Ex Parte Cavazza et al

Board of Patent Appeals and Interferences

Sep 6, 2012

11402961 (B.P.A.I. Sep. 6, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte CLAUDIO CAVAZZA,
CLAUDIO PISANO, and LOREDANA VESCI
__________

Appeal 2011-005615
Application 11/402,961
Technology Center 1600
__________

Before DONALD E. ADAMS, LORA M. GREEN, and
FRANCISCO C. PRATS, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner‟s rejection of claims 52-62. We have jurisdiction under 35 U.S.C.
§ 6(b).
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Application 11/402,961

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STATEMENT OF THE CASE
Claim 52 is representative of the claims on appeal, and reads as
follows:
52. A method of treating cisplatin-induced peripheral neuropathy in
subjects having a tumor and receiving treatment with said cisplatin and
suffering from said cisplatin-induced neuropathy, comprising administering
an effective amount of acetyl L-carnitine or a pharmaceutically acceptable
salt thereof.

The following ground of rejection is before us for review:
Claims 52-62 stand rejected under 35 U.S.C. § 103(a) as being
rendered obvious by the combination of Cavazza
1
and Narayanan.
2
As
Appellants do not argue the claims separately, we focus our analysis on
claim 52, and claims 53-62 stand or fall with that claim. 37 C.F.R.
§ 41.37(c)(1)(vii).
We affirm.

ANALYSIS
The Specification teaches that the invention “relates to the use of L-
carnitine and alkanoyl L-carnitines in the preparation of medicaments useful
in the treatment of tumours, particularly in combination with anticancer
agents” (Spec. 1).
According to the Specification,
It is well-known that the use of anticancer agents in human
therapy causes a large number of toxic or side effects which
may be life-threatening for the patients. These complications,

1
Cavazza et al., WO 00/06134, published February 10, 2000.
2
Narayanan et al., US 4,599,352, issued Jul. 8, 1986.
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in fact, may lead to a reduction in the doses of the agents, and
occasionally to discontinuation of the therapy itself.

(Id.)
The Specification teaches that “[p]revious uses of L-carnitine in
combination with anticancer agents are already known” (id. at 2). The
Specification teaches further:
In the context of the invention described herein, it has also been
found, in an entirely unexpected way, that the co-ordinated use
of a therapeutically effective amount of a peripheral
neuropathy-inducing anticancer agent, in particular of the
taxane, platin, epothilone and vinca alkaloid families and
Bleomycin, in particular Taxol, Carboplatin, Cisplatin,
Oxaliplatin, Epothilone, Vinorelbine, and Vincristine, and a
detoxifying amount of L-carnitine or of an alkanoyl L-carnitine,
in which the linear or branched alkanoyl has 2-8 carbon atoms,
or one of its pharmacologically acceptable salts, affords a
potent protective effect against the toxicity and side effects of
the anticancer agent, without impairing its efficacy, thus giving
rise, amongst other things, to a substantial improvement in the
quality of life and a prolonging of life itself in the subjects
treated, whether human subjects or animals.

(Id. at 8.)
The Examiner finds that Cavazza teaches “a method of treating
chemotherapy-induced neuropathy in subjects having a tumor, receiving
treatment with an anticancer agent and suffering from or at risk of suffering
from chemotherapy induced neuropathy induced by said anticancer agent,
comprising administering acetyl-L-carnitine” (Ans. 4).
According to the Examiner, Cavazza “does not specify cisplatin as the
neuropathy inducing anticancer agent” (id. at 5).
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The Examiner relies on Narayanan for teaching that “cisplatin induces
neuropathy” (id.). The Examiner concludes that it would have been obvious
to “practice the method of Cavazza et al in patients with cisplatin induced
peripheral neuropathy, since the compound was known to induce neuropathy
upon administration” (id.).
Specifically, Cavazza teaches that the described invention “relates to
the use of L-carnitine and alkanoyl L-carnitines in the preparation of
medicaments useful in the treatment of tumours, particularly in combination
with anticancer agents for the treatment of tumours” (Cavazza, p. 1, ll. 3-6).
Cavazza teaches:
[I]t has also been found, in an entirely unexpected way, that the
co-ordinated use of a therapeutically effective amount of an
anticancer agent, in particular taxol, carboplatin, bleomycin and
vincristine, and a detoxifying amount of L-carnitine or of an
alkanoyl L-carnitine, in which the linear or branched alkanoyl
has 2-8 carbon atoms, or one of its pharmacologically
acceptable salts, affords a potent protective effect against the
toxicity and side effects of the anticancer agent, without
impairing its efficacy, thus giving rise, amongst other things, to
a substantial improvement in the quality of life and a
prolonging of life itself in the subjects treated, whether human
subjects or animals.

(Id. at 5, ll. 6-17.)
Cavazza teaches that alkanoyl L-carnitines are non-toxic and have no
side effects, and thus their use is safe for long periods of treatment, and “for
the prevention or treatment of toxic or side effects, such as weight loss,
heart, kidney and central nervous system damage, peripheral nervous system
damage, particularly neuropathy or neutropenia caused by taxol, or lung
damage induced by bleomycin” (id. at 6, ll. 17-23). Cavazza also
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specifically teaches the L-carnitine or alkanoyl L-carnitine may be used in
the prevention or treatment of peripheral neuropathy (id. at 9, ll. 25-20). In
the Examples, Cavazza looks at the protective effect of acetyl-L-carnitine on
an experimental model of taxol-induced peripheral neuropathy (id. at 17,
Example 2).
Appellants argue that as explained in the Declaration of Dr. Claudio
Pisano
3
(Pisano Declaration), “platinum drugs are among the most
neurotoxic antineoplastic agents known” (App. Br. 9). Appellants assert that
while cisplatin and carboplatin share some structural similarities, they are
“markedly different to each other with regard to therapeutic use,
pharmacokinetics and adverse effect profiles” (id. (citing Pisano
Declaration, p. 2, ll. 16-19)).
Appellants assert that as set forth in the Pisano Declaration and as
supported by the Specification, the class of anticancer agents is broad and
“includes different types of active agents which exert their cytotoxicity
through different mechanism of action, but also compounds with relatively
similar structures (e.g., carboplatin and cisplatin) can behave completely
differently with regard to peripheral neuropathy” (App. Br. 10-11 (citing
Pisano Declaration, p. 2, ll. 21-22)).
As to Cavazza, Appellants argue that the reference “only discloses a
method for mitigating the known side effects of some anticancer agents such
as taxol, bleomycin, carboplatin and vincristine and discloses the effects of
acetyl L-carnitine with regard to taxol only” (App. Br. 11). Appellants
assert that cisplatin, however, “binds tightly and irreversibly to the nerve

3
Declaration of Dr. Claudio Pisano executed May 4, 2010.
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tissue causing neuropathy which continues even after the cessation of
cisplatin-based therapy,” whereas “taxol-induced neuropathy usually
improves or is resolved completely within several months after
discontinuation of taxol-based therapy” (id.). Appellants further assert that
the list of anticancer compounds of Cavazza does not include cisplatin, but
that cisplatin is only mentioned for its structural similarity to carboplatin
(id.).
Appellants thus assert that “due to the amount of knowledge available
to one skilled in the art at the time of filing, a skilled artisan cannot predict
the effectiveness of the combination between acetyl L-carnitine and cisplatin
in reducing cisplatin-induced neuropathy on the basis of a teaching limited
to taxol as disclosed in Cavazza” (id.). Appellants assert that the only basis
of the Examiner‟s rejection is “the general definition that all of these drugs
are „anticancer agents‟” (id. at 12). According to Appellants, equivalency
can only be “rightly extrapolated if there is an equivalency in the mechanism
of action,” but that taxol and cisplatin are “chemically and physiologically
unrelated” (id.). Appellants assert further that Narayanan does not remedy
the deficiencies of Cavazza, as Narayanan is drawn to new platinum (IV)
compounds that are less toxic than cisplatin (id.). Appellants thus argue that
there is no reason to combine the references without the use of improper
hindsight (id.).
We have carefully considered Appellants‟ arguments and the Pisano
Declaration, but agree that the preponderance of the evidence of record
supports the Examiner‟s conclusion that the combination of Cavazza and
Narayanan renders the method of claim 52 obvious.
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We agree with Dr. Pisano and Appellants‟ arguments that different
anticancer agents have different mechanisms of action, and that even though
cisplatin and carboplatin share some structural similarities, they are
markedly different to each other with regard to “therapeutic use,
pharmacokinetics and adverse effect profiles” (Pisano Declaration, p. 2, ll.
16-19)).
Cavazza, however, teaches the use of anticancer agents generally,
wherein the preferred anticancer agents are particular taxol, carboplatin,
bleomycin and vincristine. As noted by the Examiner (Ans. 6), and not
disputed by Appellants, Cavazza thus specifically teaches a broad range of
anticancer agents that act via different mechanisms, whose side effects may
be ameliorated by the administration of L-carnitine or alkanoyl L-carnitine.
The Examiner only cited Narayanan as evidence that a side effect of
cisplatin is neuropathy. Thus, the combination of Cavazza and Narayanan
provides a reasonable expectation of success that neuropathy associated with
cisplatin may be treated with the administration of L-carnitine or alkanoyl L-
carnitine. See In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988) (noting
that all that is required is a reasonable expectation of success, not absolute
predictability of success).

SUMMARY
We affirm the rejection of claim 52 stand rejected under 35 U.S.C.
§ 103(a) as being rendered obvious by the combination of Cavazza and
Narayanan. As claims 53-62 stand or fall with claim 52, we affirm the
rejection as to those claims as well.
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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

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