Ex Parte Huang et al

Board of Patent Appeals and Interferences

Oct 21, 2010

10836911 (B.P.A.I. Oct. 21, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte GLENN T. HUANG, BRITTANY JACKSON,
JAMES A. BURKE, TON LIN, PATRICK M. HUGHES,
LARRY A. WHEELER and ROSY SHENG DONN
____________

Appeal 2010-004999
Application 10/836,911
Technology Center 1600
____________

Before SALLY GARDNER LANE, RICHARD E. SCHAFER, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL1
This is a decision on the appeal under 35 U.S.C. § 134 by the Patent
Applicant from the Patent Examiner’s rejections of claims 12-16, 20, 45, and

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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59-64. The Board’s jurisdiction for this appeal is under 35 U.S.C. § 6(b).
We affirm.

STATEMENT OF THE CASE
The claims are directed to a biodegradable intraocular implant which
comprises brimonidine tartrate, an alpha-2-selective adrenergic receptor
agonist effective in treating open-end glaucoma (Spec. 1:18-21). The
implant provides extended release of the brimonidine when placed in the eye
(id. at 1:12-15.)
Claims 12-16, 20, 45, and 59-64 are pending and appealed. The
claims stand rejected as follows:
Claims 12-16, 20, 59, 61, 63, and 64 under 35 U.S.C. § 103(a) as
obvious in view of Burke,2 Wong3 ‘188, and Oljenik,4 as “evidenced by”
Moshfeghi,5 and Stewart6 (Answer 3); and
Claims 45, 60, and 62 under 35 U.S.C. § 103(a) as obvious in view of
Burke, Wong ‘188, Oljenik, and Wong7 ‘116 as “evidenced by” Moshfeghi
and Stewart (id. at 6).

2 U.S. Pub. No. 2002/0094998 A1 published Jul. 18, 2002.
3 U.S. Patent No. 5,164,188 issued Nov. 17, 1992.
4 U.S. Pub. No. 2002/0032201 A1 published Mar. 14, 2002.
5 Darius M. Moshfeghi, MD et al., Retinal and Choroidal Vascular
Occlusion After Posterior Sub-Tenon Triamcinolone Injection, 134
American Journal of Ophthalmology, 132-134 (2002).
6 William C. Stewart, MD et al., The Efficacy and Safety of Latanoprost
0.005% Once Daily Versus Brimonidine 0.2% Twice Daily in Open-Angle
Glaucoma or Ocular Hypertension, 131 American Journal of
Ophthalmology, 631-635 (2001).
7 U.S. Patent No. 6,369,116 B1 issued Apr. 9, 2002.
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Claim 59 is representative and reads as follows:
A biodegradable intraocular implant comprising
brimonidine tartrate associated with a biodegradable polymer
matrix that releases the brimonidine tartrate at a rate effective to
sustain release of an amount of the brimonidine tartrate from
the implant for a time effective to reduce ocular vascular
occlusion in an eye in which the implant is placed, the time
being at least about one week after the implant is placed in the
eye, wherein the brimonidine tartrate is provided in an amount
of from 10 to 40% by weight of said implant.

OBVIOUSNESS IN VIEW OF BURKE, WONG ‘188, & OLJENIK
Issues
1. Whether persons of ordinary skill in the art would have had reason to
have combined Burke and Wong ‘188 to have made the claimed
biodegradable polymer matrix comprising brimonidine.
2. Whether the cited prior art publications suggest the claimed limitation
that the intraocular implant comprise “brimonidine tartrate . . . in an amount
of from 10 to 40% by weight” of the implant.
3. Whether the evidence of “unexpected results” was sufficient, in view of
the totality of the evidence of record, to overcome the Examiner’s
determination that the claimed invention was obvious.

Principles of Law
When there is a range disclosed in the prior art, and the claimed
invention overlaps or falls within that range, there is a presumption of
obviousness. In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003); Iron
Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004).
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The law is replete with cases in which the difference between
the claimed invention and the prior art is some range or other
variable within the claims. These cases have consistently held
that in such a situation, the applicant must show that the
particular range is critical, generally by showing that the
claimed range achieves unexpected results relative to the prior
art range.
In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990). (Internal citations
omitted.)
“One way for a patent applicant to rebut a prima facie case of
obviousness is to make a showing of ‘unexpected results,’ i.e., to show that
the claimed invention exhibits some superior property or advantage that a
person of ordinary skill in the relevant art would have found surprising or
unexpected. In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995).

Findings of Fact (FF)
The following disclosure appears in Wong ‘188:
1. “Any pharmacologically active agent for which sustained release is
desirable may be employed including drugs, pharmaceutical agents, bacterial
agents, etc.” (Wong ‘188, col. 3. ll. 58-60.)
2. “The amount of agent employed in the implant will vary widely
depending on the effective dosage required and rate of release. Usually the
agent will be from about 1 to 80, more usually 20 to 40 weight percent of the
implant.” (Id. at col. 5, ll. 1-5).
3. “The ratio of agent to polymer will vary with the desired rate of release,
the amount of agent generally varying in the range of 1 to 80 weight percent
of the polymer.” (Id. at col. 5, l. 68-col. 6, l. 3.)
The following disclosure appears in Burke:
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4.
[0036] Another delivery method provides for sustained delivery
of the noeuroprotective [sic] agent using an intraocular implant.
Such implants may be, for example, a biodegradable and/or
biocompatible implant or insert such as the ocular implants and
inserts disclosed in U.S. Pat. Nos. 5,443,505, 5,824,072,
5,766,242; 4,853,224; 4,997,652; 5,164,188 [Wong ‘188];
5,632,984; and 5,869,079, incorporated by reference herein.
Such implants may be inserted into a chamber of the eye, such
as the anterior, posterior or anterior chambers, or may be
implanted in the sclera, transchoroidal space, or an
avascularized region exterior to the vitreous.
5.
[0024] In these methods, the alpha adrenergic receptor agonist
is preferably an alpha 2 selective agonist, even more preferably
an alpha 2B and/or alpha 2C selective agonist, most preferably,
an alpha 2B selective agonist. In one preferred embodiment the
alpha 2 selective agonist is selected from brimonidine and
clonidine.
Analysis
Claim 59 in this appeal is directed to a “biodegradable intraocular
implant comprising brimonidine tartrate associated with a biodegradable
polymer matrix,” where “the brimonidine tartrate is provided in an amount
of from 10 to 40% by weight” of the implant and is “effective to reduce
vascular occlusion in an eye.” The matrix is effective to “sustain release” of
the brimonidine for “at least about one week.”
The Examiner found that Burke described an ocular implant with
brimonidine, but not brimonidine tartrate and not in the recited amount of
10-40% by weight (Answer 3-4). However, the Examiner found that Oljenik
taught brimonidine tartrate and Wong ‘188 taught therapeutic agents in the
same ranges as claimed (id. at 4-5). The Examiner determined it would have
been obvious to modify Burke’s implant with the teachings of Oljenik and
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Wong ‘188 for their expected advantages (id. at 5-6). Because the
Examiner’s reasoning was fact-based and supported by the evidence, we
adopt it as our own.
Issue 1
Appellants contend that persons of ordinary skill in the art would not
have had reason to apply Wong’s ‘188 teachings to Burke.
Wong does not teach that brimonidine may be the active agent.
The Examiner argues, that Wong teaches beta blockers and
therefore this would suggest brimonidine. However,
brimonidine is not a beta blocker. It is an alpha adrenergic.
(App. Br. 11.)
The Examiner did not argue that Wong’s ‘188 teaching of beta-
blockers would suggest brimonidine, an alpha adrenergic drug. Rather, the
Examiner found that “Wong [‘188] teaches that the implant can effectively
delivery any pharmacologically active agent for which sustained release is
desirable.” (Final Rejection 5: ¶ 14.) This finding appears expressly in
Wong’s ‘188 disclosure (FF1). Thus, the Examiner did not err in
characterizing Wong ‘188.
While Appellant is correct that Wong ‘188 does not disclose
brimonidine in its list of drugs at column 4, this omission does not denigrate
the Examiner’s prima facie case of obviousness. The Examiner found that
Burke listed several patents which described intraocular implants that could
be used for sustained delivery of its “neuroprotective agents,” of which
brimonidine was a preferred example of such agents (Answer 5; FF5).
Wong ‘188 is among those list of patents (Answer 5 & 8-9; FF4). Based on
this disclosure, persons of ordinary skill in the art would have been guided
by Burke to utilize Wong ‘188 for sustained release of brimonidine.
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Consequently, the Examiner’s determination that a person of ordinary skill
in the art would have had reason to choose Wong ‘188 as a vehicle for
brimonidine is supported by the evidence.

Issue 2
The drug ranges disclosed in Wong ‘188 overlap with those which are
claimed: 1-80 wt%, “more usually” 20-40 wt% in Wong (FF2) versus 10-40
wt% recited in claim 59. There is a well-established legal presumption that
when a range is disclosed in the prior art, and the claimed invention falls
within that range – as it does here – the claimed range is obvious. In re
Peterson, 315 F.3d at 1329; Iron Grip Barbell, 392 F.3d at 1322. See
Answer 9. Thus, the Examiner properly found that the claimed range is
presumed obvious in view of Wong’s ‘188 overlapping ranges.
Appellant contends:
Due to Wong’s teaching that the amount of agent employed in
the implant will vary widely depending on the effective dosage
required and the rate of release and the fact that Wong does not
recite brimonidine, brimonidine tartrate, or an alpha-2-
adrenergic receptor agonist, a person of ordinary skill in the art
would not have a reasonable expectation of success in creating
an efficacious biodegradable implant incorporating . . .
brimonidine tartrate.
(Reply Br. 2.)
Wong ‘188 explicitly taught that any pharmacologically active agent
could be used in sustained release formulations (FF1). Appellants only
reason for doubting this statement appears to be that Wong ‘188 did not
teach brimonidine or an alpha-2-adrenergic receptor agonist in its implant.
First, we note that the Examiner made an explicit finding that Wong
‘188 described an alpha-2-adrenergic agonist (Answer 9), which Appellants
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had the opportunity to rebut, but did not. Second, Burke taught that Wong
‘188 could be employed as a vehicle for its agents, which included
brimonidine (Answer 10; FF4 (U.S. Pat. No. 5,164,188)). Appellants did
not provide objective evidence to support their position. Consequently, the
totality of the evidence supports the Examiner’s determination that persons
of ordinary skill in the art would have had a reasonable expectation of
success that Wong’s implant could be successfully combined with
brimonidine.
Issue 3
The presumption that a range is obvious can be rebutted with
unexpected results. In re Woodruff, 919 F.2d at 1578. In this case,
Appellants provided evidence, described in the application, that as
shown by the data disclosed in Figure 3, as compared with the
data disclosed in Figure 1, it is found, surprisingly, that
reducing the brimonidine tartrate content of the implant from
50%, by weight, (Figure 1) to a range of from 15 to 25%, by
weight, (Figure 3), results in a sustained release implant. That
is, at 50 %, by weight, brimonidine, there is no sustained
release effect obtained. However, a dramatic change is observed
when the drug load was lowered from 50% down to 25%. That
is, the implant now becomes a sustained release implant.
(App. Br. 11.)
The Examiner found this evidence unpersuasive because “[a]ny
ordinarily skilled person would know and understand that an implant
comprising 50% of a biodegradable polymer with 50% of a drug will have
shorter lifetime than an implant with 70% of a biodegradable polymer with
30% of a drug.” (Answer 11.) In other words, as the Examiner put it, the
“more sustained release polymer contained by an implant, the longer the life
time of the implant will be.” (Id.)
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Appellants contend that the Examiner “cites no source for this
proposition.” (Reply Br. 2). Citing Ex parte Whelan II 8 (Appeal No. 2007-
4423), Appellants contend that when there is a critical property not taught or
appreciated in the prior art, a claimed range is not necessarily anticipated or
made obvious by an overlapping range (id.).
The Examiner’s position is logical. Because the polymer matrix is the
agent responsible for the sustained release of the drug, it was scientifically
reasonable for the Examiner to presume that increasing the amount of
polymer would enhance the drug’s sustained release. This fact is consistent
with Wong’s disclosure that the ratio of agent to polymer will vary with the
desired rate of release (FF3). Appellants have not rebutted the Examiner’s
reasonable presumption which was based on sound scientific reasoning.
Moreover, Appellants did not establish that such results and properties
observed in Figures 1 and 3 of the application (App. Br. 11) would have
been unexpected or surprising to a person of ordinary skill in the art, a
requirement necessary to establish unexpected results. In re Soni, 54 F.3d at
750. Arguments of counsel cannot take the place of evidence lacking in the
record. Estee Lauder Inc. v. L'Oreal, S.A., 129 F.3d 588, 595 (Fed. Cir.
1997).
For the foregoing reasons, we affirm the rejection of claim 59 as
obvious. Claims 12-16, 20, 61, 63, and 64 fall with claim 59 because
separate reasons for their patentability were not provided. 37 C.F.R. §
41.37(c)(1)(vii).

8 A copy of the decision was not provided by Appellants.
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OBVIOUSNESS IN VIEW OF BURKE, WONG ‘188, OLJENIK,
& WONG ‘116
Claims 45, 60, and 62 stand rejected under 35 U.S.C. § 103(a) as
obvious in view of Burke, Wong ‘188, Oljenik, and Wong ‘116, as
“evidenced by” Moshfeghi and Stewart (Answer 6).
The Examiner identified the differences between the subject matter of
claims 45, 60, and 62 and explained why such differences would have been
obvious to persons of ordinary skill in the art in view of the cited prior art
(Answer 6-7). The Examiner’s reasoning is fact-based and sound.
Appellant did not provide sufficient rebuttal arguments or evidence, but
argued as they did for the previous rejection (App. Br. 12). Consequently,
we affirm the rejection for the facts and reasoning stated by the Examiner.

SUMMARY
A person of ordinary skill in the art would have had reason to
combine Burke and Wong ‘188 to have made the claimed biodegradable
polymer matrix. The cited Burke and Wong’188 patents suggest the claimed
limitation that the intraocular implant comprise “brimonidine tartrate . . . in
an amount of from 10 to 40% by weight” of the implant. Appellants did not
provide sufficient evidence to establish “unexpected results” based on the
totality of evidence. The obviousness rejections under 35 U.S.C. § 103(a) of
claims 12-16, 20, 45, and 59-64 are affirmed.
Appeal 2010-004999
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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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