Ex Parte Trivedi et al

Patent Trial and Appeal Board

Oct 19, 2012

11176565 (P.T.A.B. Oct. 19, 2012)

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.
11/176,565 07/07/2005 Jay S. Trivedi 6102-000002/US 3940
28997 7590 10/22/2012
HARNESS, DICKEY, & PIERCE, P.L.C
7700 Bonhomme, Suite 400
ST. LOUIS, MO 63105
EXAMINER
FINN, MEGHAN R
ART UNIT PAPER NUMBER
1629
MAIL DATE DELIVERY MODE
10/22/2012 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 JAY S. TRIVEDI and
GAETAN MARCOUX
__________

Appeal 2012-000210
Application 11/176,565
Technology Center 1600
__________

Before DONALD E. ADAMS, ERIC GRIMES, and STEPHEN WALSH,
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 composition, which the Examiner has rejected as obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
“[T]he ACE inhibitor moexipril hydrochloride . . . is available by
prescription in a coated tablet formulation containing 7.5 mg or 15 mg
moexipril hydrochloride as the active agent” (Spec. 1, ¶ 2). The
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Specification discloses that “when using a tableting mix adapted for
preparation of a standard tablet formulation of an ACE inhibitor to prepare a
plurality of smaller micro-tablets, the resulting micro-tablets failed to release
from tablet compressing equipment as cleanly or efficiently as standard
tablets prepared from the same mix” (id. at 2, ¶ 9). The Specification
discloses that “by increasing the amount of one or more lubricants in the
mix, clean and efficient release of the micro-tablets from the compressing
equipment can be restored” (id. at 4, ¶ 14). The lubricant can be magnesium
stearate (id. at 8, ¶ 32).
Claims 36-40 are on appeal. The claims have not been argued
separately and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii).
Claim 36 is representative and reads as follows:
36. A pharmaceutical composition comprising a pharmaceutically
acceptable capsule shell having enclosed therewithin a plurality of coated
micro-tablets that collectively comprise (a) about 1 to about 30 mg moexipril
hydrochloride, and (b) excipient ingredients that comprise magnesium
stearate in an amount of about 0.8% to about 1.2%, said micro-tablets having
an average uncoated weight of about 5 to about 20 mg.

The Examiner has rejected claims 36-39 under 35 U.S.C. § 103(a) as
obvious based on Stofik,1 Pich,2 Sasmal,3 and Bartholomaeus4 (Answer 5).
The Examiner has also rejected claim 40 as obvious based on Stofik, Pich,

1 Stofik et al., Patent Application Publication US 2003/0215526 A1, Nov.
20, 2003.
2 Pich et al., US 4,828,843, May 9, 1989.
3 Sasmal et al., Patent Application Publication US 2005/0026992 A1, Feb. 3,
2005.
4 Bartholomaeus et al., Patent Application Publication US 2002/0156133
A1, Oct. 24, 2002.
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Sasmal, Bartholomaeus, and Laragh5 (Answer 9). The same issue is
dispositive with respect to both rejections.
The Examiner finds that Stofik discloses tablets (but not microtablets)
comprising 15 mg moexipril hydrochloride and 0.5% magnesium stearate
(Answer 6). The Examiner finds that Pich discloses that microtablets in
capsules are useful with a wide range of active agents and are preferred to
tablets (id.), and that Sasmal discloses ACE inhibitors formulated as
microtablets in capsules (id.). Finally, the Examiner finds that Bartholomaeus
discloses tramadol (an analgesic) in microtablets weighing 16.6 mg and
comprising 0.2 mg, or 1.2% by weight, magnesium stearate (id. at 7).
The Examiner concludes that “while the active agent in
Bartholomaeus et al. is different than the ACE inhibitors of Stofik et al. and
Sasmal et al., it would have been obvious to one of ordinary skill in the art
that the microtablet formulation of Bartholomaeus et al. can be used for
other active agents. Pich et al. clearly demonstrated that microtablets can be
used for a wide variety of active agents.” (Id. at 7-8.) The Examiner also
concludes that the dosage of moexipril hydrochloride recited in claim 36
would have been obvious because Stofik teaches a dosage of 7.5 to 30 mg
(id. at 8).
We agree with the Examiner that the cited references would have
made obvious the composition of claim 36 to those of ordinary skill in the
art. Stofik discloses that moexipril hydrochloride is an ACE inhibitor used
at a dosage of 7.5 to 30 mg per day (Stofik 1, ¶ 6). Stofik also discloses that

5 Laragh, Patent Application Publication US 2005/0090752 A1, Apr. 28,
2005.
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magnesium stearate is a lubricant (id. at 2, ¶ 32) and exemplifies tablets
comprising moexipril hydrochloride and magnesium stearate (id. at 3, ¶ 63).
Pich discloses that formulating drugs as “pellets which can be
introduced into, for example, capsules is generally preferred to the
administration of compact tablets because very high local concentrations of
active compound in the gastrointestinal tract are avoided” (Pich, col. 1,
ll. 12-17). Pich discloses that such pellets have disadvantages, including
nonuniform size (id. at col. 1, ll. 42-58), that are not shared by microtablets
(id. at col. 1, ll. 8-10; col. 2, ll. 8-11) weighing 1-20 mg (id. at col. 2, ll. 66-
67). Pich disclose that the microtablets are useful for pharmaceuticals (id. at
col. 4, ll. 15-17).
Sasmal discloses capsules comprising a combination of active agents,
including a microtablet containing the ACE inhibitor enalapril maleate, as
well as zinc stearate (Sasmal 4, ¶ 51; 3, ¶ 29). The Examiner finds that zinc
stearate, like magnesium stearate, is a lubricant, and calculates that Sasmal’s
microtablets contain 0.89% zinc stearate (Answer 7). Appellants do not
dispute these finding (see Appeal Br. 12), and Stofik supports the
Examiner’s finding that zinc stearate is a known lubricant (see Stofik 2,
¶ 32).
Bartholomaeus discloses “an oral administration unit that contains the
two active substances Tramadol and Diclofenac . . . , with the two active
substances, respectively, contained in separately formulated subunits in the
same administration unit” (Bartholomaeus 1, ¶ 9). “Preferably, the subunits
are present in multiparticulate form, such as for example as microtablets”
(id. at 1, ¶ 13). Bartholomaeus exemplifies capsules comprising coated
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microtablets weighing 16.6 mg that comprise tramadol hydrochloride and
0.2 mg magnesium stearate (id. at 4-5, ¶¶ 56-59). The Examiner finds that
the exemplified microtablets contained 1.2% magnesium stearate (Answer
7). Appellants do not dispute the Examiner’s calculation.
We agree with the Examiner that these disclosures would have made
obvious the composition of claim 36. Specifically, it would have been
obvious to substitute moexipril hydrochloride for the tramadol hydrochloride
in Bartholomaeus’ microtablets, because Sasmal discloses microtablets
containing any of a variety of ACE inhibitors and Pich discloses that
capsules containing microtablets have advantages over both standard-sized
tablets and capsules containing pellets of active agent. In addition, Stofik
discloses that the standard dosage of moexipril hydrochloride is 7.5 to 30 mg
per day, and therefore would have made it obvious to formulate capsules
containing a total of 1-30 mg of moexipril hydrochloride, as recited in claim
36.
Appellants argue that the cited references do not provide a teaching or
suggestion to arrive at the claimed composition (Appeal Br. 10). Appellants
point out that none of the cited references individually teaches all of the
limitations of claim 36 (id. at 10-13).
This argument is not persuasive. Appellants have not shown any error
in the Examiner’s basis for combining the elements of claim 36, all of which
are disclosed in the cited references. “The test for obviousness is what the
combined teachings of the references would have suggested to one of
ordinary skill in the art.” In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991).
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Appellants also argue that “if too much lubricant is added to a
tableting mix, the resulting tablets can be slow to disintegrate and/or
dissolve, and/or have other deficiencies” (Appeal Br. 10). Appellants argue
that “nowhere does the cited art provide any predictability that the specific
formulation of Claim 36 would be able to provide (1) clean, efficient release
of micro-tablets (2) but not retard disintegration and/or dissolution rate of
the micro-tablets” (id. at 13).
This argument is also unpersuasive. Bartholomaeus provides a
working example of microtablets containing an active agent (tramadol
hydrochloride) and 1.2% magnesium stearate. While Appellants argue that a
skilled worker would not consider Bartholomaeus relevant to the present
invention because of the difference in active agents (Appeal Br. 12-13), they
have provided no evidence or sound technical reasoning to show that
Bartholomaeus’ working example would not have provided a skilled worker
with a reasonable expectation of success in making microtablets comprising
moexipril hydrochloride and 1.2% magnesium stearate. In particular,
Appellants have provided no persuasive evidence to show that a skilled
worker would have expected 1.2% magnesium stearate to retard the
disintegration or dissolution rate of microtablets containing moexipril
hydrochloride.
With regard to the rejection of claim 40, Appellants do not admit that
Laragh is prior art (Appeal Br. 13) but do not provide evidence or reasoning
to show that it is not. Appellants otherwise rely on the same arguments
presented with respect to claim 36, which are unpersuasive for the reasons
discussed above.
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SUMMARY
We affirm the rejection of claims 36-39 under 35 U.S.C. § 103(a)
based on Stofik, Pich, Sasmal, and Bartholomaeus; and the rejection of
claim 40 under 35 U.S.C. § 103(a) based on Stofik, Pich, Sasmal,
Bartholomaeus, and Laragh.
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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