Ex Parte Berrino et al

Patent Trial and Appeal Board

Aug 24, 2016

12602827 (P.T.A.B. Aug. 24, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/602,827 05/03/2010 Liberato Berrino
20311 7590 08/26/2016
LUCAS & MERCANTI, LLP
30 BROAD STREET
21st FLOOR
NEW YORK, NY 10004
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
1108.1065 9110
EXAMINER
FINN, MEGHAN R
ART UNIT PAPER NUMBER
1629
NOTIFICATION DATE DELIVERY MODE
08/26/2016 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):
info@lmiplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte LIBERA TO BERRINO, ANTONIO CASCINO,
MARILENA CIPOLLARO, AMALIA FORTE,
FRANCESCO ROSSI, GIUSEPPE BIANCHI,
and PATRIZIA FERRARI1
Appeal2014-008522
Application 12/602,827
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
JOHN G. NEW, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellants state the real party-in-interest is Sigma-Tau Industrie
Farmaceutiche Riunite S.P.A. App. Br. 3.
Appeal2014-008522
Application 12/602,827
SU~vHvfARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner's Final Rejection of claims 1 and 3 which stand rejected as
unpatentable under 35 U.S.C. § 103 (a) as being obvious over the
combination of A. Forte et al., PST 2238 Treatment Affects Gene Expression
in Arteriotomy-Injured Milan Hypertensive Rat Strain Carotids, 23 (suppl.
2) JOURNAL OF HYPERTENSION 5244 (2005) ("Forte I"), Mariko Harada-
Shiba, Gene Transfer and Target Diseases, NON-VIRAL GENE THERAPY (K.
Taira et al., eds.) (Springer 2005) ("Harada-Shiba"), and Rohit Khurana et
al., Gene Therapy for Cardiovascular Disease: A Case for Cautious
Optimism, 38 HYPERTENSION 1210-16 (2001) ("Khurana").
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' invention is directed to a compound of formula (I) for
preparing a medicament for the prevention and/or treatment of obstructive
vascular lesions following vascular surgery and for the prevention and/or
treatment of diseases due to organ fibrosis. Abstract.
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REPRESENTATIVE CLAHv1
Independent claim 1 is representative of the claims on appeal and
recites:
1. A method for the treatment of restenosis, said method
comprising administering to a mammal in need thereof a
compound of formula (I)
wherein:
the symbol --- represents a single bond;
Y is OR4 and --- in position 3 is a single bond which can
have an alpha or beta configuration;
R is an unsubstituted or substituted 3-furyl;
R1 is hydrogen; methyl; ethyl or n-propyl substituted by
OH orNRsR6•
'
R2 is hydrogen;
R3 is hydrogen;
R4 is hydrogen, methyl; or C2-C6 alkyl wherein the alkyl
can be unsubstituted or substituted by a quaternary ammonium
group or OR7- or NR8R9;
Rs, R6 are independently hydrogen; methyl or Rs and R6
taken together with the nitrogen atom form an unsubstituted or
substituted saturated or unsaturated penta- or hexa-
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Application 12/602,827
rnonoheterocyclic nng, optionally containing another
heteroatom chosen from oxygen or sulfur or nitrogen;
R7 is hydrogen or methyl;
R 8, R9 are independently hydrogen; methyl; or C2-C6 alkyl
wherein the alkyl can be unsubstituted or substituted by one
NR10R11 , or R8 and R9 taken together with the nitrogen atom form
an unsubstituted penta- or hexa-monoheterocyclic ring;
R 10, R11 are independently hydrogen, C1-C6 alkyl, or R 10
and R11 , taken together with the nitrogen atom form a saturated
penta- or hexa-monoheterocyclic ring,
App. Br. 11-12.
ISSUES AND ANALYSES
We agree with, and explicitly adopt, the Examiner's findings and
conclusion that the appealed claims are prima facie obvious over the cited
prior art references. We address the arguments raised by Appellants on
appeal below.
Issue
Appellants argue the Examiner erred because the combined cited prior
art fails to teach or suggest the limitations of the claims on appeal. App. Br.
9.
Analysis
Appellants argue Forte I provides only for variations of gene
expression in MHS rats following arteriotomy: Appellants assert Forte I is
silent with respect to using PST2238 for the treatment of stenosis induced by
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Application 12/602,827
arteriotorny. App. Br. 9. According to Appellants, Forte I teaches data that
suggest early molecular events involved in arteriotomy-induced stenosis are
influenced mainly by hypertension and not by the genetic background shared
by the MHS rats employed in the study. Id. Therefore, argue Appellants, in
the absence of additional experiments involving MHS rats (i.e.,
normotensive rats with wild-type genetic backgrounds) a skilled person
would not arrive at the conclusion that genetic background has no role in the
evolution of gene expression. Id. at 9-10. Rather, Appellants argue, the
only plausible conclusion is that PST2238 has some effects on gene
expression at an early stage when given to rats which are genetically
modified. Id. at 10.
Furthermore, Appellants point to Forte I's conclusion "that stenosis
was more influenced by hypertension than by genetic background" and
argue this conclusion is not supported by the experiments conducted and/or
any data. App. Br. 10 (quoting Forte I 5244). To arrive at such a
conclusion, Appellants argue, the same experiment should have been
conducted on wild-type rats, and a person of ordinary skill in the art would
have therefore been forced to conduct undue experimentation. Id.
Appellants next argue that Mariko fails to cure the deficiencies of
Forte I. App. Br. 10. Appellants point out that Mariko is a chapter in a
volume entitled "Non-viral Gene Therapy" and assert that a skilled person in
gene therapy is necessarily not a skilled person in medicinal chemistry. Id.
Consequently, Appellants contend, to arrive at Appellants' claimed
invention, a skilled person could not learn from Mariko the type of
molecules required to solve the technical problem of restenosis, nor would
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Application 12/602,827
this person have ever sought this kind of prior art after learning the teachings
of Forte I. Id.
Appellants argue Mariko teaches antisense approaches and
overexpression of negative regulators of cell growth, both approaches being
anti-proliferative in nature. App. Br. 10. However, Appellants argue, the
compounds of their claimed invention do not target proliferation, therefore
Mariko would never be considered by a person skilled in the art interested in
treating restenosis. Id.
Appellants argue further that Khurana is also directed to the field of
gene therapy. App. Br. 11. Appellants also contend Khurana is cautious
with respect to the expectation of positive results using gene therapy. Id.
Appellants point out the only positive results mentioned in Khurana are
those of the PREVENT trial that involved transfection with antisense
nucleotides aimed at E2F transcription factor; other antisense constructs
demonstrated various degrees of efficacy. Id. (citing Khurana 1213).
Appellants contend all the experiments taught by Khurana have led to an
apoptosis-mediated approach to the regression of intimal disease and,
consequently, a person skilled in the art would not have been motivated to
use molecules having a mechanism of action different from those taught in
Khurana (i.e., not directed to favor apoptosis). Id. (citing, e.g., Khurana
1213).
Appellants point to an additional prior art reference they have
submitted, viz.: Shahin Assadnia et al., Strain Differences in Neointimal
Hyperplasia in the Rat, 84 CIRC. RES. 1252-57 (1999) ("Assadnia"). App.
Br. 11-12. According to Appellants, Assadnia teaches, contrary to the
teachings of Forte I, that genetic background is highly involved in
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Application 12/602,827
progression of stenosis. Id. at 12. Appellants disagree with the Examiner's
finding that Assadnia does not teach anything about the influence of the
genetic background, arguing that Assadnia teaches analysis of intima growth
differences between spontaneously hypertensive and normotensive rats
following injury to the left iliac artery. Id. (citing Assadnia Abstr.).
Appellants contend Assadnia further teaches that patients with certain allelic
combinations will be susceptible to such a complication, whereas patients
with different alleles of the crucial genes will be resistant to restenosis. Id.
(citing, e.g., Assadnia 1257). Consequently, Appellants argue, unlike the
allegedly unsupported conclusion of Forte I, a person skilled in the art would
have concluded from the teachings of Assadnia that genetic factors do have
an important role in the development of restenosis. Id.
The Examiner responds that Forte I teaches the effect of PST2238 on
gene expression in MHS rats, which is necessarily directly measuring the
effect of a pharmaceutical compound on the expression of genes that are
known to be involved in stenosis progression. Ans. 6. The Examiner finds
Forte I is not silent with respect to using PST2238 for treatment of stenosis,
rather, it teaches treatment of MHS rats with PST2238 induces a change in
the expression of genes involved in stenosis progression, in particular
delaying and/or lowering activation of transcription factors. Id. at 6-7
(citing Forte I 5244).
The Examiner finds that, although Forte I does not explicitly recite the
word "treatment," a person of ordinary skill would understand that the focus
of the reference is based on measuring the effect of PST2238 in reducing the
expression of stenosis-related genes in rat model. Ans. 7. The Examiner
finds this teaching demonstrates that PST2238 has a beneficial effect in
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reducing the progression of stenosis, at least in a mammalian model. Id.
The Examiner therefore disagrees with Appellants' argument that Forte I is
silent with respect to "treatment"; the Examiner finds treatment of stenosis is
an obvious goal of studying the effect of a pharmaceutical active agent (i.e.,
PST2238) already known in the art to lower blood pressure in an animal
model for stenosis/restenosis. Id.
The Examiner further finds Appellants' argument with respect to
wild-type, normotensive rats does not invalidate Forte I's conclusions. App.
Br. 10. The Examiner finds Forte I teaches comparing the effects of
hypertension and the genetic background solely of MHS rats. Id. The
Examiner finds the conclusions of Forte I are directly supported by the data
showing that the PST 223 8 lowered levels of gene expression, such as c-
myc, and not others such as apoptosis-related genes. Id. (citing Forte I
5244).
With respect to Mariko, the Examiner finds there is no requirement
that a person be a skilled artisan in both medicinal chemistry and gene
therapy areas to render the teachings relevant or the invention obvious. Ans.
11. The Examiner finds Forte I teaches both the relationship between
PST2238 administration and gene expression and is therefore directed
towards both gene therapy and medicinal chemistry. Id. The Examiner
finds Forte I is thus directed to persons of ordinary skill in the art in both
areas. Id. The Examiner finds a person of ordinary skill would be motivated
to look to Mariko because the teachings of Forte I does not provide much
background beyond the effects of PST223 8 upon the downregulation of
stenosis-related genes. Id. at 11-12. The Examiner finds a person of
ordinary skill would be motivated to look for other references directed to the
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expression of c-rnyc (and other) stenosis-related genes and treatment of
restenosis which are subjects to which both the Mariko and Khurana
references are directed. Id. at 12. The Examiner finds, by way of example,
that Khurana teaches upregulation of inactivating genes (including c-myc) as
a treatment for inhibiting restenosis in animal models. Id. (citing Khurana,
1213).
We are not persuaded by Appellants' arguments. As an initial matter,
we are not persuaded by Appellants' argument that a person of ordinary skill
would have been forced to conduct undue experimentation in wild-type rats
to arrive at the conclusions of Forte I. See App. Br. 10. "Undue
experimentation" is part of the test for determining whether a claim is
enabled by the specification. See Nat 'l Recovery Techs., Inc. v. Magnetic
Separation Sys., Inc., 166 F.3d 1190, 1196 (Fed. Cir. 1999) ("The scope of
enablement, in tum, is that which is disclosed in the specification plus the
scope of what would be known to one of ordinary skill in the art without
undue experimentation"). The proper test for obviousness, rather, "is what
the combined teachings of the references would have suggested to those of
ordinary skill in the art." In re Keller, 642 F.2d 413, 425 (C.C.P.A. 1981).
Moreover, we find Forte I is enabling to the extent that it teaches
administration of PST2238 to an animal with an induced stenosis and a risk
(due to hypertension) of developing restenosis. See Forte I 5244.
The main thrust of Appellants' arguments with respect to Forte I is
that Forte I does not teach the portion of claim 1 reciting: "A method for the
treatment of restenosis, said method comprising administering to a mammal
in need thereof a compound of formula (I)" and specifically, that neither
Forte I, nor the other cited prior art, teaches the "treatment of restenosis."
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See App. Br. 9. However, the "treatment of restenosis" is part of the
language of the preamble to the claims, and such language is generally not
limiting upon the claim "where a patentee defines a structurally complete
invention in the claim body and uses the preamble only to state a purpose or
intended use for the invention." Rowe v. Dror, 112 F.3d 473, 478 (Fed. Cir.
1997)). See In re Montgomery, 677 F.3d 1375, 13801381 (Fed. Cir 2012)
(We are skeptical that a proper interpretation of the claims would
include an efficacy requirement. In Bristol-Myers Squibb Co. v.
Ben Venue Laboratories, Inc., we construed a similar method-of-
treatment claim-involving ' [a] method for reducing
hematologic toxicity' by administering taxol to a cancer
patient-and held that it "merely express[ ed] a purpose of
reducing hematologic toxicity" rather than requiring a particular
result.)
Such a construction is even more appropriate here in the examination
context, where we apply the "broadest reasonable interpretation
consistent with the specification." In re Am. Acad. of Sci. Tech Ctr.,
367 F.3d at 1364").
In the appeal at bar, the body of the claim recites: "administering to a
mammal in need thereof a compound of formula (I)" and the subsequent
limitations further define the physical scope of formula (I). Appellants do
not dispute the Examiner's finding that Forte I teaches administration of
PST2238 (i.e., l 7B-(3-furyl)-5B-androstane-3a, 14B, l 7a-triol, a selected
embodiment of formula (I)) to a mammal in need of treatment for steno sis.
See Final Act. 3. Nor do Appellants dispute the Examiner's finding that
Forte I teaches hypertension is a risk factor for restenosis. Id. at 4; see also
Forte I 5244 ("Hypertension, diabetes and hypercholesterolemia are
recognized as risk factors for restenosis occurrence in patients").
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Furthermore, we agree with the Examiner that Forte teaches
administration of PST223 8 to animals with an induced stenosis and which
are at risk (due to hypertension) of restenosis. We agree that a person of
ordinary skill in the art would therefore realize from the teachings of Forte I
that the purpose of the study was to determine the effects of administration
of PST2238 on events (i.e., downregulation of genes) that are known in the
art to promote restenosis in a mammal at risk of restenosis, and therefore in
need of the treatment.
We consequently find that, because the preambular language of claim
1 does not limit the scope of the claim, and because Forte I teaches the
remaining limitations of claim 1 (i.e., administration of formula (I) to a
mammal in need thereof), Appellants' arguments are moot. We
consequently affirm the Examiner's rejection of claims
DECISION
The Examiner's rejection of claims 1 and 3 as unpatentable 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. § l.136(a).
AFFIRMED
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