Ex Parte LIU et al

Patent Trials and Appeals Board

May 14, 2019

15184667 - (D) (P.T.A.B. May. 14, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
15/184,667 06/16/2016
60601 7590 05/16/2019
Muncy, Geissler, Olds & Lowe, P.C.
4000 Legato Road
Suite 310
Fairfax, VA 22033
FIRST NAMED INVENTOR
Yee-Chien LIU
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.
5454/0119PUS2 7169
EXAMINER
KOSTURKO, GEORGE W
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
05/16/2019 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):
MAILROOM@MG-IP.COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YEE-CHIEN LIU and PEI-LING WU
Appeal2018-007715
Application 15/184,667
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN G. NEW, and JAMIE T. WISZ,
Administrative Patent Judges.
WISZ, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellants 1 seek review of claims
1, 2, and 5. We have jurisdiction under 35 U.S.C. § 6(b).
For the reasons set forth below, we AFFIRM.
STATEMENT OF THE CASE
The specification describes the use of an agent that enhances
transdermal delivery of a PDE-5 inhibitor. Spec. 20. Claim 1, the only
independent claim, is set forth below:
1 Appellants identify the Real Party in Interest as Yee-Chien Liu. App. Br.
3.
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Application 15/184,667
1. A transdermal pharmaceutical gel or patch composition
consisting of:
an effective amount of vardenafil or a pharmaceutically
acceptable salt thereof, and an enhancer for enhancing
transdermal delivery of vardenafil; wherein the enhancer is
cocamidopropyl betaine, and vardenafil and the enhancer are
present in a ratio from 20: 1 to 2: 1 by weight in the transdermal
pharmaceutical gel or patch composition; and
a pharmaceutically acceptable excipient.
The Examiner rejected claims 1, 2, and 5 under 35 U.S.C. § 103(a) as
being obvious over Toque2, Thomfeldt3, and Friedman.4
ISSUES AND ANALYSIS
We affirm the Examiner's obviousness rejections. We address the
arguments raised by Appellants below.
Obviousness
A claimed invention is unpatentable if the differences between it and
the prior art are "such that the subject matter as a whole would have been
obvious at the time the invention was made to a person having ordinary skill
in the art." 35 U.S.C. § 103(a) (pre-AIA). To assess whether the subject
matter would have been obvious, the Board follows guidance in Graham v.
2 Toque et al., Vardenafil, but not sildenafil or tadalafil, has calcium-
channel blocking activity in rabbit isolated pulmonary artery and human
washed platelets, 154 British Journal of Pharmacology, 787-796 (2008)
("Toque").
3 Thomfeldt et al., U.S. Patent No. 5,760,096, issued June 2, 1998
("Thomfeld").
4 Friedman et al., US 2005/0271596 Al, published Dec. 8, 2005
("Friedman").
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John Deere Co., 383 U.S. 1 (1966) and KSR Int'! Co. v. Teleflex, Inc., 550
U.S. 398 (2007). Under that guidance, the "combination of familiar
elements according to known methods is likely to be obvious when it does
no more than yield predictable results." KSR, 550 U.S. at 416. Thus, 35
U.S.C. § 103 requires an inquiry into "'whether the improvement is more
than the predictable use of prior-art elements according to their established
functions."' Monolithic Power Sys., Inc. v. Micro Int'! Ltd, 558 F.3d 1341,
1352 (Fed. Cir. 2009) (quoting KSR, 550 U.S. at 417).
Applying this standard, we conclude that the Examiner did not err in
determining that the claims would have been obvious to an ordinarily-skilled
artisan over the cited prior art.
The Examiner finds that Toque teaches that vardenafil is an art-
recognized phosphodiesterase 5 inhibitor (PDE5) with advantageous calcium
channel blocking activity. Final Act. 5 ( citing Toque abstract, 792-93). The
Examiner also finds that Thomfeld discloses gel formulations consisting of
cocamidopropyl betaine with propylene glycol and ethanol, which are
synergistic excipients for transdermally delivering therapeutic agents,
including calcium channel blockers, due to their desirable penetration
enhancing properties. Id. at 5-6 (citing Thomfeld abstract, 3:20, 3:65-4:40,
Table 7). Furthermore, according to the Examiner, Friedman teaches topical
pharmaceutical compositions comprising PDE5-inhibitors such as
vardenafil, formulated with penetration enhancers/emollients, including
propylene glycol, and surfactants, including cocamidopropyl betaine. Id.
(citing Friedman abstract ,i,i 23, 60, 98, 100, 119, 122, 171, 134, 173, 177).
The Examiner further finds that Friedman discloses topical compositions
comprising a PDE5 inhibitor with cocamidopropyl betaine, wherein the
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PDE5 inhibitor to cocamidopropyl betaine ratio is 20: 1. Id. at 7 ( citing
Friedman ,i 1 77).
The Examiner concludes:
Therefore, one of ordinary skill in the art of formulating
transdermal delivery of calcium channel blockers/PD ES
inhibitors knowing that gel compositions consisting of
cocamidopropyl betaine, ethanol and propylene glycol are
efficacious for transdermal delivery of calcium channel
blockers/PDE5 inhibitors, as taught by Thomfeldt and
Friedman above, one would have found it prima facie obvious
to formulate the art-recognized calcium channel blocker/PDE5
inhibitor vardenafil, as taught by Toque et al with
cocamidopropyl betaine, ethanol and propylene glycol in order
to arrive at the instantly claimed composition.
Id. The Examiner also finds that one of skill in the art would have been
motivated to formulate vardenafil with cocamidopropyl betaine, ethanol, and
propylene glycol since the art teaches that such reagents are advantageous
for enhancing the permeability of calcium channel blockers/PD ES inhibitors
across dermal membranes. Id. The Examiner further finds that one skilled
in the art would have predicted that such a formulation, wherein the ratio of
PDE5 inhibitor to cocamidopropyl betaine is 20: 1, would have effectively
delivered vardenafil to the targeted tissue across dermal membranes. Id.
Appellants assert that Thomfeld does not teach propylene glycol and
ethanol as being inert excipients but, rather, as active penetration enhancers,
at a weight range of 1:0.1 to 1:10, with additional components. App. Br. 9-
10. Appellants also contend that, in view of the teaching of Thomfeld as a
whole, the skilled artisan would have only modified the formulation of
Toque by adding glycol and alcohol as the penetration compositions and
would not have chosen cocamidopropyl betaine since Thomfeld does not
teach its use as a penetration enhancer. Id. at 10. Appellants further argue
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Application 15/184,667
that if the skilled artisan were to include additional components to the
formulation, he/she would choose from the preferred surfactants, branched
chain ester fatty acids, or membrane fluidizers taught in Thomfeld, rather
than choosing cocamidopropyl betaine. Id. Appellants also contend that
neither Torque nor Thomfeld teach vardenafil and the enhancer in a ratio of
20:lto2:l. Id.at 11.
The Examiner responds that the ethanol and propylene glycol as
taught by Thomfeldt fall within the recited limitation of "a pharmaceutically
acceptable excipient." Ans. 17. The Examiner explains that the
specification states, "[ s Jpecifically, as used herein and in the claims, the
singular forms 'a' and 'an' include the plural reference unless the context
clearly indicates otherwise." Id. at 17-18 ( citing Spec. ,i 23). In addition,
the Examiner finds that ethanol and propylene glycol fall within the
definition of "pharmaceutically acceptable" and "excipient" in the
specification, which explicitly includes ethyl alcohol ( ethanol) and
propylene glycol as "[t]ypical inert excipients." Id. at 18 ( citing Spec. ,i,i
28, 31, pp. 10-11 ). The Examiner concludes that the broadest reasonable
interpretation of the phrase "and a pharmaceutically acceptable excipient"
recited in claim 1 "encompasses one or more excipients including ethyl
alcohol and propylene glycol." Id.
We agree with the Examiner's claim construction of "a
pharmaceutically acceptable excipient." Appellants expressly defined the
word "a" in the specification to include the plural. Spec. ,i 23. "A claim
term will not receive its ordinary meaning if the patentee acted as his own
lexicographer and clearly set forth a definition of the disputed claim term in
either the specification or prosecution history." CCS Fitness, Inc. v.
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Brunswick Corp., 288 F.3d 1359, 1366 (Fed. Cir. 2002). Therefore, the
claim includes one or more "pharmaceutically acceptable excipient[s]." We
also agree that the claim term "pharmaceutically acceptable excipient"
includes propylene glycol and ethanol ( ethyl alcohol) since "excipient" is
defined in the specification at ,-J 31 as "any inert substance ... that forms a
vehicle/carrier for the PDE-5 inhibitor or enhancer" and propylene glycol
and ethyl alcohol are specifically listed as "inert excipients" at page 10 of
the specification.
In response to Appellants' argument that the skilled artisan would
need to choose from various other components and would not have chosen
cocamidopropyl betaine combined with propylene glycol and ethanol, the
Examiner points out that formulations 41-44 of Table 7 in Thomfeldt
disclose formulations consisting of cocamidopropyl betaine, propylene
glycol, and ethanol, and that these formulations are efficacious for delivering
topically applied calcium channel blockers to targeted tissue by penetrating
dermal layers. Id. ( citing Thomfeldt col. 6-7). Regarding Appellants'
contention that Thomfeldt does not teach cocamidopropyl betaine as a
"penetration enhancer," the Examiner finds that "[a] chemical composition
and its properties are inseparable. Therefore, if the prior art teaches the
identical chemical structure, the properties applicant discloses and/or claims
are necessarily present." Id. at 20 (citing In re Spada, 911 F.2d 705, 709
(Fed. Cir. 1990)). Furthermore, the Examiner finds that Thomfeldt teaches
that formulations of propylene glycol and ethanol with cocamidopropyl
betaine ( entries 41-44 at cols. 7-8) have higher penetrative properties
compared to formulations without cocamidopropyl betaine ( entry 2 at cols.
5-6). Id. (citing Thomfeldt abstract, 3-4:60, 6-8).
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We agree with the Examiner that, based on the disclosure in
Thomfeldt, one of skill in the art would have been motivated to use a
formula consisting of propylene glycol and ethanol with cocamidopropyl
betaine as shown in formulations 41-44. Thomfeld cols. 7-8. Thomfeld
teaches that surfactants are used for topical/transdermal delivery purposes
and cocamidopropyl betaine is a disclosed surfactant, which increases the
penetrative properties of formulations containing propylene glycol and
ethanol. Thomfeld col. 1:13-16, 2:44-47, 3, 6-8. Furthermore, even
assuming arguendo that cocamidopropyl betaine is not a preferred
surfactant, "'all disclosures of the prior art, including unpreferred
embodiments, must be considered."' Merck & Co., Inc. v. Biocraft
Laboratories, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (quoting In re
Lamberti, 545 F.2d 747, 750 (CCPA 1976)).
In response to Appellants' argument that neither Toque nor Thomfeldt
disclose the ratio ofvardenafil to cocamidopropyl betaine of20:l to 2:1, the
Examiner finds that one cannot show nonobviousness by attacking
references individually where the rejections are based on combinations of
references. Id. at 21. We agree with the Examiner and are not persuaded by
the Appellants' arguments because Friedman, in combination with Toque
and Thomfeld, is relied on for the claimed ratio. "Non-obviousness cannot
be established by attacking references individually where the rejection is
based upon the teachings of a combination of references. . . [The reference]
must be read, not in isolation, but for what it fairly teaches in combination
with the prior art as a whole." In re Merck & Co., 800 F.2d 1091, 1097
(Fed. Cir. 1986).
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Appellants also argue that a skilled artisan would not have turned to
Friedman for the ratio of PDE5 inhibitor and the penetration enhancer in a
topical formulation. App. Br. 12. First, Appellants assert that propylene
glycol is just one of many suggested selections of emollient and/or
penetration enhancer, which is optional. Id. at 12-13. Appellants also assert
that cocamidopropyl betaine, which is an ionic surfactant, is not preferred in
Friedman, which states that "[i]onic surfactants are known to be irritants.
Therefore, non-ionic surfactants are preferred in applications including
sensitive tissue." Id. ( citing Friedman ,i 120). Appellants also argue that, in
the case where ionic surfactant is included, Friedman teaches that "[a]
combination of non-ionic surfactant and an ionic surfactant (such as sodium
lauryl sulfate and cocamidopropyl betaine) is employed at a ratio of between
1: 1 to 20: l." Id. ( citing Friedman ,i 122). Therefore, Appellants further
assert that Friedman does not teach using cocamidopropyl betaine alone but
suggests that it is used with a non-ionic surfactant at an indicated ratio. Id.
Appellants conclude that the Examiner failed to give "sound
reasoning" as to why a skilled artisan would know that gel compositions
consisting of cocamidopropyl betaine, ethanol, and propylene glycol are
efficacious for transdermal delivery of calcium channel blockers/PD ES
inhibitors based on the cited prior art when:
neither Thomfeldt nor Friedman taught or suggested
cocamidopropyl betain exhibits any penetration efficacy, and
Thomfeldt teach that cocamidopropyl betain is one of the
additional surfactant that may be used with the active
penetration enhancers (i.e., the combination of propylene glycol
and ethanol), and Friedman suggest cocamidopropyl betain, an
ionic surfactant, if used, should be used together with non-ionic
surfactant at indicated range. In other words, the skilled artisan,
in view of the combined teaching of the cited references would
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NOT have arrived at the alleged composition - "a gel or patch
compositions consisting of vardanafil, cocamidopropyl betaine,
and inert excipients of ethanol, and propylene glycol."
Id. at 13-14. Appellants also assert that the Examiner failed to give "sound
reasoning" as to why a skilled artisan would look for the ratio between
PDE5 inhibitor and cocamidopropyl betain, "when the entire teaching of
Friedman gave no such clues that cocamidopropyl betain is a penetration
enhancer." Id.
In response, the Examiner explains that Friedman teaches that PDE5
compositions formulated with cocamidopropyl betain and propylene glycol
are safe and effective for transdermal administration of a therapeutic agent.
Ans. 22 (citing Friedman abstract, ,i,i 8, 60, 120-122, 177, claim 1, claim
11). With regard to Appellants' argument that a skilled artisan would have
used a non-ionic surfactant with cocamidopropyl betain, the Examiner
asserts that the incorporation of a non-ionic surfactant does not teach away
from the claimed invention because the limitation of "pharmaceutically
acceptable excipient" does not exclude the addition of PEG-40 stearate. Id.
at 23-24. With regard to the claimed ratio, the Examiner finds that a skilled
artisan would have reasonably expected that "vardenafil, formulated in a
topical composition consisting of cocamidopropyl betain in a ratio of 20: 1 in
combination with pharmaceutically acceptable excipients propylene glycol
and ethanol would have been a safe and effective formulation." Id. at 27.
Furthermore, the Examiner finds that there are no unexpected results of the
claimed ratio relative to the prior art. Id.
We are not persuaded by the Appellants' arguments. Again,
Appellants are improperly dismissing the non-preferred embodiments and
arguing the references individually rather than as a combination. As
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presented by the Examiner, Toque teaches that vardenafil is a known PDE5
inhibitor with calcium-channel blocking activity. Furthermore, Thomfeld
teaches that calcium channel blockers and vasodilators can be delivered
topically/transdermally in formulations consisting of propylene glycol and
ethanol, in combination with cocamidopropyl betaine, which increases the
penetrative properties of the formulation. Lastly, Friedman discloses
formulations of vardenafil with propylene glycol and cocamidopropyl
betaine for topical delivery in which the ratio of vardenafil to
cocamidopropyl betaine is 20: 1. Because the combination of Toque,
Thomfeld, and Friedman teaches every limitation of the claims, we are not
persuaded that the Examiner erred.
Having considered Appellants' arguments in support of claim 1, we
are not persuaded of any reversible error in the Examiner's rejection of
claim 1. For the reasons described herein and those already of record, we
sustain the Examiner's rejection of independent claim 1 under 35 U.S.C.
§ 103(a) as being obvious over Toque, Thomfeldt, and Friedman. Claims 2
and 5 are not argued separately, and fall with claim 2. See 37 C.F.R.
§ 41.37(c)(l)(iv).
CONCLUSION
We affirm the Examiner's obviousness rejections of claims 1, 2, and
5. No time period for taking any subsequent action in connection with this
appeal may be extended under 37 C.F.R. § l.136(a)(l)(iv).
AFFIRMED
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