Ex Parte Bissery

Board of Patent Appeals and Interferences

Dec 16, 2010

11149178 (B.P.A.I. Dec. 16, 2010)

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.
11/149,178 06/10/2005 Marie-Christine Bissery 03806.0281-15000 9609
22852 7590 12/16/2010
FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER
LLP
901 NEW YORK AVENUE, NW
WASHINGTON, DC 20001-4413
EXAMINER
MARX, IRENE
ART UNIT PAPER NUMBER
1651
MAIL DATE DELIVERY MODE
12/16/2010 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MARIE-CHRISTINE BISSERY
__________

Appeal 2010-006261
Application 11/149,178
Technology Center 1600
__________

Before ERIC GRIMES, FRANCISCO C. PRATS, 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 a
method of treating a neoplastic disease. The Patent Examiner rejected the
claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We
affirm.

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.
Appeal 2010-006261
Application 11/149,178

2
STATEMENT OF THE CASE
Claims 15, 19, 21, 22 and 26-36 are on appeal.2 Claim 15 is
representative and reads as follows:
15. A method of treating a neoplastic disease in a human patient in need
thereof, comprising administering to the patient an effective amount
of a combination of at least one taxane chosen from paclitaxel,
docetaxel, and derivatives thereof, and at least one topoisomerase
inhibitor chosen from camptothecin, irinotecan, topotecan, and
pyridobenzoindole, wherein the combination of at least one taxane
and at least one topoisomerase inhibitor has greater anticancer activity
against said neoplastic disease in the human patient, or the optimum
dose of the at least one topoisomerase inhibitor alone against said
neoplastic disease in the human patient.

The Examiner rejected claims 15, 19, 21, 22 and 26-36 under
35 U.S.C. § 103(a) as unpatentable over Bissery 1992,3 Bissery 1991,4 and
Masuda.5
Claims 19, 21, 22 and 26-36 have not been argued separately and
therefore stand or fall with claim 15. 37 C.F.R. § 41.37(c)(1)(vii).

2 Claim 18 was withdrawn from consideration. (App. Br. 5.) There are no
other pending claims. (Id.)
3 Bissery, M.C., et al., In vivo evaluation of Taxotere (RP56976,
NSC628503) in combination with cisplatinum, doxorubicin, or vincristine,
Abstract 2645, 33 PROC. AMER. ASSOC. CANCER RES. 443 (1992).
4 Marie-Christine Bissery et al., Experimental Antitumor Activity of
Taxotere (RP 56976, NSC 628503), a Taxol Analogue, 51 CANCER RES.
4845-4852 (1991).
5 Noriyuki Masuda et al., CPT-11: A New Derivative of Camptothecin for
the Treatment of Refractory or Relapsed Small-Cell Lung Cancer, 10 J.
CLIN. ONCOL. 1225-1229 (1992).
Appeal 2010-006261
Application 11/149,178

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OBVIOUSNESS
The Issue
The Examiner found that (1) Bissery 1992 taught the treatment of
cancer in mice by the combination of docetaxel with various other anti-
cancer agents; (2) Bissery 1991 taught that docetaxel was useful to treat a
variety of cancers such as adenocarcinomas, leukemia, sarcoma and colon
carcinoma; and (3) Masuda demonstrated that irinotecan was known to be
suitable for treating cancer. (Ans. 4.) The Examiner concluded that it would
have been obvious to modify the process of Bissery 1992 by administering
docetaxel in combination with irinotecan for the treatment of a neoplastic
disease or cancer, “for the expected benefit of improving the effectiveness of
the treatment of a cancer by maximizing cytotoxicity to the cancer cells and
reducing side effects as well as avoiding multidrug resistance by using
chemotherapeutic agents targeting different cellular pathways.” (Id.)
According to the Examiner, there would have been a reasonable expectation
of success in treating a neoplastic disease or cancer with the combination “in
view of their known favorable effects in the treatment of various cancers.”
(Id.)
Appellant points out that the claims “recite combinations of docetaxel
and irinotecan having greater anticancer activity than either (or both)
agent(s) alone,” and argues that because the references “fail to teach or
suggest these elements,” they “cannot render the claimed invention
obvious.” (Replacement Arg. 1-2.6) According to Appellant, the

6 Appellant filed an Appeal Brief on March 5, 2009, and later filed a
“Response To Notice Of Non-Compliant Appeal Brief” dated May 4,
Appeal 2010-006261
Application 11/149,178

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Examiner’s finding that at least additive results would have been expected is
“conclusory,” and lacks a rational underpinning. (Id. at 4.) Appellant
further contends that drug interactions can have various outcomes, but the
Examiner’s references “fail to teach or suggest docetaxel and irinotecan used
in combination, let alone provide any guidance as to whether the
pharmacodynamic interactions between docetaxel and irinotecan will be,
e.g., (1) synergistic . . . , (2) antagonistic . . . , (3) additive . . . , or (4)
sequence-dependent . . . .” (Id. at 4-5, citing Scripture,7 Beijnen,8 and
McLeod.9)
Appellant argues that the Specification “has surprisingly shown that
docetaxel combination chemotherapies exhibit greater antitumor activity
than the individual agents administered as monotherapies.” (Id. at 6, citing
Tables 1-4.) The Examiner responds that “one of ordinary skill in the art
would have reasonably expected the results to be at least additive,” that the
Specification “does not demonstrate unexpected results,” and that “there are
no results in the instant written disclosure directed to the use of docetaxel in
combination with irinotecan in any environment” (Ans. at 4-5.) The
Examiner found that Scripture, Beijnen, and McLeod were not specific to
the claimed invention, and gave them little weight. (Id. at 5.)

2009. The Response contained a replacement, six-page “Argument” section.
We cite to the pages in the replacement Argument.
7 Charity D. Scripture et al., Drug interactions in cancer therapy, 6 NATURE
REVIEWS CANCER 546-558 (2006).
8 Jos H Beijnen et al., Drug interactions in oncology, 5 LANCET ONCOL.
489-496 (2004).
9 Howard L. McLeod, Clinically relevant drug-drug interactions in
oncology, 45 BR. J. CLIN. PHARMACOL. 539-544 (1998).
Appeal 2010-006261
Application 11/149,178

5
The issues with respect to this rejection are:
do the references support a prima facie case of obviousness against
the claimed combination therapy; and, if so,
has Appellant rebutted the prima facie case?

Findings of Fact
We adopt the Examiner’s findings of fact.

Principles of Law
“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).

Analysis
We agree with the Examiner that the prior art suggested treating a
neoplastic disease in humans with a combination of docetaxel and
irinotecan. We also agree that there would have been a reasonable
expectation of successfully treating cancer with the combination, and that
improving the effectiveness of the treatment of a cancer by maximizing
cytotoxicity to the cancer cells and reducing side effects as well as avoiding
multidrug resistance by using chemotherapeutic agents targeting different
cellular pathways would have been expected benefits. Bissery 1992 and
Masuda both show that combination chemotherapy was conventional.
The claims on appeal, however, define a method in which the
combination has greater anticancer activity than the optimum dose of either
Appeal 2010-006261
Application 11/149,178

6
drug alone. The Examiner found that targeting different cellular pathways
was expected to provide that advantage. Masuda taught that irinotecan (aka
CPT-11; see amendment filed Aug. 1, 2008) “is a potent inhibitor of DNA
topoisomerase.” (Masuda 1225.) Bissery 1991 taught that taxotere (aka
docetaxel) inhibits microtubule depolymerization. (Bissery 1991 at 4845.)
We agree with the Examiner that a person of ordinary skill in the art would
have reasonably expected additive effects for the claimed combination
therapy. In other cases where synergy was expected because drugs targeted
different cellular pathways, and no evidence of unexpected synergy was
produced, the conclusion of obviousness has been sustained. In re Diamond,
360 F.2d 214, 217 (CCPA 1966) (affirming obviousness in the absence of
evidence that synergy was unexpected; “[w]e are not convinced of the non-
obviousness of the combination of two drugs, A5MP and a glucocorticoid . .
. particularly since the record supports the [PTO’s] contention that the drugs
selected are two of the commonly used drugs in the treatment of such
collagen diseases”). See also, Merck & Co., Inc. v. Biocraft Labs., Inc.,
874 F.2d 804, 809 (Fed. Cir. 1989) (“Given the prior art teaching that both
amiloride and hydrochlorothiazide are natriuretic, it is to be expected that
their co-administration would induce more sodium excretion than would
either diuretic alone”).
Like the Examiner, we find Scripture, Beijnen, and McLeod not
specific to the claimed combination, and we agree that the more specific
evidence in Bissery 1992, Bissery 1991, and Masuda suggests the claimed
combination therapy would be successful.

Appeal 2010-006261
Application 11/149,178

7
We agree with the Examiner that the evidence in Specification Tables
1-4 concerns combinations of other drugs, not irinotecan (or even any of the
other topoisomerase inhibitors recited in claim 15), with docetaxel, and it is
therefore not persuasive of nonobviousness regarding claims using
irinotecan. “Although it is well settled that comparative test data showing an
unexpected result will rebut a prima facie case of obviousness, the
comparative testing must be between the claimed invention and the closest
prior art.” In re Fenn, 639 F.2d 762, 765 (CCPA 1981) (emphasis added).

CONCLUSIONS
Bissery 1992, Bissery 1991, and Masuda support a prima facie case of
obviousness against the claimed combination therapy.
Appellant has not rebutted the prima facie case of obviousness.

SUMMARY
We affirm the rejection of claims 15, 19, 21, 22 and 26-36 under
35 U.S.C. § 103(a) as unpatentable over Bissery 1992, Bissery 1991, and
Masuda.
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

lp

Appeal 2010-006261
Application 11/149,178

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FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER
LLP
901 NEW YORK AVENUE, NW
WASHINGTON DC 20001-4413