Ex Parte NECKEBROCK et al

Patent Trial and Appeal Board

Dec 28, 2015

12507584 (P.T.A.B. Dec. 28, 2015)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO.
12/507,584
27573 7590
CEPHALON, Inc,
41 MOORES ROAD
POBOX4011
FRAZER, PA 19355
FILING DATE FIRST NAMED INVENTOR
0712212009 Olivier NECKEBROCK
12/30/2015
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
CP247B US 6296
EXAMINER
KUMAR, SHAILENDRA
ART UNIT PAPER NUMBER
1672
NOTIFICATION DATE DELIVERY MODE
12/30/2015 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
following e-mail address( es):
intlpatentcounsel@tevapharm.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte OLIVIER NECKEBROCK,
LAURENT COURVOISIER, STEPHANIE GRAF, GILLES SERRURE,
GERARD FRANCOIS COQUEREL, SEBASTIEN ROSE,
CHRISTINE BESSELIEVRE, FRANCK PATRICK MALLET,
and ADRIAAN JAN VAN LANGEVELDE
Appeal2013-004383 1
Application 12/507,584
Technology Center 1600
Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
JACQUELINE T. HARLOW, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to a
polymorphic form of the organic compound modafinil. The Examiner
entered rejections for anticipation and obviousness.
We have jurisdiction under 35 U.S.C. § 6(b ). We affirm-in-part.
1 The real party in interest is Cephalon France, the assignee of record, which
is a wholly owned subsidiary of Cephalon, Inc., which is a wholly-owned
subsidiary of Teva Pharmaceutical Industries, Ltd. App. Br. 2
Appeal2013-004383
Application 12/507,584
STATEMENT OF THE CASE
The Specification discloses that the organic compound modafinil, in
racemic and enantiomeric forms, has been described in the art in the art as
capable of stimulating the central nervous system, allowing its use "as an
antidepressant or stimulant agent in the treatment of hypersomnia and
disorders associated with Alzheimer's disease." Spec. 1.
Appellants' invention "relates to a process for obtaining crystalline
forms of the enantiomers of modafinil, and the crystalline forms which it is
possible to obtain according to this process." Id. According to the
Specification, "the inventors have shown that the crystalline form obtained
mainly depends on the nature of the crystallisation solvent used." Id. at 3.
In one embodiment, the Specification discloses that a process in
which one of the optical enantiomers of modafinil is dissolved in a solvent
"selected from isopropanol, ethyl acetate, n-propanol, or ethanol denatured
with toluene[, followed by] a stage of crystallisation by rapid cooling leads
to a polymorphic form described as Form II or CRL 40982 form II." Id. at
11. In a variant of that process, Form II "can also be obtained by slow
cooling from isopropanol." Id. The Specification discloses an X-ray
powder diffraction spectrum obtained for Form II of modafinil. Id. at 12-13,
44; Fig. 9.
Claims 1-8 and 19-34 stand finally rejected as follows:
(1) Claims 1-8 and 19-28, under 35 U.S.C. § 102(e) as anticipated by
Ceausu2 (Final Action 2); and
2 U.S. Patent Appl. Pub. No. 2005/0038124 Al (published Feb. 17, 2005).
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Application 12/507,584
(2) Claims 29--34, under 35 U.S.C. § 103(a) for obviousness over
Ceausu and Largeau3 (Final Action 2-3).
Claims 1, 19, and 3 4 illustrate the appealed subject matter and read as
follows:
1. A polymorphic form of (-)-modafinil that produces a
powder X-ray diffraction spectrum comprising intensity peaks
corresponding to interplanar spacings of about 8.54,4.56, and
3.78 A.
19. A Form II polymorph of ( -)-modafinil.
34. A process for preparing the Form II polymorph of
(-)-modafinil of claim 19, comprising the steps of:
(a) providing a solution of (-)-modafinil dissolved in a
hot solvent;
(b) cooling the solution from step (a) to produce crystals;
( c) filtering the crystals;
( d) drying the crystals; and
( e) obtaining the crystals of said Form II polymorph of
(-)-modafinil,
wherein the solvent of step (a) is selected from
isopropanol, ethyl acetate, n-propanol, and ethanol denatured
with toluene.
App. Br. 5, 6, 9.
ANTICIPATION
The Examiner finds that Ceausu describes Form II of modafinil
"having same X-ray characteristic as claimed in herein. See for example Fig
2, section [0050] and section [0051, 0052 and 0053]." Final Action 2 (italics
removed).
3 U.S. Patent Appl. Pub. No. 2004/0002547 Al (published Jan. 1, 2004).
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Application 12/507,584
Appellants contend that the claimed Form II polymorph of
(-)-modafinil "is characterized by an X-ray diffraction pattern comprising
high intensity reflections at, inter alia, 29.1 and 35.3 degrees 28
(corresponding to interplanar spacings of 4.56 A and 3.78 A, respectively)."
App. Br. 3. In contrast, Appellants contend, the X-ray diffraction pattern of
the Form II modafinil polymorph described in Fig. 2 and i-f 50 of Ceausu,
cited by the Examiner, "contains no discernible reflections at about 29.1 or
35.3 degrees 28. Accordingly, that polymorph is not the same as the form II
polymorph of (-)-modafinil as presently claimed, and Ceausu et al. does not
anticipate claims 1-8 or 19-28." Id.
The Examiner does not dispute that the powder X-ray diffraction
spectrum of Form II modafinil disclosed in Ceausu lacks the two peaks
Appellants contend are recited in the rejected claims. Rather, the Examiner
contends, "the difference pattern seen in the X-Ray characteristic is due to
the source of being different X-ray machine, type of electrode, the base line
manipulation, the noise level etc." Ans. 5. The Examiner contends that
"Appellants are only providing and claiming two peaks, rather than entire
Figure for that matter. That suggests that they themselves are not sure of
their data, due to the noise level. The reference is expressly suggesting that
the X-ray pattern of Figure 2 belongs to Form II polymorph." Id. Further,
the Examiner contends, "[i]nasmuch as crystallization process is similar,
solvents are similar, thus the form II of polymorph of (-)-modafinil is
anticipated. Additionally, purer form of an old and known compound is
unpatentable, absent evidence to the contrary." Id. (citing In re Bergstrom,
427 F.2d 1394 (CCPA 1970)).
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Application 12/507,584
As stated in In re Oetiker, 977F.2d1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability ....
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
In the instant case, Appellants persuade us that a preponderance of the
evidence does not support the Examiner's prima facie case of anticipation as
to claims 1-8 and 25-28.
As Appellants contend, each of independent claims 1, 3, 5, and 7
recites a polymorphic form of (-)-modafinil that produces a powder X-ray
diffraction spectrum having either "intensity peaks" at interplanar spacings
of 4.56 A and 3. 78 A (claims 1 and 5), or "reflections" at the corresponding
values of about 29.1 and 35.3 degrees 28 (claims 3 and 7). App. Br. 5.
As the Examiner finds, Ceausu describes the preparation of Form II of
modafinil by crystallization in isopropanol. Ceausu i-fi-153, 98. Nonetheless,
as Appellants contend, and as the Examiner concedes, Ceausu does not
describe its Form II as having a powder X-ray diffraction spectrum with the
reflections or peaks required by claims 1, 3, 5, and 7. See Ceausu i150.
Accordingly, because the Form II of modafinil described by Ceausu does not
have the powder X-ray diffraction peaks/reflections required by claims 1, 3,
5, and 7, Appellants persuade us that a preponderance of the evidence does
not support the Examiner's finding of anticipation as to those claims.
The Examiner's arguments do not persuade us to the contrary. The
Examiner does not advance any evidence supporting the contention that the
conceded significant difference between claims 1, 3, 5, and 7 and Ceausu is
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Application 12/507,584
attributable to the use of a different machine, type of electrode, the base line
manipulation, or the noise level. In contrast, as Appellants contend, Ceausu
discloses that powder X-ray diffraction spectroscopy "yields a fingerprint
that is unique to the crystalline form and is ab le [to] distinguish it from the
amorphous compound and all other crystalline forms of the compound."
Ceausu i-f 13.
We acknowledge, as noted above, the disclosure in the Specification
that Appellants' invention is directed to the discovery that the solvent used
to crystallize modafinil strongly influences the polymorph obtained, with
isopropanol yielding Form II of modafinil. See Spec. 3, 11-13, 44. We
acknowledge, as also noted above, that Ceausu also discloses producing its
Form II of modafinil by crystallization in isopropanol. Ceausu i-fi-153, 98.
Nonetheless, as the Examiner concedes, the Form II of modafinil described
in Ceausu does not produce a powder X-ray diffraction spectrum having the
peaks/reflections required by independent claims 1, 3, 5, and 7.
Accordingly, we reverse the Examiner's anticipation rejection of those
claims, and their dependents.
Independent claim 19, however, stands on a different footing. Rather
than requiring the claimed compound to have a powder X-ray diffraction
spectrum with specific peaks or reflections, claim 19 simply recites "[a]
Form II polymorph of (-)-modafinil." Br. 6.
As noted above, Appellants' Specification discloses that a form II
polymorph of (-)-modafinil is obtained by crystallizing (-)-modafinil in
isopropanol. Spec. 11. As also noted above, Ceausu describes the
preparation of a Form II modafinil by crystallization in isopropanol, the
same solvent taught in Appellants' Specification. Ceausu i-fi-153, 98.
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Because Ceausu' s Form II modafinil is prepared in the same manner as
described in Appellants' Specification as producing Form II modafinil, we
are persuaded that a preponderance of the evidence supports the Examiner's
finding of anticipation as to claim 19.
Moreover, because claim 19 does not require the claimed polymorph
to exhibit any particular powder X-ray diffraction spectrum, Appellants'
arguments, which are all directed to the powder X-ray diffraction properties
of the claimed compounds, are not persuasive. Accordingly, because
Appellants' arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner's finding of anticipation as to claim
19, we affirm the Examiner's anticipation rejection of that claim, and its
dependent claims 20-24, over Ceausu.
OBVIOUSNESS
In finally rejecting claims 29-34 for obviousness over Ceausu and
Largeau, the Examiner finds that the "difference between the [Ceausu]
reference and herein claimed process is that the [ Ceausu] reference does not
mention toluene." Final Action 3 (italics removed). To address that
deficiency, the Examiner cited Largeau as "teaching that to crystallize
modafinil in pure form, toluene is old solvent in the art, see section [0050]."
Id. (italics removed).
Based on the references' teachings, the Examiner reasoned that an
ordinary artisan would have considered it obvious to "modify the
crystallization process of Ceausu et al by including toluene as solvent, as
taught by Largeau et al, because the latter reference is expressly teaching
that combination of the various solvents is old in the art." Id. (italics
removed).
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Appellants do not argue the claims subject to this ground of rejection
separately. We select claim 34 as representative of the rejected claims. 37
C.F.R. § 41.37(c)(iv). Appellants' arguments do not persuade us that a
preponderance of the evidence fails to support the Examiner's prima facie
case of obviousness as to claim 34.
As seen above, claim 34 recites a process for preparing the Form II
polymorph of (-)-modafinil of claim 19. App. Br. 9. The polymorph is
prepared by first dissolving (-)-modafinil in a hot solvent which may be
isopropanol, ethyl acetate, n-propanol, ethanol denatured with toluene,
cooling the solution to produce crystals, and then filtering, drying, and
thereby obtaining the crystals of the Form II polymorph. Id.
Appellants do not dispute that Ceausu describes a process including
all of the claimed steps, and in fact concede that Ceausu uses isopropanol to
crystallize its Form II modafinil polymorph. See App. Br. 3 ("Paragraph
[0053] of Ceausu et al. does not teach or suggest crystallization from ethyl
acetate, n-propanol, or ethanol denatured with toluene, but does teach
crystallization from isopropanol or ethanol.") (emphasis added). Instead,
Appellants' arguments are based on the assertion that Ceausu's Form II
modafinil produces a powder X-ray diffraction "with no discernible
reflections at about 29.1 or 35.3 degrees 28." Id.; see also Reply Br. 5
("The claimed polymorph is characterized by an XRPD [X-Ray powder
diffraction] pattern having intense reflections at about 15 .4, 29 .1, and 3 5 .3
degrees 28.").
As noted above, however, claim 19, from which claim 34 depends,
does not require the claimed polymorph to have a powder X-ray diffraction
spectrum with specific peaks or reflections. Rather, claim 19 simply recites
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"[a] Form II polymorph of (-)-modafinil." Br. 6. Accordingly, claim 34 also
does not require the Form II polymorph of (-)-modafinil produced by the
claimed process to have a powder X-ray diffraction spectrum with specific
peaks or reflections. Because Appellants' arguments traversing the
obviousness rejection are directed to a feature not present in the claims,
Appellants' arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner's prima facie case of obviousness as
to claim 34. Because Appellants do not advance secondary evidence of
nonobviousness, we affirm the Examiner's obviousness rejection of claim 34
over Ceausu and Largeau. Because they were not argued separately, claims
29-33 fall with claim 34. 37 C.F.R. § 41.37(c)(iv).
SUMMARY
For the reasons discussed, we reverse the Examiner's rejection of
claims 1-8 and 25-28 under 35 U.S.C. § 102(e) as anticipated by Ceausu.
However, we affirm the Examiner's rejection of claims 19-24 under
35 U.S.C. § 102(e) as anticipated by Ceausu.
We also affirm the Examiner's rejection of claims 29-34 under 35
U.S.C. § 103(a) for obviousness over Ceausu and Largeau.
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-IN-PART
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