AQTIS I.P. B.V.

Patent Trials and Appeals Board

Oct 14, 2021

2021000231 (P.T.A.B. Oct. 14, 2021)

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.
14/321,392 07/01/2014 Henderikus Supèr 17-1363-US-CON 1971
20306 7590 10/14/2021
MCDONNELL BOEHNEN HULBERT & BERGHOFF LLP
300 S. WACKER DRIVE
32ND FLOOR
CHICAGO, IL 60606
EXAMINER
CABRAL, ROBERT S
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
10/14/2021 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):
docketing@mbhb.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HENDERIKUS SUPÈR, PAUL WILLEM MIJNEN,
PIETER GERARD ZIJLSTRA, and DIRK WYBE GRIJPMA
Appeal 2021-000231
Application 14/321,392
Technology Center 1600

Before LINDA M. GAUDETTE, JOHN E. SCHNEIDER, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims directed to polycaprolactone (PCL)
microparticles and a process for making them as lacking enablement and/or
as being obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

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 AQTIS I.P. B.V.
(Appeal Br. 4.)
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STATEMENT OF THE CASE
Several medical fillers have been developed, including for use as an
implant. (Spec. ¶ 2.) Prior art implant fillers include “particle suspension or
emulsion of particles of a polymer comprising lactic acid and/or glycolic
acid repeat units.” (Id.) Prior art fillers in gel form, however, do not have
“optimal” mixing and flowing properties. (Id. ¶ 3.) Appellant’s invention is
directed to microspheres for use as fillers having improved properties over
the prior art. (Id. ¶ 5.)
Claims 16–21, 23, 24, 26–29, 31–35, 40, 41, and 44–47 are pending.
The Examiner has indicated that claim 41 is allowable.2
Claims 16 and 27, reproduced below, are illustrative of the claimed
subject matter:
16. A process for preparing microparticles comprising
polycaprolactone (PCL), wherein the process comprises:
(a) dissolving a PCL polymer in a solvent to form a PCL
polymer solution,

2 The Examiner has not expressly stated that claims 31, 32, 34, and 35 are
allowable, although they are not claims at issue in the rejections presented
for our review. In reviewing the record, however, we note there was a
rejection of these claims on the ground of nonstatutory double patenting as
unpatentable over US 8,795,694, which Appellant asked to be held in
abeyance until there is an indication of allowable subject matter. (See Final
Office Action dated Aug. 23, 2017 (“Regarding, the double patenting
rejection, the applicant has not provided arguments traversing the instant
grounds of rejection, but instead has asked that the rejections be held in
abeyance until there is an indication of allowable subject matter. The
rejection stand until such time that Applicant traverses the grounds of
rejection by providing specific arguments, or has filed a terminal disclaimer
to overcome the rejection.”).) In light of the foregoing, we understand the
Examiner to maintain the rejection of these claims on the ground of
nonstatutory double patenting as unpatentable over US 8,795,694.
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(b) mixing the PCL polymer solution with a liquid
comprising a single surfactant which is methylcellulose and
which is present in a concentration of at least 1 w/w%; and
(c) forming the microparticles, wherein the microparticles
have essentially spherical and smooth surfaces, homogeneous
PCL content throughout the microparticles and a diameter
distribution range between 20 and 200 μm.

27. A biodegradable, injectable gel comprising microparticles,
each microparticle comprising polycaprolactone (PCL) and
having:
i) a diameter distribution range between 20 and 200 μm,
ii) homogenous density and form,
iii) homogenous PCL content throughout the
microparticle, and
iv) essentially spherical and smooth surfaces.
(Appeal Br. 16–17.)
The prior art relied upon by the Examiner is:
Name Reference Date
Rashba-Step et al. US 2008/0248122 A1 Oct. 9, 2008
Chen et al. Polycaprolactone
microparticles and
their biodegradation,
67 Polymer
Degradation and
Stability 455–59
2000
Iooss et al. A new injectable bone
substitute combining
poly(ε-caprolactone)
microparticles with
biphasic calcium
phosphate granules, 22
Biomaterials 2785–94
2001

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The following grounds of rejection by the Examiner are before us on
review:
Claims 16–19, 21, 23, 24, 26, 40, 44, and 46 under 35 U.S.C. § 112,
first paragraph, as lacking enablement for their full scope.
Claims 16–21, 23, 24, 26–29, 33, and 44–47 under 35 U.S.C. § 103(a)
as unpatentable over Chen, Rashba-Step, and Iooss.3

DISCUSSION
Non-Enablement
The Examiner found that the Specification describes PCL
microparticles having the claimed features that were made with the PCL
polymer having been dissolved in dichloromethane, but does not reasonably
provide enablement for preparing microparticles with the claimed features
that were made by dissolving the PCL in any other solvent. (Non-Final
Action 3.) According to the Examiner, “one of ordinary skill in the art
would have to resort to undue experimentation to reach the claimed method
and resultant microparticles.” (Id.)
Appellant states that the feature at issue has been in the claim since
the filing of the application and the “rejection could and should have been
made in a far earlier stage of prosecution.” (Appeal Br. 15.) That argument
does not establish error in the rejection. We conclude Appellant has waived
substantive argument and we, therefore, summarily affirm the Examiner’s
rejection. Hyatt v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008) (“When the

3 We note that the Examiner’s statement of rejection in the Non-Final
Action from which Appeal was taken inadvertently included canceled claim
42. The Examiner in the Office Action Summary page recognized that claim
42 was not pending.
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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.”).

Obviousness
The Examiner found that Chen teaches making PCL microparticles by
an emulsification-solvent evaporation technique where PCL is dissolved first
in methylene chloride. (Non-Final Action 4.) The Examiner further found
that Chen teaches adding the dissolved PCL into a solution containing the
surfactant Tween 60 and gelatin as a stabilizer or PAM (hydrophobically
modified polyacrylamide derivative) or PVA (polyvinyl alcohol) as a
stabilizer. (Id.) The Examiner found that Chen teaches that no matter which
stabilizer was used, a microparticle with spherical form was produced. (Id.)
On the other hand, those produced with the gelatin stabilizer had a smooth
surface and a narrow particle size distribution, though having a smaller size
(13.4 ± 4.7 microns in diameter). (Id.)
The Examiner also found that Rashba-Step teaches preparation of
“microparticles” using an emulsification/solvent extraction process. (Non-
Final Action 5 (citing Rashba-Step ¶ 109).) The Examiner found that
Rashba-Step includes a step of transferring the emulsification into a
hardening medium, which “extracts the solvent in the discontinuous/
dispersed phase from the embryonic microencapsulated particles” thereby
forming “solid microencapsules having the surface modified microparticles
and/or the core microparticles dispersed in a solid, amorphous polymeric
matrix.” (Id. (citing Rashba-Step ¶ 112).) The Examiner also found that
Rashba-Step teaches the “microencapsules” have a smooth surface and can
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be “substantially spherical” and can have a maximum diameter of between
30 and 200 microns. (Id. (citing Rashba-Step ¶¶ 121, 122).)
In addition, the Examiner found that Example 1 of Rashba-Step
provides for “microencapsulation of surface-modified microparticles using
poly-L-arginine (PLA) coated insulin microspheres, a 10% solution of 24 kD
50:50 PLGA, and an aqueous phase solution of 0.1% (w/v)
methylcellulose.” (Non-Final Action 5.) The Examiner also found that
Rashba-Step teaches that methylcellulose “is a preferred nonionic
surfactant.” (Id. (citing Rashba-Step ¶ 119).) The Examiner further found
that Rashba-Step teaches that the surfactant can be present in a variety of
amounts including “1%, 5%, 10%, 15%, and 30%” or in ranges between any
two of the disclosed values. (Id. at 5–6 (citing Rashba-Step ¶ 117).)
The Examiner found that Iooss teaches using a similar solvent
evaporation process to Chen in forming PCL microspheres to obtain
microparticles in the 80 to 200 micron size range, where methylene chloride
is combined with PCL and methylcellulose at a concentration of 0.1%. (Id.
at 6.)
The Examiner concluded from the foregoing teachings of the prior art
that it would have been obvious to substitute methylcellulose for the gelatin
in Chen’s process because Iooss teaches that the “use of methyl cellulose . . .
resulted in particles having larger size.” (Id.) In addition, the Examiner
found that it would have been obvious to incorporate methylcellulose in
amounts of greater than 1% w/w in the method of making PLC
microparticles taught by Chen because Rashba-Step teaches such can be
used and because “it is prima facie obvious[] to select a known material
based on its suitability for its intended use.” (Id.)
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We agree with the Examiner’s conclusion of obviousness. We agree
with the Examiner that one of ordinary skill in the art would have
understood from Chen and Iooss that different surfactants can be used to
make PCL microparticles in an evaporation extraction process where the
PCL was first dissolved in methyl chloride, and that methylcellulose was a
surfactant that was known to be used at 0.1% in such a process. (Chen 457;
Iooss 2788–89.) Moreover, we agree with the Examiner that one of ordinary
skill in the art would have been motivated to use methylcellulose instead of
gelatin in order to achieve a larger size of PCL particles as the spherical
particles of Iooss were in the range of 80–200 microns (Iooss 2788), whereas
the particles of Chen were about 13.4 microns (Chen 457). Iooss further
teaches that the particle size depends on the organic phase volume in the
emulsion and the stirring speed. (Iooss 2788–89.)
In light of Iooss’ teachings, we do not find persuasive of non-
obviousness Appellant’s argument that one of ordinary skill in the art would
have been discouraged from using a different stabilizer than gelatin by
Chen’s teaching that gelatin provided an even particle size distribution, as
compared to PVA and PAM, and a second stabilizer was required to produce
smooth particles. (Appeal Br. 9–10; Reply Br. 3.) Although Chen teaches
that gelatin plus Tween 60 achieved smooth particles, nothing in Chen
suggests that the only way to achieve smooth PCL particles is through the
use of these two surfactants. And, as discussed, Iooss would have provided
a reason to substitute methylcellulose for gelatin, i.e., to achieve a larger
particle size than was achieved in Chen with gelatin and Tween 60. And, as
the Examiner explained, Chen teaches that different properties of stabilizers
will affect the size distribution of the microparticles because of the
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hydrophilic/hydrophobic balance effect which prevents the emulsion
droplets from coagulation. (Chen 457.) As the Examiner further explained
(Ans. 5), Iooss would have provided a reasonable expectation of success of
making microparticles with methylcellulose with a larger particle size than
achieved by Chen.
Regarding the use of at least 1 w/w% methylcellulose, we agree with
the Examiner that Rashba-Step’s teachings render this limitation obvious.
Rashba-Step, as Appellant acknowledges (Appeal Br. 11–12), teaches an
evaporation extraction process to make a microcapsule that can contain
microparticles. (Rashba-Step ¶¶ 7, 109, 111–113.) Rashba-Step further
teaches that the microcapsule can have the physical characteristics of the
microparticles, such as “being substantially spherical” and having a particle
size of 200 microns or less (id. ¶¶ 113, 122), as well as being smooth (id.
¶ 121). Rashba-Step teaches an emulsion of microparticles is made and then
it is dried, and the dried powder of microparticles is combined with a matrix
forming material, such as PLGA, in methylene chloride (id. ¶ 110 and
Example 1) which is then added to an aqueous solution of methylcellulose,
and that emulsified composition is placed into a hardening bath to extract
solvent, (id. at Example 1) In the Example, Rashba-Step teaches that 0.1%
methylcellulose is sufficient to result in the microcapsule. (Id.)
However, Rashba-Step does teach that larger percentages of a
surfactant can be used, and that this is a result effective variable. (Id.
¶¶ 110, 117.4) In particular, Rashba-Step teaches that the size of the

4 Thus, we do not find persuasive Appellant’s argument that Rashba-Step,
in Example 1, uses 0.1% methylcellulose to produce microcapsules, (Reply
Br. 3). See In re Fritch, 972 F.2d 1260, 1264 (Fed. Cir. 1992) (“It is well
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microcapsule, both the average particle size and the size distribution, is
affected by the viscosity of the phase containing the methylcellulose (the
continuous phase), as well as the viscosity of the discontinuous phase, the
shear forces during emulsification, the type and concentration of the surface
active compound, and the weight ratio between the phases. (Rashba-Step
¶ 110.) Thus, Rashba-Step would have provided one of ordinary skill in the
art with motivation to modify the amount of methylcellulose used in the
method of Chen with a reasonable expectation of success in achieving
spherical microparticles within the diameter distribution range claimed. In
re Boesch, 617 F.2d 272, 276 (CCPA 1980) (“[D]iscovery of an optimum
value of a result effective variable in a known process is ordinarily within
the skill of the art.”); In re Aller, 220 F.2d 454, 456 (CCPA 1955). One of
ordinary skill in the art would have understood from Iooss and Rashba-Step
that there are, in fact, a number of result effective variables that can be
modified to affect the size of the microparticle made through emulsification
evaporation using methylene chloride and methylcellulose. Nevertheless,
one of ordinary skill in the art would have had a reasonable expectation of
success in obtaining microparticles in the size range claimed. “[W]here the
general conditions of a claim are disclosed in the prior art, it is not inventive
to discover the optimum or workable ranges by routine experimentation.”
Aller, 220 F.2d at 456.
Although Rashba-Step is concerned with the formation of spherical
microcapsules (Appeal Br. 10), they are spherical polymeric particles that

settled that a prior art reference is relevant for all that it teaches to those of
ordinary skill in the art.”).

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are biodegradable (e.g., poly-lactide/poly-glycolide copolymers or
homopolymers of polylactic acids). (See e.g., Rashba-Step ¶ 115.) Chen
teaches these materials as well as polycaprolactone (PCL) are biodegradable
polymers that show good biodegradability and biocompatibility which is
useful for making microparticles. (Chen 455.) Thus, Rashba-Step is
analogous prior art. In re Clay, 966 F.2d 656, 658–59 (Fed. Cir. 1992).
Appellant’s argument that a person of ordinary skill in the art would
not have had a reasonable expectation of success of producing smooth PCL
microparticles by using methylcellulose as a surfactant from the prior art
(see, e.g., Appeal Br. 9–10, 14) is not persuasive of non-obviousness. “In
determining whether the subject matter of a patent claim is obvious, neither
the particular motivation nor the avowed purpose of the patentee controls.
What matters is the objective reach of the claim. If the claim extends to
what is obvious, it is invalid under § 103.” KSR Int’l Co. v. Teleflex Inc.,
550 U.S. 398, 419 (2007). It is not necessary that references be combined or
modified for the same reasons as Appellant’s. The reason or motivation
to modify the reference may often suggest what the inventor has done, but
for a different purpose or to solve a different problem. In re Dillon, 919
F.2d 688, 693 (Fed. Cir. 1990); In re Lintner, 458 F.2d 1013, 1016 (CCPA
1972). And discovery of a property inherent to a prior art process does not
render that process patentable, even if the prior art did not appreciate the
property. Verdegaal Bros. Inc. v. Union Oil Co., 814 F.2d 628, 633 (Fed.
Cir. 1987). Here, whether or not one of ordinary skill in the art would have
had a reasonable expectation of achieving smooth microparticles, the
Examiner has established the reason to modify the amount of
methylcellulose is to modify the size of the particles depending on the
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amount of methylene chloride used, the stirring speed during the emulsion
process and the weight ratio between the phases. As noted above, one of
ordinary skill in the art would have had a reasonable expectation of success
in forming spherical particles in the diameter range claimed. Absence
evidence to the contrary, we conclude that the achievement of a smooth
surface of the microparticle is an inherent result of the process rendered
obvious from Chen, Rashba-Step, and Iooss. Indeed, Appellant’s
Specification states that surface smoothness is “preferably due to a
surfactant which is being used, more preferably 1% MC (Mn=63000).
(Spec. ¶ 36.) Thus, for this reason, we do not find persuasive of non-
obviousness Appellant’s arguments that one of ordinary skill in the art
would not have had a reasonable expectation that using methylcellulose as a
surfactant would produce smooth PCL microparticles (see, e.g., Appeal Br.
14; Reply Br. 3). And, we also do not find persuasive of non-obviousness
Appellant’s argument that because Iooss teaches particles made using 0.1%
methylcellulose as a surfactant are shown in Figure 5 to have non-smooth
surfaces, i.e., they are shriveled, “[t]he person skilled in the art would thus
conclude from Iooss that using methylcellulose would not result in particles
with smooth surface” (Appeal Br. 13).
In light of the foregoing, we affirm the Examiner’s rejection of claims
16–21, 23, 24, 26–29, 33, and 44–47 under 35 U.S.C. § 103(a) as being
unpatentable over Chen, Rashba-Step, and Iooss.

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DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
16–21, 23,
24, 26–29,
33, 44–47
103(a) Chen, Rashba-
Step, Iooss
16–21, 23,
24, 26–29,
33, 44–47

16–19, 21,
23, 24, 26,
40, 44, 46
112 Enablement 16–19, 21,
23, 24, 26,
40, 44, 46

Overall
Outcome
16–21, 23,
24, 26–29,
33, 40, 44–
47

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) (2019).
AFFIRMED