PETER SUPHASA WUD, RALPH BROWN, and
DAVID BROWN
Appeal2018-000824
Application 11/102,726
Technology Center 1600
Before ULRIKE W. JENKS, TA WEN CHANG, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
JENKS, Administrative Patent Judge.
DECISION ON APPEAL
Appellants1 submit this appeal under 35 U.S.C. § 134(a) involving
claims directed to a diphenhydramine containing pharmaceutical dosage
form. Examiner rejected the claims as obvious and on the ground of non-
1 The Appeal Brief lists Sovereign Pharmaceuticals, LLC of Fort Worth,
Texas, the assignee of record, as the real party in interest. Appeal. Br. 3.
We have considered, and herein refer to, the Specification of April 11, 2011
("Spec."); Final Office Action of Oct. 21, 2016 ("Final Act."); Appeal Brief
of April 14, 2017 ("Appeal Br."); Examiner's Answer of Aug. 16, 2017
("Ans.").
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Application 11/102,726
statutory obviousness type double patenting. We have jurisdiction under
35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
Without special formulation, "a single dose of diphenhydramine
provides relief of the indicated symptoms for only about four to six hours,
requiring the patient to take three to four dosage forms per day in order to
maintain the effects of diphenhydramine for 24 hours." Spec. ,-J 3. The
Specification discloses a "dosage form [that] is capable of providing a
diphenhydramine plasma concentration within a therapeutic range for at
least about 24 hours per single dose." Id. ,-i 2, Abstract, see id. ,-i,-i 8, 14, 22,
72, see also id. ,-i 24 ("the dosage form may be administered not more than
about once every 24 hours").
Claims 133-176 are on appeal, and can be found in the Claims
Appendix of the Appeal Brief. Claim 133 is representative of the claims on
appeal, and reads as follows:
133. A pharmaceutical dosage form which comprises at least one
of diphenhydramine and a pharmaceutically acceptable salt
thereof, wherein the dosage form (i) comprises at least 100 mg
of diphenhydramine hydrochloride or an equivalent amount of
diphenhydramine or an equivalent amount of at least one other
pharmaceutically acceptable salt of diphenhydramine and (ii)
provides a diphenhydramine plasma concentration within a
therapeutic range for at least 24 hours per single dose.
Br. 14 (Claims Appendix).
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Application 11/102,726
Appellants request review2 of following rejections made by Examiner:
I. Claims 148 and 150 under 35 U.S.C. § 112, 4th paragraph as failing to
further limit the subject matter of the claims from which they depend.
Br. 7.
II. Claims 133-176 under 35 U.S.C. § 103(a) as unpatentable over
Gonzales3 in view ofBabu.4 Br. 7-10.
III. Claims 133-176 under 35 U.S.C. § 103(a) as unpatentable over
Gonzales in view of Babu and Lech. 5 Id.
I. Failure to further limit the claim
Appellants contend that Examiner's rejection of claims 148 and 150 is
in error because the Examiner relies on the incorrect base claim. Br. 7.
Specifically, Examiner cites that claim 148 depends from claim 147, when it
actually depends from claim 142; and that claim 150 depends from claim
2 Appellants do not request review of the obviousness-type double patenting
rejection of claims 133-176 over claims in U.S. Application No. 11/012,267,
now US 9,592,197 B2 issued Mar. 14, 2017 and U.S. Application No.
11/115,321. See Br. 13 ("These provisional rejections are not presented for
review"). Appellants note that U.S. Application No. 11/115,321 was
abandoned on January 9, 2017 (id.); we agree that the abandonment renders
the double patenting rejection relying on this application moot. With respect
the rejection that relies on U.S. Application No. 11/012,267, now US
9,592,197 B2, we summarily affirm this rejection because Appellants failed
to argue the merits of the rejection. See MPEP § 1205.02 ("If a ground of
rejection stated by the examiner is not addressed in the appellant's brief,
appellant has waived any challenge to that ground of rejection and the Board
may summarily sustain it, unless the examiner subsequently withdrew the
rejection in the examiner's answer.").
3 Gonzales et al., US 6,979,689 B2, issued Dec. 27, 2005 ("Gonzales").
4 Babu et al., US 5,073,380, issued Dec. 17, 1991 ("Babu").
5 Lech et al., US 5,681,577, issued Oct. 28, 1997 ("Lech").
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149, when it actually depends from claim 142. Id. Examiner does not
address this rejection in the Answer other than stating that all rejections from
the Final Office Action mailed October 21, 2016 are maintained. See
Ans. 2. We have reviewed the claims and their respective dependency, as
set out in the Claims Appendix, and agree with Appellants that Examiner's
rejection is in error. Accordingly, we reverse this rejection.
11.-111. Obviousness over Gonzales and Babu
Since both of these rejections (11.-111.) rely upon the combination of
Gonzales and Babu regarding a single dose extended release
diphenhydramine formulation, the same issue is dispositive for both of these
rejections. We therefore consider the rejections together.
The issue is whether the preponderance of the evidence of record
supports Examiner's conclusion that the combination of Gonzales and Babu
renders obvious a single dose diphenhydramine formulation that maintains a
therapeutically sufficient plasma concentration of diphenhydramine over a
24 hour period.
Findings of Fact
FF 1. Gonzales teaches diphenhydramine formulations. "Amounts of the
diphenhydramine in the [] composition are within a dosage range from
about 3 mg to about 100 mg in a single dose of the formulation."
Gonzales 3: 12-14. "Clinically effective amounts are generally in the
range from about 6 mg diphenhydramine to about 50 mg
diphenhydramine in a single dose." Id. at 5:34-40. "[I]t is
recommended that the dose of the diphenhydramine, the antitussive,
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Application 11/102,726
and the decongestant be ingested 4-6 times daily for effective relief of
symptoms over a 24 hour period." Id. at 7:32-35.
FF2. Gonzales teaches that diphenhydramine in "[ a ]mounts greater than
about 100 mg in a single dose may cause toxic side-effects in the
patient, and amounts greater than about 300 mg in a single dose are
very likely to cause toxicity." Id. at 5:34-40.
FF3. Babu teaches that combining immediate release and extended release
therapeutics in a single tablet would reduce the number of doses
administered, "thereby making therapy more convenient ... such that
the dosing interval can be extended to at least eight (8) hours." Babu
1:27-35 (emphasis added), see id. at 8:43-46 ("The tablets of
Example I Provide the opportunity to dose 30% more acetaminophen
in a more convenient manner by extending the dosing interval to at
least eight hours").
FF4. Babu teaches "bi-layer tablet containing both an immediate release
layer and a sustained release layer" in order to achieve sustained
plasma concentration. Id. at 2:67-68. Babu teaches
a multi-layered tablet containing an immediate or quick-
release layer to elevate the blood levels of active
medicament quickly and also containing a sustained
release portion to maintain the elevated blood level.
Hence, the present ... [ method] can be used to prepare
tablets with two or more layers, each with a significantly
different release rate of the same component, or to prepare
tablets of different components.
Id. at4:14-21.
FF5. Babu teaches a bilayer tablet having acetaminophen in not only the
immediate release layer but also in the sustained release layer. Id. at
6:5-68 (see Example 1 and Table 1 ). Babu also teaches bilayer
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tablets containing two active ingredients, such as a combination of
acetaminophen and pseudoephedrine hydrochloride. See id. 9:34-
10: 15. Babu teaches that the pharmaceutical active can also be
selected from a group of compounds including diphenhydramine and
pseudoephedrine; and any pharmaceutically acceptable salts thereof,
among others. Id. at 12:53-58 ( claim 11 ).
Analysis
We begin with claim construction of the phrase "provides a
diphenhydramine plasma concentration within a therapeutic range for at
least 24 hours per single dose," giving the claims their broadest reasonable
interpretation consistent with the Specification. In re Hyatt, 211 F.3d 1367,
1372 (Fed. Cir. 2000). The Specification discloses that the formulation is
administered once a day and maintains the diphenhydramine concentration
within a therapeutic range. See Spec. ,-J 24 ("the dosage form may be
administered not more than about once every 24 hours"), see id. ,-i,-i 8, 14, 22,
72. Therefore, we interpret the phrase "provides a diphenhydramine plasma
concentration within a therapeutic range for at least 24 hours per single
dose," as read in light of the Specification, to mean that the ingestion of a
pharmaceutical formulation at one time point will provide a therapeutically
effective level of diphenhydramine over a 24 hour period. In other words,
the "single dosage" can encompass multiple tablets so long as the tablets are
only administered at one time point during the day.
Appellants contend that Gonzales teaches diphenhydramine split up
into several doses in order to maintain a therapeutically effective
concentration over a 24-hour period. Appeal Br. 9. Appellants contend that
this teaches away from a single dose formulation. Id. Appellants contend
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that Gonzales does not suggest diphenhydramine released over extended
periods of time. Id. Appellants also contend that the dosages of about 300
mg in a single dose are likely to cause toxicity. Id. at 10. Appellants
contend that Babu, alone or in combination with Lech, fails to cure the
deficiencies in Gonzales. Id.
Examiner responds that Gonzales teaches providing antihistamine
relief over a 24 hour period. Ans. 8. Examiner acknowledges that
"Gonzalez states [ diphenhydramine] may cause toxicity over 100 mg and
likely causes toxicity over 300 mg, but does not in fact show that it causes
toxicity." Id. Examiner's position is that Gonzales suggests there is a
possibility for toxicity when employing diphenhydramine at dosages that
exceed 300 mg. This teaching, however, suggests that anything less than
300 mg could reasonably be used without fear of toxicity. See id.
("Gonzales contemplates employing up to 300 mg of diphenhydramine
without toxicity."). Additionally, Examiner does not rely on Gonzales alone
to teach controlled release formulations. Examiner's rejection relies on the
combined teachings Gonzales and Babu for providing extended release
formulations. Id.
We do not find Appellants' arguments persuasive. We note that
Appellants' arguments focus on Gonzales alone (see, e.g., Br. 8-12);
however, where the rejection is based on a combination of references, it is
improper to argue the references separately. In re Keller, 642 F.2d 413, 426
( CCP A 19 81 ). As Examiner explains, Gonzales "teaches that the active
agent is administered such that the composition provides therapeutic relief
for 24 hrs." Ans. 5; FFl ("ingested 4-6 times daily for effective relief of
symptoms over a 24 hour period"). Examiner acknowledges that Gonzales
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does not teach sustained release tablets, but finds that such formulations are
suggested in Babu. Ans. 3; FF3-FF5. Babu teaches that formulating
therapeutics into extended release forms makes "therapy more convenient."
FF3. Additionally, Babu teaches combination therapeutics that include
diphenhydramine. FF5; see Ans. 5 ("Babu teaches diphenhydramine
containing composition to provide therapeutic relief for up to 24 hours in the
form of immediate spike in the plasma level and further prolonged release
for 24 hours").
Examiner finds that "a skilled artisan would be able to choose
between a single dose of immediate and prolonged release or divided doses
of small amounts of drugs, and still be able to provide therapeutic
availability of the active agent for [a] 24 hour[] period." Ans. 5; FF 1, FF3,
FF5. Examiner acknowledges the Gonzales fails to teach a bilayer tablet or
including a second drug; however, Examiner relies on Babu for teaching a
bilayer tablet, as well as including a second drug. Ans. 3; FF5. Specifically,
Babu teaches multilayered tablets containing an immediate release or quick
release layer that brings the blood levels of the active agent into a
therapeutic range quickly, while maintaining the therapeutic window with
the sustained release portion of the tablet. FF4. Furthermore, Babu teaches
that the advantage of a bi-layer tablet is that it can prolong therapy and
thereby make "therapy more convenient." FF3.
Appellants contend that Gonzales teaches away from incorporating
diphenhydramine in amounts greater than 100mg. See Br. 9-10. We are not
persuaded and agree with Examiner that
[t]he disclosure in col. 7-8 of Gonzales [(FF2)] does not teach
away from employing diphenhydramine in amounts greater than
100 mg. The fact that Gonzales teaches amounts 100 mg may
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cause side effects, and greater than 300 mg very likely causes
side effects does not render the instant claims unobvious because
instant claims do not negate side effects.
Ans. 10 (emphasis added). Appellants' argument does not take into account
that the rejection is based on the combination of references. Here, the
combination, as set out by Examiner, suggests putting some
diphenhydramine into an immediate release layer, while reserving some of
the active agent for the extended release portion of the formulation. Ans. 3-
4; FF4. With such a combination, it is not expected that the
diphenhydramine is released in a single bolus and hence the issue of toxicity
would be reduced.
We recognize that Appellants purports to have presented arguments
with respect to claims 155 and 165-176 (Appeal Br. 11) and claims 147-
152, 160, 161, 163, 164, 167, and 174-176 (id. at 12), but note that the
arguments presented repeat those presented with respect to claim 133. Such
arguments do not suffice as separate arguments of the claims. Cf In re
Lovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011) ("[T]he Board reasonably
interpreted Rule 41.37 to require more substantive arguments in an appeal
brief than a mere recitation of the claim elements and a naked assertion that
the corresponding elements were not found in the prior art.").
SUMMARY
We reverse the rejection of claims 148 and 150 under 35 U.S.C.
§ 112, 4th paragraph.
We affirm the rejection of claims 133-176 under 35 U.S.C. § 103(a)
over Gonzales and Babu.
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We affirm the rejection of claims 133-176 under 35 U.S.C. § 103(a)
over Gonzales, Babu, and Lech.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 3 7 C.F .R. § 1.13 6( a).
AFFIRMED
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