Ex Parte Gil et al

Board of Patent Appeals and Interferences

Oct 9, 2009

10607439 (B.P.A.I. Oct. 9, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________________

Ex parte DANIEL W. GIL,
SCOTT WHITCUP, MITCHELL F. BRIN, and
JOHN E. DONELLO,
Appellants
____________________

Appeal 2009-012,867
Application 10/607,4391
Technology Center 1600
____________________

Decided: October 9, 2009
____________________

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

SPIEGEL, Administrative Patent Judge.

DECISION ON APPEAL
Appellants appeal under 35 U.S.C. § 134 from an Examiner's rejection
of claims 17, 19, and 22, all of the pending claims. We have jurisdiction
under 35 U.S.C. § 134. We AFFIRM.

1 Application 10/607,439 ("the 439 application," the disclosure of which is
cited herein as "Spec."), Methods of preventing and reducing the severity of
stress-associated conditions, was filed 25 June 2003. The real party in
interest is ALLERGAN, INC. (Appeal Brief filed 26 August 2008 ("Br.") at
2).
Appeal 2009-012,867
Application 10/607,439

2
I. Statement of the Case
The subject matter on appeal is directed to methods of preventing or
reducing the severity of sensory hypersensitivity associated with migraine,
e.g., nausea, photophobia, and phonophobia, comprising systemically
administering an effective amount of brimonidine (Spec. 2:1-15; 22:5-
23:23). Claim 17 is illustrative and reads (Br. 18):
17. A method of preventing or reducing the
severity of sensory hypersensitivity associated
with migraine, the method comprising systemically
administering to a subject in need of such
prevention or reduction an effective amount of
brimonidine or a pharmaceutically acceptable salt,
ester, amide, sterioisomer [sic] or racemic mixture
thereof.
The Examiner rejected claims 17, 19, and 22 as unpatentable under 35
U.S.C. § 103(a) as obvious over Abdulrazik,2 Gil,3 and Saunders4 (Ans.5 7).
The Examiner rejected claims 17, 19, and 22 as unpatentable under 35
U.S.C. § 112, first paragraph (enabled for reducing but not preventing the
severity of sensory hypersensitivity) (Ans. 3).

2 U.S. Patent Application Publication US 2003/0181354 A1, Method for
Central Nervous System Targeting through the Ocular Route of Drug
Delivery, published 25 September 2003, based on application 10/354,173,
filed 30 January 2003, by Muhammad Abdulrazik ("Abdulrazik").
3 International Patent Application Publication WO 03/099289 A2, Novel
Methods and Compositions for Alleviating Pain, published 4 December
2003, based on U.S. Patent Application 10/153,154, filed 21 May 2002, by
Gil et al. ("Gil").
4 SAUNDERS MANUAL OF MEDICAL PRACTICE, W.B. Saunders
Company 1032-33 (1996) ("Saunders").
5 Examiner's Answer mailed 31 March 2009 ("Ans.").
Appeal 2009-012,867
Application 10/607,439

3
Appellants have not separately argued any particular claim on appeal.
Therefore, we decide this appeal on the basis of claim 17. 37 C.F.R.
§41.37(c)(1)(vii).
II. Obviousness
A. The Examiner's position
The Examiner found that Abdulrazik reports that a patient with a
history of migraine reported a substantial relief of migraine related
symptoms after topical treatment with a composition containing brimonidine
(Ans. 7). Acknowledging that Abdulrazik does not teach administering the
composition systemically or expressly teach relieving a sensory
hypersensitivity migraine symptom, the Examiner found that Gil teaches
systemic, e.g., oral and intravenous, administration of a composition
containing brimonidine and a selective α-2A antagonist for relieving
headache pain and that Saunders teaches that the symptoms associated with
migraine include photophobia and visual aura (Ans. 7-8). The Examiner
concluded that it would have been obvious to treat sensory hypersensitivity
associated with migraine, e.g., photophobia and visual aura as taught by
Saunders, by systemically administering a composition containing
brimonidine because Abdulrazik teaches that compositions containing
brimonidine relieve symptoms associated with migraine and Gil teaches that
brimonidine can be administered systemically (Ans. 8).
B. Appellants' position
Appellants argue that since Abdulrazik fails to disclose which
migraine symptoms were relieved with topical brimonidine, sensory
hypersensitivity symptoms may not have been treated, i.e., the Examiner has
failed to articulate a reason for combining the teachings of Abdulrazik and
Appeal 2009-012,867
Application 10/607,439

4
Saunders (Br. 14-16). Appellants further argue that the Examiner has failed
to explain why one of ordinary skill in the art would have reasonably
believed that a drug used to treat headaches as taught by Gil would also have
been effective in treating sensory hypersensitivity associated with migraine
(Br. 16-17).
C. Issue
Two questions are at issue. First, have Appellants shown that the
Examiner failed to articulate a reasoned basis for concluding that the
migraine symptoms relieved by topical administration of a composition
containing brimonidine as taught by Abdulrazik included sensory
hypersensitivity? Second, have Appellants shown that the Examiner erred in
concluding that effective treatment of headaches by systemic administration
of a composition containing brimonidine as taught by Gil provides a
reasonable basis for believing that systemic administration of a composition
containing brimonidine would have been effective to treat sensory
hypersensitivity associated with migraine?
D. Findings of fact ("FF")
The following facts are supported by a preponderance of the evidence
of record.
[1] Abdulrazik discloses a method of treating migraines in humans
comprising ocular administration of an effective amount of a
composition comprising an established anti-migraine therapeutic
agent in combination with the α2-adrenoreceptor agonist brimonidine
(Abdulrazik ¶¶ 35-36).
[2] Abdulrazik Example 1 reports that a patient with a history of migraine
reported a substantial relief of migraine related symptoms following
Appeal 2009-012,867
Application 10/607,439

5
the prescription of brimonidine tartrate 0.2% as a third topical
antiglaucoma agent for the left eye (Abdulrazik ¶ 53).
[3] While specific symptoms often vary with the specific type of migraine
headache, Saunders identifies visual aura; deep, throbbing headache;
and, nausea and photophobia as key symptoms of migraine headaches
(Saunders 1032, col. 1, Symptoms).
[4] According to Saunders, migraine is treated by a combination of
medication, diet, activity, and patient education (Saunders 1033, col.
1, Treatment).
[5] Specifically, drug treatment of migraine headache involves a three-
sided approach: abortive (at the immediate onset of the headache),
interval (during the headache), and prophylactic (to prevent the
headache) (Saunders 1033, col. 1, Medication).
[6] In particular, prophylactic therapy, with drugs such as ß-blockers,
calcium channel blockers, and selective serotonin-reuptake inhibitors,
is used to prevent or reduce the frequency and/or severity of migraines
(Saunders 1033, col. 1, Medication).
[7] Gil discloses a method of alleviating chronic pain, including headache
pain, by peripheral, either local or systemic, administration of a
composition containing effective amounts, generally in the range of
0.1-1,000 mg/day, of an α-adrenergic agonist, such as brimonidine,
and a selective α-2A antagonist, such as a 4-imidazole (Gil abstract;
3:4-4:5; 52:1-9; 52:19-53:2; 53:25-26).
E. Legal principles
An invention is obvious if "the differences between the subject matter
sought to be patented and the prior art are such that the subject matter as a
Appeal 2009-012,867
Application 10/607,439

6
whole would have been obvious . . . to a person having ordinary skill in the
art to which said subject matter pertains." 35 U.S.C. § 103. The factual
inquiries underlying obviousness include (1) the scope and content of the
prior art, (2) the differences between the prior art and the claims at issue, (3)
the level of ordinary skill in the art at the time the invention was made, and
(4) any objective evidence of nonobviousness. Graham v. John Deere Co.,
383 U.S. 1, 17-18 (1966). “The consistent criterion for determination of
obviousness is whether the prior art would have suggested to one of ordinary
skill in the art that this process should be carried out and would have a
reasonable likelihood of success, viewed in the light of the prior art.” In re
Dow Chem. Co., 837 F.2d 469, 473 (Fed. Cir. 1988). "Obviousness does not
require absolute predictability of success . . . all that is required is a
reasonable expectation of success." In re O'Farrell, 853 F.2d 894, 903-04
(Fed. Cir. 1988). In determining whether obviousness is established by
combining the teachings of the prior art, “the test is what the combined
teachings of the references would have suggested to those of ordinary skill
in the art.” In re Keller, 642 F.2d 413, 425 (CCPA 1981).
F. Analysis
Saunders' teaching that sensory hypersensitivity, such as photophobia
and visual aura, is a key symptom of migraine headaches (FF 3) together
with Abdulrazik's teaching that a patient with a history of migraine reported
substantial relief of his migraine symptoms following ocular administration
of a composition comprising brimonidine (FF 1-2) reasonably suggests that
the migraine symptoms relieved included sensory hypersensitivity, such as
photophobia or visual aura. Thus, the Examiner reasonably combined a
teaching of relieving migraine symptoms (Abdulrazik) with a teaching of
Appeal 2009-012,867
Application 10/607,439

7
the key symptoms of migraine, e.g., photophobia (Saunders), especially in
view of Abdulrazik's teaching that the other two therapeutic agents
administered to the patient were also administered to his eye (FF 2).
Appellants' argument that Abdulrazik fails to teach which migraine
symptoms were relieved with topical administration of a brimonidine-
containing composition fails to demonstrate reversible error because it
attacks the references individually and does not explain why the combined
teachings do not suggest the claimed method to those of ordinary skill in the
art. Keller, 642 F.2d at 425.
Furthermore, Gil teaches that compositions containing an effective
amount of brimonidine may be peripherally, i.e., systemically or locally,
administered to relieve chronic pain, including headaches (FF 7), thereby
providing a reasonable basis for concluding that the locally administered
brimonidine-containing composition of Abdulrazik would have been
effective in relieving migraine headache pain if administered systemically.
Again, Appellants' second argument fails to demonstrate reversible error
because it does not explain why the combined teachings of Abdulrazik and
Gil do not suggest the claimed method to those of ordinary skill in the art.
G. Conclusion
Based on the foregoing, we sustain the rejection of claims 17, 19, and
22 under § 103 as obvious over the combined teachings of Abdulrazik, Gil,
and Saunders. Appellants have failed to show that the Examiner did not
have a reasoned basis for concluding that the migraine symptoms relieved by
administration of the brimonidine-containing composition of Abdulrazik
included sensory hypersensitivity. Appellants have also failed to show that
successful treatment of headache by systemic administration of a
Appeal 2009-012,867
Application 10/607,439

8
brimonidine-containing composition as taught by Gil fails to provide a
reasonable basis for believing that systemic administration of the
brimonidine-containing composition of Abdulrazik would have been
effective.
III. Scope of Enablement
A. The Examiner's position
According to the Examiner, the specification is enabling for treatment,
but not prevention, of the severity of sensory hypersensitivity associated
with migraine (Ans. 3-4, 10). Citing to the Merck Manual,6 the Examiner
interprets "prevention" to include "prophylaxis" which encompasses the
actual prevention of migraine symptoms having no known cause (Ans. 10).
The Examiner finds that decreasing the frequency of the symptoms, rather
than absolute prevention as claimed, is the best prophylactic treatment
known (Ans. 5). The Examiner further finds that actual prevention of the
severity of a stress-associated condition is extremely complex and that all of
the guidance provided in the specification is limited to reducing, rather than
to preventing, the severity of the symptoms (Ans. 4-5). In short, the
Examiner finds that it would require undue experimentation (e.g., testing one
combination of compound dosage, pharmaceutical carrier, administration
route, and appropriate animal model after another until a combination
effective to prevent a sensory hypersensitivity associated with migraine is
found) to enable the claimed method of preventing the severity of sensory
hypersensitivity associated with migraine because Appellants have not

6 THE MERCK MANUAL, sixteenth edition, Berkow et al., eds., Merck
Research Laboratories, 1425-1426 (1992) ("the Merck Manual").
Appeal 2009-012,867
Application 10/607,439

9
presented any means by which the identity of the factor that causes the
migraine might be identified (Ans. 6 and 10-11).
B. Appellants' position
Appellants argue that requiring enablement for "absolute prevention"
is too harsh a standard for enablement (Br. 8). "[T]he Merck Manual refers
to decreasing the frequency of attacks as a species of prophylaxis. If
'preventing,' or to use the medical term, 'prophylaxis,' encompasses a
'decrease in frequency,' then 'prevention' can mean something that is short of
absolute success" (Br. 10). According to Appellants, the Merck Manual
evidences that means for decreasing the frequency of migraine attacks are
known, i.e., the state of the prior art of migraine prophylaxis is a developed
one (Br. 10) and Saunders teaches that prophylactic therapy is used to
prevent or reduce the frequency and/or severity of migraines (id. 11).
Appellants further argue that since the specification does not distinguish
between the steps required for prevention or reduction of the severity of
sensory hypersensitivity associated with migraine, if one method is enabled,
the other one is as well (Br. 11). Appellants point out that one need not wait
for sensory hypersensitivity to occur before treating it any more than one
need wait for a headache to occur before taking aspirin will have any effect
(Br. 12).
C. Issue
At issue is whether Appellants have shown that the Examiner erred in
concluding that the specification fails to enable a method of preventing the
severity of sensory hypersensitivity associated with migraine as claimed.

Appeal 2009-012,867
Application 10/607,439

10
D. Additional findings of fact
[8] The 439 application describes a method of preventing or reducing the
severity of a stress-associated condition, such as sensory
hypersensitivity associated with migraine occurring prior to, during,
or subsequent to migraine headache, by systemic administration of an
effective amount of brimonidine (Spec. 2:2-15; 22:5-23:23).
[9] The 439 application defines "an effective amount" as the minimum
dose necessary to achieve the desired prevention or reduction in
severity of one or more symptoms to tolerable levels, generally in the
range of 0.1-1000 mg/day (Spec. 31:28 - 2:15).
[10] According to the Merck Manual, the cause of migraine is unknown
but its mechanism is believed to be related to episodic reductions in
systemic serotonin concentrations, which in turn lead to vasomotor
changes (the Merck Manual 1425 ¶ 5).
[11] According to the Merck Manual, the most effective prophylaxis is
supportive counseling, but propanolol 20 to 40 mg orally three times a
day offers long term relief in about half the patients (the Merck
Manual 1426 ¶¶ 2-3).
E. Legal principles
“[T]o be enabling, the specification . . . must teach those skilled in the
art how to make and use the full scope of the claimed invention without
‘undue experimentation.’” In re Wright, 999 F.2d 1557, 1561 (Fed. Cir.
1993). “When rejecting a claim under the enablement requirement of
section 112, the PTO bears an initial burden of setting forth a reasonable
explanation as to why it believes that the scope of protection provided by
Appeal 2009-012,867
Application 10/607,439

11
that claim is not adequately enabled by the description of the invention
provided in the specification of the application . . . .” Id. at 1561-1562.
“That some experimentation may be required is not fatal; the issue is
whether the amount of experimentation required is ‘undue.’” In re Vaeck,
947 F.2d 488, 495 (Fed. Cir. 1991) (emphasis in original).
F. Analysis
Here, the 439 specification describes preventing or reducing the
severity of sensory hypersensitivity associated with migraine occurring prior
to migraine headache by systemic administration of a composition
containing an effective amount of brimonidine (FF 8). The 439 specification
explicitly defines what an effective amount of brimonidine means, i.e.,
generally in the range of 0.1 to 1,000 mg/day (FF 9). Thus, the 439
specification provides express guidance as to dosage amounts and
administration routes. Moreover, the prior art recognizes that prophylactic
therapy entails preventing the migraine headache and its associated
symptoms (FF 5). In addition, while the cause of migraine is unknown (FF
10), both its mechanism of action and medications useful in preventing or
reducing the frequency and/or severity of migraines are known in the prior
art (FF 5, 6, 10, and 12). Thus, the disclosure of the 439 specification,
combined with the prior art, reasonably teaches a skilled artisan how to
make and use even a composition comprising a combination of brimonidine
and another therapeutic agent. In short, the Examiner has failed to provide
evidence establishing that it is necessary to identify the actual causes of a
migraine before its symptoms can be successfully prevented; and, therefore,
why it would require undue experimentation to practice the claimed method
of preventing the severity of sensory hypersensitivity associated with
Appeal 2009-012,867
Application 10/607,439

12
migraine given the disclosure of the 439 specification and the state of the
prior art.
G. Conclusion
Based on the foregoing, we reverse the rejection of claims 17, 19, and
22 under § 112, first paragraph. Appellants have shown that the Examiner
erred in concluding that the specification fails to enable a method of
preventing the severity of sensory hypersensitivity associated with migraine
as claimed.
IV. Order
Upon consideration of the record, and for the reasons given, it is
ORDERED that the decision of the Examiner to reject claims 17, 19,
and 22 as unpatentable under 35 U.S.C. § 103(a) as obvious over
Abdulrazik, Gil, and Saunders is AFFIRMED;
FURTHER ORDERED that the decision of the Examiner to reject
claims 17, 19, and 22 as unpatentable under 35 U.S.C. § 112, first paragraph
(lacking enablement for the full scope of the claimed invention) is
REVERSED; and,
FURTHER ORDERED that no time period for taking any subsequent
action in connection with this appeal may be extended under 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED

KMF

ALLERGAN, INC.
2525 Dupont Drive, T2-7H
Irvine, CA 92612-1599

Appeal 2009-012,867
Application 10/607,439

13