Ex Parte Sasmal et al

Patent Trial and Appeal Board

Feb 21, 2013

10898549 (P.T.A.B. Feb. 21, 2013)

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.
10/898,549 07/28/2004 Badal Kumar Sasmal 934-014-US 8252
83336 7590 02/21/2013
PERGAMENT GILMAN & CEPEDA LLP
1480 Route 9 North
Suite 204
Woodbridge, NJ 07095
EXAMINER
LOVE, TREVOR M
ART UNIT PAPER NUMBER
1611
MAIL DATE DELIVERY MODE
02/21/2013 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 PATENT TRIAL AND APPEAL BOARD
__________

Ex parte BADAL KUMAR SASMAL, BILLA PRAVEEN REDDY,
VIJAY DINANATHJI NASARE, and
MAILATUR SIVARAMAN MOHAN
__________

Appeal 2011-011335
Application 10/898,549
Technology Center 1600
__________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and ERIC GRIMES,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
pharmaceutical dosage form. The Examiner has rejected the claims for
obviousness and obviousness-type double patenting. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
The Specification discloses a pharmaceutical composition for treating
“patients having an elevated risk of cardiovascular events” (Spec. 1:5-7).
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The composition is “a combination of active agents of different categories
…, which can be conveniently administered once-daily to reduce a risk of
cardiovascular event” (id. at 4:11-13).
Claims 1, 2, 4, 5, 7, 8, 10, and 25 are on appeal. Claims 1 and 7 are
representative and read as follows:
1. A pharmaceutical dosage form comprising therapeutic amounts of
drugs consisting of:
a β-adrenergic receptor antagonist or a diuretic;
a cholesterol-lowering agent;
an inhibitor of the renin-angiotensin system; and
aspirin.
7. The pharmaceutical dosage form of claim 1, wherein the
cholesterol-lowering agent comprises simvastatin.

The claims stand rejected as follows:
• Claims 1, 2, 4, 5, 7, 8, 10, and 25 under 35 U.S.C. § 103(a) as
obvious in view of Hess,
1
Patrono,
2
Pfisterer,
3
Goa,
4
AHA,
5
and Wald
6

(Answer 5-7);

1
David C. Hess and Susan C. Fagan, Pharmacology and clinical experience
with simvastatin, 2 EXPERT OPINION ON PHARMACOTHERAPY 153-163
(2001).
2
Patrono, Prevention of Myocardial Infarction and Stroke by Aspirin:
Different Mechanisms? Different Dosage?, 92 THROMBOSIS RESEARCH S7-
S12 (1998).
3
Pfisterer et al., Atenolol Use and Clinical Outcomes After Thrombolysis for
Acute Myocardial Infarction: The GUSTO-1 Experience, 32 JACC 634-640
(1998).
4
Goa et al., Lisinopril: A review of its pharmacology and clinical efficacy in
the early management of acute myocardial infarction, 52 DRUGS 564-588
(abstract only) (1996).
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• Claims 1, 2, 4, 5, 8 and 10, provisionally,
7
for obviousness-type
double patenting in view of claims 1, 2, 4-9 and 11-23 of copending
Application No. 11/561,624 (Answer 10-11); and
• Claims 1, 7 and 25, provisionally, for obviousness-type double
patenting in view of claims 1, 2, 4, 5, 6-9, 11-15, and 18-23 of the „624
application in view of Barvian
8
(Answer 12-13).
I.
Issue
The Examiner has rejected all of the claims on appeal under 35 U.S.C.
§ 103(a) as obvious in view of Hess, Patrono, Pfisterer, Goa, AHA, and
Wald. The claims have not been argued separately and therefore stand or
fall together. 37 C.F.R. § 41.37(c)(1)(iv).
The Examiner finds that Wald discloses that “formulations which
comprise components such as aspirin, β-blockers, angiotensin converting
enzyme inhibitors, and simvastatin are known in the art to „achieve a large
effect in preventing cardiovascular disease with minimal adverse effects‟”
(Answer 6). The Examiner finds that Hess, Patrono, Pfisterer, and Goa
provide evidence that simvastatin, aspirin, atenolol, and lisinopril,

5
American Heart Association (AHA), Woman, Heart Disease and Stroke,
web.archive.org/web/20011116134259/http://www.americanheart.org/
presenter.jhtml ?identifier=4786, pp. 1-3 (2010).
6
N. J. Wald and M. R. Law, A strategy to reduce cardiovascular disease by
more than 80%, 326 BMJ 1419 (2003).
7
In both double patenting rejections, the Examiner does not expressly state
that the rejections are provisional, but since none of the relevant claims have
been patented, an actual rejection would be premature.
8
Barvian et al., US 7,205,295 B2, issued Apr. 17, 2007.
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respectively, are known to reduce risk of cardiovascular disease (id. at 5).
The Examiner finds that AHA discloses that women who have had a heart
attack are at higher risk for a second heart attack (id. at 6).
The Examiner concludes that it would have been obvious
to utilize aspirin, atenolol, and lisinopril in combination with
the simvastatin of Hess … [because] Wald teaches that
combinations of drugs such as aspirin, simvastatin, β-blockers,
and angiotensin converting enzyme inhibitors are known in the
art, and AHA teaches that women who have experienced a heart
attack are at a higher risk of having a second heart attack.
(Id.) The Examiner reasons that “therefore, one would have been motivated
to provide said patient with simvastatin and aspirin to prevent a further
myocardial event, and provide said patient with atenolol and lisinopril to
treat the effects of the most recent myocardial infarction” (id.).
Appellants contend that Wald does not teach the actual combination
of the cited drugs into a single formulation, but describes a hypothetical
Polypill (Appeal Brief 10). Appellants argue that one of skill in the art
would not have had a reasonable expectation of success in combining the
drugs recited in claim 1 into a single dosage form, and cite Frantz
9
as
evidence supporting their position (id. at 11).
The issue presented is: Does the evidence of record support the
Examiner‟s conclusion that one of ordinary skill in the art would have had a
reasonable expectation of success in combining the drugs recited in claim 1
into a dosage form?

9
Frantz, The trouble with making combination drugs, 5 NATURE REVIEWS
DRUG DISCOVERY 881-882 (2006).
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Findings of Fact
1. Wald discloses that
randomised trials show that drugs to lower three risk factors—
low density lipoprotein (LDL) cholesterol, blood pressure, and
platelet function (with aspirin)—reduce the incidence of
ischaemic heart disease (IHD) events and stroke. Evidence that
lowering serum homocysteine (with folic acid) reduces the risk
of these diseases is largely observational but still compelling.
(Wald 1.)
2. Wald discloses a combination formulation comprising “a statin (for
example, atorvastatin … or simvastatin …); three blood pressure lowering
drugs (for example, a thiazide, a β blocker, and an angiotensin converting
enzyme inhibitor) …; folic acid …; and aspirin” (id.).
3. Wald discloses that the combination, referred to as the “Polypill,”
is estimated to reduce “IHD events by 88% … and stroke by 80%” (id.).
4. Wald discloses that the “Polypill strategy could largely prevent
heart attacks and stroke if taken by everyone aged 55 and older and everyone
with existing cardiovascular disease” (id.).
5. Wald discloses that “the three classes of blood pressure lowering
drugs with the lowest prevalence of adverse effects [are] thiazide,
angiotensin II receptor antagonist, and calcium channel blocker” (id. at 4),
while “the three least expensive blood pressure lowering drugs [are] a
thiazide, a β blocker, and an ACE inhibitor” (id.).
6. The Specification discloses that a preferred cholesterol lowering
agent is an HMG CoA reductase inhibitor such as atorvastatin or simvastatin
(Spec. 6:5-18).
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7. The Specification discloses that β-adrenergic receptor antagonists
include atenolol (id. at 5:28 to 6:2).
8. The Specification discloses that diuretics include thiazides (id. at
7:10-14).
9. The Specification discloses that inhibitors of the renin-angiotensin
system include angiotensin converting enzyme (ACE) inhibitors (id. at 6:19-
25).
10. Frantz discloses that “[c]ombining treatments into one tablet is
becoming a more popular strategy than ever.… Reducing the number of
treatments that a patient needs to take increases compliance for long term
drug therapies.” (Franz 881, left col.)
11. Frantz cautions that
[j]ust because two or more treatments work in
combination in a patient does not mean that they are amenable
to packing into a single tablet. If the solid form of one drug is
less soluble than another, this can affect how each drug gets
released into the bloodstream. If one dose is much lower than
another there can be problems in making sure that the low-dose
drug is distributed uniformly in the tablet. Compounds can
react with each other, either chemically or physically, or one
compound might be chemically more stable than another, or
more sensitive to moisture than another, all of which can affect
the shelf-life of the drug.
(Id. at 882, left col.)
12. Frantz discloses that formulating drug “combinations relies to a
large degree on trial and error” (id.).
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Analysis
Claim 1 is directed to a pharmaceutical dosage form comprising
“therapeutic amounts of drugs consisting of” (1) a β-adrenergic receptor
antagonist or a diuretic, (2) a cholesterol-lowering agent, (3) an inhibitor of
the renin-angiotensin system, and (4) aspirin.
Wald discloses a pharmaceutical dosage form for reducing incidence
of heart attacks and stroke. Wald‟s formulation comprises “a statin (e.g.
atorvastatin or simvastatin), three blood pressure lowering drugs (e.g.
thiazide, a β blocker, and an angiotensin converting enzyme (ACE)
inhibitor), folic acid, and aspirin” (FF2).
Thus, Wald‟s dosage form meets the limitations of claim 1 except that
it contains folic acid and contains three blood pressure lowering drugs (a
thiazide, a β blocker, and an ACE inhibitor), rather than no folic acid and
two blood pressure lowering drugs (an inhibitor of the renin-angiotensin
system (e.g., an ACE inhibitor) and either a β-adrenergic receptor antagonist
(β blocker) or a diuretic), as claimed. However, it would have been obvious
to omit the folic acid from Wald‟s dosage form because Wald discloses that
folic acid has not been shown in randomized trials to reduce the risk of
cardiovascular disease (FF1). In addition, it would have been obvious to
modify Wald‟s formulation to include only the thiazide (diuretic) and ACE
inhibitor for blood pressure, because Wald discloses that β blockers are not
among those having the lowest prevalence of adverse effects, and therefore
eliminating them would have been expected to reduce the incidence of side
effects.
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In view of Wald‟s disclosure that each of the drugs in its Polypill was
individually known to reduce risk of cardiovascular disease, a skilled worker
would have expected the Polypill minus folic acid and β blocker would also
be effective in reducing risk of cardiovascular disease. The disclosures of
Hess, Patrono, Pfisterer, Goa and AHA further illuminate the basis for
Wald‟s combination but are not necessary to support a prima facie case of
obviousness.
Appellants argue that Wald only describes a hypothetical Polypill
(Appeal Brief 10). Appellants argue that one of skill in the art would not
have had a reasonable expectation of success in combining the drugs recited
in claim 1 into one dosage form (id. at 11), and cite Frantz as providing
evidence that formulating combination drugs is problematic (id.).
10

Appellants‟ arguments are not persuasive. Wald discloses a dosage
form that includes all of the drugs recited in claim 1, and that disclosure is
entitled to a presumption of enablement. See In re Antor Media Corp., 689
F.3d 1282, 1288 (Fed. Cir. 2012) (“[A] prior art printed publication cited by
an examiner is presumptively enabling barring any showing to the contrary
by a patent applicant.”). Given the presumption that Wald‟s six-component
Polypill is enabled, Wald provides a sufficient basis to conclude that a
person of ordinary skill in the art would have had a reasonable expectation

10
In the Reply Brief, Appellants also cite an “article by J. Wechsler that
accompanied the Amendment and Response submitted by Appellants
October 11, 2010” (Reply Br. 3). However, “[a]ny bases for asserting error,
whether factual or legal, that are not raised in the principal brief are waived.”
Ex parte Borden, 2010 WL 191083 at *2 (BPAI 2010) (informative). Since
the Appeal Brief did not rely on Wechsler as a basis for asserting error,
Appellants have waived that argument.
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of successfully formulating a dosage form containing four of those same
components.
Appellants‟ arguments regarding the Frantz reference are not
sufficient to rebut that presumption. Although Frantz discloses that
formulating dosage forms with drug combinations can be problematic and
typically requires experimentation, Frantz also discloses that combining
treatments into a single tablet is a “popular strategy”; thus, combination
dosage forms appear to be routinely undertaken in the field of drug
formulation. Franz also discloses that, in the opinion of an engineer in the
relevant field (id. at 881-882), “All the problems are, in a sense, solvable ….
It is just a matter of time and money.” (Id. at 882, left col.) Thus, Frantz
does not provide persuasive evidence that a person of ordinary skill in the art
would have lacked a reasonable expectation of successfully producing a
four-component version of Wald‟s Polypill. Obviousness does not require
absolute predictability of success, only a reasonable expectation of success.
In re O’Farrell , 853 F.2d 894, 903-04 (Fed. Cir. 1988).
Conclusion of Law
The evidence of record supports the Examiner‟s conclusion that one
of skill in the art would have had a reasonable expectation of success in
combining the drugs recited in claim 1 into a dosage form.
II.
The Examiner has rejected claims 1, 2, 4, 5, 8 and 10 for obviousness-
type double patenting in view of claims 1, 2, 4-9, and 11-23 of copending
Application No. 11/561,624 (Answer 10-11). Appellants argue that the
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rejection should not maintained if the double patenting rejection is the only
rejection remaining in the case (Appeal Br. 12-13). This argument is not
persuasive because, for the reasons discussed above, we affirm the rejection
of all of the claims on appeal under 35 U.S.C. § 103(a).
III.
The Examiner has provisionally rejected claims 1, 7, and 25 for
obviousness-type double patenting in view of claims 1, 2, 4, 5, 6-9, 11-15,
18-23 of copending Application No. 11/561,624 in view of Barvian (Answer
12-13). Claims 1 and 6 of the „624 application read:
11

1. A pharmaceutical dosage form, comprising a capsule
containing:
(a) a capsule, tablet, or particles comprising both aspirin and a statin;
and
(b) a capsule, tablet or particles comprising two or more of a beta-
adrenergic receptor clocking [sic] agent, a diuretic, and an inhibitor of the
renin-angiotensin system;
wherein at least one of a) and b) is in the form of a capsule.

6. The pharmaceutical dosage form of claim 1, wherein a statin
comprises at least one of atorvastatin, pravastatin, cerivastatin, fluindostatin,
fluvastatin, lovastatin, mevastatin, rosuvastatin, pivastatin, dalvastatin and
velostatin.

The Examiner finds that claim 1 of the „624 application is directed to
a pharmaceutical dosage that contains the same ingredients as recited in
instant claim 1 (Answer 12), and therefore claim 1 is rendered obvious (id.).
Likewise, the Examiner concludes that instant claims 7 and 25, which recite
simvastatin, are not patentably distinct from the claims of the „624

11
The claims are shown as amended May 9, 2012.
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application that recite statins, in view of Barvian‟s disclosure that
“simvastatin is useful as a statin” (id.). We agree with the Examiner‟s
reasoning and conclusion.
Appellants argue that Barvian discloses compounds that “inhibit[ ] the
activity of phosphoinositide-3-kinases (PI3Ks) in the body” and are useful in
treating various diseases (Appeal Br. 13). Appellants acknowledge that the
Examiner “points specifically to column 32, lines 4-13 as showing that
simvastatin or rosuvastatin are useful in combination with aspirin, atenolol,
and lisinopril” (id.), but argue that this passage “does not contemplate
combining more than two drugs, one of which would be a PI3K inhibitor”
(id. at 13-14). Appellants argue that “[s]ince the Appellants‟ claims do not
include any mention of a PI3K inhibitor, Barvian is not applicable to the
rejected claims” (id. at 14).
Appellants‟ argument is not persuasive. As the Examiner pointed out
(Answer 13), “Barvian is only relied upon as providing a clear teaching that
simvastatin is a useful statin in dosage formulations.” Barvian discloses that
its PI3K inhibitors are useful in treating various disorders (see Barvian, col.
1, ll. 14-35), and can “be combined in a pharmacetical [sic] composition
with compounds that are useful for the treatment of a thrombolytic disease,
heart disease, stroke, etc., (e.g., … a statin (e.g., LIPITOR® (Atorvastatin
calcium), ZOCOR® (Simvastatin), CRESTOR® (Rosuvastatin), etc.)” (id.
at col. 32, ll. 4-11).
Thus, since Barvian discloses that simvastatin and rosuvastatin are
both statins known to be useful in treating heart disease, it would have been
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obvious to one of ordinary skill in the art to substitute simvastatin for the
rosuvastatin recited in claim 6 of the „624 application.
SUMMARY
We affirm all of the rejections on appeal.
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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