Ex Parte MULDOON et al

Patent Trial and Appeal Board

Dec 15, 2017

14210630 (P.T.A.B. Dec. 15, 2017)

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.
02911.012660. 1015
EXAMINER
BASQUILL, SEAN M
ART UNIT PAPER NUMBER
1613
MAIL DATE DELIVERY MODE
14/210,630 03/14/2014 Brendan MULDOON
5514 7590 12/15/2017
FITZPATRICK CELLA HARPER & SCINTO
1290 Avenue of the Americas
NEW YORK, NY 10104-3800
12/15/2017 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 BRENDAN MULDOON and STEPHEN MCCULLAGH
Appeal 2016-006885
Application 14/210,63 01
Technology Center 1600
Before ULRIKE W. JENKS, JOHN G. NEW, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a soft
gelatin capsule dosage form, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
“[Sjoft gelatin capsules have been known to have a decrease in
dissolution during storage, which eventually may retard or deleteriously
impact drug release.” (Spec. 13.) Appellant’s “invention relates to a
1 Applicant is the Appellant, which is Warner Chilcott Company, LLC, also
identified as the Real Party in Interest. (Appeal Br. 1.)
Appeal 2016-006885
Application 14/210,630
pharmaceutical soft gelatin capsule dosage form that has a stable dissolution
profile over the time of storage.” {Id. 12.)
Claims 1, 3—9, 11 and 12 are on appeal. Claim 1 is representative and
reads as follows:
1. A pharmaceutical soft gelatin capsule dosage form
comprising:
a shell comprising gelatin and a plasticizer; and
a fill comprising at least one pharmaceutically active
ingredient, polyethylene glycol, polyacrylic acid, a neutralizing
agent, and water,
wherein the neutralizing agent is a primary amine or a
secondary amine and is present in an amount of about 0.05% to
about 0.5% by weight of the total weight of the fill so as to
provide a soft gelatin dosage form having stable dissolution
after storage, and wherein stable dissolution after storage is
achieved when the soft gelatin capsule stored for one month at
40°C and a relative humidity of 75% had less than about 30%
change in dissolution after one month storage.
(Appeal Br. 10.)
The following grounds of rejection by the Examiner are before us on
review:
Claims 1 and 3—9 under 35 U.S.C. § 103(a) as unpatentable over Gao2
and Acharya.3
Claims 11 and 12 under 35 U.S.C. § 103(a) as unpatentable over Gao,
Acharya, and Zeng.4
2 Gao, US 2004/0131670 Al, published July 8, 2004.
3 Acharya, US 5,102,666, issued Apr. 7, 1992.
4 Zeng et al., US 2007/0104778 Al, published May 10, 2007.
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DISCUSSION
Obviousness over Gao and Acharya
The Examiner finds that Gao teaches soft gelatin capsule dosage
forms that provide a stable and predictable dissolution rate of drugs that
have a low water solubility after storage. (Final Action 3.) The Examiner
notes that the capsules include a shell that contains gelatin, a primary or
secondary amine, and plasticizers. (Id.) The fill material includes
polyethylene glycol and water (as a cosolvent), and optionally includes a
primary or secondary amine, such as diethanolamine. (Id. at 4.) The
Examiner explains that Gao teaches that if an amine is included, the total
amount in the dosage form should be within the range of about 0.1 —2 % of
the composition, with most preferably 70% of the amine being present in the
shell. (Id.) The Examiner contends, therefore, that “in a most preferred
embodiment, Gao indicates that the fill material contains between 0.03-0.6%
of the primary or secondary amines contained within the composition as a
whole, overlapping the ranges of the instant claims.” (Id.)
The Examiner further notes that Gao teaches the fill material may also
optionally include a wetting agent such as a surfactant, hydrophilic polymer
or certain clays, which would serve to aid in the dissolution and/or
dispersion of a hydrophobic drug. (Id.)
The Examiner recognizes that Gao does not teach inclusion of a
polyacrylic acid, e.g., polycarbophil, as the hydrophilic polymer being
including in the fill material, but contends that it would have been obvious to
include that ingredient in light of the teachings of Acharya. (Id. at 4—5.) In
particular, explains the Examiner, Acharya teaches that polycarbophil when
combined with water and other cosolvents, such as polyethylene glycol,
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provides for controlled release of pharmaceutical active agents incorporated
into a matrix, including estrogens and other steroids. (Id. at 4.) According
to the Examiner, Acharya teaches that compositions including polycarbophil
are “capable of being formulated into any of a variety of physical forms,
including capsules.” (Id. at 5.) In light of these teachings, the Examiner
concludes that it would have been obvious to one of ordinary skill in the art
to have selected polycarbophil as the hydrophilic polymer to be included in
the Gao composition to aid in the dissolution and dispersion of the active in
Gao with controlled release.
We agree with the Examiner’s factual findings and conclusion that the
claimed capsule dosage form would have been obvious to one of ordinary
skill in the art in light of the teachings of Gao and Acharya.
Appellant argues that incorporating a primary or secondary amine in a
capsule fill composition in an amount of about 0.05 to about 0.5% by weight
of the fill would not have been obvious to one of ordinary skill in the art
because “the problem of decreased dissolution during storage of soft gelatin
capsules containing a polyacrylic acid fill” was not recognized at the time of
Appellant’s invention. (Appeal Br. 3.) We do not find this argument
persuasive. As the Examiner explained, Gao teaches a capsule formulation
where a primary or secondary amine is included in the fill at about 30% of
0.1—2% by weight of the composition. (Gao 28, 110-111; Final Action
4.) In other words, the amine is included in the fill at between about 0.03—
6%. This range overlaps the claimed range.
Therefore, the issue for obviousness is not whether it would have been
obvious to incorporate an amine in the capsule fill material in the claimed
range, but rather, whether it would have been obvious to select a polyacrylic
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acid, like polycarbophil, as the hydrophilic polymer to include in the Gao fill
composition that includes an amine in the claimed range. We agree with the
Examiner that in light of the teachings of Acharya, one of ordinary skill in
the art would have found it obvious to include such a hydrophilic polymer.
As the Examiner noted (Final Action 4—5; see also Ans. 8), Acharya teaches
that the combination of calcium polycarbophil with water and/or other
cosolvents “provides a means for achieving a rate-controlled release of the
active composition.” (Acharya 2:64—3:6.) Furthermore, Acharya teaches
that the dosage form for which the compositions are “especially useful”
includes encapsulated capsules (id. atl: 10—14) and that the polymeric system
and active composition can be “in either dry form, as a semi-solid or as a
liquid suspension” (id. at 8:48—52). Thus we disagree with Appellant’s
apparent position that Acharya only “suggests the way the composition
would be encapsulated in a gelatin capsule would be to prepare a dry
granulation” (Appeal Br. 7).
“When determining the patentability of a claimed invention which
combines two known elements, ‘the question is whether there is something
in the prior art as a whole to suggest the desirability, and thus the
obviousness, of making the combination.’” In re Beattie, 974 F.2d 1309,
1311-12 (Fed. Cir. 1992) (quoting Lindemann Maschinenfabrik GMBH v.
American Hoist & Derrick Co., 730 F.2d 1452, 1462 (Fed. Cir. 1984)).
Appellant argues that Acharya “does not provide adequate suggestion or
motivation for substituting the polycarbophil of Acharya into the liquid
filled capsule of Gao.” (Appeal Br. 6.) However, for the reasons just
discussed, we find that the Examiner has provided evidence from the prior
art that there is a suggestion of the desirability of using polycarbophil as the
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hydrophilic polymer of the Gao fill formulation. Moreover, contrary to
Appellant’s argument (Appeal Br. 4, Reply Br. 2), “we do not view the
rejection as deficient merely because [A]ppellant[] allege[s] a different
advantage resulting from” the inclusion of a primary or secondary amine in
the particularly claimed percentage when polycarbophil is also included in
the fill composition. In re Kronig, 539 F.2d 1300, 1304 (CCPA 1976).
Appellant argues that Gao does not teach or suggest the use of
polyacrylic acid. (Appeal Br. 4.) This argument is not persuasive in that the
Examiner relied on Acharya for the obviousness of selecting this hydrophilic
polymer for the composition taught by Gao. For similar reasons, we do not
find persuasive Appellant’s argument that Acharya does not “suggest using a
primary or secondary amine” as claimed {id. at 6—7). The Examiner relied
upon Gao for such a teachings. “Non-obviousness cannot be established by
attacking references individually where the rejection is based upon the
teachings of a combination of references. . . . [The reference] must be read,
not in isolation, but for what it fairly teaches in combination with the prior
art as a whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Appellant further argues that Gao teaches away from the “addition” of
a primary or secondary amine in the claimed amount. (Appeal Br. 5, Reply
Br. 2—3.) We do not find this argument persuasive. Gao teaches fill
compositions that include tromethamine. (Gao 1135 (Example 3).) And as
discussed above Gao teaches that the fill composition can include a primary
or secondary amine in the range of from about 0.03% —0.6% {id. ]ff[ 28, 110—
111), a range that fully overlaps the claims range of 0.05-0.5% claimed. It
is true, as Appellant contends (Appeal Br. 5, Reply Br. 3), that a specific fill
composition of Gao that includes 0.5% tromethamine resulted in pellicle
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formation after 4 weeks. (Gao 1135 (Table 5) and 1136 (Table 6) and 1
137.) However, Gao’s example F3 also included 3.3%
dimethylethanolamine (DMAE). (Id.) Fill formulation 1 (FI) that includes
tromethamine at 2.6% and no dimethylethanolamine (DMAE) or other
primary or secondary amine resulted in no pellicle formation after 4 weeks.
(Id.) Thus, Gao indicates that lowering the amount of total primary and
secondary amine can assist in preventing pellicle formation. Consequently,
we do not find the single fill formulation that employs 0.5% tromethamine in
a particularly described formulation that also includes DMAE in 3.3% that
results in pellicle formation on storage to teach away from the claimed range
of including a primary or secondary amine in an amount of about 0.05% to
about 0.5%, where Gao specifically describes including a primary or
secondary amine in the fill in a range of from 0.03% to 0.6%.
Furthermore, Appellant has not established unexpected properties in
the claimed range. In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997)(“[A]
prima facie case of obviousness based on overlapping ranges can be rebutted
if the applicant (1) can establish ‘the existence of unexpected properties in
the range claimed’ or (2) can show ‘that the art in any material respect
taught away’ from the claimed invention.”). “To be particularly probative,
evidence of unexpected results must establish that there is a difference
between the results obtained and those of the closest prior art, and that the
difference would not have been expected by one of ordinary skill in the art at
the time of the invention.” Bristol-Myers Squibb Co. v. Teva Pharms. USA,
Inc., 752 F.3d 967, 977 (Fed. Cir. 2014). Rather than provide any
comparison, Appellant points only to the F3 fill formulation of Gao that
contained 0.5% tromethamine exhibited pellicle formation after 30 days.
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However, Appellant fails to appreciate that the addition of tromethamine to a
composition that also contained dimethylethanolamine (F3) at 3.3% resulted
in less pellicle formation than a composition that contained DMAE at 3.4%
and no tromethamine, i.e., composition F2. (Gao Table 5 and 6.) Combined
with the fact that tromethamine used in a fill composition at 2.6% without
DMAE and pellicle formation was not observed {id.), Gao suggests that
tromethamine in the fill in various amounts may assist in stabilizing the
formulation on storage. Thus the use of tromethamine or any other primary
or secondary amine in the claimed range has not been established by
Appellant to be unexpected.
Claims 3—9 have not been argued separately and therefore fall with
claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
Obviousness over Gao, Acharya, and Zeng
The Examiner explains that while Gao does not teach the use of
diisopropanolamine in a fill composition as claimed, selecting that amine
would have been obvious in light of the teachings of Zeng. (Final Action 8.)
The Examiner explains that “Zeng, . . . indicate[s] that diisopropanolamine is
a pharmaceutically acceptable primary or secondary amine for use in drug
delivery, particularly with controlled release gelling agent carriers such as
polycarbophil” and in a capsule dosage form that contains active agents such
as estradiol. {Id. at 9.)
Appellant contends that “the deficiencies of Gao and Acharya”
regarding claim 1 “are not remedied by Zeng.” (Appeal Br. 7.) For the
reasons discussed above, we do not find the Examiner’s rejection of claim 1
over Gao and Acharya to be deficient. Consequently, Appellant does not
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persuade us that the Examiner erred in rejection claims 11 and 12 for
obviousness over Gao, Acharya, and Zeng.
SUMMARY
We affirm the rejection of claims 1 and 3—9 under 35 U.S.C. § 103(a)
as unpatentable over Gao and Acharya.
We affirm the rejection of claims 11 and 12 under 35 U.S.C. § 103(a)
as unpatentable over Gao, Acharya, and Zeng.
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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