Ex Parte Liversidge et al

Board of Patent Appeals and Interferences

Sep 29, 2010

11274887 (B.P.A.I. Sep. 29, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte GARY LIVERSIDGE, SCOTT JENKINS,
and ELAINE MERISKO LIVERSIDGE
__________

Appeal 2010-007072
Application 11/274,887
Technology Center 1600
__________

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

WALSH, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134(a) involving claims to an
injectable nanoparticulate olanzapine composition. The Patent Examiner

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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Application 11/274,887

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rejected the claims as obvious and on the ground of non-statutory
obviousness-type double patenting. We have jurisdiction under 35 U.S.C.
§ 6(b). We reverse.
STATEMENT OF THE CASE
The invention concerns “injectable nanoparticulate olanzapine
formulations … with durations of action that can be controlled to give
efficacious blood levels through manipulation of particle size and hence
dissolution for periods of about one week or greater.” (Spec. p. 10, ll. 14-
18).
Claims 1-6 and 8-18 are on appeal. Claim 1 is representative and
reads as follows:
1. An injectable nanoparticulate olanzapine composition
comprising: (a) olanzapine nanoparticles having an effective average
particle size that results in a therapeutic efficacy of about one week or
greater; (b) at least one surface stabilizer; and (c) a pharmaceutically
acceptable carrier, wherein said effective average particle size is between
about 300 nm and about 5000 nm.

The Examiner rejected the claims as follows:
• claims 1-6 and 8-18 under 35 U.S.C. § 103(a) over Hassan,2 Lee,3
Love,4 and Tohen;5 and

2 Patent Application Publication No. US 2002/0119916 A1 by EmadEldin
M. Hassan, published Aug. 29, 2002.
3 Patent Application Publication No. WO 2004/032980 A1 by Robert Lee et
al., published Apr. 22, 2004.
4 Raymond C. Love, Strategies for increasing treatment compliance: The
role of long-acting antipsychotics, 59 AM. J. HEALTH-SYST. PHARM. S10-
S15 (2002).
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• claims 1-12, 17 and 18 on the ground of non-statutory obviousness-
type double patenting as unpatentable over claims 1, 4 and 7 of Liversidge
‘684,6 Love, Tohen and Bosch copending Application No. 10/697,716
(Bosch ‘716).7
Additionally, the Examiner provisionally rejected the claims as
follows:8
• claims 1, 11 and 14 on the ground of non-statutory obviousness-
type double patenting as unpatentable over claims 1, 3 and 9 of Liversidge
copending Application No. 11/354,249;9
• claims 1, 11 and 14 on the ground of non-statutory obviousness-
type double patenting as unpatentable over claims 1, 5 and 14 of
Cunningham copending Application No. 10/978,695;10
• claims 1, 11 and 14 on the ground of non-statutory obviousness-
type double patenting as unpatentable over claims 1, 18 and 25 Liversidge
copending Application No. 10/979,792;11

5 Mauricio Tohen et al., Efficacy of Olanzapine and Olanzapine-Fluoxetine
Combination in the Treatment of Bipolar I Depression, 60 ARCH. GEN.
PSYCHIATRY 1079-1089 (2008).
6 US Patent No. 5,145,684 issued to Gary G. Liversidge et al., Sep. 8, 1992.
7 Patent Application No. 10/697,716 (Publication No. US 2004/0141925 A1)
by H. William Bosch et al.
8 See Ans. 12-19.
9 Patent Application No. 11/354,249 (Publication No. US 2006/0198896 A1)
by Gary Liversidge et al.
10 Patent Application No. 10/978,695 (Publication No. US 2005/0238725
A1) by James Cunningham et al.
11 Patent Application No. 10/979,792 (Publication No. US 2005/0147664
A1) by Elaine Liversidge et al.
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• claims 1, 11 and 14 on the ground of non-statutory obviousness-
type double patenting as unpatentable over claims 1, 9 and 17 of Pruitt
copending Application No. 10/912,552;12
• claims 1, 11 and 14 on the ground of non-statutory obviousness-
type double patenting as unpatentable over claims 1, 23 and 31 of Bosch
copending Application No. 10/619,539;13 and
• claims 1, 11 and 14 on the ground of non-statutory obviousness-
type double patenting as unpatentable over claims 14, 20 and 21 of Bosch
‘716.
OBVIOUSNESS
The Issue
The Examiner’s position is that Hassan disclosed a method of making
nanoparticles of water insoluble pharmaceutical compounds from an
emulsion, wherein the nanoparticles have a diameter of about 10 nm to 200
nm. (Ans. 6). The Examiner found that Hassan disclosed that olanzapine
and risperidone are useful active ingredients for its composition. (Id.). The
Examiner also found that Hassan disclosed that its composition also
comprised surfactants, such as polyoxyethylene sorbitan fatty acid esters.
(Id.). Additionally, the Examiner found that Hassan taught that its
composition may be administered as an injection and provided controlled
release of the active agent for prolonged drug effects. (Id.).

12 Patent Application No. 10/912,552 (Publication No. US 2005/0063913
A1) by John D. Pruitt et al., published Mar. 24, 2005.
13 Patent Application No. 10/619,539 (Publication No. US 2004/01258757
A1) by H. William Bosch et al.
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The Examiner found that Lee disclosed gamma irradiation of solid
nanoparticle active agents, including olanzapine and risperidone, having an
average particle size of less than 2 microns and compositions comprising
these agents. (Id.). In particular, the Examiner found that Lee disclosed that
the particles of its invention have an effective average particle size ranging
from less than about 1900 nm to less than 200 nm. (Id. at 7). The Examiner
also found that Lee disclosed that its compositions further comprise surface
stabilizers such as polyoxyethylene sorbitan fatty acid esters. (Id. at 6).
Additionally, the Examiner found that Lee taught that its compositions may
be administered parenterally as an injection and formulated as controlled
release and extended release dosage forms. (Id. at 7).
The Examiner found that Love taught that strategies for improving
compliance of antipsychotics include altering the formulation of the drug,
e.g., from an oral formulation to depot formulation. (Id.). The Examiner
also found that Love disclosed that depot formulations of antipsychotics
significantly reduce the number of hospital days compared with oral
formulations. (Id.). Additionally, the Examiner found that Love disclosed
long-acting risperidone injections providing a steady release of the drug over
several weeks. (Id.).
According to the Examiner, it would have been obvious to a person of
ordinary skill in the art at the time the invention was made to combine the
injectable olanzapine nanoparticulate formulations of Hassan and Lee with
the extended release depot of Love because combining the elements of the
prior art would produce a more effective extended release antipsychotic
formulation resulting in better patient compliance and decreased cost of
patient care. (Id. at 9).
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Appellants contend that the claims are not obvious over the combined
prior art because the combination is improper and does not yield the claimed
invention. (App. Br. 15-16). In particular, Appellants assert that Hassan
taught away from using nanoparticles greater than 200 nm for extended
release compositions. (Id. at 16-22). Additionally, Appellants assert that
Love’s disclosure of a long-acting risperidone injection “does not
contemplate particulate forms of the drug, nor is it even a depot
formulation.” (Id. at 27). According to Appellants, “the formulations of the
instant invention achieve results which are not predicted by the references.”
(Id. at 30.)
The dispositive issue with respect to this rejection is whether the
combined prior art taught or suggested an injectable nanoparticulate
composition comprising “olanzapine nanoparticles having an effective
average particle size that results in a therapeutic efficacy of about one week
or greater,” as claimed.
Findings of Fact
1. We agree with the Examiner’s findings of fact concerning the explicit
teachings of each prior art reference. (See Ans. 6-8).
2. Love stated that its long-acting formulation of risperidone comprised
a “new technology that uses a copolymer matrix that can be administered as
an aqueous suspension. The drug is embedded in the matrix, which slowly
and completely hydrolyzes at the site of injection to allow a steady drug
release over several weeks.” (Love, S12).

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Principles of Law
When determining whether a claim is obvious, an Examiner must
make “a searching comparison of the claimed invention – including all its
limitations – with the teaching of the prior art.” In re Ochiai, 71 F.3d 1565,
1572 (Fed. Cir. 1995).
Analysis
We agree with Appellants that the combined prior art did not teach or
suggest a composition comprising “olanzapine nanoparticles having an
effective average particle size that results in a therapeutic efficacy of about
one week or greater,” as recited in independent claim 1. While Love
disclosed a long-acting risperidone injection that allowed a steady release of
drug over several weeks, the formulation did not comprise particulate forms
of the drug. (See FF-2). Instead, Love disclosed that the formulation
comprised a “new technology that use[d] a copolymer matrix that [could] be
administered as an aqueous suspension.” (Id.). The Examiner has not
explained how this disclosure would have suggested to a skilled artisan at
the time of the invention the preparation of olanzapine nanoparticles having
an effective average particle size that results in a therapeutic efficacy of
about one week or greater, as claimed.
In the Answer, the Examiner explained that Love was relied upon
only for disclosing a depot formulation. (Ans. 25). According to the
Examiner, Hassan and Lee taught long-acting nanoparticulate injectable
formulations. (Id.). However, the Examiner did not find that the controlled
release formulations of Hassan and Lee provided therapeutic efficacy of
about one week or greater. (See Ans. 6-8). Because the rejection did not
account for that claim limitation, we reverse.
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OBVIOUSNESS-TYPE DOUBLE PATENTING
The Issues
The Examiner’s position is that several of the instant claims, including
independent claim 1, are not patentably distinct from certain claims of the
referenced patents and applications. (See Ans. 10-19).
Appellants contend that the Examiner failed to properly consider all of
the instant claim limitations, in particular, the requirement that the
formulation should provide therapeutically effective amounts of olanzapine
for one week or more. (App. Br. 33-39).
Further, regarding the rejections over Liversidge ‘249, Appellants
assert that Liversidge ‘249 was filed after the priority date of the instant
application and that claims 1, 3 and 9 of Liversidge ‘249 were rejected in a
non-final office action. (Id. at 34-35). Therefore, Appellants assert that “the
examiner should withdraw the rejection and permit the earlier-filed
application to issue as a patent without a terminal disclaimer.” (Id. at 35).
Findings of Fact
3. We agree with the Examiner’s findings of fact concerning the explicit
teachings of each prior art reference. (See Ans. 11-19).
Principle of Law
An obviousness-type double patenting analysis entails two steps:
(1) construction of the claims of the patent and the claim in the application
to identify any differences, and (2) determination of whether the differences
in subject matter between the claims render the claims patentably distinct.
See Eli Lilly & Co. v. Barr Labs., Inc., 251 F.3d 955, 968 (Fed Cir. 2001).

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Analysis
We agree with Appellants that the Examiner failed to conduct a
complete obviousness-type double patenting analysis on the record. For
each rejection, the Examiner did not address the claim limitation requiring
the olanzapine nanoparticles to have “an effective average particle size that
results in a therapeutic efficacy of about one week or greater.” (See Ans. 10-
19). That is, the Examiner did not identify whether this limitation represents
a difference between those claims and instant independent claim 1. Nor has
the Examiner discussed whether any such difference in the subject matter
between the claims renders the claims patentably distinct. See Lilly,
251 F.3d at 968. Consequently, we do not find that the Examiner has
properly supported these rejections.
CONCLUSIONS OF LAW
The obviousness rejection did not establish that “therapeutic efficacy
of about one week or greater” as claimed would have been obvious over the
combined teachings of Hassan, Lee, Love, and Tohen.
The Examiner has not established on this record that the instant claims
requiring “therapeutic efficacy of about one week or greater” are patentably
indistinct from the referenced patent and application claims.
SUMMARY
We reverse the rejection of claims 1-6 and 8-18 under 35 U.S.C.
§ 103(a) over Hassan, Love, Tohen, and Lee;
we reverse the rejection of claims 1-12, 17 and 18 on the ground of
non-statutory obviousness-type double patenting as unpatentable over claims
1, 4 and 7 of Liversidge ‘684 in view of Bosch ‘716, Love and Tohen;
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we reverse the rejection of claims 1, 11 and 14 on the ground of non-
statutory obviousness-type double patenting as unpatentable over claims 1, 3
and 9 of Liversidge ‘249;
we reverse the rejection of claims 1, 11 and 14 on the ground of non-
statutory obviousness-type double patenting as unpatentable over claims 1, 5
and 14 of Cunningham ‘695;
we reverse the rejection of claims 1, 11 and 14 on the ground of non-
statutory obviousness-type double patenting as unpatentable over claims 1,
18 and 25 Liversidge‘792;
we reverse the rejection of claims 1, 11 and 14 on the ground of non-
statutory obviousness-type double patenting as unpatentable over claims 1, 9
and 17 of Pruitt ‘552;
we reverse the rejection of claims 1, 11 and 14 on the ground of non-
statutory obviousness-type double patenting as unpatentable over claims 1,
23 and 31 of Bosch ‘539; and
we reverse the rejection of claims 1, 11 and 14 on the ground of non-
statutory obviousness-type double patenting as unpatentable over claims 14,
20 and 21 of Bosch ‘716.

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

REVERSED

lp
Appeal 2010-007072
Application 11/274,887

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