Benjamin M. Wu et al.

Patent Trials and Appeals Board

Aug 1, 2019

14498005 - (D) (P.T.A.B. Aug. 1, 2019)

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.
14/498,005 09/26/2014 Benjamin M. Wu 206030-0037-00-
US.603472
1129
10872 7590 08/01/2019
Riverside Law LLP
Glenhardie Corporate Center, Glenhardie Two
1285 Drummers Lane, Suite 202
Wayne, PA 19087
EXAMINER
LEONARD, ARTHUR S
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
08/01/2019 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte BENJAMIN M. WU, MAIE A.R. ST. JOHN,
ARNOLD SUWARNASAM, LINDA WANG, YUAN LIN, JIE LUO,
ERIC ZHU, ONTARIO D. LAU, and SHERVEN SHARMA1
__________

Appeal 2019-002780
Application 14/498,005
Technology Center 1600
__________

Before RYAN H. FLAX, RACHEL H. TOWNSEND, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.

HARDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
modular polymer platform comprising two or more therapeutic agents
releasable from a stratified polymeric substrate comprising at least a
hydrogel, polymer, and backing layer, wherein each of the layers has a
particular degradation rate relative to the other layers. The Examiner
rejected the claims as obvious over the prior art. We have jurisdiction under
35 U.S.C. § 6(b).
We affirm.

1 Appellants identify “The Regents of the University of California” as the
real party in interest. Appeal Br. 3.
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STATEMENT OF THE CASE
According to the Specification, “[t]he present invention provides a
modular polymer platform for the controlled delivery of two or more
therapeutic agents.” Spec. 2:10–12. “[T]he platform comprises an
impermeable backing layer or film, which prevents release of the one or
more therapeutic agents through the backing layer.” Id. at 17:17–19.
Claims 1–6, 9, 10, 12, and 31–34 are on appeal. Final Act. 2. Claim
1, the only independent claim, reads as follows:
1. A modular polymer platform comprising
two or more therapeutic agents releasable from a
stratified polymeric substrate comprising at least three
continuous planar layers,
wherein a first continuous planar layer is a hydrogel
having a degradation rate,
wherein a second continuous layer is a polymer
matrix having a degradation rate slower than the
degradation rate of the hydrogel, and
wherein a third continuous planar layer is an
impermeable and biodegradable backing layer having a
degradation rate slower than the degradation rate of the
polymer matrix, and
wherein at least one of the two or more therapeutic
agents is an anti-tumor agent.
Appeal Br. 20 (Claims Appendix).
The following rejections are before us on appeal:
Claims 1, 2, 5, 6, 10, 12, 31, 32, and 33 stand rejected under 35 U.S.C.
§ 103 as being unpatentable over Carpenter2 and Ding.3 Final Act. 3.

2 Carpenter et al., US 2008/0020015 A1, published Jan. 24, 2008.
3 J. Ding et al., Multilayered mucoadhesive hydrogel films based on
thiolated hyaluronic acid and polyvinylalcohol for insulin delivery, 8 ACTA
BIOMATERIALIA 3643–51 (2012).
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Claims 3 and 4 stand rejected under 35 U.S.C. § 103 as being
unpatentable over Carpenter, Ding, and Yung.4 Id. at 8.
Claim 9 stands rejected under 35 U.S.C. § 103 as being unpatentable
over Carpenter, Ding, and Peponi.5 Id. at 9.
Claim 34 stands rejected under 35 U.S.C. § 103 as being unpatentable
over Carpenter, Ding, and Mawad.6 Id. at 10.
ANALYSIS
“[T]he examiner bears the initial burden . . . of presenting a prima
facie case of unpatentability. If that burden is met, the burden of coming
forward with evidence or argument shifts to the applicant.” In re Oetiker,
977 F.2d 1443, 1445 (Fed. Cir. 1992). We have considered those arguments
made by Appellants in the Appeal Brief and those properly presented in the
Reply Brief; arguments not so presented in Appellants’ briefs are waived.
See 37 C.F.R. § 41.37(c)(1)(iv) (2015); see also Ex parte Borden IV, 93
USPQ2d 1473, 1474 (BPAI 2010) (informative) (“Any bases for asserting
error, whether factual or legal, that are not raised in the principal brief are
waived.”).
Appellants focus their arguments on the limitations of independent
claim 1 and claim 31, which depends from claim 1, and upon the first
obviousness rejection (noted above) and do not provide separate substantive

4 Chong Wing Yung et al., Diffusion of interleukin-2 from cells overlaid with
cytocompatible enzyme-crosslinked gelatin hydrogels, 95(A) J. BIOMED.
MAT. RES. 25–32 (2010).
5 Laura Peponi et al., Nanostructured morphology of a random P(DLLA-co-
CL) copolymer, 7 NANO. RES. LET. 1–7 (2012).
6 Damia Mawad et al., Synthesis and Characterization of Radiopaque
Iodine-containing Degradable PVA Hydrogels, 9 BIOMACROMOL. 263–68
(2008).
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arguments over the other rejections or for any of the other dependent claims.
Statements in a brief that “merely mention [a] claim . . . and lack any type of
separate, substantive argument concerning the claim” are not sufficient to
constitute separate argument regarding that claim under 37 C.F.R.
§ 41.37(c)(1)(iv). In re Kao, 639 F.3d 1057, 1065 (Fed. Cir. 2011).
Accordingly, dependent claims 2–6, 9, 10, 12, and 32–34 stand or fall with
independent claim 1. 37 C.F.R. § 41.37(c)(1)(iv).
With respect to claim 1, the Examiner found that Carpenter teaches a
modular drug delivery platform comprising separate, but contiguous,
polymer layers and hydrogel layers, wherein the layers comprise therapeutic
agents and degrade at different rates so as to release their therapeutic agents
at different rates. Final Act. 3. The Examiner found that
Since Carpenter suggests the (i) hydrogel layer is composed of
simple polysaccharid[e]s such as alginate (see Examples 1&2)
with a relatively rapid degradation rate, while the (ii) polymer
layer is composed of polyesters [103–104] with relatively long
degradation rates, the polymer layer would naturally degrade
slower than the hydrogel layer.
Id. at 3–4. The Examiner further found that Ding teaches “a multilayered
hydrogel drug delivery platform comprising an impermeable backing layer
comprising the biodegradable polymer polyvinylalcohol (PVA).” Id. at 5.
The Examiner found that a person of ordinary skill in the art would have
been motivated to combine Ding’s backing layer with Carpenter’s polymer
and hydrogel layers, as arranged in Appellants’ claims, “to allow
unidirectional release of the therapeutic compounds.” Id. at 5, 7. The
Examiner stated that because the impermeable backing layer allows for
unidirectional release, it “must have a half-life longer than the hydrogel and
polymer layers comprising the therapeutic agents.” Id. at 5.
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We adopt the Examiner’s findings of fact regarding the scope and
content of the prior art (id. at 3–11; Ans. 4–11), and determine that the
Examiner has established a prima facie case of obviousness of the appealed
claims. We address Appellants’ arguments below.
With respect to Carpenter and Ding’s teaching about the relative
arrangement of the polymer, hydrogel, and backing layers, Appellants argue
that “Carpenter can only teach a sandwich type wound dressing where the
hydrogel layer is in between the polymer layer and the optional occlusive
layer,” and “it would be illogical and dysfunctional to have a middle
hydrogel layer with a degradation rate faster than both the polymer layer and
occlusive layer on either side of it.” Appeal Br. 12; see also id. at 13
(arguing that modifying the membrane of Carpenter to have the same
degradation rates as the present invention would render the device of
Carpenter inoperable for its intended purpose, and adhering Ding’s backing
layer to Carpenter’s wound dressing would not prevent the inoperability), id.
at 14 (“Carpenter can only support the arrangement of layers shown in Fig.
1.”).
We are not persuaded. Appellants’ arguments focus on a specific
arrangement of the polymer, hydrogel, and occlusive layers, but as noted by
the Examiner, “the arrangement of layers upon which [Appellants’]
argument relies (i.e., the polymer layer is between the backing layer and
hydrogel layer) is not recited” in claim 1. Final Act. 7. Accordingly,
arguments based on the arrangement of the layers are irrelevant to claim 1—
the only claim argued by Appellants—because claim 1 lacks any limitation
on the relative positioning of the claimed layers.
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Claim 31 does recite that the polymer layer is between the backing
layer and hydrogel layer. Appeal Br. 23 (Claims Appendix). Nevertheless,
we also find Appellants’ arguments regarding the arrangement of the layers
unpersuasive with respect to claim 31, because they disregard the specific
embodiment in Carpenter the Examiner cited in support of the rejection of
claim 31. See Final Action 4 (citing Carpenter ¶ 258 for claim 31), 7 (same).
Specifically, Carpenter teaches an embodiment that is useful for
treating a chronic wound. Carpenter ¶ 258. This embodiment—which does
not require the optional occlusive layer—comprises a wound dressing
having hydrogel and polymer layers, where the hydrogel layer “can be
placed in contact with the wound bed.” Carpenter ¶ 258.7 We agree with
the Examiner that a person of ordinary skill in the art would have been
motivated to combine Ding’s backing layer with this embodiment, and to
place the backing layer on the side of the stratified platform facing away
from the wound, so that the backing layer would not prevent drug release to
the tissue in need thereof, to obtain unidirectional release of the therapeutic
agents into the wound, and to protect the underlying wound and layers.
Final Act. 7; Ans. 9. This arrangement, which reads on the configuration
recited in Appellants’ claim 31, would also decrease drug loss and enhance
bioavailability. Ding 3643.
Further, even with respect to Carpenter’s alternate teaching of an
optional occlusive layer atop the hydrogel layer (Carpenter ¶ 251), we agree

7 Based on the express teaching in Carpenter ¶ 258 that “the wound dressing
used in treatment of a chronic wound will include a biodegradable hydrogel
layer (i.e., non-stick layer), which can be placed in contact with the wound
bed,” we disagree with Appellants’ argument that “Carpenter never states
that the hydrogel layer should be the bottom layer.” Reply Br. 3.
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with the Examiner that Appellants “ha[ve] not established the critical nature
of this arrangement with respect to the function of the modular polymer
platform.” Ans. 7. Accordingly, we agree with the Examiner that a person
of ordinary skill in the art would have found it obvious to arrange the layers
to have the polymer layer in the middle, with the hydrogel and the backing
layers on either side of the polymer layer. Ans. 6. This configuration would
allow the artisan to obtain unidirectional drug release and the other benefits
of the backing layer taught by Ding.
Appellants additionally argue that “Carpenter merely states in
paragraph [0258] that the polymer layer and the hydrogel layer can be
selected to have differing release rates, with no discussion of their relative
degradation rates.” Reply Br. 3. Again, we are not persuaded by this
argument. We agree with the Examiner that Carpenter teaches “[a] polymer
layer [that] would naturally degrade slower than the hydrogel layer.” Final
Act. 3–4, discussing Carpenter ¶ 260 (disclosing alginate hydrogel layers,
which have a relatively rapid degradation rate), and ¶¶ 103–04 (disclosing
polyester polymer layers, which would naturally degrade more slowly than
an alginate hydrogel layer). We additionally note that Carpenter suggests
that selecting the relative release rates is within the skill in the art. See, e.g.,
Carpenter ¶ 254 (“Factors that typically affect the length of time over which
the bioactive agent is released from the formulation include, e.g., the nature
and amount of polymer, the nature and amount of bioactive agent, and the
nature and amount of additional substances present in the formulation.”).
Appellants further argue that Ding does not cure the deficiencies of
Carpenter because Ding (i) “describes a hydrogel film system that releases a
loaded drug not by degradation, but by diffusion”; (ii) “found that the
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backing layer actually permitted a degree of drug release”; and (iii) does not
teach any multi-layered device or system having a structure that specifically
permits a hydrogel layer to have a degradation rate faster than a polymer
layer, and a backing layer with a degradation rate slower than the polymer
layer. Appeal Br. 12; see also id. at 14 (“Ding describes a system using a
means of drug release completely unrelated to degradation . . . .”). We
address each of these arguments in turn.
First, we are not persuaded by argument (i) because, as an initial
matter, we disagree with any suggestion that Ding is limited to drug release
by diffusion. Ding teaches that at least one of its multilayer films released
drug through both diffusion and polymer erosion. Ding 3648 (“The
exponent n for CU-Vac film was between 0.45 and 0.89, suggesting that the
mechanism was regarded as anomalous transport owning to the coupling of
Fickian diffusion and polymer erosion.”), 3650 (“Insulin release from CU-
Vac would be controlled by the erosion of hydrogel films as well as insulin
diffusion.”). But, more importantly, whether Ding’s hydrogel films release
drug by degradation or diffusion is immaterial to the rejection, which relies
on the drug-releasing hydrogel and polymer layers taught in Carpenter. The
rejection cites Ding for its teachings regarding the impermeable backing
layer, and appealed claim 1 contains no requirement regarding incorporation
or release of drug from the backing layer.8 Further, Appellants have not
pointed to any evidence of record indicating that Ding’s backing layer would

8 The appealed claims likewise do not require that drug release from the
hydrogel and polymer layers occur by any specific mechanism, whether it be
degradation, diffusion, or any other mechanism.
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be inoperable or undesirable in combination with hydrogel and polymer
layers that release drug by degradation rather than diffusion.
Second, as to argument (ii), the import Appellants assign to Ding’s
teaching that “the backing layer actually permitted a degree of drug release”
is unwarranted. Ding indicated that drug release from the backing layer was
“slight.” Ding 3648. And despite a small amount of drug release, Ding
nevertheless concluded that several of the devices “exhibited unidirectional
release of insulin from the muco-adhesive side” (Ding 3650), indicating that
the backing layer achieved its intended function.
Finally, we are not persuaded by Appellants’ argument (iii), because
Appellants cannot show nonobviousness by attacking references individually
as failing to teach all of the claimed limitations when the rejection is based
on a combination of references. In re Keller, 642 F.2d 413, 426 (CCPA
1981). Appellants argue that Ding does not comment on the degradation
rates of his hydrogel layers, and thus does not teach a multi-layered system
as recited in Appellants’ claims, but the rejection relies on Ding in
combination with other references, whose teachings together render obvious
the claimed invention. See supra, including discussion of Carpenter at
¶¶ 103–04, 254, 260.
SUMMARY
We affirm the rejection of claims 1, 2, 5, 6, 10, 12, 31, 32, and 33
under 35 U.S.C. § 103 as being unpatentable over Carpenter and Ding.
We affirm the rejection of claims 3 and 4 under 35 U.S.C. § 103 as
being unpatentable over Carpenter, Ding, and Yung.
We affirm the rejection of claim 9 under 35 U.S.C. § 103 as being
unpatentable over Carpenter, Ding, and Peponi.
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We affirm the rejection of claim 34 under 35 U.S.C. § 103 as being
unpatentable over Carpenter, Ding, and Mawad.
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)(1)(iv).

AFFIRMED