Ex Parte Pesenti et al

Patent Trial and Appeal Board

Jan 29, 2016

13054868 (P.T.A.B. Jan. 29, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/054,868 01119/2011
23389 7590 02/02/2016
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.
23034 1502
EXAMINER
PAGONAKIS, ANNA
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
02/02/2016 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ENRICO PESENTI, DARIO BALLINARI, and
JUERGEN MOLL 1
Appeal2013-008868
Application 13/054,868
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
RICHARD J. SMITH, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
therapeutic combination comprising a compound and one or more
antineoplastic agents. (Br. 11-12.) We have jurisdiction under 35 U.S.C.
§ 6(b ).
We affirm.
1 According to Appellants, the real party in interest is N erviano Medical
Sciences, S.R.L. (Br. 2.)
Appeal2013-008868
Application 13/054,868
STATEMENT OF THE CASE
Claims on Appeal
Claims 12-14, 17, and 19 are on appeal. 2 (Br. 11-12.) Claim 12 is
illustrative and reads as follows:
12. A therapeutic combination comprising (a) Compound 1 of formula
(A):
(A)
and (b) one or more antineoplastic agents selected from the group consisting
of bevacizumab and bortezomib, 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.
Examiner's Rejections
1. Claims 12-14 and 17 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Fancelli '212 3 in view ofDai. 4 (Ans. 3.)
2 Claims 1-11 and 18 are cancelled, and claims 15 and 16 are withdrawn.
(Br. 11-12.)
3 WO 2007/113212 A2, published Oct. 11, 2007 ("Fancelli '212").
4 Dai, et al., Bortezomib and flavopiridol interact synergistically to induce
apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate
through both Ber/Ahl-dependent and -independent mechanisms, 104 BLOOD
2, at 509-18 (2004) ("Dai").
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Application 13/054,868
2. Claims 12-14, 17, and 19 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Fancelli '427 5 and the Fancelli Article 6 in view of Dai.
(Ans. 6.)
3. Claim 12 stands rejected on the ground of nonstatutory obviousness-
type double patenting as unpatentable over claims 1-5 ofFancelli '628. 7
(Ans. 9.)
4. Claim 12 stands rejected on the ground of nonstatutory obviousness-
type double patenting as unpatentable over claims 4---6 ofFancelli '568. 8
(Ans. 10.)
Appellants have presented arguments for the patentability of claims
12-14, 17, and 19 as a group. (Br. 4--10.) In accordance with 37 C.F.R.
§ 41.37(c)(l)(iv), we select claim 12 as the representative claim to decide
the appeal of the rejection of these claims.
FINDINGS OF FACT
We adopt the Examiner's findings and analysis concerning the scope
and content of the prior art. The following findings are included for
emphasis and reference convenience.
FF 1. The Examiner finds that F ancelli '212, F ancelli '4 2 7, the F ancelli
Article, claim 1 of Fancelli '628, and claim 4 of Fancelli '568 disclose or
5 WO 2005/005427 Al, published Jan. 20, 2005 ("Fancelli '427").
6 Fancelli, et al., l,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. 24, at 7247-51 (2006) ("the Fancelli
Article").
7 U.S. Patent No. 7,582,628 B2, issued Sept. 1, 2009 ("Fancelli '628").
8 U.S. Patent No. 7,141,568 B2, issued Nov. 28, 2006 ("Fancelli '568").
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Application 13/054,868
encompass Compound 1 of formula (A) as claimed. (Ans. 4 and 6-10.)
Appellants do not dispute this finding.
FF 2. The Examiner finds that the compounds disclosed by Fancelli '212 are
useful in the treatment of imatinib-resistant chronic myelogenous leukemia,
and may be used alone or in combination with other cytostatic or cytotoxic
agents. (Ans. 5.)
FF 3. The Examiner finds that Dai teaches a method of "synergistically
interacting to induce apoptosis in chronic myeloid leukemia cells resistant to
imatinib mesylate with administration of bortezomib and flavopiridol."
(Ans. 4.)
DISCUSSION
Issues
The issues presented are whether a preponderance of evidence of
record supports the Examiner's conclusion that
(a) claim 12 is obvious based on Fancelli '212 and Dai,
(b) claim 12 is obvious based on Fancelli '427, the Fancelli
Article, and Dai,
(c) claim 12 is unpatentable on the ground of nonstatutory
obviousness-type double patenting over claims 1-5 of
Fancelli '628,and
( d) claim 12 is unpatentable on the ground of nonstatutory
obviousness-type double patenting over claims 4---6 of
Fancelli '568.
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Application 13/054,868
Analysis
Appellants argue all of the rejections together, and group Fancelli
'212, the Fancelli Article, Fancelli '628, and Fancelli '568 together as the
"Fancelli References."9 (Br. 4--10.) Accordingly, we address the two
obviousness rejections and two obviousness-type double patenting rejections
together. See Procter & Gamble Co. v. Teva Pharms. USA, Inc., 566 F.3d
989, 999 (Fed. Cir. 2009) ("In general, the obviousness analysis applies to
double patenting").
Appellants argue that there is no motivation or reason to combine the
compound of the Fancelli References (FF 1) with bortezomib as disclosed by
Dai, and no reasonable expectation of success in doing so. (Br. 5-8.)
Furthermore, Appellants argue that "[t]he circumstances strongly suggest
that improper hindsight has been applied: that the combination only comes
to mind by benefit of the instant specification." (Id. at 6.)
We are not persuaded by Appellants' arguments. "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." In re Kerkhoven, 626 F.2d
846, 850 (CCPA 1980). Here, the obviousness of using Compound 1 of
formula (A) in combination with bortezomib is based on the fact that both
are known in the prior art for the same purpose, and both are encouraged in
9 Appellants refer to Fancelli '212 rather than Fancelli '427 in connection
with Rejection No. 2 (Br. 4), and do not list Fancelli '427 among the
Fancelli References. (Br. 5.) However, although Appellants do not argue
Fancelli '427, we include it as part of the Fancelli References for purpose of
the appeal.
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Appeal2013-008868
Application 13/054,868
the prior art to be used in combination therapy. (Ans. 4--5, 12; FF 2, 3.)
Thus, the art provides a motivation to combine Compound 1 of formula (A)
with bortezomib, and it is prima facie obvious to do so.
We are also unpersuaded by Appellants' arguments regarding
expectation of success and hindsight. Here, the reasonable expectation of
success is shown in the art itself, which encourages both Compound 1 of
formula (A) and bortezomib to be used with another agent. (FF 2, 3.)
Furthermore, any concern regarding hindsight bias is overcome because the
Examiner points to specific disclosures in the prior art that give a reason or
motivation to make the claimed combination. See Otsuka Pharm. Co., Ltd.
v. Sandoz, Inc., 678 F.3d 1280, 1292 (Fed. Cir. 2012).
Accordingly, we find that the Examiner has established a prima facie
case of obviousness and obviousness-type double patenting, and Appellants'
arguments do not overcome that prima facie case.
Unexpected Results
Appellants argue that "the data presented in Tables 2 and 3 of the
specification are compellingly indicative of an unexpected and surprisingly
dramatic slowing in tumor growth, as indicated by a higher T-C number, 10
for administration of the claimed combination as opposed to administration
of either agent singularly." (Br. 6.) Tables 2 and 3 are reproduced below.
10 According to Appellants, "[ t ]he T-C figure indicates the difference of
time, in days, required for treatment group (T) and control group (C) tumors
to reach a size of one gram. [] As an example, if the T-C was 2 days, it
would take 2 days longer for treatment group tumors to reach one gram as
compared to the time it takes for the control group tumors to reach one
gram." (Br. 6.)
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Application 13/054,868
Table 2
Trcattll('.lli
Compound 1
15 mg/kg*
Bevacizumab
20 mg/kg**
Bcvacizumab
20mgikg +
Compound I
15 mgikg***
Time to reach
lg (days)
23,9
18.5
28.2
T-C (days) Toxicity
8.5 O//S
3.l 0/8
12.8 OiS
*Treatments made intrnpcritonca!ly nvice at days 9,1OJIJ2,13)4)5, 16, l7, l8 and
19
**Treatment~ made intrapcritoncally at days 9, l 3 and ! 7
*** Days 9, 13 and l 7 bcvacizurm1b treatments; day~ 9, 10, l l, 12, 13, 14, 15, 16, 17,
18 and 19 Compound l treatments
(Spec. 14.)
Table 3
Treatment
T in:ic to reach l g
{days)
T-C (days) Toxicity
--~~);;~:;~1~; ___ 1 _____________________________ :~:~------------------- ____________________ ?:_! __________________________________ ?:/? ___________
Bo rtczon1 ·ib
0.5 mg/kg**
19 3.4 0/7
Bortczomib
__ L_'.'.~~r~~},?-~~~'. ______________ ------------------=~:-~------------------- --------------------~:=-------------------- -----------~'..~------------
Ho rtczom i b
0.5 mg/kg+
Cornpound l
29.2 B.5 0/7
___ \_~--~~'.Â¥:'.~:\:l~-~~-------- ----------------------------------------------- ----------------------------------------------- ------------------------------
Bortezo mib
l mg/kg+
Compound 1
15 mg/kg***
51.4 35.7 3/7
*cfrci:(!n1cn-is-:111;at:-ii1-rri:;i;-crii(ii1cd-i>-:--i\\.:-r;:c -~;i:--ai:i):s--L2:-1IT{T5-Jl;:r;-:-rs:T9~-2 o, n ,
22. 23.
**Treatments made by intravenous route at days 12.16,20,24
"'** Day;; 12,l 6, 20 24 bortczornib treatments, 13, 14, l 5,l 7,18, 19, 2 l, 22, 23, 25,
26 and 27 Compound l treatments.
(Spec. 15-16.)
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Appeal2013-008868
Application 13/054,868
We do not find that the data in the Specification, as argued by
Appellants and when weighed with the evidence supporting the prima facie
case, provides sufficient evidence of unexpected results to rebut the prima
facie case. Appellants state that "only the T-C column needs consideration,"
but then argue the results from the column entitled "Time to reach 1 g
(days)." (Br. 6.) Furthermore, when arguing the T-C column results,
Appellants refer to the "average" of the T-C results for compound 1 and
bortezomib (or bevacizumab) independently, rather than the "addition" of
the T-C results as referenced in the Specification. (See Br. 7 and Spec. 13, 1.
22; 15, 1. 14.) As pointed out by the Examiner, when the results of the
individual components argued by Appellants are added rather than
averaged, "the difference in actual delays in tumor growth is approximately
1 day for each combination." 11 (Ans. 16.)
Also, Appellants do not sufficiently establish that a person of ordinary
skill in the art would have found the data regarding the claimed therapeutic
combination to be unexpected. See Pfizer, Inc. v. Apotex, Inc., 480 F .3d
1348, 1371 (Fed. Cir. 2007) ("any superior property must be unexpected to
be considered as evidence of non-obviousness"). Here, some improved
efficacy would not appear to be unexpected given that the effectiveness of
both Compound 1 of formula (A) and bortezomib was already known in the
11 From Table 2, Appellants average 8.5 and 3.1 (yielding 5.8 days), but
when the individual results are added, the result is 11.6 days (compared to
12.8 days for the combination). From Table 3, Appellants average 9.1 and
3.4 (yielding 6.25 days), but when the individual results are added, the result
is 12.5 days (compared to 13.5 days for the combination). Appellants do not
explain why they average the results in their argument when the
Specification adds the results.
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Appeal2013-008868
Application 13/054,868
art. (FF 1-3.) See Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752
F.3d 967, 977-78 (Fed. Cir. 2014) (effectiveness of claimed compound was
not unexpected in light of the activity of structurally similar compound in
prior art reference).
We also find that the data in the Specification regarding improved
slowing in tumor growth reflects a difference in degree rather than a
difference in kind. "[D]ifferences in degree" of a known and expected
property are not as persuasive in rebutting obviousness as differences in
"kind" (i.e., a new property dissimilar to the known property). Id. at 977;
see also In re Merck, 800 F.2d 1091, 1099 (Fed. Cir. 1986) (finding
evidence that the new drug was a more potent sedative and stronger
anticholinergic effect than the prior art was insufficient to outweigh the
evidence of obviousness).
Accordingly, we find that Appellants' evidence of unexpected results
is insufficient to rebut the prima facie case established by the Examiner.
Conclusions of Law
A preponderance of evidence of record supports the Examiner's
conclusion that
(a) claim 12 is obvious under 35 U.S.C. § 103(a) based on Fancelli '212
and Dai,
(b) claim 12 is obvious under 35 U.S.C. § 103(a) based on Fancelli '427,
the Fancelli Article, and Dai,
(c) claim 12 is unpatentable on the ground ofnonstatutory obviousness-
type double patenting over claims 1-5 of Fancelli '628, and
(d) claim 12 is unpatentable on the ground of nonstatutory
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Application 13/054,868
obviousness-type double patenting over claims 4---6 of Fancelli '568.
Furthermore, Appellants have not provided sufficient evidence of
unexpected results, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of nonobviousness.
Claims 13, 14, 17, and 19 were not argued separately and therefore
fall with claim 12.
SUMMARY
We affirm all rejections of all appealed claims.
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
tc
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