Ex Parte Bissery

Board of Patent Appeals and Interferences

Dec 16, 2010

10747279 (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.
10/747,279 12/30/2003 Marie-Christine Bissery 3806.0281-11 4781
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 2010-003599
Application 10/747,279
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
methods of treating a cancer. The Patent Examiner rejected the claims on
the ground of 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 2010-003599
Application 10/747,279

2
STATEMENT OF THE CASE
Claims 28-38 and 40-46, which are all the pending claims, are on
appeal. Claim 28 is representative and reads as follows:
28. A method of treating a cancer in a human patient comprising
administering an effective amount of a combination of docetaxel and
5-fluorouracil to the patient, wherein the combination of docetaxel
and 5-fluorouracil has greater anticancer activity in the human patient
than the optimum dose of docetaxel alone against said cancer in the
human patient or the optimum dose of 5-fluorouracil alone against
said cancer in the human patient.

The Examiner rejected the claims under 35 U.S.C. § 103(a) as
unpatentable over Bissery 1992,2 Bissery 1991,3 Kline,4 Corbett,5 and
Speicher.6
Claims 29-38 and 40-46 have not been argued separately and
therefore stand or fall with claim 28. 37 C.F.R. § 41.37(c)(1)(vii).

2 M.C. Bissery et al., In vivo evaluation of Taxotere (RP56976, NSC628503)
in combination with cisplatinum, doxorubicin, or vincristine, Abst. No. 2645
in 33 PROC. AMER. ASSOC. CANCER RES. 443 (1992).
3 Marie-Christine Bissery et al., Experimental Antitumor Activity of
Taxotere (RP 56976, NSC 628503), a Taxol Analogue, 51 CANCER RES.
4845-4852 (1991).
4 Ira Kline et al., The Antileukemic Effectiveness of 5-Fluorouracil and
Methotrexate in the Combination Chemotherapy of Advanced Leukemia
L1210 in Mice, 26 CANCER RES. 848-852 (1966).
5 Thomas H. Corbett et al., 5-Fluorouracil containing combinations in
murine tumor systems, 7 INVESTIGATIONAL NEW DRUGS 37-49 (1989).
6 Lisa A. Speicher et al., Combined Antimicrotubule Activity of
Estramustine and Taxol in Human Prostatic Carcinoma Cell Lines,
52 CANCER RES. 4433-4440 (1992).
Appeal 2010-003599
Application 10/747,279

3
OBVIOUSNESS
The Issue
The Examiner found that Bissery (1992) taught treating cancer with a
combination of docetaxel and another chemotherapeutic agent with various
treatment regimens; that Bissery (1991) taught the effectiveness of docetaxel
for various cancers, as well as disclosing that both 5-fluorouracil and
docetaxel were used against colon cancer; that Kline and Corbett both
“demonstrate that the administration of 5-fluorouracil combined with other
chemotherapeutic agents is old and well known in the art for the treatment of
a cancer such as at least leukemia;” that Speicher disclosed the use of
paclitaxel, closely related to docetaxel, in combination with other agents for
treating cancer, and that Speicher “sets forth that the rationale for using the
combination therapy is to decrease the dosage of the chemotherapeutic
agents and to maximize cytotoxicity to cancer cells.” (Ans. 3-4.) The
Examiner found that one of ordinary skill in the art would have reasonably
expected the results of combination anticancer chemotherapy to be “at least
additive.” (Id.)
Appellant contends that the rejection fails to establish a prima facie
case of obviousness because it does not show “that one skilled in the art
would have predicted, based on the cited references, that the combination of
docetaxel and 5-fluorouracil would result in greater anticancer activity than
either or both drugs alone.” (App. Br. 12.) Appellant further contends that
the Examiner failed to support the “conclusion that one skilled in the art
would have reasonably expected . . . at least additive results.” (Id.)
According to Appellant, “the Examiner’s mere conclusory statement
is contrary to several established principles of combination chemotherapy.”
Appeal 2010-003599
Application 10/747,279

4
(Id. at 12-13, citing Scripture,7 Beijnen,8 and McLeod.9) According to
Appellant, Examiner’s references “fail to even teach or suggest the claimed
combination of docetaxel and 5-fluorouracil, let alone provide any guidance
as to whether the pharmacodynamic interactions between docetaxel and 5-
fluorouracil will be, e.g., (1) synergistic . . . , (2) antagonistic . . . ,
(3) additive . . . , or (4) sequence-dependent . . . .” (Id. at 13.) “[A]lthough
Kline, Corbett, and Speich[]er disclose combination chemotherapies that
show greater anticancer activity than the individual components
administered as monotherapies, none of these references, alone or in
combination, would lead one skilled in the art to predict that the claimed
combinations of docetaxel and 5-fluorouracil would have greater anticancer
activity than either (or both) compound(s) alone.” (Id. at 14.)
Appellant argues that results shown in the Specification demonstrate
“a combined effect that is significantly above the additive effect alleged by
the Examiner.” (Id. at 16, citing Table 3.) The Examiner responds that the
results in Table 3 fail to provide conclusive results in this regard, as the data
obtained against one cancer in mice is not commensurate in scope with the
claims to treat any kind of human cancer. (Ans. 6-7.)
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,

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 2010-003599
Application 10/747,279

5
has Appellant rebutted the prima facie case?

Findings of Fact
1. 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 find the Examiner’s evidence and reasoning persuasive. 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.
See, e.g., 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, Kline, Corbett and Speicher
suggests the claimed combination therapy would be successful. Corbett, for
example, disclosed that over 20 different 5-fluorouracil combinations had
been reported to be therapeutically synergistic. (Corbett 37.)
Appeal 2010-003599
Application 10/747,279

6
We are not persuaded by Appellant that Speicher disclosed hit-or-miss
results, and that Speicher stands for the failure of prediction. Speicher
described its plan to “investigate[] the hypothesis that taxol used in
combination with EM [estramustine] would be a logical approach to enhance
cytotoxicity through combined, though distinct, antimicrotubule activity.”
(Speicher 4433.) Speicher demonstrated the correctness of their hypothesis:
taxol used in combination with estramustine had greater than additive
cytotoxic effects, which Speicher attributed to the known fact that the two
drugs had different microtubule protein targets. (Id. at 4438.) Speicher
distinguished the comparison negative result: “[s]uch is not the case with
vinblastine and taxol, with both drugs interacting directly with tubulin.”
(Id.) Appellant has not provided any evidence that a person of ordinary skill
would have expected docetaxel and 5-fluorouracil to behave like drugs that
have the same target. The evidence shows they were known to have
different targets: Kline disclosed that 5-fluorouracil “inhibits thymidylate
synthetase” which “results in a reduced synthesis of DNA” (Kline 848), and
Bissery 1991 disclosed that taxotere (i.e., docetaxel) inhibits microtubule
depolymerization (Bissery 1991 at 4845).
We conclude that the rejection set out a prima facie case of
obviousness for an expected additive effect. Under these circumstances, it
was Appellant’s burden to rebut that case. See e.g., In re Susi, 440 F.2d 442,
446 (CCPA 1971) (“to overcome a finding of prima facie obviousness by
establishing that the claimed compositions are superior to what one of
ordinary skill in the art would expect, it was up to appellant to bring forward
reasonable evidence”); In re Diamond, 360 F.2d 214, 217 (CCPA 1966)
(where synergy was held expected because the combined drugs targeted
Appeal 2010-003599
Application 10/747,279

7
different cellular mechanisms, and in the absence of evidence that synergy
was unexpected, “[w]e are not convinced of the non-obviousness of the
combination of the 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.”).
We agree with the Examiner that Table 3’s demonstration of an effect
against one kind of cancer in mice is not evidence of an unexpected result
supporting claims of the treatment scope claimed. “Establishing that one (or
a small number of) species gives unexpected results is inadequate proof, for
it is the view of this court that objective evidence of non-obviousness must
be commensurate in scope with the claims which the evidence is offered to
support.” In re Greenfield, 571 F.2d 1185, 1189 (CCPA 1978) (quotations
omitted).

CONCLUSIONS
The Bissery 1992, Bissery 1991, Kline, Corbett, and Speicher
references support a prima facie case of obviousness against the claimed
combination therapy.
Appellant has not rebutted the prima facie case of obviousness.

Appeal 2010-003599
Application 10/747,279

8

SUMMARY
We affirm the rejection of claims 28-38 and 40-46 under 35 U.S.C.
§ 103(a) as unpatentable over Bissery 1992, Bissery 1991, Kline, Corbett,
and Speicher.

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

alw

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