Ex Parte Pesenti et al

Patent Trial and Appeal Board

Nov 18, 2016

13054646 (P.T.A.B. Nov. 18, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/054,646 01/18/2011
23389 7590 11/22/2016
SCULLY SCOTT MURPHY & PRESSER, PC
400 GARDEN CITY PLAZA
SUITE 300
GARDEN CITY, NY 11530
FIRST NAMED INVENTOR
Enrico Pesenti
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.
23033 8481
EXAMINER
PAGONAKIS, ANNA
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
11/22/2016 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):
Docket@SSMP.COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ENRICO PESENTI, MAURIZIO D'INCALCI, DARIO
BALLINARI, and JUERGEN MOLL 1
Appeal2015-006259
Application 13/054,646
Technology Center 1600
Before RICHARD J. SMITH, JOHN E. SCHNEIDER, and
RYAN H. FLAX, Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to a therapeutic combination of an Aurora kinase inhibitor
and an antimetabolite agent for cancer treatment. Claims 1, 4, 5, 10, 12, and
15 are on appeal as rejected under 35 U.S.C. § 103(a) and on the ground of
nonstatutory obviousness-type double patenting. We have jurisdiction under
35 U.S.C. § 6(b).
We affirm.
1 We understand the Real Party in Interest to be Nerviano Medical Sciences,
S.R.L. Br. 2.
Appeal2015-006259
Application 13/054,646
STATEMENT OF THE CASE
The appealed claims can be found in the Claims Appendix of the
Appeal Brief. Claim 1 is the sole independent claim, is representative, and
reads as follows:
1. A therapeutic combination comprising (a) Compound 1 of
formula (A):
(A)
, and (b)
one or more antineoplastic agents selected from the group
consisting of antimetabolite agents, wherein the active
ingredients of the combination are present in each case in free
form or in the form of a pharmaceutically acceptable salt thereof.
Br. 10 (Claims App'x).
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Application 13/054,646
The following rejections are on appeal:
Claims 1, 4, 5, 10, 12, and 15 stand rejected under 35 U.S.C. § 103(a)
over Fancelli 1,2 Fancelli 2, 3 Nair, 4 and Kleespies. 5 Final Action 3.
Claims 1, 4, and 5 stand rejected on the ground of nonstatutory
obviousness-type double patenting over claims 1-5 of Fancelli 628 6 and
Nair and Kleespies. Final Action 6.
Claims 1, 4, 5, 12, and 15 stand rejected on the ground ofnonstatutory
obviousness-type double patenting over claims 1-5 of Fancelli 5687 and
Nair and Kleespies. Final Action 7-8.
We adopt the Examiner's findings of fact, reasoning on scope and
content of the prior art, and conclusions set out in the Final Action and
Answer. Any findings of fact set forth below are provided only to highlight
certain evidence of record.
2 International Patent Application Pub. No. WO 2005/005427 Al (published
Jan. 20, 2005) (hereinafter "Fancelli 1 ").
3 Daniele Fancelli et al., 1,4,5, 6-Tetrahydropyrrolo[3,4-c]pyrazoles:
Identification of a Potent Aurora Kinase Inhibitor with a Favorable
Antitumor Kinase Inhibition Profile, 49 J. MED. CHEM. 7247-51 (2006)
(hereinafter "Fancelli 2").
4 J. S. Nair et al., A Novel Aurora B Kinase Inhibitor with Potent Anticancer
Activity Either as a Single Agent or in Combination with Chemotherapy, 22
J. CLIN. ONCOLOGY 9568 (2004) (July 15 Supplement) (hereinafter "Nair").
5 Axel Kleespies et al., Tyrosine Kinase Inhibitors and Gemcitabine: New
Treatment Options in Pancreatic Cancer?, 9 DRUG RESISTANCE UPDATES 1-
18 (2006) (hereinafter "Kleespies").
6 U.S. Patent No. US 7,582,628 B2 (issued to Fancelli et al. on Sept. 1,
2009) (hereinafter "Fancelli 628").
7 U.S. Patent No. US 7,141,568 B2 (issued to Fancelli et al. on Nov. 28,
2006) (hereinafter "Fancelli 568").
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DISCUSSION
Appellants contend no single reference "discloses the combination of
Compound 1 of formula (A) and one or more antimetabolite agents," but do
not argue that the combination of references fails to set forth all of the
limitations of the claimed invention. Br. 5. Appellants argue the
combination of prior art would not be made as set forth in the final rejection
because there would have been "no reasonable expectation that compound 1
of formula (A) would work in an antimetabolite's milieu and vice versa, let
alone that the combination would work together as claimed, and then to the
level of efficacy shown." Id. The Appellants' final argument on the
aforementioned "level of efficacy" is that the combined elements of the
invention create a "synergistic effect based on the equation of Chou-
Talalay" and, in relation thereto, the invention provides unexpectedly good
results. Id. These arguments were presented by Appellants most directly
regarding the obviousness rejection; however, they are referenced as the
only arguments over the double patenting rejections as well and, so, we
address all arguments together.
As to Appellants' first argument, "[ n ]on-obviousness cannot be
established by attacking references individually where the rejection is based
upon the teachings of a combination of references. . . . [The references]
must be read, not in isolation, but for what [they] fairly teach[] in
combination with the prior art as a whole." In re Merck & Co., 800 F.2d
1091, 1097 (Fed. Cir. 1986). Therefore, the fact that no single reference
teaches the precise combination of elements as claimed is not determinative.
The combined art was determined by the Examiner to disclose each element
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of the claims, and this is not persuasively contested by Appellants.
Therefore, we move on to Appellants' second argument.
Appellants argue there would be no reasonable expectation of success
in combining pyrrolo[3,4-c]pyrazole compounds of formula (A), for
example, the claimed N-{ 5-[(2R)-2-methoxy-2-phenylethanoyl]-1,4,5,6-
tetrahydropyrrolo[3,4-c ]pyrazol-3-yl }-4-( 4-methylpiperazin-1-yl)benzamide
(also identified as compound 9d of Fancelli 2's Table 2), disclosed by
Francelli 1 and Francelli 2 to be inhibitors of Aurora-2 and/or Aurora
kinases A and B, with antimetabolite agents, e.g., gemcitabine, oxaliplatin
and 5-FU, as disclosed by Nair and Kleespies (as being combinable with an
Aurora B kinase inhibitor or a tyrosine kinase inhibitor), such as proposed
by the Examiner in finally rejecting the claims. Compare Br. 5---6 with Final
Action 3-5 and Ans. 9-10. Appellants concede that each cited reference is
directed to a treatment for cancer, but contend "[t]he Office Action's
reasoning boils down to the premise that if one compound is good at
alleviating a problem, and a second compound is also good at alleviating the
problem, it is obvious that their combination must be even better and will be
successful." Br. 6. Appellants' argument is not persuasive.
"It is prima facie obvious to combine two compositions each of which
is taught by the prior art to be useful for the same purpose, in order to form a
third composition which is to be used for the very same purpose .... [T]he
idea of combining them flows logically from their having been individually
taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980).
Further, the
case law is clear that obviousness cannot be avoided simply by a
showing of some degree of unpredictability in the art so long as
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there was a reasonable probability of success. . . . Indeed, a rule
of law equating unpredictability to patentability ... would mean
that any new salt-including those specifically listed in the [prior
art] itself-would be separately patentable, simply because the
formation and properties of each salt must be verified through
testing. This cannot be the proper standard since the expectation
of success need only be reasonable, not absolute.
Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007).
The Specification identifies the claimed compound 1 of formula (A)
as "an aurora kinase inhibitor" and also that Francelli 1 disclosed how to
prepare this claimed compound. Spec. 1, 4--5. Nair disclosed successfully
combining cancer therapies by pairing an Aurora B inhibitor with several
other cancer-therapy compounds, including docetaxel, vinorelbrine,
gemcitabine, oxaliplatin, and 5-fluoruracil. Nair Abstract. Nair also
reported "a more than additive effect" in "all [such] combinations." Id.
Kleespies also disclosed compound combinations for cancer therapy,
specifically, "a strong case for combining gemcitabine with TKis [tyrosine
kinase inhibitors]," calling gemcitabine "the cornerstone of chemotherapy
for advanced and metastatic pancreatic cancer," and, further, "[ c ]ombination
regimens of gemcitabine with other cytotoxic drugs have shown promising
[but limited] activity in Phase II studies ... [and n]ew conventional
cytotoxic agents and other gemcitabine combinations might improve
survival for patients with pancreatic cancer[,] ... [ t ]herefore, novel
therapeutic strategies are urgently needed." Kleespies 1 (abstract), 2 (left
col.), and 3 (paragraph spanning left and right cols.).
It is well established that an invention "composed of several elements
is not proved obvious merely by demonstrating that each of its elements was,
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independently, known in the prior art. Although common sense directs one
to look with care at a patent application that claims as innovation the
combination of two known devices according to their established functions,
it can be important to identify a reason that would have prompted a person
of ordinary skill in the relevant field to combine the elements in the way the
claimed new invention does." KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007). That being so, however, the "interrelated teachings of multiple
[prior art references]; the effects of demands known to the design
community or present in the marketplace; and the background knowledge
possessed by a person having ordinary skill in the art, all [can provide] an
apparent reason to combine the known elements in the fashion claimed." Id.
Here, the primary cancer-therapy compounds of the claims, that is,
Aurora kinase inhibitors, were known, as was their combination with a
variety of other chemotherapeutic agents, and the prior art teaching of those
compounds was expressly referenced in the Specification. See Francelli 1
Abstract, 3:15-5:5, 16:8-17, 17(Table1), 17:22-18:8; Francelli2 7247
(Abstract), 7248 (Scheme 1, Table 2), 7249 (left col.), 7250 (Figure 4).
Further, the secondary cancer-therapy compounds of the claims, that is,
antimetabolite agents, were also known in the art and, moreover, their
combination with other cancer-therapeutics, including from the family of
Aurora kinase inhibitors like recited by the claims, was expressly suggested
by the cited references. See Nair (Abstract); Kleespies 1 (Abstract), 2-3.
The references themselves provide ample reason for the skilled artisan to
believe that the combination of an Aurora kinase inhibitor and an
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antimetabolite would be reasonably successful, if not more successful than
either component alone.
We tum now to the final argument presented by Appellants, that is,
that the claimed invention provides unexpected synergism and, thereby,
unexpected results.
In determining obviousness and assessing evidence of unexpected
results and synergism, it is proper to consider the closest prior arts'
disclosure of synergistic effects when combining therapeutic compounds
similar to those claimed. Novo Nordisk A/S v. Caraco Phama. Labs., Ltd.,
719 F.3d 1346, 1355 (Fed. Cir. 2013) (upholding district court's finding that
the closest prior art combination of similar compounds, with similar
mechanism of action, yielded synergistic effects and one would expect
similar synergy from claimed combination). Moreover, "[ s ]ynergism, in and
of itself, is not conclusive of unobviousness in that synergism might be
expected." In re Kollman, 595 F.2d 48, 55 n.6 (CCPA 1979). "[B]y
definition, any superior property must be unexpected to be considered
evidence of non-obviousness. Thus, in order to properly evaluate whether a
superior property was unexpected, the [fact-finder] should have considered
what properties were expected." Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348,
1371 (Fed. Cir. 2007).
Here, the closest prior art expressly suggests combining an Aurora
kinase inhibitor, as recited by the claims, with a variety of other
chemotherapeutic agents (see Fanceli 1 17:22-18:8; see also Final Action 4--
5) and also discloses that combining an antimetabolite agent, e.g., the also-
recited gemcitabine, with an Aurora kinase inhibitor "revealed more than
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[an] additive effect," i.e., it was synergistic in combination (see Nair
Abstract; see also Final Action 4--5). Thus, the synergistic effect of
combining the claimed Aurora kinase inhibitor and an antimetabolite agent,
specifically the also-claimed gemcitabine, was not unexpected, but was
obvious and expected based on the closest prior art. 8
For the reasons above, we affirm the obviousness rejection and the
obviousness-type double patenting rejections.
SUMMARY
The rejection of claims 1, 4, 5, 10, 12, and 15 under 35 U.S.C.
§ 103(a) over Fancelli 1, Fancelli 2, Nair, and Kleespies is affirmed. Claims
4, 5, 10, 12, and 15 were not argued separately and fall with claim 1. 37
C.F .R. § 41.3 7 ( c )(1 )(iv).
The rejection of claims 1, 4, and 5 on the ground of nonstatutory
obviousness-type double patenting over claims 1-5 of Fancelli 628 and Nair
and Kleespies is affirmed.
The rejection of claims 1, 4, 5, 12, and 15 on the ground of
nonstatutory obviousness-type double patenting over claims 1-5 of Fancelli
568 and Nair and Kleespies is affirmed.
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
8 We consider, but find unpersuasive, the mere conclusory statements of the
Declaration of Enrico Pesenti under 37 C.F.R. § 1.132, dated Nov 22, 2012.
9