Ex Parte Caldwell et al

Patent Trial and Appeal Board

Dec 27, 2012

11115968 (P.T.A.B. Dec. 27, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte LARRY J. CALDWELL and BRADLEY S. GALER
__________

Appeal 2011-002324
Application 11/115,968
Technology Center 1600
__________

Before DEMETRA J. MILLS, RICHARD M. LEBOVITZ, and
MELANIE L. McCOLLUM, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a pain
treatment method. The Examiner has rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
Claims 1, 3, 4, 6, 7, 10-12, 14, 15, 26, and 28-44 are pending and on
appeal (App. Br. 3). Claims 1, 26, 29, and 38 are illustrative and read as
follows:
1. A method for treating a subject for pain, said method consisting of:
(a) providing a storage stable topical formulation consisting of:
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a backing layer;
a matrix on a surface of the backing layer, wherein the matrix
consists of:
methadone;
a thermoplastic elastomer;
a resin;
a wax; and
a solvent; and
a release film positioned on a surface of the matrix opposite the
backing;
(b) removing the release film to expose the matrix;
(c) positioning the exposed matrix on a skin surface of said subject;
and
(d) maintaining said matrix on said skin surface for a period of time
sufficient for an effective amount of said methadone agent to be systemically
delivered to treat said subject for pain.
26. The method of Claim 1, wherein said methadone agent is
administered to provide for a therapeutic level of said methadone agent in
blood of the subject for an extended period of time.
29. The method of Claim 1, wherein said methadone agent is
administered to provide for a blood concentration of said methadone agent in
said subject of about 50 ng/ml to about 500 ng/ml.
38. The method according to Claim 1, wherein the topical
formulation is one that has been stored for 3 months or longer.
Claims 1, 3, 4, 7, 26, and 29-44 stand rejected under 35 U.S.C.
§ 103(a) as obvious over Solomon et al. (US 2005/0287195 A1, Dec. 29,
2005) in view of Bracher (US 5,989,585, Nov. 23, 1999) and Yamada et al.
(US 5,362,497, Nov. 8, 1994) (Ans. 4).
Claim 6 stands rejected under 35 U.S.C. § 103(a) as obvious over
Solomon in view of Bracher, Yamada, and Miranda et al. (US 5,656,286,
Aug. 12, 1997) (Ans. 8).
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Claims 10-12, 15, and 28 stand rejected under 35 U.S.C. § 103(a) as
obvious over Solomon in view of Bracher, Yamada, and Cameron et al.
(US 6,796,429 B2, Sep. 28, 2004) (Ans. 9).
Claim 14 stands rejected under 35 U.S.C. § 103(a) as obvious over
Solomon in view of Bracher, Yamada, Cameron,1 and Miranda (Ans. 12).
I
The Examiner rejects claims 1, 3, 4, 7, 26, and 29-44 as obvious over
Solomon in view of Bracher and Yamada (Ans. 4). Claims 1, 26, 29, and
38-44 are representative.
The Examiner finds:
Solomon et al teach a transdermal drug delivery system
comprising solvents, which include DEET. . . . According to
Solomon et al, DEET showed sufficiently high dissolution
properties for a range of hydrophilic and hydrophobic drugs.
. . . Active ingredients used in the transdermal drug delivery
system include analgesics, such as methadone, preferably in an
amount of 0.3-30 wt.%. . . . The transdermal drug delivery
system is coated as a layer onto a siliconized release paper and
laminated onto a backing strip. In addition to the active agent
and solvent, an adhesive is part of the system. According to
Solomon et al, the adhesive is selected from polyisobutylene,
acrylate, and silicone. Besides an active agent, solvent, and
adhesive no other elements are required in the transdermal
system of Solomon et al.
(Id.) However, the Examiner finds: “Solomon et al do not teach a
transdermal delivery system that further consists of a wax and a resin.

1 The Examiner’s Answer does not list Cameron in the statement of the
rejection (Ans. 12). However, from the body of the rejection, it is clear that
Cameron is included (id. at 13). Appellant also included Cameron in the
statement of the rejection on page 31 of the Appeal Brief.
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Furthermore, Solomon et al do not immediately envisage methadone in a
transdermal patch.” (Id. at 5.)
The Examiner finds that “Bracher exemplifies a transdermal
therapeutic system for the administration of L-methadone as a single active
agent present as a free base in an amount of 3-20 wt.%” (id.). The Examiner
finds that “Yamada et al teach a transdermal therapeutic composition in the
form of a patch that can comprise bees-wax, carnauba wax, silicone resin,
etc.” and that “these ingredients can be incorporated in the transdermal
compositions for modulating the transdermal absorption” (id.). The
Examiner concludes that it would have been obvious “to incorporate
methadone as an active agent” and “to incorporate wax and resin into the
transdermal patches of Solomon” (id. at 5-6).
Analysis
We affirm the rejection of claim 1 for the reasons set forth in the
Examiner’s Answer. We include the following additional comments.
Appellant contends that Bracher requires vitamin E in its formations
(App. Br. 13). We recognize that Bracher includes vitamin E, a known skin
penetration enhancer,2 in its examples (Bracher, col. 4, l. 21, to col. 5, l. 20).
We also recognize that Bracher teaches:
In the experiments underlying [the] invention, it was
surprisingly found that for example with L-methadone as the
agent, the amount of agent which permeates in an in vitro test
with mouse skin did not increase linearly with the increase in

2 As evidence that vitamin E is a known skin penetration enhancer, the
Examiner relies on Jay S. Trivedi et al., Vitamin E as a human skin
penetration enhancer, 3 EUROPEAN J. OF PHARMACEUTICAL SCIENCES 241-
243 (1995) (Ans. 15-16).
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agent concentration in the matrix, but was overproportional or
greater than linear. This is surprising, because it could not be
expected from the prior art that a transdermal therapeutic
system, for example with L-methadone as the active agent,
would deliver a permeation rate as high as that required for a
rational transdermal therapy with amounts of 10 to 15 mg/day.
(Id. at col. 2, l. 66, to col. 3, l. 9.) However, we do not agree that Bracher
suggests that vitamin E is the only skin penetration enhancer that would be
expected to provide a therapeutically effective amounts of methadone. For
example, Bracher generally teaches a formulation in its Summary of the
Invention that is not restricted to one which comprises vitamin E (id. at
col. 2, ll. 21-44). Thus, given that Solomon’s composition already includes
DEET as a solvent/skin penetration enhancer (Solomon ¶ [0006]), we do not
agree with Appellants’ arguments that one of ordinary skill in the art would
not have had reason to incorporate methadone in Solomon’s matrix without
also including vitamin E or that there would not have been a reasonable
expectation for success.
With regard to the references listed in the Evidence Appendix, as well
as reference by Walters discussed in both Briefs (App. Br. 18 & Reply
Br. 10), we note that these references do not appear to be of record. In
particular, they do not appear to have been included with the Appeal Brief,
nor do they appear to have been included with the March 6, 2009, response
mentioned in the Evidence Appendix.
Moreover, we do not find the description of these references in the
Appeal and Reply Briefs (App. Br. 10-11 & 18-19 & Reply Br. 8-10)
sufficient to demonstrate that there would not have been a reasonable
expectation for success. In particular, we do not agree that the alleged lack
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of transdermal methadone on the market at the time of filing is sufficient by
itself to show that there would not have been a reasonable expectation for
success. There may be other reasons why a commercial transdermal
methadone product had not been developed. Certainly, the fact that Bracher
suggested methadone in a transdermal formation is evidence that one of
ordinary skill in the art would have expected one to work. In addition,
Appellant has not provided sufficient evidence that in vitro data is not
predictive of in vivo results, leading one of ordinary skill in the art to not
believe Bracher’s teachings.
We also do not agree that the “Examiner has erred in relying on
assertions of inherency and operability” (App. Br. 20). On the contrary, the
Federal Circuit has held that inherency can be used in the context of an
obviousness rejection. In re Huai-Hung Kao, 639 F.3d 1057, 1070 (Fed.
Cir. 2011). In the present case, given the structural similarity between the
claimed topical formulation and the formulation that would result from
combining the applied references, we conclude that the Examiner provided a
reasonable basis to believe that the combination would result in a storage
stable topical formulation that systemically delivers methadone and
therefore shifted the burden to Appellants to demonstrate that this would not
have been inherent. Appellants have not met this burden.
In addition, we do not agree that “there is no reason provided in the
art or any evidence provided by the Office that one of ordinary skill in the
art would go to the trouble of includ[ing] a resin or wax in Solomon’s type
of formulation” (Reply Br. 5). Yamada teaches the incorporation, in its
transdermal therapeutic compositions, of various ingredients, including bees-
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wax, carnauba wax, and silicone resin, to modulate transdermal absorption
(Yamada, col. 6, ll. 6-15). We agree with the Examiner that one of ordinary
skill in the art would have incorporated bees-wax, carnauba wax, and/or
silicone resin in Solomon’s transdermal drug delivery system in order to
modulate transdermal absorption (Ans. 6).
With regard to claims 26 and 29, we interpret these method claims to
require that the methadone be administered so as to provide the claimed
effect. However, Solomon teaches incorporating the active substance in an
amount of from 0.1% to 50%, preferably 0.3% to 30%, by weight of the
coating material (Solomon, ¶ [0050]), which substantially overlaps with the
range recited in present claims 7 and 15. In addition, Bracher teaches
incorporating methadone in an amount of at least 5%, preferably 15-20%, by
weight and delivering amounts as high as 10 to 15 mg/day (Bracher, col. 3,
ll. 4-9 & 17-23). We conclude that the Examiner has provided a reasonable
basis to believe that the applied references suggest amounts that would
inherently provide a therapeutic level of methadone in blood for an extended
period of time, “e.g., from about 4 hrs to about 24 hrs” (Spec. 6: 8-9), as
recited in claim 26, and would inherently provide a blood concentration of
methadone of about 50 ng/ml to about 500 ng/ml, as recited in claim 29.
With regard to claims 38-44, which recite that the topical formulation
has been stored for increasingly higher periods of time from at least
3 months in claim 38 to at least 24 months in claim 44, we interpret these
method claims to require that the topical formulation be stored for the
claimed period of time. However, Solomon teaches that its delivery systems
“can reliably and repeatedly attain” the goal of “a shelf life of at least two
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yea[r]s without loss of therapeutic activity per unit dosage form” (Solomon,
¶ [0053]). Thus, we agree with the Examiner that there would have been a
reasonable expectation that the topical formulation resulting from the
combination of the applied references would also have a shelf life of at least
two years without loss of therapeutic activity. We understand that Solomon
does not exemplify methadone. However, we agree with the Examiner that
Appellants have not provided sufficient evidence to demonstrate that there
would not have been a reasonable expectation of success.
Conclusion
The evidence supports the Examiner’s conclusion that claims 1, 26,
29, and 38-44 would have been obvious. We therefore affirm the
obviousness rejection of these claims.
Claims 3, 4, 7, and 35-37 are argued with claim 1 and claims 30-34
are argued with claim 29 (App. Br. 8). Thus, claims 3, 4, 7, and 30-37 fall
with claims 1 and 29. 37 C.F.R. § 41.37(c)(1)(vii).
II
The Examiner rejects claim 6 as obvious over Solomon in view of
Bracher, Yamada, and Miranda; claims 10-12, 15, and 28 as obvious over
Solomon in view of Bracher, Yamada, and Cameron; and claim 14 as
obvious over Solomon in view of Bracher, Yamada, Cameron, and Miranda
(Ans. 8-13). Claims 6, 10, and 14 are representative.
Appellants traverse these rejections for the same reasons as claim 1
(App. Br. 30-32). We are not persuaded by these arguments for the reasons
stated in the Examiner’s Answer and above. We therefore affirm the
obviousness rejections of claims 6, 10, and 14. Claims 11, 12, 15, and 28
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are not separately argued and therefore fall with claim 10. 37 C.F.R.
§ 41.37(c)(1)(vii).
SUMMARY
We affirm the obviousness rejections of claims 1, 3, 4, 7, 26, and 29-
44 over Solomon in view of Bracher and Yamada, of claim 6 over Solomon
in view of Bracher, Yamada, and Miranda, of claims 10-12, 15, and 28 over
Solomon in view of Bracher, Yamada, and Cameron, and of claim 14 over
Solomon in view of Bracher, Yamada, Cameron, and Miranda.
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).

AFFIRMED

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