Ex Parte Injac et al

Patent Trial and Appeal Board

Jan 24, 2018

13121612 (P.T.A.B. Jan. 24, 2018)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O.Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/121,612 07/11/2011 Rade Injac 029489.00052 1469
4372 7590 01/26/2018
ARENT FOX LLP
1717 K Street, NW
WASHINGTON, DC 20006-5344
EXAMINER
PARAD, DENNIS J
ART UNIT PAPER NUMBER
1612
NOTIFICATION DATE DELIVERY MODE
01/26/2018 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte RADE INJAC and SARA CESAR1
Appeal 2017-001795
Application 13/121,612
Technology Center 1600
Before JEFFREY N. FREDMAN, RICHARD J. SMITH, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
formulation of ezetimibe that have been rejected as obvious and on the
ground of nonstatutory double patenting.
We have jurisdiction under 35 U.S.C. § 6(b).
We affirm the obviousness rejection and reverse the nonstatutory
double patenting rejection.
1 According to Appellants, the real party in interest is LEK
PHARMACEUTICALS D.D. (Appeal Br. 1.)
Appeal 2017-001795
Application 13/121,612
STATEMENT OF THE CASE
Claims on Appeal
Claims 1, 2, 4, 6, 9, 13, 14, 16, and 17 are on appeal.2 (Appeal Br.
15-18 (APPENDIX I).) Claim 1 is illustrative and reads as follows:
1. A formulation of ezetimibe, comprising a hydrophilic excipient
in particulate form having primary particles of ezetimibe
adsorbed on a surface thereof, wherein the formulation is
granulated in admixture with from 1 wt % up to 10 wt. % of a
nonaqueous liquid excipient.
Examiner’s Rejections
1. Claims 1, 2, 4, 6, 9, 13, 14, 16, and 17 stand rejected under pre-AIA
35 U.S.C. § 103(a) as unpatentable over Zalit.3 (An. 2-5.)
2. Claims 1, 2, 4, 6, 9, 13, 14, 16, and 17 stand provisionally rejected on
the ground of nonstatutory double patenting over the claims of copending
Application Nos. 13/996,330, 13/147,956 (nowU.S. Patent No. 9,089,486
B2),4 and 13/132,055.5 {Id. at 6.)
FINDINGS OF FACT
The following findings are provided for emphasis and reference
purposes. Additional findings may be found in this Decision and the
Examiner’s Answer.
2 Claims 3, 7, 8, 11, 12, and 15 are withdrawn from consideration. (Non-
Final Act., dated June 17, 2015, at 2.)
3 Zalit et al., US 2007/0275075 Al, pub. Nov. 29, 2007 (“Zalit”).
4 Because Application No. 13/147,956 issued as U.S. Patent No. 9,089,486
B2 on July 15, 2015, the double patenting rejection based on Application
No. 13/147,956 is no longer provisional.
5 The double patenting rejection based on Application No. 13/132,055 is
moot because Application No. 13/132,055 is abandoned.
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Application 13/121,612
FF 1. The Examiner finds that Zalit teaches pharmaceutical formulations
comprising ezetimibe and at least one hydrophilic excipient wherein
ezetimibe and the hydrophilic excipient are co-milled to form particles.
(Ans. 2, citing Zalit Abstract and ^ 22.)
FF 2. The Examiner finds that, in an exemplary embodiment of Zalit, the
formulation is granulated in an admixture comprising primary particles of
ezetimibe and starch (a hydrophilic adsorbing agent excipient) and 14.7% by
weight of povidone in solution (a non-aqueous liquid excipient), and that the
blend of granulated particles are compressed together into tablets. (Ans. 2-
3, citing Zalit Example 2 and 36, 56, and 62.)
FF 3. The Examiner finds that Zalit teaches the formulation wherein the
primary particles, comprising ezetimibe and the starch adsorbing agent, are
pressed into slugs before being granulated in the admixture with povidone in
solution. (Ans. 3, citing Zalit 29, 30, 42, and 58.)
FF 4. The Examiner finds that “[sjince the surface of the primary particle
slugs comprise a mixture of an adhesion of ezetimibe and excipients (i.e., by
being compressed together into slug particles), ezetimibe is necessarily
adsorbed on the surfaces of the particles.” (Ans. 3.)
FF 5. Zalit teaches that the excipient povidone is a dispersing agent in the
wet granulation solution, and that “[t]he selection of excipients and the
amounts to use can be readily determined by an experienced formulation
scientist in view of standard procedures and reference works known in the
art.” (Zalit ^ 25, 28, 40, and 41.)
FF 6. The Examiner finds that
it would have been prima facie obvious to one of ordinary skill
in the art at the time the invention was made to modify the
formulation of Zalit [] by optimizing the concentration of the
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Application 13/121,612
non-aqueous liquid dispersing agent excipient that is granulated
in the admixture to between from 1 wt.% up to 10 wt.% because
Zalit [] teach[es] that the amount of excipient used in the
formulation admixture is a result-effective variable for
determining optimum or workable ranges by routine
experimentation based on its use as a dispersing agent.
(Ans. 4.)
DISCUSSION
Rejection No. 1
Issue
Whether a preponderance of evidence of record supports the
Examiner’s rejection under pre-AIA 35 U.S.C. § 103(a).
Analysis
We limit our consideration to claim 1 because the claims were not
argued separately.
We adopt the Examiner’s findings and conclusion of obviousness as
set forth in the Answer (Ans. 2-12), and discern no error in the rejection of
claim 1 as obvious in view of Zalit. (See FF 1-6.) We address Appellants’
arguments below.
a hydrophilic excipient in particulate form having primary particles of
ezetimibe adsorbed on a surface thereof
Appellants contend that Zalit does not disclose or suggest the above
limitation of claim 1. (Appeal Br. 7-8; Reply Br. 3-4.) In particular,
Appellants argue that neither compression of granules to form slugs before
being granulated, nor compression of granules to form tablets, is “adsorption
of ezetimibe primary particles onto the surface of a hydrophilic excipient
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Application 13/121,612
particulate.” (Appeal Br. 7-8; Reply Br. 3-4.) Appellants also refer to
statements in the Specification that “it has been surprisingly found . . . that
formulation of ezetimibe can be provided in a more robust and economical
way . . . when attention is paid . . . to . . . ezetimibe in the form of primary
particles . . . adsorbed on the surface of particles of the hydrophilic
excipient,” and that “it has been found beneficial to use . . . relatively small
primary ezetimibe particles ... for covering a relatively larger excipient
particle by adsorption thereon.” (Appeal Br. 8, citing Spec. 3,11. 25-33, 4,
11. 30-34, and claim 10.)
We are not persuaded. This limitation of claim 1 is established by the
Examiner’s findings based on the express teachings of Zalit. (FF 1—4.) In
particular, the Examiner established that Zalit discloses milling of particles
of ezetimibe with the hydrophilic excipient (starch) and that starch was an
adsorbing agent. (See Id. and Ans. 3; see also Fig. 4 of Zalit (ezetimibe
milled with starch).) Moreover, Appellants describe the use of starch as a
hydrophilic excipient (see, e.g., Spec. 2,11. 10-12), and the Specification’s
description of adsorption of primary particles of ezetimibe on the surface of
particles of the hydrophilic excipient appears functionally identical to what
is taught and suggested by Zalit. (See Ans. 3—4, 7-9.) Appellants’
arguments to the contrary, without evidence, are unpersuasive, and fail to
overcome the Examiner’s finding that the claim limitation at issue is taught
and suggested by Zalit. See In re Pearson, 494 F.2d 1399, 1405 (CCPA
1974) (attorney argument in a brief cannot take the place of evidence); see
also In re Best, 562 F.2d 1252, 1254-55 (CCPA 1977) (burden of producing
contrary evidence or arguments shifted to Appellants).
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Application 13/121,612
wherein the formulation is granulated in admixture with from 1 wt%
up to 10 wt. % of a nonaqueous liquid excipient
Appellants contest the Examiner’s finding that the amount of
dispersing agent used in the granulation mixture of Zalit (Example 2) is a
result-effective variable, arguing that “a particular parameter must first be
recognized as a result-effective variable . . . before the determination of the
optimum or workable ranges of said variable might be characterized as
routine experimentation.” (Appeal Br. 8-9, quoting MPEP § 2144.05(11)
(citing In re Antonie, 559 F.2d 618 (CCPA 1977); see also Reply Br. 2-3.)
In particular, Appellants argue that the claimed parameter of 1 wt % up to 10
wt. % of nonaqueous liquid excipient was not recognized in Zalit to be a
result effective variable for improving “an ezetimibe formulation where free­
flow characteristics, cohesive characteristics and compressibility of the
ezetimibe formulation [are] enhanced, and where good dissolution properties
are displayed.” (Appeal Br. 9-10.)
We are not persuaded. Our reviewing court has held that “the prior art
need not provide the exact method of optimization for the variable to be
result-effective. A recognition in the prior art that a property is affected by
the variable is sufficient to find the variable result-effective.” In re Applied
Materials, Inc., 692 F.3d 1289, 1297 (Fed. Cir. 2012). Here, Zalit is
directed to formulations of ezetimibe having improved solubility and
increased bioavailability, wherein an exemplary formulation is prepared
using 14.7% of a nonaqueous liquid excipient (dispersing agent) in a wet
granulation mixture, and Zalit expressly teaches that the amounts of
excipients (e.g., dispersing agent) can be varied “in view of standard
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procedures and reference works known in the art.” (See Zalit Abstract, FF 2,
5, 6.)
Zalit also states that “[a]n ezetimibe composition may be prepared by
methods known in the art, such as dry granulation, wet granulation,
blending, or direct compression.” (Id. 28.) Zalit further states that the
exemplary formulation is prepared by “wet granulation” (using “about 15%”
povidone in a granulation solution), wherein the active ingredients and
excipients in powder form are “mixed in the presence of a liquid . . . which
causes the powders to clump up into granules.” (Zalit 28, 41.) Moreover,
Appellants state that
wet granulation is in general and widely used in the industry to
prepare solid dosage forms. Wet granulation is often preferred
over dry granulation[6] and direct compression because wet
granulation has a greater chance of overcoming any problems
associated with the physical characteristics of various ingredients
- active or as excipient - in the formulation, with a view of
providing material which has the required flow and cohesive
properties necessary to obtain an acceptable solid dosage form.
(Spec. 12,11. 5-10.)
Based on the foregoing, we find that a person of ordinary skill in the
art would have appreciated that the amount of nonaqueous liquid excipient
used in a wet granulation method would affect a property of the ezetimibe
formulation. See KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007)
(the obviousness analysis “can take account of the inferences and creative
steps that a person of ordinary skill in the art would employ.”).
6 According to Appellants, “classical dry granulation” does not use a
granulation liquid. (Spec. 11,11. 32-33.)
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We thus find that Zalit, as would be viewed by one of ordinary skill in
the art, recognizes the amount of nonaqueous liquid excipient to be a result
effective variable, at least because it recognizes that a property (e.g.,
solubility/dissolution profile) “is affected by the variable” (amount of
nonaqueous liquid excipient used in the wet granulation step).7 See Applied
Materials, 692 F.3d at 1297. Moreover, based on the foregoing, we agree
with the Examiner that the claimed amount (concentration range) of
nonaqueous liquid excipient would have been a matter of routine
optimization of a result effective variable. See In re Aller, 220 F.2d 454,
456 (CCPA 1955).
Notwithstanding the foregoing, “[t]he outcome of optimizing a result-
effective variable may still be patentable if the claimed ranges are ‘critical’
and ‘produce a new and unexpected result which is different in kind and not
merely in degree from the results of the prior art.’” Applied Materials, 692
F.3d at 1297 (quoting Aller, 220 F.2d at 456). Among other requirements,
unexpected results must be shown to be unexpected compared with the
closest prior art. In re Baxter TravenolLabs., 952 F.2d 388, 392 (Fed. Cir.
1991) (citing In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984)). Here,
Appellants refer to “the corresponding evidence of unexpected results
presented in the specification.” (Appeal Br. 10.) However, although the
7 The court in Applied Materials distinguished Antonie as a case in which
“there was essentially no disclosure of the relationship between the variable
and the result in the prior art.” Applied Materials, 692 F.3d at 1297. That is
not the case here. Zalit discloses an ezetimibe formulation with desired
properties, an amount of nonaqueous liquid excipient used in preparing an
exemplary formulation with wet granulation, and that the amount of the
excipient can be varied. (FF 1-6.)
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Specification includes various formulation examples and graphs, Appellants
do not point us to any evidence of results that would have been unexpected
to a person of ordinary skill in the art, or any comparison of Appellants’
claimed formulation to the Zalit formulation (the closest prior art). (See
Ans. 10-11.) We thus find no persuasive evidence of unexpected results
sufficient to rebut the Examiner’s prima facie case of obviousness.
We are also unpersuaded by Appellants’ argument that one of
ordinary skill in the art would not have been motivated to lower the amount
of povidone in the Zalit formulation because doing so “could result in poorer
tablet physical properties.” (Appeal Br. 10.) As explained by the Examiner
(Ans. 11-12), such contention by Appellants amounts to mere attorney
argument without evidence. See Pearson, 494 F.2d at 1405.
Accordingly, for the reasons of record and as set forth above, we
affirm the rejection of claim 1 for obviousness. Claims 2, 4, 6, 9, 13, 14, 16,
and 17 fall with claim 1 because they were not argued separately.
Rejection No. 2
Issue
Whether a preponderance of evidence of record supports the
Examiner’s rejection on the ground of nonstatutory double patenting.
Analysis
The Examiner’s nonstatutory double patenting rejection states (in its
entirety) that “[ajlthough the claims at issue are not identical, they are not
patentably distinct from each other because the claims of the above
copending applications recite a pharmaceutical formulation comprising
ezetimibe as a pharmaceutically active ingredient that is in an admixture
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and/or granulated with excipients.” (Ans. 6.) Appellants contest the
rejection. (Appeal Br. 11-13; Reply Br. 4-6.)
The Examiner bears the initial burden of establishing a prima facie
case of nonstatutory double patenting and has not done so. See In re
Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). In this case, we do not find
that the Examiner’s conclusory statement of rejection meets that burden,
including because it does not address the specific limitations of claim 1 and
demonstrate that they would have been obvious over the corresponding
claim(s) of the copending application or patent.
Accordingly, we reverse the rejection of claims 1, 2, 4, 6, 9, 13, 14,
16, and 17 on the ground of nonstatutory double patenting over the claims of
copending Application Nos. 13/996,330 and 13/147,956 (nowU.S. Patent
No. 9,089,486 B2).
Conclusions of Law
A preponderance of evidence of record supports the Examiner’s
rejection of claims 1, 2, 4, 6, 9, 13, 14, 16, and 17 under pre-AIA 35 U.S.C.
§ 103(a).
A preponderance of evidence of record fails to support the Examiner’s
rejection of claims 1, 2, 4, 6, 9, 13, 14, 16, and 17 on the ground of
nonstatutory obviousness-type double patenting over the claims of either
copending Application No. 13/996,330 or U.S. Patent No. 9,089,486 B2.
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Application 13/121,612
SUMMARY
We affirm the obviousness rejection and reverse the nonstatutory
double patenting rejection.
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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