Ex Parte Remon et al

Patent Trial and Appeal Board

Feb 1, 2019

13454592 (P.T.A.B. Feb. 1, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/454,592
31217 7590
Henkel Corporation
One Henkel Way
Rocky Hill, CT 06067
04/24/2012
02/05/2019
FIRST NAMED INVENTOR
Jean Paul Remon
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.
N-3268D.TDM-US 1855
EXAMINER
RODRIGUEZ, RAYNA B
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
02/05/2019 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):
rhpatentmail@henkel.com
trish.russo@henkel.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JEANPAUL REM ON,
CHRIS VERVAET, and
PAUL FOREMAN
Appeal 2018-000831
Application 13/454,592
Technology Center 1600
Before JEFFREY N. FREDMAN, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134 involving claims to a
method of intra vaginally administering pellets, including a de branched
starch and a therapeutic agent. The Examiner rejected the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b ). We affirm.
1 Appellants identify the Real Party in Interest as Henkel IP & Holding
GmbH (see Br. 3).
2 We have considered and herein refer to the Specification of Apr. 24, 2012
("Spec."); Final Office Action of Sep. 15, 2016 ("Final Act."); Appeal Brief
of Feb. 16, 2017 (" Br."); and Examiner's Answer of Jun. 1, 2017 ("Ans.").
Appeal 2018-000831
Application 13/454,592
Statement of the Case
Background
"Vaginal drug delivery is a promising route for local and systemic
delivery" (Spec. ,r 3). "There is a need for the development of a new vaginal
delivery form which assures an acceptable retention time, combined with a
good spreading over the vaginal epithelium" (Spec. ,r 8). "It has been
discovered that pharmaceutical pellets made using a crystalline debranched
amylase resistant starch are particularly useful for the vaginal delivery of
active agents" (Spec. ,r 11 ). "Vaginal drug delivery using the pellets of the
invention combines the advantages of the fast spreading semi-solid
formulations with a better retention time" (Spec. ,r 12). "A specific starch
grade has been identified as a material suitable for use as an excipient for
pellets prepared via extrusion/spheronization" (Spec. ,r 16).
The Claims
Claims 1-5, 7, 8, 15-17, and 19-22 are on appeal. Independent claim
1 is representative and reads as follows:
1. A method of treating or preventing a condition in a
patient comprising administering to a patient a composition
comprising pellets, said pellets comprising at least one
excipient and a therapeutic agent,
wherein at least one excipient is a crystalline debranched
amylase resistant starch comprising D-anhydroglucose units
organized into double-helical crystalline chains
wherein said crystalline debranched amylase resistant
starch is greater than 50 % by total weight of the excipient,
wherein said pellets are administered intravaginally, and
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Application 13/454,592
wherein the size of the pellets range from 300 to 1000
micrometer.
The Rejection
The Examiner rejected claims 1-5, 7, 8, 15-17, and 19-22 under 35
U.S.C. § 103(a) as obvious over Besemer, 3 De Luigi Bruschi, 4 and Dukic5
(Final Act. 4--12).
The Examiner finds that Besemer teaches "debranched starches are
useful in vaginal drug delivery, and have the beneficial property of minimal
disintegration" (Final Act. 5). The Examiner finds although "Besemer does
not explicitly teach the debranched amylase resistant starch comprises D-
glucose units organized into double-helical crystalline chains[,]" Besemer
teaches a matrix material including "an essentially crystalline straight-chain"
of a-1,4-anhydroglucose units (Final Act. 5---6). The Examiner finds that
"Besemer suggests starch derivatives are obtained from debranching
branched glucans ... [which] would result in a debranched amylase resistant
starch comprising a-1,4-anhydroglucose in a helix structure" (Final Act. 6.)
The Examiner acknowledges that "Besemer does not explicitly teach a
method of treating a vaginal disorder or condition" (Final Act. 6.) The
Examiner finds that De Luigi Bruschi teaches "a method of treatment of
vaginal disorders, such as vulvovaginal candidiasis, comprising
administering a vaginal bioadhesive controlled release matrix comprising an
antifungal as a pharmaceutical active and starch derivatives such as amylose,
3 Besemer, EP 0648116 B 1, published Oct. 9, 1996
4 De Luigi Bruschi et al., WO 2008/000683 Al, published Jan. 3, 2008
5 Dukie et al., US 2006/0246192 Al, published Nov. 2, 2006
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Application 13/454,592
wherein the matrix is granulated (granules are a form of pellet)" (Final Act.
7.)
The Examiner determines
it would have been obvious to one of ordinary skill in the art to
utilize the straight-chain debranched amylose starch comprising
composition taught by Besemer in the method taught by De
Luigi Bruschi, since the prior art establishes that starch
derivatives such as amylose are suitable for intravaginal
treatment with an antifungal and debranched straight-chain
amylose is a starch derivative subject to little or no
disintegration and little or no attack by a-amylase.
(Final Act. 7-8).
The Examiner acknowledges that "De Luigi Bruschi and Besemer do
not explicitly teach a granule in the claimed size range or that the pellets are
prepared by extrusion followed by spheronization" (Final Act. 8). The
Examiner finds that Dukie teaches "the use of crystalline debranched starch
in the preparation of pharmaceutical pellets by extrusion-spheronization"
and "the diameter of the pellets ranges from about 0.70 to 1.40 mm" (Final
Act. 8-9). The Examiner determines
(Id.).
it would have been obvious to one of ordinary skill in the art to
formulate the pellets taught by De Luigi Bruschi and Besemer
utilizing the methods taught by Dukie since the prior art
establish that extrusion-spheronization is a suitable method for
forming pharmaceutical pellets comprising a debranched starch
and an antifungal.
The issue with respect to this rejection is: Does the evidence of record
support the Examiner's conclusion that the combination of Besemer, De
Luigi Bruschi, and Dukie renders the claims obvious?
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Application 13/454,592
Findings of Fact ("FF'')
1. Besemer teaches "a composition for delayed release of an
active substance in a target environment, the active substance being
incorporated in a polysaccharide matrix" (Besemer 1 :3---6).
2. Besemer teaches "that the matrix material in which the active
substance is incorporated comprises an essentially crystalline, straight-chain
glucan. The glucan is preferably an a-glucan and in particular an a-1,4-
glucan and preferably has essentially a helix structure" (Besemer 2:8-11).
3. Besemer teaches "[ t ]he a-1,4-glycan can, for example, be an
amylose. Amylose is a straight chain of a-1,4-anhydroglucose units"
(Besemer 2: 19-22).
4. Besemer teaches "administration forms which comprise such
crystalline straight-chain glucans as matrix-forming material are subject to
little or no disintegration and little or no attack by a-amylase" (Besemer
3:17-19).
5. Besemer teaches "[ t ]he composition can also be in the form of a
capsule in which the matrix material containing active substance is present,
for example in granular form or powder form" (Besemer 4:42--45).
6. Besemer teaches compositions "characteri[ z Jed in that the
matrix material comprises at least 50% by weight of a crystalline, straight-
chain a-glucan having essentially a helix structure" (Besemer 9:9-16).
7. Besemer teaches "[ t ]he active substance can be of diverse
natures. For example it can be medicaments for oral, rectal, vaginal or
transdermal administration" (Besemer 4: 15-17).
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Application 13/454,592
8. Besemer teaches "[r]elease can take place in an aqueous
medium, such as the gastrointestinal tract of animals, or in plants or in the
soil, but also into the air" (Besemer 4:25-27).
9. De Luigi Bruschi teaches a hydrophilic matrix "used in
combination with at least one pharmaceutically acceptable active principle
for manufacturing solid bioadhesive controlled release formulations for the
treatment of vaginal disorders, such as vulvovaginal candidiasis" (De Luigi
Bruschi Abstract).
10. De Luigi Bruschi teaches that "[ u ]nfortunately in the specific
case of the bioadhesive controlled release vaginal delivery, the small vaginal
daily secretions are not sufficient to hydrate conventional matrix tablets.
This means that matrix tablets not achieving the swollen state, in practice
arrest or slow down the drug diffusion process" (De Luigi Bruschi 4:4--8).
11. De Luigi Bruschi teaches that "it has been discovered that the
inclusion of a disintegrant in an hydrophilic matrix made by one or more
ether of cellulose and one or more polyacrylic acid derivatives, promoted a
rapid achievement of the swollen state even in presence of limited quantities
of vaginal secretions" (De Luigi Bruschi 5:11-14).
12. De Luigi Bruschi teaches "[d]isintegrating agents suitable to be
used in the present invention can be chosen from different classes" including
"starch derivatives such as amylose" (De Luigi Bruschi 7 :25-31) where the
composition may comprise "at least one disintegrant in amounts of 2 - 50%,
with respect to the weight of the matrix" (De Luigi Bruschi 20: 11-12).
13. De Luigi Bruschi teaches "[t]he controlled release properties of
the vaginal tablets may be modified by the presence in the dosage form of
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Application 13/454,592
soluble and insoluble fillers ... [t]he soluble excipients can be selected from
... amylose" (De Luigi Bruschi 8: 12-20).
14. De Luigi Bruschi teaches "[a]mong the variety of drugs that can
be incorporated into the controlled release bioadhesive vaginal tablets object
of the present invention are the antimycotics, used in the treatment of the
vulvovaginal candidiasis" (De Luigi Bruschi 9: 14--16).
15. Dukie teaches "the use of crystalline debranched starch in the
preparation of pharmaceutical pellets by extrusion-spheronization. Such
excipients are useful in any dry dosage form, including tablets and capsules,
for either immediate or sustained release" (Dukie ,r 28).
16. Dukie teaches "[t]he active agents may be distributed inside the
pellets" (Dukie ,r 75).
1 7. Dukie teaches
[ u ]se of debranched starches provides a yield of greater than
80% and in one embodiment greater than 90%. Yield is
intended to mean the percent of the extruded composition
which resulted in usable pellets, that is pellets which are
substantially spherical solid particles whose diameter size range
from about 100 microns to about 3 mm. In one embodiment,
the diameter of the pellets ranges from about O. 7 0 to 1.40 mm.
(Dukie ,r 70).
18. Dukie teaches "[ t ]he active principles which may be
vehiculated by the pellets of this invention include ... antifungals" (Dukie ,r
74).
Principles of Law
A prima facie case for obviousness require "a reason that would have
prompted a person of ordinary skill in the relevant field to combine the
elements in the way the claimed new invention does." KSR Int'! Co. v.
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Application 13/454,592
Teleflex Inc., 550 U.S. 398, 418 (2007).
Analysis
We adopt the Examiner's findings of fact and conclusion of law (see
Final Act. 4--16, FF 1-18) and agree that the combination of Besemer, De
Luigi Bruschi, and Dukie renders the claims obvious. We address
Appellants' arguments below.
Appellants contend "that Besemer only describes formulations
intended to pass through the gastrointestinal system" and that "[a] skilled
person would not have predicted that a formulation - only established as
useful for oral administration - could be successfully used intravaginally"
(Br. 6).
We do not find this argument persuasive because Besemer expressly
teaches that composition may include "medicaments ... for vaginal
administration" (FF 7). Contrary to Appellants' arguments, there is no
teaching limiting Besemer to only oral compositions. Even if oral
compositions are preferred, "the fact that a specific [embodiment] is taught
to be preferred is not controlling, since all disclosures of the prior art,
including unpreferred embodiments, must be considered." Merck & Co. Inc.
v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989).
Appellants contend that:
[I]n view of the challenges presented by vaginal drug delivery,
as discussed by DeLuigi Bruschi, a skilled artisan would not
have considered the teachings of Besemer, which relate to oral
compositions for delayed release in the gastrointestinal tract, to
be applicable to the teachings of DeLuigi Bruschi, which relates
to vaginal formulations.
( Br. 7-8).
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We do not find this argument persuasive. As discussed above,
Besemer is not limited to oral compositions, and expressly teaches
medicaments for vaginal administration (FF 7). Moreover, while De Luigi
Bruschi describes the problems associated with "conventional matrix
tablets" (FF 11 ), De Luigi Bruschi explains that "the inclusion of a
disintegrant ... promoted a rapid achievement of the swollen state even in
presence of limited quantities of vaginal secretions" (FF 11 ). De Luigi
Bruschi teaches that desirable disintegrants may include amylose (FF 12).
Therefore, the ordinary artisan, interested in addressing De Luigi Bruschi's
concerns with hydration, would have had reason to include amylose based
disintegrants as directly suggested by De Luigi Bruschi (FF 12). A "given
course of action often has simultaneous advantages and disadvantages, and
this does not necessarily obviate motivation to combine." Medichem, S.A. v.
Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006).
In addition, the rejection relies upon the combination of Besemer, De
Luigi Bruschi, and Dukie to reasonably suggest formulation of the
composition into granules or pellets contained in a capsule (FF 5, 15, 16).
Appellants provide no evidence that Besemer's starch-based granules in a
capsule would be subject to the concerns of De Luigi Bruschi. Finally, De
Luigi Bruschi teaches amylose is a suitable excipient for intravaginal
administration (FF 12, 13).
Appellants contend that "Besemer teaches a matrix material
comprising at least 50% by weight of crystalline, straight chain alpha-glucan
composition" and "DeLuigi Bruschi teaches to utilize large quantities, in the
range of 30-90 or 40-80 wt%, of MCC [ microcrystalline cellulose] ... as
the excipient matrix" ( Br. 8). Appellants contend "[g]iven the importance
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of using large quantities of MCC in DeLuigi Bruschi, a skill artisan would
not be led to simply disregard MCC in the matrix and to minimize the use of
such excipient" (id.).
We do not find this argument persuasive because "[t]he test for
obviousness is not whether the features of a secondary reference may be
bodily incorporated into the structure of the primary reference ... Rather,
the test is what the combined teachings of the references would have
suggested to those of ordinary skill in the art." In re Keller, 642, F.2d 413,
425 (CCPA 1977). We note that De Luigi Bruschi teaches that amylose may
be used in amounts of 2 to 50% as a disintegrant (FF 12), directly adjacent to
the range of "greater than 50%" required by claim 1, and reasonably
expected to share the same properties. See In re Peterson, 315 F.3d 1325,
1329 (Fed. Cir. 2003) ("We have also held that aprimafacie case of
obviousness exists when the claimed range and the prior art range do not
overlap but are close enough such that one skilled in the art would have
expected them to have the same properties.)
We find the combination of the references suggests intra vaginally
administering the Besemer's formulations for treating vaginal disorders,
such as vulvovaginal candidiasis, as taught by De Luigi Bruschi using
compositions comprising amylose. The prior art need not suggest
incorporating the De Luigi Bruschi's formulation wholesale into Besemer's
formulation.
Appellants contend that Besemer and De Luigi Bruschi are directed to
tablets, not "capsules with pellets" ( Br. 9). Appellants further contend that
Dukie "is solely directed to compositions for oral delivery, and does not
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teach or suggest any compositions or methods that would be suitable for
vaginal delivery" (id.).
We do not find these arguments persuasive because they fail to
address the combined teachings of the references. "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). As discussed above, Besemer teaches "[t]he
composition can also be in the form of a capsule in which the matrix
material containing active substance is present, for example in granular form
or powder form" (FF 5) and is not limited to tablet formulations. Moreover,
the Examiner cites Dukie for extrusioning and spheronizing crystalline
debranched starch pellets ranging in size from 700 to 1,400 micrometer (FF
1 7), not for vaginal administration. When the references are considered
together, Dukie complements Besemer's and De Luigi Bruschi's method of
intravaginally administering active agent containing formulations, by
providing appropriately sized pellets including an antifungal active agent.
As the Examiner points out, Dukie demonstrates that "extrusion-
spheronization is a suitable method for forming pharmaceutical pellets
comprising a debranched starch and an antifungal" (Ans. 19), useful "for
either immediate or sustained release" (FF 15) and Besemer is interested in
delayed release compositions (FF 1) for vaginal administration (FF 7).
Conclusion of Law
A preponderance of the evidence of record support the Examiner's
conclusion that the prior art renders claim 1 obvious.
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SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Besemer, De Luigi Bruschi, and Dukie. Claims 2-
5, 7, 8, 15-17, and 19-22 fall with claim 1.
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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