Ex Parte Frome

Board of Patent Appeals and Interferences

Nov 30, 2010

10483509 (B.P.A.I. Nov. 30, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte BRUCE FROME
__________

Appeal 2010-009216
Application 10/483,509
Technology Center 1600
__________

Before CAROL A. SPIEGEL, ERIC GRIMES, and STEPHEN WALSH,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of treating a headache. The Examiner has rejected the claims for

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
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obviousness and lack of adequate written description. We have jurisdiction
under 35 U.S.C. § 6(b). We reverse.
STATEMENT OF THE CASE
The Specification discloses “[m]ethods and compositions … which
are employed to target cerebral circulation and to treat headache” (Spec.
2:21-22).
Claims 1-9 and 13 are on appeal. Claim 1 is the only independent
claim and reads as follows:
1. A method of directing a topically applied pharmacologically active
substance to a cerebral circulation, comprising:
providing a composition that includes a pharmacologically active
substance selected from the group consisting of xanthine derivative, vitamin
B6, and angiotensin-converting enzyme inhibitors;
including the composition in a transdermal formulation other than a
patch; and
topically applying the transdermal formulation to a tender spot
associated with the headache or at least one area of skin superficial to a
temporal artery and a vertebral artery, wherein the pharmacologically active
substance is applied in an amount of less than 5mg per dose to the cerebral
circulation.

The claims stand rejected as follows:
• Claims 1-9 and 13 under 35 U.S.C. § 112, first paragraph, for lack
of adequate written description;
• Claims 1, 4-9, and 13 under 35 U.S.C. § 103(a) in view of
Theoharides,2 Liedtke,3 and Mohiuddin;4 and

2 Theoharides, US 5,250,529, Oct. 5, 1993
3 Liedtke, US 5,840,755, Nov. 24, 1998
4 Mohiuddin et al., “Theophylline, aminophylline, caffeine and analogues for
acute ischaemic stroke (review),” 2 Cochran Database System Review 1-2
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• Claims 2 and 3 under 35 U.S.C. § 103(a) in view of Theoharides,
Liedtke, Mohiuddin and Hsu.5
I.
Issue
The Examiner has rejected claims 1-9 and 13 under 35 U.S.C. § 112,
first paragraph, on the basis that the claim limitation that “the
pharmacologically active substance is applied in an amount of less than 5mg
per dose to the cerebral circulation” is not adequately described in the
Specification (Answer 4).
Appellant contends that the disputed limitation is adequately
described because Specification discloses that the amount of the
pharmacologically active substance can be 2 mg, which is less than 5 mg per
dose (Appeal Br. 5).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s finding that the Specification does not adequately
describe applying an active agent “in an amount of less than 5mg per dose to
the cerebral circulation”?

(2000). Mohiuddin was cited in the PTO-892 mailed Nov. 16, 2006. The
Image File Wrapper does not include a copy of Mohiuddin but does include
a reference with the same title but different author (Bath) and publication
date (2006). Since we do not need to rely on Mohiuddin to decide the
obviousness issue, its absence from the record is not critical.
5 Hsu et al., US 6,582,724 B2, June 24, 2003
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Findings of Fact
1. The Specification states that “preferred pharmacologically active
substances include xanthine derivatives (e.g., caffeine, theophylline, or
aminophylline) in a concentration of at least 1% to 70%” (Spec. 3: 1-2).
2. The Specification states that “contemplated compounds may be in
the range of less than 0.1% w/w to 90% w/w, and even more. More
typically, contemplated compounds may be in the range of about 1% w/w to
20% w/w” (id. at 5: 24-27).
3. The Specification states that “[i]n a preferred aspect…,
approximately 200mg to 1 g of contemplated compositions (e.g., 3.2% w/w
theophylline and 2% w/w ketoprofen in a transdermal formulation in cream
form) is applied” (id. at 9: 1-5).
Analysis
We agree with Appellant that the Specification demonstrated to those
of ordinary skill in the art that the inventor was in possession of what is
claimed. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351
(Fed. Cir. 2010)(en banc) (“[T]he test for sufficiency is whether the
disclosure of the application relied upon reasonably conveys to those skilled
in the art that the inventor had possession of the claimed subject matter as of
the filing date.”). “It is not necessary that the application describe the claim
limitations exactly … but only so clearly that persons of ordinary skill in the
art will recognize from the disclosure that appellants invented processes
including those limitations.” In re Wertheim, 541 F.2d 257, 262 (CCPA
1976).
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Here, the Specification indicates that the active substance can be
present in a concentration as low as 0.1% w/w (FF 2), and that xanthine
derivatives can be present at a concentration of 1% w/w (FF 1). The
Specification also discloses application of 200 mg of the final composition
(FF 3). We agree with Appellant that the Specification shows possession of
a method in which the active agent is applied in amounts at least as low as 2
mg (i.e., 1% of 200 mg). The Examiner has not persuasively explained why
the Specification does not reasonably convey to one of skill in the art the
“less than 5 mg per dose” limitation. We therefore reverse the rejection of
claims 1-9 and 13 under 35 U.S.C. § 112, first paragraph.
Conclusion of Law
The evidence of record does not support the Examiner’s finding that
the Specification does not adequately describe applying an active agent “in
an amount of less than 5mg per dose to the cerebral circulation.”
II.
Issue
The Examiner has rejected claims 1, 4-9, and 13 under 35 U.S.C.
§ 103(a) as being obvious in view of Theoharides, Liedtke and Mohiuddin,
and claims 2 and 3 based on the same references combined with Hsu. Since
the same issue is dispositive with respect to both rejections, we will consider
them together.
The Examiner finds that Theoharides discloses alleviating migraine
headaches by “administering a pharmaceutically effective amount of a mast
cell degranulation blocking agent,” such as methyl xanthines (Answer 5).
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The Examiner finds that Liedtke discloses treating headaches by topically
applying a carrier containing a local anesthetic to the forehead or temples
(id. at 6) and that Mohiuddin discloses that theophylline “causes potent
cerebral vasoconstriction, which … increases collateral blood flow
surrounding the ischaemic region” (id.).
The Examiner concludes that it would have been obvious to one of
ordinary skill in the art to apply a transdermal formulation containing a
pharmacologically active substance “to a tender spot or at least one area of
skin superficial to a temporal artery or a vertebral artery … because
Mohiuddin et. al. teaches that xanthine derivatives such as theophylline,
increase collateral blood flow surrounding the ischaemic region of the brain
… [and] Liedtke teaches that anesthetics may be administered transdermally
to the forehead or/and temples to treat headaches” (id. at 6-7).
Appellant contends that the Examiner erred in concluding that the
claimed method would have been obvious because, among other things, the
cited references do not suggest that “the pharmacologically active substance
is applied in an amount of less than 5mg per dose to the cerebral circulation”
(Appeal Br. 8; Reply Br. 3).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the cited references suggest
applying a “pharmacologically active substance … in an amount of less than
5mg per dose to the cerebral circulation”?
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Additional Findings of Fact
4. Theoharides discloses that the “administration of mast cell
blocking agents … will prevent or alleviate the onset of the two later stages
in the migraine process” (Theoharides, col. 5, ll. 28-32).
5. Theoharides discloses that drugs that are useful in its method
include methyl xanthines such as aminophylline, caffeine, and theophylline
(id. at col. 6, ll. 33-38).
6. Theoharides discloses that the compositions can be administered
transdermally (id. at col. 9, l. 67 to col. 10, l. 5).
7. Theoharides discloses that caffeine “is administered in the
pharmaceutically effective amount. A pharmaceutically effective amount
denotes a dosage from 5 to 50 milligrams per kilogram body weight.” (Id. at
col. 11, ll. 35-39).
8. Liedtke discloses “a composition for topical therapy of headaches,
which contains a topical carrier system for application to … a mammalian
forehead or temples or both and a local anesthetic for delivery to a region of
skin underneath the topical carrier system” (Liedtke, col. 2, ll. 25-30).
9. Liedtke discloses that its method “makes possible a locally targeted
and prolonged therapeutically effective treatment of the terminal and
functionally interlinked nerve paths in the area of the head. Since this area
also has good cutaneous absorption capacity, topical doses which are very
low can also be used.” (Id. at col. 3, ll. 23-30.)
10. Liedtke discloses that “it is preferred that the therapeutically
effective topical amount of local anesthetic in the carrier, be for lidocaine,
for example, in the range of about 10 mg to 50 mg” (id. at col. 3, ll. 40-44).
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Analysis
Claim 1 is directed to a method comprising topically applying a
transdermal formulation comprising, for example, a xanthine derivative,
“wherein the pharmacologically active substance is applied in an amount of
less than 5mg per dose to the cerebral circulation.”
Appellant argues that the cited references do not suggest the
transdermal application of less than 5 mg of a xanthine derivative (Appeal
Br. 8, Reply Br. 3). Appellant argues that “Theoharides teaches that the
dosage of caffeine has to be somewhere between 5 mg to 50 mg per
kilogram body weight” (Appeal Br. 7). Appellant also argues that
“[a]lthough, Liedtke contemplates using low [doses] of anesthetic,” it
discloses a topical local anesthetic in the range of 10 mg to 50 mg (id.).
We agree with Appellant that the Examiner has not shown that the
cited references would have made obvious the dosage recited in the claims.
Theoharides discloses treating a migraine headache by transdermally
administering a mast cell blocking agent, which can be a xanthine derivative
such as caffeine. However, Theoharides discloses that a pharmaceutically
effective amount of caffeine “denotes a dosage from 5 to 50 milligrams per
kilogram body weight” (FF 7), which corresponds to a dosage of 300-3000
mg for a patient weighing 60 kg (132 pounds). Liedtke discloses that
treating headaches by topical application of a local anesthetic to the forehead
or temples allows for “doses which are very low” (FF 9) but discloses that
preferred doses for lidocaine are 10-50 mg (FF 10).
In view of these disclosures, we agree with Appellant that the
Examiner has not adequately explained how a person of ordinary skill in the
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art would have reached the claimed dosage of less than 5 mg per dose
through routine optimization of the prior art dosages. The only disclosed
prior art dosage range for a xanthine derivative (caffeine) is roughly one-
hundred-fold higher than the dosage required by the claims and, while
Liedtke’s dosage range for lidocaine is only twice what is required by the
claims, the Examiner has not provided evidence or sound reasoning to
support a conclusion that a skilled worker would have expected a xanthine
derivative to be effective at doses even lower than Liedtke’s preferred
dosage for lidocaine.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the cited references suggest the claim 1 limitation that “the
pharmacologically active substance is applied in an amount of less than 5mg
per dose to the cerebral circulation.”
SUMMARY
We reverse the rejections of claims 1-9 and 13 under 35 U.S.C.
§ 103(a) and under 35 U.S.C. § 112, first paragraph.

REVERSED

lp

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