Ex Parte Bissery

Board of Patent Appeals and Interferences

Dec 16, 2010

10747372 (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.
10/747,372 12/30/2003 Marie-Christine Bissery 3806.0281-09 6500
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 2010-003609
Application 10/747,372
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 cancer with a combination of docetaxel and etoposide.
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 2010-003609
Application 10/747,372

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STATEMENT OF THE CASE
Claims 24-34 and 36-42, which are all the pending claims, are on
appeal. Claim 24 is representative and reads as follows:
24. A method of treating a cancer in a human patient comprising
administering an effective amount of a combination of docetaxel and
etoposide to the patient, wherein the combination of docetaxel and
etoposide 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 etoposide 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 Jett,4 Watts,5 and
Speicher.6
Claims 25-34 and 36-42 were not argued separately and therefore
stand or fall with representative claim 24. 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, Abstract 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 James R. Jett et al., Treatment of Limited-Stage Small-Cell Lung
Cancer With Cyclophosphamide, Doxorubicin, and Vincristine With or
Without Etoposide: A Randomized Trial of the North Central Cancer
Treatment Group, 8 J. CLIN. ONCOL. 33-38 (1990).
5 Raymond G. Watts, Combination Chemotherapy With Ifosfamide and
Etoposide Is Effective in the Treatment of Central Nervous System
Metastasis of Childhood Neuroblastoma, 69 CANCER 3012-3014 (1992).
6 Lisa A. Speicher et al., Combined Antimicrotubule Activity of
Estramustine and Taxol in Human Prostatic Carcinoma Lines, 52 CANCER
RES. 4433-4440 (1992).
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Application 10/747,372

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OBVIOUSNESS
The Issue
The Examiner found that (1) Bissery (1992) described the treatment of
cancer in mice with a combination of docetaxel and another
chemotherapeutic agent in various regimens; (2) Bissery (1991) taught
docetaxel for treating various cancers, and compared its effectiveness to
recognized chemotherapeutic agents; (3) Jett taught etoposide in
combination therapy for small cell lung cancer; (4) Watts taught etoposide in
combination therapy for neuroblastoma; (5) Speicher disclosed using
paclitaxel, a compound closely related to docetaxel, in combination with
other chemotherapeutic agents for treating cancers; and (6) Speicher taught
“that the rationale for using combination therapy is to decrease the dosage of
the chemotherapeutic agents and to maximize cytotoxicity to cancer cells.”
(Ans. 3-4.)
The Examiner concluded that it would have been obvious to combine
docetaxel and etoposide because “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.” (Id. at 4, citing In re Susi, 440 F.2d 442 (CCPA
1971), and In re Kerkhoeven, 626 F.2d 846 (CCPA 1980)). Regarding the
greater anticancer activity of the combination compared to the optimum or
tolerated dose of each, the Examiner found that “one of ordinary skill in the
art would have reasonably expected the results to be at least additive.” (Id.)
The Examiner reviewed the Specification’s data but found that it “does not
demonstrate unexpected results in this regard.” (Id.) Ultimately the
Examiner concluded that it would have been obvious to administer a
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combination of docetaxel and etoposide “either simultaneously or
sequentially 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. at 4-5.)
Appellant contends that the appealed claims recite that the
combination of docetaxel and etoposide has greater anticancer activity than
either agent alone, but the references “fail to lead one skilled in the art to
predict these novel and non-obvious elements of the claimed invention.”
(App. Br. 10.) Appellant argues that the Examiner did not properly “support
her conclusion that one skilled in the art would have reasonably expected the
combination of docetaxel and etoposide to produce at least additive results.”
(Id. at 12.) According to Appellant, the Examiner’s “statement is contrary to
several established principles of combination chemotherapy.” (Id. at 12-13,
citing Scripture,7 Beijnen,8 and McLeod.9) Appellant argues the rejection
should be reversed because the references “do not enable one skilled in the
art to predict that the combination of docetaxel and etoposide exhibits
greater anticancer activity than either (or both) compounds(s) alone,” as
recited in the claims. (Id. at 14.) Appellant finds that Watts did not compare
the anticancer activity of its drugs alone to its combination, that Bissery
1992 taught only that its combined drugs were as active as the most active

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).
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agent in the combination, and that Jett taught its combined drugs showed no
difference in the response rate and did not lead to a meaningful improvement
in survival. (Id. at 14-15.) Because Speicher disclosed that the combination
of estramustine and paclitaxel exhibited a greater than additive effect, but
the combination vinblastine and paclitaxel did not, Appellant argues that
“one skilled in the art would not predict that the results of any given
combination chemotherapy would ‘be at least additive,’ as alleged by the
Examiner.” (Id. at 15.)
The Examiner responds that the information in Scripture, Beijnen, and
McLeod is not specific to the claimed invention, and gives these references
little weight. (Ans. 5.) The Examiner finds that the results shown in Table 2
for treatment of early B16 melanoma are not commensurate with the claims
to treating “any” cancer, and finds that “the probative value of the data is not
commensurate in scope with the degree of protection sought by the claim.”
(Id. at 6-8.)
The issues with respect to this appeal are:
did the rejection state a prima facie case of obviousness; and if so,
did Appellant rebut 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
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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
cancer in humans with a combination of docetaxel and etoposide. 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,
reducing side effects, and avoiding multidrug resistance by using
chemotherapeutic agents targeting different cellular pathways would have
been expected benefits. The references establish that combination
chemotherapy was conventional. For example, Jett explained:
“[c]ombination chemotherapy with or without thoracic radiation has been
standard therapy for SCC [small cell carcinoma] since the mid-1970s,” and
“[w]ith the reported efficacy of single-agent etoposide against SCC, it was
only natural to add this agent to a previously accepted standard combination
therapy of CAV [cyclophosphamide, doxorubicin, and vincristine].” (Jett,
36.)
The claims on appeal, however, define a method in which the
combination has greater anticancer activity than the optimum dose of either
drug alone. 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
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7
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, Jett, Watts, and Speicher suggests
the claimed combination therapy would be successful.
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 etoposide to behave like drugs that have
the same target. The evidence shows they were known to have different
targets: Jett disclosed that etoposide’s “mechanism of action is thought to be
interference with the scission-reunion action of topoisomerase II with
resultant DNA damage” (Jett 33), and Bissery 1991 disclosed that taxotere
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
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8
was Appellant’s burden to rebut that case. See e.g., Susi, 440 F.2d at 446
(“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 drugs were
expected to exhibit synergy because they targeted different cellular
pathways, and no evidence of unexpected synergy was produced, “[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”).
We agree with the Examiner that Table 2’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
Bissery (1992), Bissery (1991), Jett, Watts, and Speicher support a
prima facie case of obviousness against the claimed method of combination
chemotherapy.
Appellant did not rebut the prima facie case.
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Application 10/747,372

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SUMMARY
We affirm the rejection of claims 24-34 and 36-42 under 35 U.S.C.
§ 103(a) as unpatentable over Bissery (1992), Bissery (1991), Jett, Watts,
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

lp

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