Ex Parte Delaet et al

Patent Trials and Appeals Board

Jun 18, 2019

14131282 - (D) (P.T.A.B. Jun. 18, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/131,282 01/07/2014
27777 7590 06/20/2019
JOSEPH F. SHIRTZ
JOHNSON & JOHNSON
ONE JOHNSON & JOHNSON PLAZA
NEW BRUNSWICK, NJ 08933-7003
FIRST NAMED INVENTOR
Urbain Alfons C Delaet
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.
TIP0257USPCT 6922
EXAMINER
LEE, ANDREW P
ART UNIT PAPER NUMBER
1621
NOTIFICATION DATE DELIVERY MODE
06/20/2019 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):
jnjuspatent@corus.jnj.com
lhowd@its.jnj.com
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte URBAIN ALFONS C. DELAET,
PHILIP ERNA H. HEYNS, EUGEEN MARIA JOZEF JANS,
ROEL JOS M. MERTENS,
and GEERT VAN DER A VOORT 1
Appeal2017-008306
Application 14/131,282
Technology Center 1600
Before JOHN G. NEW, TA WEN CHANG, and JOHN E. SCHNEIDER,
Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1 Appellants identify Janssen Sciences Ireland UC, an affiliate of Johnson &
Johnson, and Gilead Sciences, Inc., as the real parties-in-interest. App.
Br. 1.
Appeal2017-008306
Application 14/131,282
SUMMARY
Appellants file this appeal under 35 U.S.C. § I34(a) from the
Examiner's Final Rejection of claims 1---6, 9, and 10. Specifically, claims 1,
2, 4, 9, and 10 stand rejected as unpatentable under 35 U.S.C. § I03(a) as
being obvious over Koziara et al. (WO 2009/135179 A2, November 5, 2009)
("Ko ziara").
Claims 3 and 5 stand rejected as unpatentable under 35 U.S.C.
§ I03(a) as being obvious over the combination of Koziara and Shen (US
2008/0113021 Al, May 15, 2008) ("Shen").
Claim 6 stands rejected as unpatentable under 35 U.S.C. § I03(a) as
being obvious over the combination of Koziara and Allaway et al. (US
2008/0039428 Al, February 14, 2008) ("Allaway").
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' invention is directed to solid oral dosage forms of the
HIV inhibitor darunavir and/or a pharmaceutically acceptable salt or solvate
thereof, and combination formulations thereof. Abstract.
REPRESENTATIVE CLAIM
Independent claim 1 is representative of the claims on appeal and
recites:
1. An oral dosage form comprising about 0.4 to 0.6%
by weight (w/w) of a lubricant, about 3% by weight (w/w) of a
disintegrant, 17 to 20% by weight (w/w) of silicon dioxide
loaded with GS-9350 corresponding to a total amount of about
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150 mg free form equivalent of GS-9350 and about 50 to 60%
by weight (w/w) of darunavir granulate, said darunavir granulate
consisting of darunavir and/or a pharmaceutically acceptable salt
or solvate thereof, Hypromellose and any residual water from the
granulation.
App. Br. 8.
ISSUE AND ANALYSIS
We are persuaded by the Examiner's findings and conclusion that the
claims on appeal are prima facie obvious over the combined cited prior art.
We address Appellants' dispositive arguments below.
A. Claims 1, 2, 4, 9, and 10
Issue
Appellants argue that the Examiner erred in failing to establish why a
person of ordinary skill in the art would have been motivated to prepare an
oral dosage formulation that includes granulates consisting of darunavir,
hypromellose and any residual water from the granulation. App. Br. 5.
Analysis
The Examiner finds that Koziara teaches compositions comprising a
compound of Formula I,2 in an amount of 5 to 500 mg, which can be loaded
with colloidal silicon dioxide. Final Act. 3 ( citing Koziara 2, 10). The
2 Formula I is depicted in Koziara as:
r·''·''~,
( )
"
'Y*'';A,J~,rv(l,,'1'..l
~ :,:!.: ?'C'
Koziara 1. It is not disputed by Appellants that Koziara's Formula I
corresponds to GS-9350, as recited in the claims.
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Examiner finds that Koziara teaches that such compositions may also
comprise darunavir, which can be formulated in amounts of 2% to 60%, and
be granulated in form. Id. (citing Koziara 7, 8, 12). The Examiner finds that
Koziara teaches that such compositions may further comprise magnesium
stearate in amounts of 0.5% to 1.5%, silicon dioxide in amounts of 0.2% to
30%, croscarmellose sodium in amounts of 3% to 7%, and hydroxypropyl
methylcellulose (hypromellose ). Id. ( citing Koziara 5-9).
The Examiner concludes that although Koziara does not expressly
teach an exemplary composition of a lubricant, disintegrant, silicon dioxide,
GS-9350, darunavir, and hypromellose in the amounts recited in the claims,
it would have been obvious to a person of ordinary skill in the art to
formulate such a composition and arrive at Appellants' claimed
composition. Final Act. 3. The Examiner further concludes that a skilled
artisan would have been motivated to do so to formulate a composition with
the improved stability and drug release properties taught by Koziara, and
would have had a reasonable expectation of success in so doing, absent any
evidence of the criticality of Appellants' claimed formulation. Id. at 4.
The Examiner notes that, although the ranges for the component
concentrations taught by Koziara is not the same as the claimed ranges,
Koziara teaches overlapping ranges of the component concentrations, and,
therefore a prima facie case of obviousness exists. Final Act. 4. The
Examiner further concludes that it would have been prima facie obvious to
optimize the component amounts to arrive at the overlapping ranges to
increase the therapeutic activity of the formulation, with a reasonable
expectation of success. Id.
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Appellants argue that the Examiner has failed to establish why a
person of ordinary skill in the art would have been motivated to prepare an
oral dosage formulation that includes granulates consisting of darunavir,
hypromellose and any residual water from the granulation. App. Br. 5.
Specifically, Appellants assert that the Examiner does not address the
limitations of the claims in view of the "consisting of' transitional language
recited in the claims, or the individual components of such granulates. Id.
According to Appellants, Koziara neither teaches nor suggests in any
way that the darunavir drug load can be increased by first making a
granulate of darunavir and hypromellose, drying it, and only then using it to
make a final pharmaceutical formulation. App. Br. 5. Appellants argue that
the Examiner has failed to establish that the claimed inventions would have
been obvious, and instead has merely recited Koziara's teaching of the
individual components Applicants used to make their granulates, and
ultimately their oral dosage form. Id.
Appellants contend that Koziara teaches that darunavir can be added
to GS-93 SO-containing compositions, and that such compositions can be
granulated along with additional excipients. App. Br. 5. However,
Appellants argue, these teachings do not address the problem of high pill
burden as the amounts of darunavir and GS-9350 are increased in such GS-
93 SO-containing compositions to the levels provided for in the claimed
composition. Id. Appellants note that the Examiner recognizes that Koziara
does not teach a composition of darunavir in a composition with lubricant,
disintegrant, silicon dioxide, GS-9350 and hypromellose in the claimed
amounts. Id. Furthermore, Appellants assert, the Examiner provides no
rationale as to how one would overcome the challenges presented in
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achieving a high loading of darunavir in a GS-9350 combination formulation
of an acceptable size, requiring less frequent dosing and beneficial in terms
of pill burden and drug compliance for a patient. Id. Appellants argue that
their Specification demonstrates in Example 1 how such compositions can
fail or are unpredictable; Appellants assert that, for example, direct
compression of concept A did not occur because of bad flowability. Id. at
5-6 (citing Spec. 12).
The Examiner responds that Koziara teaches that granulation can
comprise loading the active compound, silicon dioxide, hypromellose, and
water for wet granulation. Ans. 5 (citing Koziara 29-30, Fig. 1, Example 1).
The Examiner finds that such granulation would overcome issues arising
from high loading of darunavir, with a reasonable expectation of success.
Additionally, the Examiner points out that the teachings of Koziara are not
limited to preferred embodiments. Id.
We are not persuaded by Appellants arguments. Claim 1 is directed
to an oral dosage form comprising: (1) about 0.4 to 0.6% by weight (w/w) of
a lubricant; (2) about 3% by weight (w/w) of a disintegrant; (3) 17 to 20 %
by weight (w/w) of silicon dioxide loaded with GS-9350 corresponding to a
total amount of about 150 mg free form equivalent of GS-9350; and ( 4)
about 50 to 60 % by weight (w/w) of darunavir granulate, said darunavir
granulate consisting of darunavir and/or a pharmaceutically acceptable salt
or solvate thereof, hypromellose and any residual water from the
granulation.
The Examiner finds that Koziara teaches oral dosages comprising,
respectively: (1) pharmaceutically acceptable lubricants at, e.g., 1 % ± 0.5%.
(Koziara 8); (2) a disintegrant ( e.g., croscarmellose sodium) at 5% ± 2%
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(Koziara 7); (3) and GS-9350 (Formula 1 of Koziara) combined with silicon
dioxide as a carrier, with at least 0.1 % and about 2%---60% of GS-9350
(Koziara 8, 5); combined with (4) darunavir at 2---60% (Koziara, e.g., 7, 8-
12, 13, 15, 16-20).
With respect to the latter, Koziara teaches, in an exemplary
embodiment: ( 1) mixing GS-93 50 with: "a suitable solvent, and a plurality
of solid carrier particles to provide a first mixture;" (2) optionally mixing the
first mixture; (3) optionally adding one or more pharmaceutically acceptable
excipients (e.g., a filler, a binder and a disintegrant) to the mixture to provide
a second mixture; ( 4) optionally adding another therapeutic agent (i.e.,
darunavir) to the mixture; (5) optionally mixing the second mixture;
optionally adding water to the second mixture to provide a wet granulate; ( 6)
optionally de-agglomerating the wet granulate; optionally drying to provide
a dried material that comprises solid particles. Koziara 29-30. Koziara also
teaches that adding hydroxypropyl cellulose (i.e., hypromellose) as a binder
in step 3 is particularly compatible with the subsequent wet granulation
process. Id. at 7.
In summary, Koziara teaches the limitations of claim 1 with
concentrations of ingredients that overlap those recited in claim 1. Our
reviewing court has consistently held that "even a slight overlap in range
establishes a prima facie case of obviousness." In re Peterson, 315 F .3d
1325, 1329 (Fed. Cir. 2003).
Appellants argue that Koziara does not teach adding a darunavir
granulate to the existing GS-9350 mixture, but rather teaches adding
darunavir to GS-9350 and its lubricants, hypromellose, etc., and then wet
granulating the mixture of the actives, etc. This, Appellants contend, is
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inconsistent with the claims' requirement of: "about 50 to 60% by weight
(w/w) of darunavir granulate, said darunavir granulate consisting of
darunavir and/or a pharmaceutically acceptable salt or solvate thereof,
Hypromellose and any residual water from the granulation."
We are not persuaded by Appellants' argument. Claims 1, 2, 4, 9, and
10 are directed to a composition, and not to a method of making that
composition. These claims require only that the composition contain: "about
50 to 60% by weight (w/w) of darunavir granulate, said darunavir granulate
consisting of darunavir and/or a pharmaceutically acceptable salt or solvate
thereof, Hypromellose and any residual water from the granulation."
Koziara teaches a composition that, when mixed, contains a darunavir
granulate that meets the recited requirements. That the complete oral dosage
form also contains granulated GS-93 50 is immaterial, because the claim
language employs the transitional term "comprising" which does not exclude
the GS-9350 also being granulated. See Crystal Semiconductor Corp. v.
TriTech Microelectronics Int'!, Inc., 246 F.3d 1336, 1348 (Fed. Cir. 2001)
(holding that use of the transition "comprising" in the language of a claim
"creates a presumption ... that the claim does not exclude additional,
unrecited elements").
In other words, it is enough to establish a prima facie case of
obviousness that the oral dosage composition taught by Koziara comprises
darunavir granulate, in the claimed range, consisting of: "darunavir and/or a
pharmaceutically acceptable salt or solvate thereof, Hypromellose and any
residual water from the granulation."
For similar reasons, we are not persuaded by Appellants' argument
that Koziara does not teach that the darunavir drug load can be increased by
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first making a wet granulate of darunavir and hypromellose, drying it, and
only then using it to make a final pharmaceutical formulation. Again,
Appellants' claims are directed to a composition, and not to a method of
making that composition, and it is uncontested that Koziara teaches the
recited constituents of the claimed composition within the claimed
concentration ranges.
Because Koziara teaches the recited constituents of the claimed
composition with the claimed concentration ranges, we affirm the
Examiner's rejection of the claims.
B. Claims 3 and 5
Appellants repeat their argument supra, adding that Shen does not
cure the alleged deficiencies of Koziara. App. Br. 6.
We are not persuaded. Claims 3 and 5, like claims 1, 2, 4, 9, and 10,
are composition claims and are not directed to a method of making the
claimed composition. For the reasons we have explained supra, we
similarly affirm the Examiner's rejection of claims 3 and 5.
C. Claim 6
Appellants repeat their argument supra, adding that Allaway does not
cure the alleged deficiencies of Koziara. App. Br. 6.
We are not persuaded. For the reasons we have explained supra, we
similarly affirm the Examiner's rejection of claim 6.
DECISION
The Examiner's rejection of claims claims 1-6, 9, and 10 under
35 U.S.C. § 103(a) is affirmed.
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l)(iv).
AFFIRMED
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