Ex Parte King et al

Board of Patent Appeals and Interferences

Nov 8, 2010

10738423 (B.P.A.I. Nov. 8, 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.
10/738,423 12/16/2003 Ivan C. King 873-Z-US 8783
7590 11/09/2010
Albert Wai-Kit Chan
ALBERT WAI-KIT CHAN, LLC
141-07 20th Avenue
World Plaza, Suite 604
Whitestone, NY 11357
EXAMINER
LI, QIAN JANICE
ART UNIT PAPER NUMBER
1633
MAIL DATE DELIVERY MODE
11/09/2010 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 IVAN C. KING and LI-MOU ZHENG
__________

Appeal 2009-014775
Application 10/738,423
Technology Center 1600
__________

Before TONI R. SCHEINER, MELANIE L. McCOLLUM, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to a cancer
treatment method. The Examiner has rejected the claims on appeal as
obvious. 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.
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STATEMENT OF THE CASE
Claims 113, 115-117, and 119-124 are on appeal (App. Br.2 4).
Claims 118 and 125 are also pending but have been withdrawn from
consideration by the Examiner (Final Rej. 2-3).3
We will focus on claims 113, 115, and 123, which read as follows:
113. A method of inhibiting the growth of, or reducing the volume of a
solid tumor cancer, comprising administering to a subject having a solid
tumor cancer an effective amount of cytoxan or cisplatin and an effective
amount of a pharmaceutical composition comprising a pharmaceutically
acceptable carrier and an attenuated tumor-targeted Salmonella, wherein the
Salmonella comprises an msbB- mutant.
115. The method of claim 113 wherein, the solid tumor or cancer is either a
lung cancer or colon cancer.
123. A method of inhibiting the growth of, or reducing the volume of a
solid tumor cancer, comprising administering to a subject having a solid
tumor cancer an effective amount of,
(a) a pharmaceutical composition consisting essentially of an anti-
cancer compound and one or more pharmaceutically acceptable carriers, and
(b) an effective amount of a pharmaceutical composition comprising a
pharmaceutically acceptable carrier and an attenuated tumor-targeted
Salmonella, wherein the Salmonella comprises an msbB- mutant.

2 As used herein, “App. Br.” refers to the Response to Notification of Non-
Compliant Appeal Brief dated January 9, 2009. In addition, “Final Rej.”
refers to the Final Rejection dated December 20, 2007; “Ans.” refers to the
Examiner’s Answer dated February 5, 2009; “Reply Br.” refers to the Reply
Brief dated March 12, 2009; “Supp. Ans.” refers to the Supplemental
Examiner’s Answer dated May 11, 2009; and “2d Reply Br.” refers to the
Reply Brief dated June 29, 2009.
3 Appellants filed an Amendment canceling claims 122-125 on June 29,
2009. However, the Examiner has not indicated whether this Amendment
had been entered. Thus, we include these claims in our decision.
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The other claims on appeal have been argued with and therefore stand or fall
with claims 113, 115, or 123. 37 C.F.R. § 41.37(c)(1)(vii).
The Examiner relies on the following references:
K. Brooks Low et al., Lipid A mutant Salmonella with suppressed virulence
of TNFα induction retain tumor-targeting in vivo, 17 NAT. BIOTECH. 37-41
(1999) (hereinafter “Low”).
J. Schachter et al., A Sequential Four-drug Chemotherapy and Biotherapy
with Interferon Alpha and GM-CSF – An Innovative Protocol for the
Treatment of Metastatic Melanoma, 13 CANCER BIOTHER. RADIOPHARM.
155-164 (1998) (hereinafter “Schachter”).
John M. Pawelek et al., Tumor-targeted Salmonella as a Novel Anticancer
Vector, 57 CANCER RES. 4537-4544 (1997) (hereinafter “Pawelek”).
E. Jirillo et al., Relationship Between Immune System and Gram-Negative
Bacteria. Acid-Treated Salmonella Minnesota R 595 (Re) Enhances
Immune Responsiveness in Patients with Gynecologic Malignancies, 8 INT.
J. IMMUNOPHARMAC. 881-886 (1986) (hereinafter “Jirillo”).
Appellants additionally rely on the following references:
KU Chow et al., In AML cell lines Ara-C combined with purine analogues is
able to exert synergistic as well as antagonistic effects on proliferation,
apoptosis and disruption of mitochondrial membrane potential, 44 LEUK.
LYMPHOMA 165-173 (2003) (Abstract only) (hereinafter “Chow”).
DR Budman et al., Synergistic and antagonistic combinations of drugs in
human prostate cancer cell lines in vitro, 13 ANTICANCER DRUGS 1011-1016
(2002) (Abstract only) (hereafter “Budman”).
Girija P. Dasmahapatra et al., In vitro Combination Treatment with
Perifosine and UCN-01 Demonstrates Synergism against Prostate (PC-3)
and Lung (A549) Epithelial Adenocarcinoma Cell Lines, 10 CLIN. CANCER
RES. 5242-5252 (2004) (hereinafter “Dasmahapatra”).
Alison G. Freifeld et al., Fever in the Neutropenic Cancer Patient, in
CLINICAL ONCOLOGY, chap. 46, pp. 925-926 (3d ed. 2004) (hereinafter
“Freifeld”).
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The claims on appeal stand rejected as follows:
Claims 113, 116, 117, 119, 120, 123, and 124 under 35 U.S.C.
§ 103(a) as obvious over Low in view of Schachter (Ans. 5); and
Claims 115, 121, and 122 under 35 U.S.C. § 103(a) as obvious over
Low in view of Schachter and Pawelek (id. at 8).
ISSUE
With regard to each of claims 113, 115, and 123, the issue on appeal
is: Does the evidence of record support the Examiner’s conclusion that it
would have been obvious to treat a solid tumor cancer with both a
Salmonella msbB¯ mutant, as disclosed in Low, and cisplatin, as disclosed in
Schachter?
FINDINGS OF FACT
FF1. We agree with the Examiner’s explicit findings regarding the
scope and content of the Low, Schachter, and Pawelek (Ans. 5-9).
FF2. For example, as found by the Examiner, Low discloses “that the
msbB¯ bacteria can be safe for use in humans” (Low 40; Ans. 5-6).
FF3. Chow discloses that Ara-C combined with certain purine
analogues “exhibited additive to antagonistic effects,” but that the
combination of Ara-C with another purine analogue “exclusively yielded
synergistic effects” (Chow, Abstract).
FF4. Budman discloses that “[d]ocetaxel demonstrated cytotoxic
additive effects or synergy” with certain drugs, but that other drugs,
including cisplatin, carboplatin, or etoposide, “were antagonistic when
combined with docetaxel.” In particular, Budman states that
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“[c]ombinations of docetaxel with platinum or etoposide may lead to
subadditive effects in treatment.” (Budman, Abstract.)
FF5. Dasmahapatra discloses that, at the concentrations used,
perifosine and UCN-01 “did not significantly affect the growth of” two
cancer cell lines, but that, “in combination at the same respective individual
concentrations . . . , virtually complete growth inhibition of both the cell
lines resulted” (Dasmahapatra, Abstract).
FF6. Freifeld discloses:
Neutropenia is a common and predictable consequence of many
cytotoxic cancer therapies. . . . [A] deficit of neutrophils (i.e.,
neutropenia) is associated with an increase in susceptibility to
infections as well as an attenuation of inflammatory responses
to infections. . . . Infection unopposed by innate neutrophil
responses can progress rapidly and relentlessly, leading to high
levels of morbidity and mortality.
(Freifeld 925.)
PRINCIPLES OF LAW
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “An obviousness
determination requires that a skilled artisan would have perceived a
reasonable expectation of success in making the invention in light of the
prior art.” Amgen Inc. v. F. Hoffman-LA Roche Ltd, 580 F.3d 1340, 1362
(Fed. Cir. 2009). However, “[o]bviousness does not require absolute
predictability of success.” In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir.
1988).
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ANALYSIS
We adopt the Examiner’s reasoning and response to arguments as set
forth in the Examiner’s Answer as our own, except that we have not relied
on Jirillo in reaching our decision. We provide the following additional
comments with regard to arguments raised in the Reply Briefs.
Chow, Budman, and Dasmahapatra teach that a drug combination
may be synergistic, additive, or antagonistic4 (FF3-5). In addition, we agree
that these references support Appellants’ position that one of ordinary skill
in the art would not be able to predict prior to testing a particular
combination whether it will provide a synergistic, additive, or antagonistic
effect. However, we do not agree that that degree of predictability is
required. Instead, we find it sufficient to establish a prima facie case of
obviousness that one of ordinary skill in the art would have been able to
reasonably predict that the combination would be effective in treating
cancer.
We recognize that “[n]eutropenia is a common and predictable
consequence of many cytotoxic cancer therapies” (FF6). However, given
the disclosure in Low “that the msbB¯ bacteria can be safe for use in
humans” (FF2), we do not agree that the risk of neutropenia, assuming that

4 Appellants argue that the term antagonistic should be interpreted based on
the second definition of the term “antagonism” in the Merriam-Webster
online dictionary (2d Reply Br. 6). Based on the recited definition, the term
“antagonistic” would include a result that is subadditive but not less than
either drug alone. This interpretation appears to be consistent with how the
term is being used in Budman, which alternately refers to the combination of
docetaxel with etoposide as “antagonistic” or “subadditive” (FF4). Thus, we
adopt this definition of the term.
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this risk was known at the time of the invention,5 is sufficient to overcome
the prima facie case of obviousness.
With regard to the alleged evidence of synergism, we agree with the
Examiner that it is not commensurate with the scope of the claims (Supp.
Ans. 6). More importantly, it is not even directed to the elected species,
which contains cisplatin (Ans. 4).
CONCLUSION
The evidence of record support the Examiner’s conclusion that it
would have been obvious to treat a solid tumor cancer with both a
Salmonella msbB¯ mutant, as disclosed in Low, and cisplatin, as disclosed in
Schachter. We therefore affirm the obviousness rejections of claims 113,
115, and 123. Claims 116, 117, 119, and 120 fall with claim 113;
claims 121 and 122 fall with claim 115; and claim 124 falls with claim 123.
37 C.F.R. § 41.37(c)(1)(vii).
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

5 Freifeld, which is relied upon by Appellants for teaching this, is not prior
art as to the present application.
Appeal 2009-014775
Application 10/738,423

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cdc

ALBERT WAI-KIT CHAN
ALBERT WAI-KIT CHAN, LLC
141-07 20TH AVENUE
WORLD PLAZA, SUITE 604
WHITESTONE, NY 11357