LABORATORIOS DEL DR. ESTEVE S.A.

Patent Trials and Appeals Board

Jan 12, 2021

2020003706 (P.T.A.B. Jan. 12, 2021)

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.
14/379,613 08/19/2014 Pratibha S. Pilgaonkar 16326.0018FPWO 6655
23552 7590 01/12/2021
MERCHANT & GOULD P.C.
P.O. BOX 2903
MINNEAPOLIS, MN 55402-0903
EXAMINER
BECKHARDT, LYNDSEY MARIE
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
01/12/2021 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):
USPTO23552@merchantgould.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte PRATIBHA S. PILGAONKAR, MAHARUKH T. RUSTOMJEE,
and ANILKUMAR S. GANDHI
____________

Appeal 2020-003706
Application 14/379,613
Technology Center 1600
____________

Before ERIC B. GRIMES, JOHN E. SCHNEIDER, and
MICHAEL A. VALEK, Administrative Patent Judges.

VALEK, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving
claims to compositions of two distinct types of particles and capsules
containing the same, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.2

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies Esteve Pharmaceuticals, S.A., as the
real party in interest. Appeal Br. 1. Herein, we refer to Appellant’s Appeal
Brief filed December 6, 2019 (“Appeal Br.”) and Examiner’s Answer mailed
February 19, 2020 (“Ans.”).
2 An oral hearing was held on January 7, 2021. A transcript of the hearing
will be made of record.
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Application 14/379,613

2
STATEMENT OF THE CASE
“Dabigatran is a potent, reversible, univalent direct thrombin
inhibitor” that is “currently available as dabigatran etexilate mesylate (DEM)
under the brand name Pradaxa®.” Spec. 2:6–17. The Specification explains
that “the aqueous solubility of DEM is strongly pH dependent with rather
high solubility in acidic media and very poor solubility in neutral and basic
media.” Id. at 2:24–26. Moreover, while “DEM is stable in the solid state”
it “undergoes degradation by hydrolytic pathways in the presence of
moisture” and “is acid sensitive.” Id. at 2:29–31.
The Specification explains that “[d]ue to these physicochemical and
biopharmaceutical properties of DEM . . . attempts have been made to
provide compositions of DEM that are stable and/or provide desirable in
vitro release and bioavailability.” One such approach is described in
Brauns,3 which, according to the Specification:
describes pharmaceutical compositions of DEM for oral
administration in the form of pellets comprising (a)
substantially spherical core material comprised of one or more
pharmaceutically acceptable organic acids . . . and (b) an active
substance layer containing one or more binders and optionally a
separating agent, that encloses said core material. The
separating agent layer or insulating layer separates the acid core
from the active substance containing layer. . . . Such layered
pellets are later filled into hard capsules.
Spec. 3:1–10.
According to the Specification, Brauns’ “process of preparing layered
pellets is cumbersome, time consuming and uneconomical” and, therefore, a
need exists for “alternate compositions of dabigatran etexilate that are stable,

3 US 2006/0183779 A1, published Aug. 17, 2006 (“Brauns”).
Appeal 2020-003706
Application 14/379,613

3
easy or convenient to prepare,” and which “provide the desired in vitro
release and bioavailability.” Spec. 3:10–12, 3:24–26. The Specification
purports to provide such an alternate composition in a form of “a mixture of
at least two types of particles . . . wherein a) the first type of particles
comprise the active ingredient; [and] b) the second type of particles
comprise at least one pharmaceutically acceptable organic acid.” See id. at
3:28–35.
Claims 21, 23, 26, 30, 32, and 40–48 are on appeal and can be found
in the Claims Appendix of the Appeal Brief. Claim 21 is illustrative and
reads as follows:
1. A composition comprising: a mixture of at least two
distinct types of particles wherein
a) the first type of particle comprise dabigatran etexilate
in the form of the free base or in the form of a pharmaceutically
acceptable salt or polymorph thereof, wherein the first type of
particles is free from organic acids and inorganic acids: and
b) the second type of particles comprise at least one
pharmaceutically acceptable organic acid, wherein the second
type of particles is coated with a protective coating layer and is
free from dabigatran etexilate.
Appeal Br. 13.
Appellant seeks review of Examiner’s rejection of claims 21, 23, 26,
30, 32, and 40–48 under 35 U.S.C. § 103 as unpatentable over Brauns in
view of Habib4 and PubChem.5 Appeal Br. 3–12.

4 US 2008/0069891 A1, published March 20, 2008 (“Habib”).
5 “Compound Summary for CID 9578572: Dabigatran Etexilate,” available
at https://pubchem.ncbi.nlm.nih.gov (“PubChem”).
Appeal 2020-003706
Application 14/379,613

4
The issue is: Does the preponderance of evidence of record support
Examiner’s conclusion that the cited prior art renders obvious the claimed
compositions?
Analysis
Examiner finds that Brauns “teaches dabigatran etexilate and organic
acids provide[] a significantly improved formulation” and describes a
particle containing an organic acid core surrounded by “a separating layer
followed by a layer containing the active substance.”6 Ans. 4. Examiner
acknowledges that Brauns does not teach the drug and organic acid “in two
distinct types of particles,” as claimed. Id. at 8.
For that limitation, Examiner relies on Habib. Examiner determines
Habib teaches a pharmaceutical composition that “comprises two particles,
the first type containing the pharmaceutical agent and the second comprising
fat/wax material.” Ans. 8. According to Examiner, it would have been
obvious to formulate the composition taught by Brauns “as two distinct
particles as [Habib] teaches [a] pharmaceutical composition [that]
comprise[s] two distinct types of particles, one of which includes a
pharmaceutical agent” and Brauns “teaches the need for spatial separation of
the organic acid and the active substance.” Id.
Appellant argues that Examiner has not presented a sufficient prima
facie showing because Brauns describes only a single, layered particle
composition that achieves an acidic microenvironment through “immediate
diffusion” of the acid layer into the active substance layer (see Appeal Br. 4–
7) and there is no motivation or suggestion in the cited references to change

6 Examiner relies on PubChem to establish that the active substance in
Brauns is dabigatran etexilate. See Ans. 4.
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Application 14/379,613

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that composition to the “two distinct types of particles” recited in
Appellant’s claims. See id. at 9. In particular, Appellant points out that
Habib “is not related at all to, or concerned with, the necessity of a close
proximity between an acid and active ingredient to obtain a desired result,
i.e., an acidic environment that allows for diffusion.” Id. Thus, urges
Appellant, “[o]ne of skill in the art could not reasonably predict that the
single layered particles of [Brauns] could be separated to form a
composition” of two distinct particles as recited in Appellant’s claims. Id. at
10.
We are persuaded by Appellant’s argument and agree that Examiner
has not articulated a sufficient rationale for combining the two particle
composition taught in Habib to modify the single particle composition
taught in Brauns. Habib is directed to an “abuse resistant drug formulation”
(Habib, title) comprising “two particles” wherein “[t]he first particle
comprises an API” and “[t]he second particle comprises a fat/wax material
present in a an amount sufficient to inhibit administration abuse of the API
from the first particle,” e.g., if a capsule containing those particles is
crushed, dissolved or injected. Id. ¶¶ 8, 20.
It is not clear why one of ordinary skill in the art would have
considered Habib’s abuse resistant formulations to be relevant to the layered
particle compositions taught in Brauns. Indeed, Brauns teaches that an
advantage of the “spatial separation of the organic acid and active substance
by the insulating layer” in its layered particle composition is that it increases
bioavailability by facilitating the creation of “an acid microclimate in which
the active substance can dissolve” when acid from the core diffuses into the
drug layer. Brauns ¶ 11. In contrast, the second particle in Habib’s
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composition is intended to achieve the opposite result, i.e., to inhibit
dissolution of the drug. See Habib ¶ 36 (“It is believed that the combination
of particles according to the present invention produces a barrier relative to
the active ingredient-containing particles against solvent access, thereby
protecting and preserving the intended controlled release properties of the
active particles.”).
In view of these teachings, Examiner has not sufficiently explained
why a skilled artisan would be motivated to combine Habib with Brauns to
achieve a composition with the “two distinct types of particles” recited in
Appellant’s claims. For this reason, Examiner has not met the burden to
establish a prima facie showing of obviousness. Accordingly, the rejection
is not supported by the preponderance of the evidence and we, therefore,
reverse.
CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
21, 23, 26,
30, 32, 40–
48
103 Brauns, Habib,
PubChem
21, 23, 26,
30, 32, 40–
48

REVERSED