Ex Parte Abdulrazik

Board of Patent Appeals and Interferences

Sep 17, 2010

10354173 (B.P.A.I. Sep. 17, 2010)

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.
10/354,173 01/30/2003 Muhammad Abdulrazik 2117 7138
7590 09/17/2010
EDWARD LANGER
c/o SHIBOLETH YISRAELI ROBERTS, ZISMAN & CO.
60th Floor
350 Fifth Ave.
New York, NY 10118
EXAMINER
POPA, ILEANA
ART UNIT PAPER NUMBER
1633
MAIL DATE DELIVERY MODE
09/17/2010 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MUHAMMAD ABDULRAZIK
__________

Appeal 2010-003330
Application 10/354,173
Technology Center 1600
__________

Before ERIC GRIMES, CAROL A. SPIEGEL, and MELANIE L.
McCOLLUM, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to methods
for alleviating symptoms of migraines. The Examiner has rejected the

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.
Appeal 2010-003330
Application 10/354,173

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claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We
affirm.
STATEMENT OF THE CASE
The Specification discloses that it has been “found that a conventional
pharmaceutical agent, when administered by ocular route of drug delivery,
provides good CNS targeting” (Spec. 2).
Claims 38, 39, 42, 45-47, 50, 64, 75, 77, 87-89, 93-96, and 99-105 are
on appeal. The claims have not been argued separately and therefore stand
or fall together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 38 is representative and
reads as follows:
38. A method for alleviating symptoms of migraines caused by
dysregulation of alpha-2 adrenoreceptor comprising administering to a
subject in need of treatment an effective amount of alpha-2 adrenoreceptor
agonists by brisk direct non-systemically mediated, and non-axonal ocular
route of drug delivery.

Issue
The Examiner has rejected claims 38, 39, 42, 45-47, 50, 64, 75, 77,
87-89, 93-96, and 99-105 under 35 U.S.C. § 103(a) in view of Walters,2
Robichaud,3 Kim,4 Enyedi,5 Pradalier,6 Carlsen,7 and Srinivasu.8

2 Tom R. Walters, Development and Use of Brimonidine in Treating Acute
and Chronic Elevations of Intraocular Pressure: A Review of Safety,
Efficacy, Dose Response, and Dosing Studies, 41 SURVEY OF
OPHTHALMOLOGY, SUPPL. 1, S19-26 (1996).
3 Robichaud et al., US 6,610,720 B2, Aug. 26, 2003.
4 David D. Kim, A Case of Suspected Alphagan-Induced Psychosis, 118
ARCH. OPHTHALMOL. 1132-1133 (2000).
5 Laura B. Enyedi, et al., Safety and Efficacy of Brimonidine in Children
with Glaucoma, 5 JOURNAL OF AAPOS 281-284 (2001).
Appeal 2010-003330
Application 10/354,173

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The Examiner finds that Walters discloses “the treatment of …
glaucoma … via ocular administration of brimonidine tartrate drops”
(Answer 6). The Examiner finds that Kim, Enyedi, and Carlsen disclose that
brimonidine is “able to reach the CNS rapidly after intraocular
administration” (id.) and that Robichaud discloses “brimonidine could also
be used to treat migraines” (id.). The Examiner concludes that it “would
have been obvious to one of skill in the art … to use Walters’ method to
treat migraines responsive to brimonidine … because the art teaches that
delivery to the CNS via the ocular route is facile and rapid” (id. at 6-7). The
Examiner finds that the limitation of a “brisk direct non-systemically
mediated, and non-axonal ocular route of drug delivery” is inherent to the
method suggested by the references because “all that is required to achieve
such is to intraocularly administer brimonidine” (id. at 7).
Appellant contends that the references do not teach “direct, non-
systemic, eye-brain drug delivery” because Carlsen, Kim, and Enyedi do not
report “direct delivery of brimonidine from the eye to the brain, without
passing through the systemic blood circulation” (Appeal Br. 13-14;9 First
Supplemental Appeal Br. 1110).

6 A. Pradalier et al., Migraine and Glaucoma: an epidemiologic survey of
French ophthalmologists, 18 CEPHALALGIA 74-76 (1998).
7 Jeffrey O. Carlsen et al., Apparent Central Nervous System Depression in
Infants After the Use of Topical Brimonidine, 128 AMERICAN JOURNAL OF
OPHTHALMOLOGY NO. 2, 255-256 (1999).
8 P. Srinivasu et al. Lack of pharmacokinetic interaction between
sumatriptan and naproxen, 40 J. CLIN. PHARMACOL. NO. 1, 99-104 (2000).
9 Appeal Brief filed Dec. 20, 2007.
10 Supplemental Appeal Brief filed February 20, 2008.
Appeal 2010-003330
Application 10/354,173

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The issue presented in this appeal is: Does the evidence of record
support the Examiner’s conclusion that the references suggest treating
migraine symptoms by administering brimonidine via a “brisk direct non-
systemically mediated, and non-axonal ocular route of drug delivery?”
Findings of Fact
1. The Specification does not define the phrase “brisk direct non-
systemically mediated, and non-axonal ocular route of drug delivery.”
2. The Specification states that “according to preferred embodiments
of the present invention, the ocular route of drug delivery is selected from
the group consisting of eye-drops, suspensions, ointments, gels, hydrogels
and viscosified solution systems, gel-forming systems, lotions, sprays,” etc.
(Spec. 4).
3. Walters discloses “brimonidine tartrate, an α2-adrenoceptor
agonist, for treating chronically elevated intraocular pressure” (Walters,
abstract).
4. Walters discloses that the brimonidine was administered to the
subjects’ eyes (id. at S20).
5. Robichaud discloses that “[a]lpha-2 adrenergic agonists are useful
for treating a variety of disorders including: … migraine” (Robichaud, col.
1, ll. 21-30).
6. Robichaud discloses that “representative alpha-2 adrenergic
agonists [include]: imino-imidazolines, including … brimonidine” (id. at col.
4, ll. 32-36).
7. Kim discloses that brimonidine tartrate is used to treat glaucoma
(Kim, 1132).
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Application 10/354,173

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8. Kim discloses that brimonidine tartrate “is a lipid-soluble agent
that can cross the blood-brain barrier and can have, in theory, some
psychoactive properties” (id.).
9. Kim reports “acute psychosis and delirium in a patient receiving
brimonidine…, which resolved immediately after cessation of the agent”
(id.). The patient was a 68-year-old man (id.).
10. Enyedi discloses brimonidine tartrate for the treatment of
glaucoma (Enyedi, abstract).
11. Enyedi discloses that “brimonidine passes through the blood-
brain barrier, potentially causing central nervous system (CNS) toxicity”
(id.).
12. Enyedi discloses that “[b]rimonidine should be used with caution
in young children because of the potential for CNS depression” (id.).
13. Carlsen discloses brimonidine tartrate for the treatment of
glaucoma (Carlsen, 255).
14. Carlsen discloses that “[b]ecause brimonidine is a highly
lipophilic drug, it is readily absorbed through the cornea. It also passes
through the blood-brain barrier with relative ease and has potential for
central nervous system toxicity” (id.).
15. Carlsen reports “two cases in which topical brimonidine resulted
in apparent central nervous system depression and unresponsiveness in an
infant” (id., abstract).
16. Carlsen discloses that Alphagan is a known topical brimonidine
tartrate ophthalmic solution (id. at 255).
Appeal 2010-003330
Application 10/354,173

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Principles of Law
“After a prima facie case of obviousness has been established, the
burden of going forward shifts to the applicant. Rebuttal is merely a
‘showing of facts supporting the opposite conclusion,’ and may relate to any
of the Graham factors including so-called secondary considerations. If
rebuttal evidence of adequate weight is produced, the holding of prima facie
obviousness, being but a legal inference from previously uncontradicted
evidence, is dissipated.” In re Piasecki, 745 F.2d 1468, 1472 (Fed. Cir.
1984) (citations omitted).

Analysis
Claim 38 is directed to a method for treating migraine symptoms by
administering alpha-2 adrenoreceptor agonists by “brisk direct non-
systemically mediated, and non-axonal ocular route of drug delivery.”
The Specification does not define the above-quoted limitation, but
states that a preferred embodiment of the disclosed method is to administer
an alpha-2 adrenoreceptor agonist via eye drops. We therefore interpret a
“brisk direct non-systemically mediated, and non-axonal ocular route of
drug delivery” to encompass administration via eye drops.
Robichaud discloses that alpha-2 adrenergic agonists, including
brimonidine, are useful for treating migraine. Walters discloses that
brimonidine, an alpha-2 adrenoreceptor agonist, is a known treatment for
glaucoma that is administered to the eye (ocular administration). Carlsen
discloses that brimonidine is readily absorbed through the cornea, and
Carlsen, Kim, and Enyedi all disclose that brimondine passes through the
blood-brain barrier and can affect the central nervous system. In view of
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Application 10/354,173

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these disclosures, it would have been obvious to one of ordinary skill in the
art to apply brimonidine to the eye to treat migraine symptoms, with a
reasonable expectation that the brimondine would be absorbed through the
cornea and affect the central nervous system to alleviate migraine symptoms.
Appellant argues that Carlsen, Kim and Enyedi do not disclose direct,
non-systemic, eye-brain drug delivery (Appeal Br. 13-14). Appellant argues
that these references “report cases of brimonidine toxicity to infants and
young children. Non[e] of them is claiming that the toxic effects of ocular
dose of brimonidine on the brain was caused by direct delivery of
brimonidine from the eye to the brain, without passing through the systemic
blood circulation” (id. at 14).
This argument is not persuasive. The claimed method requires ocular
delivery of an alpha-2 adrenoreceptor agonist (e.g., brimonidine) to treat
migraines. The cited references suggest the ocular delivery of brimonidine
to treat migraines. Thus the claimed method and the method suggested by
the references are the same. As recognized by the Examiner (Answer 7), the
limitation “brisk direct non-systemically mediated, and non-axonal ocular
route of drug delivery” is inherent to the method suggested by the references
because the Specification discloses that one method of achieving such
delivery is by administering brimonidine in the form of eye drops.
Appellant also argues that “the target tissue of Walters’ method is the
ciliary-body, which is an intraocular tissue in the anterior segment of the
eye” (Appeal Br. 12), while the claimed method targets the brain, and “the
accumulation of this molecule in the desired target tissue with minimal
accumulation in the other tissues can be easily achieved by choosing the
suitable excipients” (id.).
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This argument is not persuasive. Claim 38 does not require any
specific formulation for brimonidine delivery, and Example 3 of the
Specification describes the analysis of brimonidine delivery in the rabbit
brain after delivery of H3-Alphagan to the rabbit eye (Spec. 11). Carlsen
discloses that Alphagan is a known topical brimonidine tartrate ophthalmic
solution. Thus, the claims are reasonably interpreted to encompass
administration of known formulations of brimonidine to the eye.
Appellant also argues that Pradalier’s disclosure that migraines are
associated with glaucoma would not have been accepted by those of
ordinary skill in the art (Appeal Br. 7-10).
This argument is not persuasive. As the Examiner noted, Robichaud
discloses that “brimonidine could also be used to treat migraines” (Answer
6) and the references together suggest treating migraine symptoms by ocular
administration of brimonidine “because the art teaches that brimonidine can
rapidly reach the CNS after local eye administration and because the art
teaches that brimonidine can be successfully used to treat migraines” (id. at
7). The cited references therefore would have made obvious the claimed
method whether or not the skilled worker would have recognized an
association between glaucoma and migraines.
Finally, Appellant argues that claims 87-89 and 93 would not have
been obvious because Carlsen, Kim, and Enyedi “report phenomena that are
unique to infants and very young children, and the one of skill in the art
would not be able to extrapolate what would be assumed to be happening in
older children and adults” (First Suppl. Appeal Br. 14-15).
This argument is also not persuasive. Kim reports that brimonidine
had central nervous system effects in a 68 year old man after ocular
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Application 10/354,173

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administration. Based on Kim, a skilled worker would reasonably expect
ocular administration of brimonidine to affect the central nervous system to
alleviate migraine symptoms in adults and older children as well as in
infants.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that the
references suggest treating migraine symptoms by administering
brimonidine via a “brisk direct non-systemically mediated, and non-axonal
ocular route of drug delivery.”
SUMMARY
We affirm the rejection of claims 38, 39, 42, 45-47, 50, 64, 75, 77, 87-
89, 93-96, and 99-105 under 35 U.S.C. § 103(a).
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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EDWARD LANGER
C/O SHIBOLETH YISRAELI ROBERTS, ZISMAN & CO.
60TH FLOOR
350 FIFTH AVE.
NEW YORK NY 10118