Ex Parte Burger et al

Patent Trial and Appeal Board

Mar 31, 2017

12408864 (P.T.A.B. Mar. 31, 2017)

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
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/408,864 03/23/2009 Angelika Burger 073430-0081 1343
20277 7590 04/04/2017
MCDERMOTT WILL & EMERY LLP
The McDermott Building
500 North Capitol Street, N.W.
WASHINGTON, DC 20001
EXAMINER
CHOI, FRANK I
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
04/04/2017 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 ANGELIKA BURGER, HANS HENDRIKS, and
BERNARDUS RADEMAKER1
Appeal 2017-000628
Application 12/408,864
Technology Center 1600
Before RICHARD M. LEBOVITZ, JOHN G. NEW, and
TAWEN CHANG, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 22, 23, 25, 26, 28 and 33, which stand
rejected under 35 U.S.C. § 103(a) as being unpatentable over Ellison et al.
(US 6,875,451 B2, Apr. 5, 2005) (“Ellison”), C.C-K Chao, Inhibition by
Arsenite of Anticancer Drug cis-Diamminedichloroplatinum(II) Induced
DNA Repair and Drug Resistance in HeLa Cells, 1 Env. Toxicol, and
Pharmacol., 199-205 (1996) (“Chao”), Lee et al. (WO 2006/121280 Al,
November 16, 2006) (“Lee”), M. Komatsu et al., Copper-transporting P-
1 Appellants state the real party-in-interest is Kominox, Inc. App. Br. 2.
Appeal 2017-000628
Application 12/408,864
type Adenosine Triphosphatase (ATP7B) is Associated with Cisplatin
Resistance, 60 Cancer Res. 1312—1316 (2000) (“Komatsu”), T. Ishibashi
and S.J. Lippard, Telomere Loss in Cells Treated with Cisplatin, 95 PROC.
Nat’l Acad. Sci. USA, 4219-23 (1998) (“Ishibashi”), and The Merck
Manual (16th Ed., 1992) (the “Merck Manual”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
REPRESENTATIVE CLAIMS
Claim 22 is representative of the claims on appeal and recites:
22. A method for the treatment of lung cancer in a patient in
need thereof comprising a treatment regimen comprising
administering to the patient sodium meta arsenite in the amount
of from 1 to 25 mg and a synergistically effective amount of
from 3 to 100 mg/m2 of cisplatin.
App. Br. Evid. App’x A.
2
Appeal 2017-000628
Application 12/408,864
ISSUE AND ANALYSIS
We agree with, and adopt, the Examiner’s reasoning and conclusion
that the claims are obvious over the cited prior art references. We address
Appellants’ arguments below.
Issue
Appellants argue the Examiner erred because the cited publications
do not suggest that the specific combination of sodium meta arsenite and
cisplatin recited in the claims reacts synergistically in the treatment of lung
cancer.
Analysis
Appellants did not dispute the Examiner’s finding that the claimed
combination of drugs in the claimed amounts would have been obvious to
one of ordinary skill in the art. However, to rebut this determination,
Appellants provided evidence of synergy. We turn to this evidence.
Appellants rely primarily upon the Second Declaration of Dr. Sujong
Kim, October 6, 2014 (the “Kim Second Declaration”). App. Br. 4.
According to Appellants, the Kim Second Declaration establishes that the
combination of sodium meta arsenite and cisplatin has a synergistic effect
in the treatment of lung cancer. Id. Appellants assert that Kim Second
Declaration includes data obtained from a side-by-side comparison of in
vivo treatment of explanted tumors in mice with: (1) sodium meta arsenite
alone; (2) cisplatin alone; and (3) a combination of sodium meta arsenite
and cisplatin. Id. Appellants explain that the explanted tumors consisted of
chemo/radiotherapy-resistant lung cancer cells (PC14E6 cells) or cisplatin-
sensitive lung cancer cells (H292 cells). Id. Appellants contend that the
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Application 12/408,864
data presented in the study demonstrate that, in each case, a combined
dosage of half of the amount of sodium meta arsenite and cisplatin
(compared to each used alone) was sufficient to treat the tumors and was
more effective than either drug alone. Id. Furthermore, Appellants argue,
the results also demonstrate that the combination is effective in the
treatment of chemo/radiotherapy-resistant tumors that had previously been
resistant to cisplatin. Id.
Appellants argue further that the data in the line and bar graphs
included in the Kim Second Declaration demonstrate the antitumor effects
of half dosage amounts of sodium meta arsenite and cisplatin in terms of
tumor explant volume from two different animal models of lung cancer,
including non-small cell lung cancer. App. Br. 4. Appellants point out that
the half dose combination of sodium meta arsenite and cisplatin
significantly decreases tumor size in the two different lung cancer
xenografts. Id.
We are not persuaded by Appellants’ arguments. The Kim Second
Declaration states:
The results show that the combination of sodium meta
arsenite and cisplatin is better than additive in the treatment of
both cisplatin sensitive and resistant lung cancer cells (i.e., the
combination is synergistic). As can be seen, a combination of
sodium meta arsenite and cisplatin is more effective than either
drug alone even though the amount of each drug in the
combination was half that used alone.
Kim Sec. Decl. 19.
The two figures presenting data in the Kim Second Declaration are
presented below:
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Application 12/408,864
Antitumor effects of KML001 in human lung cancer xenografts.
1
!
1
i XAftUftl
-.V- is ?.SCts
"I""'
Days
i.0 i-J
>.$ jtML+
*?> Ciy
Figure of Kim Second Declaration presenting decrease in tumor volume
with time (ton) and total decrease in tumor volume (bottom) in non-
cisplatin resistant (H292) human lung cancer xenografts.
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Application 12/408,864
Antitumor effects of KM LOO I in human king cancer xenografts.
KML+ 2,$ <•<1
Q -
1?
Days
CtiUttrol .SftNj/iN) fS/i KftK,-. J.'i
SMUJOl Ct«$.k.tir< Ci*
Figure of Kim Second Declaration presenting decrease in tumor volume
with time (top) and total decrease in tumor volume (bottom) in cisplatin-
resistant (PCI 4PE6) human lung cancer xenografts
Neither Appellants, nor Dr. Kim, present any evidence, beyond a
bare assertion, that the combined treatment of sodium meta arsenite (i.e.,
Kominox, KML001) is statistically significantly different than that of the
single treatment groups. Indeed, in the latter figure, and perhaps also in the
non-resistant tumor cell study, the effect appear to be no more than
additive.
With respect to the first figure, we note the downward trend.
However, Appellants have not provided evidence that the results of the
combination is non-additive, i.e., the definition of synergy. The statement
was made that the data is synergistic, but Appellants did not describe the
values obtained and establish that the combination of drugs provides a non­
additive effect.
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Application 12/408,864
In the case of the cisplatin-resistant tumors in the second figure, we
are not persuaded that Appellants have demonstrated the claimed
synergistic effect of the combined administration of cisplatin and sodium
meta arsenite.
With respect to the remaining Declarations (the Declaration of Dr.
Arif Hussain, December 19, 2011, the Declaration of Dr. Martin J.
Edelman, September 11, 2012, and the First Declaration of Dr. Sujong Kim,
November 26, 2013) Appellants state merely that the “Kim [First]
Declaration confirms the in vitro data presented in the declarations of Dr.
Martin Edelman and Dr. Arif Hussain......... with in vivo studies that
demonstrate synergy between cisplatin and sodium meta arsenite to the
same or similar extent as demonstrated in vitro.” (App. Br. 4). Appellants
adduce no evidence from the Declarations to support this conclusory
statement and, in the absence of such evidence, we accord such attorney
argument little probative weight. See In re Geisler, 116 F.3d 1465, 1470
(Fed. Cir. 1997) (Attorney arguments and conclusory statements that are
unsupported by factual evidence are entitled to little probative value).
Furthermore, if we were to consider the in vivo clinical studies of the Kim
First Declaration, the lack of quantitative data demonstrating any synergy of
the combination of sodium meta arsenite and cisplatin in the treatment of
lung cancers is not persuasive of the existence of such a synergistic effect.2
2 The clinical study of the Kim First Declaration describes responses of
patients with, inter alia, small cell lung cancer, large cell lung cancer,
colorectal cancer, cholangiocarcinoma, thyroid cancer, and breast
cancer spread across the three treatment groups.
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Finally, even assuming, arguendo, that Appellants were to
demonstrate a synergistic effect in resulting the claimed combination
therapy, Appellants must also demonstrate that the synergistic effect would
have been unexpected to a person of ordinary skill in the art. See In re
Kollman, 595 F.2d at 55 n.6. However, the prior art references cited by the
Examiner teach or suggest that the combination of sodium meta arsenite
and cisplatin can produce enhanced, potentiated, or synergistic effects. Lee,
for example, expressly suggests:
[Sodium meta arsenite] may be used alone or in combination.
Additionally the treated compounds may be utilised with other
types of treatments. For example, the subject compounds may
be used with other chemotherapies e.g.[,] tamoxifen, taxol,
methothrexate, biologicals such as antibodies, growth factors or
lymphokines, radiation etc. Combination therapies may result
in synergistic results.
Lee 39 (emphasis added.).
More explicitly, Chao teaches, from an in vitro study:
In this study, the modification of cisplatin-induced cytotoxicity
and DNA repair by arsenite was presented. A sublethal dose of
arsenite resulted in a 2.5-fold modification on the resistant cells,
whereas, a 1.6-fold on the parental cells. Thus, arsenite
dramatically potentiated cisplatin toxicity in both the parental
and the resistant HeLa cells, with a greater effect on the resistant
cells. In addition to the modification on cytotoxicity, arsenite
also effectively modified DNA repair in the cells.
Chao 202-03.
We consequently agree with the Examiner that a person of ordinary
skill in the art would have realized that it was known in the art that the
addition of sodium meta arsenite could enhance the cytotoxicity of cisplatin
against tumor cells. We therefore conclude that Appellants have not
persuasively demonstrated an unexpected synergistic effect of the
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combination of sodium meta arsenite and cisplatin, as recited in the claims,
and we affirm the Examiner’s rejection of the claims as being obvious over
the combined cited prior art.
DECISION
The Examiner’s rejection of claims 22, 23, 25, 26, 28 and 33 under
35 U.S.C. § 103(a) is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(l)(iv).
AFFIRMED
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