Ex Parte Hughes et al

Board of Patent Appeals and Interferences

Nov 2, 2010

11416929 (B.P.A.I. Nov. 2, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte PATRICK M. HUGHES,
JAMES A. BURKE, and JOAN-EN CHANG-LIN
__________

Appeal 2010-007469
Application 11/416,929
Technology Center 1600
__________

Before DONALD E. ADAMS, LORA M. GREEN, and
STEPHEN WALSH, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL1
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s rejection of claims 1, 2, 8, 12-16, and 34. We have jurisdiction
under 35 U.S.C. § 6(b).

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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STATEMENT OF THE CASE
Claim 1 is the only independent claim on appeal, and reads as follows:
1. An ophthalmically therapeutic material, comprising:
a therapeutic component comprising a therapeutically effective
amount of an alpha 2 adrenergic receptor agonist having a structure effective
in providing elimination of the agonist from the anterior chamber of an eye
to which the agonist is administered.

The following grounds of rejection are before us for review:
I. Claims 1, 2, 8, 12-16, and 34 stand rejected under 35 U.S.C.
§ 112, first paragraph, as failing to comply with the written
description requirement.
II. Claims 1, 2, 8, 12-16, and 34 stand rejected under 35 U.S.C.
§ 102(b) as being anticipated by Dean.2
We reverse.
ISSUE I
Has the Examiner established by a preponderance of the evidence that
the Specification fails to provide written descriptive support for the claims
on appeal?

FINDINGS OF FACT
FF1 The Specification teaches that the “present invention generally relates
to the use of alpha-2 adrenergic receptor agents that are cleared from the
anterior of an eye to treat an eye of a patient.” (Spec. 1.)
FF2 The Specification teaches further:

2 Dean, US 6,242,442 B1, issued June 5, 2001.
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Agents that are administered to the vitreous of an eye of a
patient can be eliminated from the vitreous by diffusion to the
retro-zonular space (anterior clearance) with clearance via the
aqueous humor, such as through the trabecular meshwork
outflow and the uveoscleral outflow, or by trans-retinal
elimination (posterior clearance). Most compounds that are
relatively hydrophilic to moderately lipophilic utilize the former
(anterior clearance) pathway unless a facilitated or active
transport mechanism exists for these while extremely lipophilic
compounds and those with trans-retinal transport mechanisms
will utilize the latter (i.e., will go out through the retina). For
example, macromolecules and peptides, including antibiotics,
are often eliminated via the anterior route. In comparison,
existing alpha 2 adrenergic receptor agonists are eliminated
via the posterior route. This is most likely the result of an
organic cationic transport mechanism in the outer blood retinal
barrier, the RPE. Unfortunately, compounds that are eliminated
across the retina have extremely short intravitreal half-lives.
Additionally, these compounds tend to have extremely small
aqueous humor/vitreous humor concentration ratios at
steadystate. This dramatically impacts the treatment of anterior
tissues from posterior administration of such compounds.

(Id. at 2-3 (emphasis added).)
FF3 The Specification teaches that “[t]wo examples of alpha agonists used
for ocular therapy include apraclonidine (IOPIDINE) and brimonidine-P
(ALPHAGAN-P).” (Id. at 1.)
FF4 According to the Specification:
[T]he therapeutic component of the present materials may
comprise a modified or engineered alpha-2 adrenergic agonist.
For example, the modified or engineered alpha-2 adrenergic
agonist may comprise a base structure effective in interacting
with or activating an alpha-2 adrenergic receptor, and a bulking
agent or modifier component associated with the base structure
to provide an enhanced anterior clearance relative to an
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identical base structure without the bulking agent or modifier
component. The bulking agent or modifier component may be
coupled to or covalently bonded with the base structure. For
example, the bulking agent or modifier component may be
directly covalently bonded to the base structure, or it may be
indirectly coupled to the base structure via one or more linking
agents. The bulking agent or modifier component can alter the
hydrophilicity or lipophilicity of the base structure to achieve
the desired anterior clearance. Preferably, the bulking agent or
modifier component does not substantially interfere with the
base structure’s interaction with an alpha-2 adrenergic receptor.

(Id. at 12.)
FF5 The Specification teaches that the alpha-2 adrenergic receptor agonist
may be coupled to polyethylene glycol, or may include one or more
lipophilic components. (Id. at 13.) The Specification provides the example
of a brimonidine base structure coupled to or associated with a polyethylene
glycol. (Id. at 14.)
FF6 The Specification also teaches that the alpha-2 adrenergic receptor
agonist may be modified such that they are not a substrate for the organic
cation transporter present in the conjunctiva, such as by using a N-Mannich
base or sulfonyl prodrug. (Id. at 15.) The Specification also provides
examples of such alpha-2 adrenergic receptor agonists. (See Spec. 16-18.)
FF7 The Specification teaches further that the “the alpha 2 adrenergic
receptor agonists of the present therapeutic components can be identified by
screening the agents for the desired pharmacokinetic properties, such as
vitreal half-life, aqueous humor/vitreous humor concentration ratios, and the
like.” (Id. at 14.)
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FF8 In Example 1 of the Specification, the intravitreal clearance of
brimonidine was examined. (Id. at 47.) The Specification concludes that
“brimonidine is eliminated from the vitreous by a trans-retinal route,”
demonstrating that “hydrophilic to moderately lipophilic alpha 2 adrenergic
receptor agonists having a trans-retinal route of clearance from the posterior
segment of the eye, cannot be effectively delivered to the anterior and/or
posterior chambers of the eye via intravitreal administration.” (Id.)
FF9 The Examiner’s statement of the rejection may be found at pages 3-4
of the Answer.
FF10 Specifically, the Examiner finds that “[w]hile some examples of such
structures effective in providing elimination of the agonist from the anterior
chamber of an eye are put forth, the other effective structures fail to meet the
written description provision of 35 USC § 112, first paragraph, due to
lacking information for what they are and highly variant and encompass a
myriad of possibilities.” (Ans. 4.)

PRINCIPLES OF LAW
“The function of the description requirement is to ensure that the
inventor had possession, as of the filing date of the application relied on, of
the specific subject matter later claimed by him.” In re Edwards, 568 F.2d
1349, 1351-52 (CCPA 1978). To comply with the written description
requirement, the Specification must “convey with reasonable clarity to those
skilled in the art that, as of the filing date sought, [the inventor] was in
possession of the invention.” Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555,
1563-64 (Fed. Cir. 1991).
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[T]he determination of what is needed to support generic
claims to biological subject matter depends on a variety of
factors, such as the existing knowledge in the particular field,
the extent and content of the prior art, the maturity of the
science or technology, the predictability of the aspect at issue,
and other considerations appropriate to the subject matter.

Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005).

ANALYSIS
Appellants argue that the Examiner admits that the Specification
discloses several structures and modifications, such as the use of bulking
agents, polyethylene glycol, and lipophilic compounds, as well as providing
examples of prodrugs that have been modified so that they are not substrates
for organic cation transporters. (App. Br. 5.) Appellants also argue that the
Specification discloses methods to identify an alpha 2 adrenergic receptor
agonist having a structure effective in providing elimination of the agonist
from the anterior chamber of the eye. (Id.) Thus, Appellants assert, the
Specification provides written descriptive support for the appealed claims.
(Id.)
We agree with Appellants. That is, we find that the Examiner has not
explained why the examples in the Specification are not sufficient to
describe the claimed genus. Therefore, we are compelled to reverse the
rejection.

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CONCLUSION OF LAW
We conclude that the Examiner has not established by a
preponderance of the evidence that the Specification fails to provide written
descriptive support for the claims on appeal. We thus reverse the rejection
of claims 1, 2, 8, 12-16, and 34 under 35 U.S.C. § 112, first paragraph, as
failing to comply with the written description requirement.

ISSUE II
Has the Examiner established by a preponderance of the evidence that
brimonidine, a relatively selective alpha-2 adrenergic receptor agonist, as
taught by a Dean, has a structure effective in providing elimination of the
agonist from the anterior chamber of the eye?

FINDINGS OF FACT
FF11 The Examiner’s statement of the rejection may be found at pages 4-6
of the Answer.
FF12 Specifically, the Examiner finds that Dean teaches an ophthalmically
therapeutic material comprising brimonidine, a relatively selective alpha-2
adrenergic receptor agonist. (Ans. 5.)
FF13 As to Example 1, the Examiner finds that the “example does not
provide evidence that brimonidine does not have the function required by
claim 1 of being eliminated from the anterior chamber of an eye to which the
agonist was administered,” as a “showing that the drug is eliminated by a
trans-retinol route does not preclude elimination of the drug from the
anterior chamber or other routes.” (Id. at 11.)
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PRINCIPLES OF LAW
In order for a prior art reference to serve as an anticipatory reference,
it must disclose every limitation of the claimed invention, either explicitly or
inherently. In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997). In
general, a limitation is inherent if it is the “natural result flowing from” the
explicit disclosure of the prior art. Schering Corp. v. Geneva Pharms., Inc.,
339 F.3d 1373, 1379 (Fed. Cir. 2003). “Inherency . . . may not be
established by probabilities or possibilities. The mere fact that a certain
thing may result from a given set of circumstances is not sufficient.”
MEHL/Biophile Int'l. Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir.
1999)( quoting In re Oelrich, 666 F.2d 578, 581 (CCPA 1981)).

ANALYSIS
We begin with claim interpretation. The Examiner notes that in an
election of species requirement, Appellants elected “brimonidine,” and that
there “was no indication in the species election that the agonist was being
elected merely as a ‘base component.’” (Ans. 10.) The Examiner further
asserts that the “language regarding the ‘base structure’ was introduced into
the claims with the amendment filed July 21, 2008.” (Id.)
We conclude that is not controlling on the analysis. Original claim 1
read:
An ophthalmically therapeutic material, comprising:
a therapeutic component comprising a therapeutically effective amount of an
alpha 2 adrenergic receptor agonist having a structure effective in providing
elimination of the agonist from the anterior chamber of an eye to which the
agonist is administered.
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When read in light of the Specification, the ordinary artisan would
have understood that an “alpha 2 adrenergic receptor agonist having a
structure effective in providing elimination of the agonist from the anterior
chamber of an eye” to be modified known alpha 2 adrenergic receptor
agonist, such as modified brimonidine.
Citing Example 1 of the Specification (see, e.g., FF8), Appellants
argue that brimonidine does not function according to the claims, that is, it
would not be eliminated anteriorly. (App. Br. 8.) Specifically, Appellants
assert that it is clear to Example 1 “that brimonidine, itself, is cleared
posteriorly.” (Id. at 9.)
We conclude that Appellants have the better position. The
Specification provides evidence that brimonidine is eliminated from the
vitreous of the eye by a trans-retinal route. The Examiner, however, has not
provided any evidence to demonstrate that the ordinary artisan would expect
the brimonidine is also eliminated anteriorly from the eye. We are thus
compelled to reverse the rejection.

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CONCLUSION OF LAW
We conclude that the Examiner has not established by a
preponderance of the evidence that brimonidine, a relatively selective alpha-
2 adrenergic receptor agonist, as taught by a Dean, has a structure effective
in providing elimination of the agonist from the anterior chamber of the eye.
We thus reverse the rejection of claims 1, 2, 8, 12-16, and 34 under 35
U.S.C. § 102(b) as being anticipated by Dean.

REVERSED

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