TUFTS UNIVERSITY

Patent Trials and Appeals Board

Dec 21, 2020

2020001951 (P.T.A.B. Dec. 21, 2020)

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.
14/414,218 01/12/2015 David L. Kaplan 166118.00564.T001780.US 7465
153544 7590 12/21/2020
Quarles & Brady LLP/Tufts University
411 E. Wisconsin Ave.
Ste. 2350
Milwaukee, WI 53202
EXAMINER
BERRIOS, JENNIFER A
ART UNIT PAPER NUMBER
1613
NOTIFICATION DATE DELIVERY MODE
12/21/2020 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):
pat-dept@quarles.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte DAVID L. KAPLAN, FIORENZO OMENETTO, and
ELEANOR M. PRITCHARD
__________

Appeal 2020-001951
Application1 14/414,218
Technology Center 1600
__________

Before ERIC B. GRIMES, 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(a) involving claims to a dry
porous silk particle, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
Encapsulating active ingredients to provide a physical barrier between
the active and the surrounding environment is known. (Spec. ¶¶ 3–5.)
“Proteins can be used as encapsulant materials because their

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as TUFTS
UNIVERSITY. (Appeal Br. 2.)
Appeal 2020-001951
Application 14/414,218

2
physicochemical properties . . . can provide various functional properties for
encapsulation.” (Id. ¶ 4.) “However, use of proteins as encapsulant
materials for certain applications can be challenging.” (Id.) Thus, according
to Appellant’s Specification there is still an unmet need for encapsulation
that can “protect and stabilize . . . labile molecules, and/or controllably
release these labile molecules.” (Id. ¶ 6.) Appellant’s invention is directed
to silk biomaterials encapsulating an oil phase including an active agent.
(See, id. ¶¶ 8, 12.)
Claims 1, 3, 4, 6–11, 17, 19, 160, and 161 are on appeal.2 Claim 1 is
representative and reads as follows:
1. A dry porous silk particle comprising a silk fibroin
layer and a lipid phase comprising an active agent, wherein the
silk fibroin layer encapsulates the lipid phase and the lipid
phase excludes a liposome.
(Appeal Br. 15.)

2 Claims 5, 12, and 18 remain pending but are withdrawn from
consideration.
Appeal 2020-001951
Application 14/414,218

3

The prior art relied upon by the Examiner is:
Name Reference Date
Schneider et al. US 2006/0025524 A1 Feb. 2, 2006
Masters et al. WO 2006/042310 A1 Apr. 20, 2006
Wieland et al. US 2008/0112989 A1 May 15, 2008
Sones US 2008/0292693 A1 Nov. 27, 2008
Kaplan ’451 et al. US 2010/0028451 A1 Feb. 4, 2010
Kaplan ’381 et al. WO 2011/005381 A2 Jan. 13, 2011
Fisher et al. US 2016/0008413 A1 Jan. 14, 2016
Polymer Standards Service, Material Safety Data Sheet for Poly(ethylene
oxide), Nov. 2008.
A. Madene et al., Flavour encapsulation and controlled release – a
review, 41 Int’l J Food Science & Tech., 1–21, 2006.
P. Ren et al., Monodisperse alginate microcapsules with oil core
generated from a microfluidic device, 343 J. Colloid & Interface Sci.,
392–395 (2010).

The following grounds of rejection by the Examiner are before us on
review:
Claims 1, 4, 7–11, 17, and 19 under 35 U.S.C. § 103(a) as
unpatentable over Masters, Kaplan ’451, and Polymer Standards Service.
Claims 1, 3, 4, 6, 17, 19, 160, and 1613 under 35 U.S.C. § 103(a) as
unpatentable over Ren, Kaplan ’381, and Schneider.
Claims 7 and 8 under 35 U.S.C. § 103(a) as unpatentable over Ren,
Kaplan ’381, Schneider, Madene, Wieland, Sones, and Fisher.

3 The Examiner’s statement of rejection also includes reference to claim
162. We conclude this was an inadvertent error as no claim 162 was ever
pending.
Appeal 2020-001951
Application 14/414,218

4
DISCUSSION
I
Obviousness: Masters and Kaplan’451
Appellant argues the rejected claims together, focusing only on the
limitations of claim 1. Claims 4, 7–11, 17, and 19 have not been argued
separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(iv). We
therefore address the Examiner’s rejection with respect to claim 1.
The Examiner finds that Masters teaches biocompatible protein
particles that encapsulate active ingredients such as proteins, enzymes, and
peptides, where the biocompatible protein used to make the particle can be
silk fibroin, and the active agents “are homogeneously dispersed throughout
each protein particle.” (Final Action 5 (citing Masters 4, 17, 18, and claim
3).) The Examiner further finds that Masters teaches that “hydrophobic
substances such as lipids can be incorporated into the particles to extend
duration of drug release.” (Id. (citing Masters 21); Ans. 12–13.) The
Examiner finds Masters teaches encapsulation of both a lipid and an active
agent, and each of those components is “considered to make up a phase and
as the phase comprises a lipid, it is considered a lipid phase, thus the
distribution of active agents and lipid inside the particle is considered a
subgroup different from the outer particle.” (Ans. 12.)
The Examiner concludes that, in view of the foregoing teachings, it
would have been obvious to one having ordinary skill in the art “to
encapsulate the active agent along with the lipid in the protein particles in
order to extend the release of the active agent.” (Final Action 5; Ans. 13.)
Regarding the claim requirement that the silk particle be dry, the
Examiner notes that the Specification at paragraph 138 indicates a “dried
Appeal 2020-001951
Application 14/414,218

5
state” refers to a composition having a water content of no more than 50%.
(Final Action 6.) The Examiner finds that Masters teaches a composition
meeting the dry requirement because it teaches a composition which forms a
cohesive body having a solvent content ranging from 20 to 50% and “when a
solidified cohesive body is used in the production of particles, the partial
drying of the film to form a cohesive body and subsequent solidification . . .
forces more solvent out of the body.” (Id.) The Examiner further finds that
Masters teaches such a solidified cohesive body “preferably has a solvent
content ranging from 20-40%.” (Id.)
Regarding the requirement that the particle be porous, the Examiner
finds Masters describes the biocompatible protein particles as being porous.
(Id. (citing Masters Fig. 1).)
Regarding the selection of silk fibroin from among the other disclosed
biocompatible proteins in Masters for the particles, the Examiner relies on
the teachings of Kaplan ’451. (Final Action 7.) In particular, the Examiner
finds that Kaplan ’451 teaches silk fibroin microspheres to encapsulate an
active agent and leaving a small amount of lipid in the microsphere together
with the active agent. (Id. (citing Kaplan ’451 abstr., ¶ 42).) The Examiner
concludes:
Based on the teachings of Kaplan one of skill in the art would
have recognized that combinations of silk proteins
encapsulating active agents and lipids are well-known drug
delivery devices, thus it would have been obvious to use the
silk as the biocompatible protein in the particles of Masters as
these are shown to be have successfully combined with lipids
and active agents.
Appeal 2020-001951
Application 14/414,218

6
(Id.)4
We agree with the Examiner’s findings and conclusion of obviousness
of claim 1 for the reasons discussed below.
Appellant argues that the Examiner’s rejection is in error because
Masters does not teach a lipid phase that comprises an active agent. (Appeal
Br. 5.) Appellant argues that follows from the fact that Masters discloses
that lipids are additives to the particles and that the particles have
“homogenous distribution of the protein, solvent and other additives, as well
as the homogenous distribution of the pharmacologically active agents.” (Id.
(quoting Masters 3).) According to Appellant a “homogeneous distribution
[of chemical entities] specifically avoids the formation of distinct phases”
and a “homogeneously distributed lipid cannot be said to be a lipid phase
that comprises an active agent that is also homogeneously distributed.” (Id.)
We do not find Appellant’s argument persuasive.
We do not agree with Appellant that, because Masters states at page 3
that “[v]arious embodiments of the protein particles of the present invention
may also include a homogenous distribution of the protein, solvent and other
additives, as well as the homogenous distribution of the pharmacologically
active agents,” Masters cannot be read as teaching a biocompatible protein
matrix that encapsulates a lipid and active agent wherein the active agent is
within a lipid phase. Rather, we find that Masters’ teaching regarding a
biocompatible protein particle encapsulating an active agent (Masters 17,
18) coupled with Masters’ teaching regarding incorporation of a lipid “into

4 The Examiner relies on Polymer Standard Service to address limitations
recited in dependent claim 11.
Appeal 2020-001951
Application 14/414,218

7
the biocompatible protein particles” (Id. at 21) can reasonably be found to be
a teaching that includes a lipid phase including an active agent within the
encapsulated space. This is because Masters teaches that the active agent
that can be encapsulated in the particle can be a number of different agents,
both hydrophilic and hydrophobic (Masters 10–17), and that the particles
may include additives besides lipids “to add structure” (id. 19:20–21) or
to facilitate the processing of the biocompatible protein
particles, to stabilize the pharmacologically active agents, to
facilitate the activity of the pharmacologically active agents, or
to alter the release characteristics of the biocompatible protein
particles
(id. at 20:25–28). A variety of hydrophobic and hydrophilic additives are
described. (Id. at 19–20.)
Furthermore, Masters teaches that the particles can encapsulate an
active with “a relatively homogeneous distribution of the components,
including a homogenous distribution of any pharmacologically active agents
and additive materials,” (Masters 5:1–3 (homogeneous distribution), 17:29–
32 (encapsulation), 18:7–11 (encapsulation of macromolecular
pharmacologically active agents).) Appellant has not explained why
Masters’ teaching of homogeneity in distribution in the context of an
encapsulated lipid, hydrophobic active agent, and other hydrophilic additives
precludes the lipid being a phase that includes an active agent where such is
in homogeneous distribution with another additive in the encapsulated space.
In light of the foregoing, we affirm the Examiner’s rejection of claim
1 as being obvious over Masters and Kaplan ’451.

Appeal 2020-001951
Application 14/414,218

8
II
Obviousness: Ren, Kaplan’381, and Schneider
Here again, Appellant argues the rejected claims together focusing
only on the limitations of claim 1. Claims 3, 4, 6, 17, 19, 160, and 161 have
not been argued separately and therefore fall with claim 1. 37 C.F.R.
§ 41.37(c)(1)(iv). We, therefore, address the Examiner’s rejection with
respect to claim 1.
The Examiner finds that Ren teaches a method to make an alginate
microcapsule with an oil core that has potential for encapsulating lipophilic
drugs or active ingredients. (Final Action 8.) The Examiner further finds
that Ren teaches alginates are known to form hydrogels and the process
described in which an oil core also involves forming a hydrogel. (Id. at 8–
9.) The Examiner further finds that the hydrogel shell formed is the only
portion that contains water, and describes an example in which that portion
corresponds to 30.8% of the composition and thus the composition as a
whole would have less than 50% water, which meets the Specification’s
teaching of a dried particle. (Id. at 9–10.)
The Examiner recognizes that Ren does not teach a silk fibroin
hydrogel, but concludes that such would have been obvious to substitute for
alginate in light of the teachings of Kaplan ’381.
In particular, the Examiner finds that Kaplan ’381 teaches a process
for forming silk fibroin hydrogels to encapsulate active agents (Id. at 10) that
can be present in a carrier oil (Ans. 14 (citing Kaplan ’381 ¶ 54)). The
Examiner concludes that it would have been obvious to substitute silk for the
alginate in the process of Ren as a functional equivalent with a reasonable
expectation of success “as they are both taught by the prior art to be
Appeal 2020-001951
Application 14/414,218

9
polymers suitable for forming hydrogels for the encapsulation of cells and
active/therapeutic agents.” (Final Action 10; see also Ans. 14 (“they are
both taught to be used for the same purpose in the same field of endeavor
(drug deliver[y] and encapsulation of lipophilic actives”).)
The Examiner relies on Schneider for teaching that “hydrogels have
the general characteristic of having a well hydrated and porous structure
[0002]” and because the hydrogel of Kaplan ’381 is a silk hydrogel, it is
considered porous. (Final Action 10–11.)
We agree with the Examiner’s findings and conclusion of obviousness
of claim 1.
Appellant argues that the Examiner’s rejection is in error because the
“Examiner has failed to properly establish functional equivalence between
the alginate of Ren and the silk fibroin of Kaplan ’381.” (Appeal Br. 10–
11.) According to Appellant, Ren teaches “at best” “the suitability of
alginate hydrogels for encapsulating an oil droplet and Kaplan ’381 teaches
the suitability of certain silk fibroin hydrogels for encapsulating active
agents or cells.” (Id. at 10.)
We do not find Appellant’s argument persuasive. The Examiner
points out the following, to which Appellant does not respond: “Ren teaches
the encapsulation of lipophilic actives.” (Ans. 14.) We agree with the
Examiner. In particular, Ren states: “we report on a microfluidic approach
to fabricate monodisperse alginate microcapsules with oil cores for
encapsulating lipophilic substances” including lipophilic drugs or active
ingredients/chemicals. (Ren 392 (abstr. and rt. col. (emphasis added); see
also id. at left col. (“design of carriers for lipophilic drugs is of great
importance and necessity”).) Furthermore, Ren teaches the gelation of the
Appeal 2020-001951
Application 14/414,218

10
alginate in the process to encapsulate the oil phase. (Id. at 392–393; see also
394 (“the boundary between alginate hydrogel membrane and inner oil
phase can also be discerned easily”).) Furthermore, as the Examiner
explains, Kaplan ’381 teaches encapsulating an active agent that can be in a
carrier oil. (Ans. 14; Kaplan ¶¶ 10, 19 (“active agent, such as for example a
therapeutic agent, a biological agent, cells”), 27 (bioactive molecule
encapsulation), ¶ 50 (active agents listing), 65–66 (excipients to include with
the active agent such as “pharmaceutically acceptable carriers” which may
include oils).) The process involves creating a silk fibroin hydrogel. (See,
e.g., id. at abstr., ¶ 7.)
The fact that neither Ren nor Kaplan ’381 describes alginate and silk
fibroin as equivalents (Appeal Br. 8–9) does not mandate a conclusion that
the Examiner has failed to establish equivalence. In light of the foregoing
teachings in Ren and Kaplan ’381 discussed above, we agree with the
Examiner that Ren and Kaplan ’381 teach the use of alginate and silk fibroin
for the same purpose, i.e., to encapsulate an active agent carried in an oil.
This is the same context as the invention requiring the silk fibroin to
encapsulate a lipid phase containing an active ingredient. Moreover, Ren
and Kaplan ’381 both involve creating a hydrogel for encapsulation. As
such, we also agree with the Examiner that alginate and silk fibroin are
obvious equivalents in the context of the claimed invention, and we agree
that it would have been obvious to substitute silk fibroin for alginate to
arrive at a composition as claimed.
Appellant additionally argues the Examiner’s rejection is in error
because Schneider, although disclosing that hydrogels generally are well
hydrated porous structures, nevertheless teaches “the need for additional
Appeal 2020-001951
Application 14/414,218

11
processing to introduce microscale porosity.” (Appeal Br. 12.) Thus,
according to Appellant, Schneider “inherently discloses that some gel
networks (and thus, owing to the context of the disclosure, hydrogel
networks) are non-porous.” (Id.) We do not find this argument persuasive
for the reasons discussed by the Examiner in the Answer (Ans. 14–15),
namely that Schneider’s teaching is directed only to the fact that on the
microscale there may not be a porous structure not that porosity is absent
altogether. (See Schneider ¶ 4.) Schneider points out that “an ideal
hydrogel has a high level of porosity (spanning nanoscale to microscale).”
(Id.; Schneider ¶ 3.) We note Appellant did not file a Reply Brief,
responding to the Examiner’s findings.
For the foregoing reasons, we affirm the Examiner’s rejection of
claim 1 as being obvious from Ren, Kaplan ’381, and Schneider.
Appellant does not address the Examiner’s rejection of claims 7 and 8
under 35 U.S.C. § 103(a) as unpatentable over Ren, Kaplan ’381, Schneider,
Madene, Wieland, Sones, and Fisher. Therefore, we summarily affirm that
rejection. Hyatt v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008) (“When the
appellant fails to contest a ground of rejection to the Board, . . . the Board
may treat any argument with respect to that ground of rejection as waived.”).
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 4, 7–11,
17, 19
103 Masters, Kaplan
’451
1, 4, 7–11,
17, 19

1, 3, 4, 6,
17, 19, 160,
161
103 Ren, Kaplan ’381,
Schneider
1, 3, 4, 6,
17, 19, 160,
161

Appeal 2020-001951
Application 14/414,218

12
7, 8 103 Ren, Kaplan ’381,
Schneider,
Madene, Wieland,
Sones, Fisher
7, 8
Overall
Outcome
1, 3, 4, 6–
11, 17, 19,
160, 161

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED