Ex Parte Lyons et al

Board of Patent Appeals and Interferences

Dec 4, 2008

10826843 (B.P.A.I. Dec. 4, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte ROBERT T. LYONS, CHIN-MING CHANG, JOAN-EN
CHANG-LIN, JAMES CHANGE and OREST OLEJNIK1
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Appeal 2008-5416
Application 10/826,843
Technology Center 1600
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Decided: December 4, 2008
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Before JAMES T. MOORE, Vice Chief Administrative Patent Judge, and
RICHARD E. SCHAFER and RICHARD TORCZON, Administrative
Patent Judges.

Opinion for the Board filed by Vice Chief Administrative Patent Judge,
MOORE, joined by Administrative Patent Judge, SCHAFER.

Opinion Concurring, filed by Administrative Patent Judge, TORCZON.

MOORE, Vice Chief Administrative Patent Judge.

1 The real party in interest is Allergan, Inc. (App. Br. 1).

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DECISION ON APPEAL

STATEMENT OF CASE
The Appellants appeal under 35 U.S.C. § 134 (2002) from a final
rejection of claims 1-19, 21-23 and 26.2 We have jurisdiction under
35 U.S.C. § 6 (b) (2002).
The Appellants’ claims are directed to medicating the interior of the
eye using a medicament and a cyclodextrin as a carrier.
Claims 1 and 19 are the only independent claims in the application.
The Appellants do not argue any claims separately regarding the enablement
or anticipation rejections. Therefore, we select independent claim 1, the
method claim, to decide the appeal regarding these rejections. See 37 C.F.R.
§ 41.37(c)(1)(vii) (2006).
For the obviousness rejection, the Appellants argue claims 16-18
together. Claim 16 is representative, and the remaining claims stand or fall
with claim 16.
Claim 1 reads as follows:
1. A method comprising topically administering a
composition to an eye of a mammal in need thereof, said
method being effective in delivering a therapeutically effective
amount of a therapeutically active agent to a structure or
combination of structures of the eye selected from the vitreous
humor and structures posterior to the vitreous humor; said
composition comprising;
a. an effective amount of the therapeutically active agent,
or a pharmaceutically acceptable salt or prodrug
thereof, to provide a therapeutically effective amount

2 Claims 20, 24, 25, and 27 have been canceled. (App. Br. 2).
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of the therapeutically active agent to said structure or
combination of structures of the eye, and
b. an effective amount of a cyclodextrin derivative to
provide said therapeutically effective amount of said
therapeutically active agent to said structure or
combination of structures of the eye[,]
wherein the cylodextrin derivative is selected from the group
consisting of hydroxypropyl-β-cyclodextrin, hydroxypropyl-γ-
cyclodextrin, sulfobutylether-β-cyclodextrin and
sulfobutylether-γ-cyclodextrin, hydroxyethyl-β-cyclodextrin,
hydroxyethyl-γ-cyclodextrin, dihydroxypropyl-β-cyclodextrin,
glucosyl-β-cyclodextrin, diglucosyl-β-cyclodextrin, maltosyl-β-
cyclodextrin, maltosyl-γ-cyclodextrin, maltotriosyl-β-
cyclodextrin, maltotriosyl-γ-cyclodextrin, dimaltosyl-β-
cyclodextrin, and combinations thereof.

(App. Br. 10, Claims Appendix).

Claim 5, from which claim 16 depends, reads as follows:

5. The method of claim 1 wherein said therapeutically
active agent is not administered to reduce intraocular pressure.

Claim 16 reads as follows:

16. The method of claim 5 which further comprises
hydroxypropylmethylcellulose having a concentration of less
than 1%.

(App. Br. 11, Claims Appendix).

THE EVIDENCE

The Examiner relies upon the following as evidence in support of the
rejections:
Loftsson US 5,472,954 Dec. 05, 1995
Guy US 5,576,311 Nov. 19, 1996
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Lyons WO 02/089815 A2 Nov. 14, 2002

THE REJECTIONS
The following rejections are before us for review:
1. Claims 1-19, 21-23 and 26 stand rejected under 35 U.S.C. § 112, first
paragraph, as failing to comply with the enablement requirement.
2. Claims 1-15, 19, 21-23 and 26 stand rejected as being anticipated
under 35 U.S.C. § 102(b) over Guy.
3. Claims 1-19, 21-23 and 26 stand rejected as being anticipated under
35 U.S.C. § 102(b) over Lyons.
4. Claims 16-18 stand rejected as being obvious under 35 U.S.C.
§ 103(a) over the combination of Guy and Loftsson.
We REVERSE the enablement rejection of claims 1-19, 21-23 and 26;
AFFIRM the anticipation rejections of claims 1-19, 21-23 and 26; and
AFFIRM the obviousness rejection of claims 16-18.
ISSUES
Have the Appellants established that the Examiner erred in
determining that the specification does not provide sufficient guidelines to
enable of one of ordinary skill in the art to know, without undue
experimentation, which therapeutically active agents may be administered
by the claimed method?
Have the Appellants established that the Examiner erred in
determining that the prior art anticipated a method of topically administering
a known topical ophthalmic composition to structures of the eye in or
posterior to the vitreous humor?
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Have the Appellants established that the Examiner erred in
determining that it would have been obvious to one of ordinary skill in the
art at the time the invention was made to topically administer a known
topical ophthalmic composition to structures of the eye in or posterior to the
vitreous humor?
FINDINGS OF FACT
The record supports the following findings of fact by a preponderance
of the evidence.
1. The specification describes that “the use of cyclodextrins in
pharmaceutical compositions is well known in the art.” (Specification p. 3,
ll. 7-8).
2. The specification also describes that “[t]he use of cyclodextrin and
cyclodextrin derivatives in ophthalmic formulations is also known.” (Id.
p. 3. ll. 20-21).
3. Additionally, the specification provides numerous examples of
“therapeutically active agent[s],” as claimed. (Id. pp. 6-7).
4. Guy describes topical ophthalmic compositions for the treatment
of inflammatory conditions of the eye. (Guy 1:8-11).
5. Guy describes that its ophthalmic compositions comprise a
therapeutic concentration of a water insoluble or poorly soluble drug and an
effective amount of cyclodextrin. (Id. 3:45-67).
6. Guy describes that the therapeutically active drug component may
be a nonsteroidal anti-inflammatory drug, an antimicotic, an antiepileptic, an
antihistamine, or a locally active steroid, such as prednisolone. (Id. 3:54-
66).
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7. Guy describes that the cyclodextrin component can be methyl
cyclodextrin, glucosyl cyclodextrin, maltosyl cyclodextrin, multiple
derivative forms of these cyclodextrins, hydroxypropyl cyclodextrin, beta-
hydroxypropyl cyclodextrin, beta cyclodextrin or hydroxyethyl cyclodextrin.
(Id. 4:1-4; 5:6-9; Table 2).
8. Lyons describes methods and ophthalmic compositions for the
topical delivery of lipophilic drugs to the eye. (Lyons pp. 9-11).
9. Lyons describes that its ophthalmic compositions comprise a
therapeutically effective amount of an active drug, such as antibiotics,
steroids, e.g., prednisolone, and nonsteroidal anti-inflammatory drugs. (Id.
10-11).
10. Lyons describes that its ophthalmic compositions also comprise
cyclodextrins selected from naturally occurring cyclodextrins or their
synthetic derivatives that are, “without limitation, formed by alkylation (e.g.
methyl- and ethyl-β-cyclodextrin) or hydroxyalkylation of the hydroxyl
groups (e.g. hydroxyproply- and hydroxyethyl –derivatives of α-, β-, and γ-
cyclodextrin) or by substituting the primary hydroxy groups with
saccharides (e.g. glucosyl- and maltosyl-β-cyclodextrin).” (Id. 12).
11. Lyons also describes that its ophthalmic composition comprises a
water soluble polymer such as hydroxypropylmethylcellulose (HPMC)
(Id. 10).
12. Loftsson describes a method of enhancing the solubilizing and
stabilizing effects of cyclodextrin derivatives in cyclodextrin-drug
complexes by adding certain polymers. (Loftsson 1:12-15).
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13. Loftsson describes that suitable polymers for its method, such as
HPMC, are water soluble and acceptable for use in pharmaceuticals.
(Id. 7:7-30).
14. Additionally, Loftsson describes that the polymer comprises
0.001-5%, preferably from about 0.01 to about 0.5% of the composition.
(Id. 4:21-30).
15. Loftsson also describes that suitable pharmaceuticals for its
method include ophthalmic compositions (eye drops) containing agents
including anti-glaucoma agent, anti-inflammatory steroid, or anti-
infective/antiseptic agent. (Id. 19:15-46).
PRINCIPLES OF LAW
Lack of Enablement
“That some experimentation is necessary does not constitute a lack of
enablement; the amount of experimentation, however, must not be unduly
extensive.” Amgen, Inc. v. Chugai Pharmaceutical Co., Ltd., 927 F.2d 1200,
1212 (Fed Cir. 1991).
Anticipation
“The discovery of a new property or use of a previously known
composition, even when that property and use are unobvious from the prior
art, can not impart patentability to claims to the known composition.” In re
Spada, 911 F.2d 705, 708 (Fed. Cir. 1990)
Obviousness
“Selecting a narrow range from within a somewhat broader range
disclosed in a prior art reference is no less obvious than identifying a range
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that simply overlaps a disclosed range.” In re Peterson, 315 F.3d 1325,
1329-1330 (Fed. Cir. 2003).
Moreover, when “the claimed ranges are completely encompassed by
the prior art, the conclusion is even more compelling than in cases of mere
overlap.” Id at 1330.
ANALYSIS
I. The Enablement Rejection. 7
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Claims 1-19, 21-23 and 26 stand rejected under 35 U.S.C. § 112, first
paragraph, as failing to comply with the enablement requirement.
The Examiner found that “the specification, while being enabling for
some agents, does not reasonably provide enablement for the broad phrase
of ‘an agent.’” (Non-Final Rejection, Nov. 30, 2006, p. 2, incorporated by
reference in Final Rejection, May 9, 2007, p. 2). In consideration of the
factors set for in In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988), the
Examiner particularly found that one of ordinary skill in the art would be
burdened with undue experimentation to determine all agents in combination
with cyclodextrin derivatives being capable of delivery to the eye. (Id. 2-3).
The Appellants assert that the Examiner’s enablement rejection was
erroneous because “[t]he specification cites about 400 different examples of
therapeutically active agents.” (App. Br. 4) (citing Specification p. 6, ll. 22
to p. 15, ll. 15). The Appellants also assert that the specification
demonstrates that cyclodextrin and its derivatives deliver the active agent
prednisolone to the back of the eye. (Id.). The Appellants further assert that
“known literature provides ample guidance to a person of ordinary skill to
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determine which compounds are likely to work in the claimed methods.”
(Id. at 5).
We agree that the Appellants’ claims are enabled by the specification.
As the court in Martin v. Johnson, 454 F.2d 746, 751 (1972) (citations
omitted) stated:
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To satisfy §112, the specification disclosure must be
sufficiently complete to enable one of ordinary skill in the art to
make the invention without undue experimentation, although
the need for a minimum amount of experimentation is not fatal.
. . . Enablement is the criterion, and every detail need not be set
forth in the written specification if the skill in the art is such
that the disclosure enables one to make the invention.

The specification describes that “the use of cyclodextrins in
pharmaceutical compositions is well known in the art.” (Specification p. 3,
ll. 7-8). The specification also describes that “[t]he use of cyclodextrin and
cyclodextrin derivatives in ophthalmic formulations is also known.” (Id.
p. 3. ll. 20-21). Further, as the Appellants have asserted, the specification
provides numerous examples of therapeutically active agents. (Id. pp. 6-7).
The Examiner has not provided sufficient reasoning as to why one
skilled in the art of ophthalmic pharmaceuticals would not be able to
determine without undue experimentation which ophthalmic agents would
work in the claimed method. The Examiner has therefore not satisfied the
initial burden of providing reasoning which would substantiate a rejection
based on lack of enablement.
Consequently, we reverse the Examiner's rejection of claims 1-19, 21-
23 and 26 under 35 U.S.C. 112, first paragraph, as failing to comply with the
enablement requirement.
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II. The Anticipation Rejections. 1
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Claims 1-15, 19, 21-23 and 26 stand rejected as being anticipated
under 35 U.S.C. § 102(b) over Guy. The Examiner found that Guy teaches
the use of the claimed cyclodextrin derivatives, e.g., hydroxypropyl
cyclodextrin, in combination with a therapeutically active agent, e.g.,
prednisolone acetate, in an ophthalmic/pharmaceutical formulation for the
treatment of ophthalmic disorders. (Non-Final Rejection, June 29, 2006,
p. 2, incorporated by reference in Final Rejection, May 9, 2007, p. 2) (citing
1:38-65, 2:55, 3:1-10, 3:30-37, 4:1-15).
The Examiner additionally rejected claims 1-19, 21-23 and 26 as
being anticipated under 35 U.S.C. § 102(b) over Lyons. For this rejection,
the Examiner similarly found that Lyons teaches the use of the claimed
cyclodextrin derivatives in combination with prednisolone acetate and
additionally with HPMC (as recited in Appellants’ claims 16-18) in an
ophthalmic formulation for the delivery to the eye. (Non-Final Rejection,
Nov. 30, 2006, p. 4, incorporated by reference in Final Rejection, May 9,
2007, p. 2) (citing Lyons p. 10, ll. 8-13, p. 12, ll. 11-26 and p. 14 Table).
The Appellants do not dispute the Examiner’s finding that Guy and
Lyons each disclose the components of the composition recited in the
Appellants’ respective claims. Nor do the Appellants dispute the finding
that each reference describes that their compositions are administered
topically to the eye. Rather, as to both rejections, the Appellants assert that
the claims are not anticipated because “[n]either of the references teaches
administration of the composition for the purpose of delivering the drugs to
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the particular structures of the eye cited in the claims.” (App. Br. 7)
(emphasis added).
This argument is not persuasive. It is not in dispute that the claimed
composition of claim 1 has been applied to the eye for therapeutic purposes
in the cited prior art. The claimed method of delivering a composition to
structures of the eye in or posterior to the vitreous humor is, at best, a
different intended use of a previously known topical ophthalmic composition
which inherently functioned in the same way as now claimed. As the
Federal Circuit has stated, “The discovery of a new property or use of a
previously known composition, even when that property and use are
unobvious from the prior art, can not impart patentability to claims to the
known composition.” In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990).
Consequently, we find that the Appellants have not established that
the Examiner erred in (a) rejecting claims 1-15, 19, 21-23 and 26 as being
anticipated by Guy, and (b) rejecting claims 1-19, 21-23 and 26 as being
anticipated by Lyons.
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Claims 16-18 stand rejected as being obvious under 35 U.S.C.
§ 103(a) over the combination of Guy and Loftsson.
Representative claim 16 reads as follows:
16. The method of claim 5 which further comprises
hydroxypropylmethylcellulose having a concentration less than
1%.

Claim 5 reads as follows:
5. The method of claim 1 wherein said therapeutically
active agent is not administered to reduce intraocular pressure.
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The Examiner found that Guy differs from the claimed invention
because Guy does not describe using HPMC in the ophthalmic composition.
(Non-Final Rejection, June 29, 2006, p. 2, incorporated by reference in Final
Rejection, May 9, 2007, p. 3). However, the Examiner found that Loftsson
teaches the use of the claimed HPMC in combination with the claimed
cyclodextrin and a therapeutically active agent, e.g., steroid, in an
ophthalmic formulation. (Id.).
According to the Examiner, it would have been obvious to a person of
ordinary skill in the art to incorporate HPMC into the teaching of the
primary reference because Loftsson describes that addition of HPMC to the
claimed cyclodextrin well known in the art. (Id.). The Examiner also found
that one skilled in the art would have been motivated to combine the
teachings of the references because references represent analogous art of
cyclodextrin-containing ophthalmic formulations. (Id. at 4). The Examiner
further found that the Appellants did not present evidence to establish the
unexpected or unobvious nature of the claimed invention. (Id.).
Here again, the Appellants assert that the Examiner’s rejection is
erroneous because “[u]sing cylodextrin derivatives to deliver drugs to the
back of the eye is not taught or suggested in the prior art.” (App. Br. 7).
The Appellants additionally assert that the Examiner failed to explain how
the prior art composition is used “in such a way that a therapeutically
effective amount of the required drug would be delivered to the back of the
eye structure.” (Id.).
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These arguments are unpersuasive. The Examiner found that Guy
teaches the use of the claimed cyclodextrin derivatives with a therapeutically
active agent, e.g., prednisolone acetate, in a topical ophthalmic
pharmaceutical formulation. Additionally, the Examiner found that Loftsson
describes adding HPMC to an ophthalmic composition comprising a
cyclodextrin and therapeutically active agent. The Examiner further found
that the combination of Loftsson’s HPMC with Guy’s topical ophthalmic
composition would have been obvious to one skilled in the art at the time of
the invention because the combination of HPMC with cyclodextrin
compositions was well known in the art and the references represent
analogous art. Additionally, Loftsson describes that adding HPMC to a
cyclodextrin-containing ophthalmic compositions enhances the solubilizing
and stabilizing effects of cyclodextrin. (Loftsson 1:12-15). The Appellant
has not challenged these findings.
Loftsson also describes the polymer (HPMC) comprises 0.001-5%,
preferably from about 0.01 to about 0.5% of the composition (Id. 4:21-30).
This disclosed range encompasses the concentration described by claim 16,
i.e., “less than 1%.” As the Federal Circuit has affirmed, “Selecting a
narrow range from within a somewhat broader range disclosed in a prior art
reference is no less obvious than identifying a range that simply overlaps a
disclosed range.” In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003).
Moreover, when “the claimed ranges are completely encompassed by the
prior art, the conclusion is even more compelling than in cases of mere
overlap.” Id.
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Therefore, the method of claim 16 recites a topically administered
composition that would have been obvious to a skilled artisan at the time of
the invention. As the Examiner stated, “the appellant is using the same
composition as [the] prior art, therefore it is expected that such composition
would inherently act the same as the composition of the instant application.”
(Ans. 6). The Appellants have put forth no persuasive evidence that this
finding is incorrect. See In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990).
Consequently, we do not find that the Appellants have established that
the Examiner erred in rejecting claims 16-18 as obvious over the
combination of Guy and Loftsson.
Accordingly, we affirm the Examiner’s rejections.
CONCLUSION OF LAW
On the record before us, the Appellants have not shown error
on the part of the Examiner regarding the anticipation rejections of claims 1-
19, 21-23 and 26, and the obviousness rejections of claims 16-18. The prior
art anticipated a method of topically administering a known topical
ophthalmic composition to structures of the eye in or posterior to the
vitreous humor. Additionally, it would have been obvious to one of ordinary
skill in the art at the time the invention was made to topically administer a
known topical ophthalmic composition to structures of the eye in or
posterior to the vitreous humor.
However, regarding the enablement rejection of claims 1-19, 21-23
and 26, the Appellants have established that the Examiner erred in
determining that the specification does not provide sufficient guidelines to
enable of one of ordinary skill in the art to know, without undue
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experimentation, which therapeutically active agents may be administered
by the claimed method.
DECISION
The Rejection of claims 1-19, 21-23 and 26 under 35 U.S.C. § 112,
first paragraph, as being unpatentable for failing to comply with the
enablement requirement is REVERSED.
The Rejection of claims 1-15, 19, 21-23 and 26 under 35 U.S.C. §
102(b) as being unpatentable over Guy is AFFIRMED.
The Rejection of claims 1-19, 21-23 and 26 under 35 U.S.C. § 102(b)
as being as being unpatentable over Lyons is AFFIRMED.
The Rejection of claims 16-18 under 35 U.S.C. § 103(a) as being
unpatentable over the combination of Guy and Loftsson is AFFIRMED.
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) (2006).

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TORCZON, Administrative Patent Judge, concurring. 1
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I join the majority in affirming the anticipation and obviousness
rejections. I would not reach the enablement rejection. Cf. Leggett & Platt,
Inc. v. VUTEk, 537 F.3d 1349, 1356 (Fed. Cir. 2008) (not reaching § 112
issue after affirming anticipation and obviousness grounds of invalidity).

rvb

ALLERGAN, INC.
2525 DUPONT DRIVE, T2-7H
IRVINE, CA 92612-1599
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