Ex Parte Galperin et al

Patent Trial and Appeal Board

Aug 21, 2017

13090999 (P.T.A.B. Aug. 21, 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.
13/090,999 04/20/2011 Anna Galperin UWOTL136548 3667
95093 7590 08/23/2017
Christensen O'Connor Johnson Kindness PLLC
1201 Third Avenue
Suite 3600
Seattle, WA 98101-3029
EXAMINER
KIM, TAEYOON
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
08/23/2017 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):
efiling @ cojk. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANNA GALPERIN, THOMAS JOSEPH LONG, and
BUDDY D. RATNER1
Appeal 2016-005642
Application 13/090,999
Technology Center 1600
Before JEFFREY N. FREDMAN, JOHN E. SCHNEIDER, and
RYAN H. FLAX, Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to a scaffold formed from a cross-linked stimuli-responsive
polymer. Claims 1—5, 7, 8, 10—18, and 33—35 are on appeal as rejected
under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the Real Party in Interest as “University of
Washington.” Br. 1.
Appeal 2016-005642
Application 13/090,999
STATEMENT OF THE CASE
The Specification explains, “[hjydrogels are networks of hydrophilic
cross-linked polymers that swell to equilibrium in the presence of water or
physiological fluids.” Spec. 1:15—16. Further,
So called “intelligent hydrogels” or “smart hydrogels” have been
a subject of special interest due to their ability to respond with
pronounced property changes to external stimuli. For example,
thermosensitive degradable hydrogels have been used for cell
entrapment and protein release. Among the intelligent
hydrogels, thermosensitive poly(N-isopropyl acrylamide)
(polyNIPAM) is probably one of the most extensively studied.
In aqueous media polyNIPAM hydrogels exhibit a volume phase
transition temperature (VPTT) at around 32-34°C. The cross-
linked polyNIPAM network undergoes an abrupt, reversible
swelling-deswelling process below and above the VPTT. The
VPTT of polyNIPAM hydrogels can be modulated by
copolymerization with hydrophilic or hydrophobic monomers to
increase or decrease the transition temperature. Due to their
thermosensitive nature, biostability, and biocompatibility,
polyNIPAM-based hydrogels are attractive candidates for
biomedical applications including tissue engineering.
Id. at 1:24—2:2. The Specification also explains, “[tjhere are examples in the
scientific literature of partially degradable polyNIPAM hydrogels where the
degradable bonds are typically introduced into the cross-linking sites but not
within the polymer backbone” and “[different biodegradable crosslinkers
have been used for this purpose, such as amino-acid derivatives, degradable
polyaspartic acid derivatives, as well as modified dextran, polylactic acid,
and poly(e- caprolactone) (PCL).” Id. at 2:19-23 (indicating that there are
drawbacks to this specific method of engineering biodegradation).
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Application 13/090,999
Claim 1 is representative and is reproduced below:
1. A scaffold formed from a cross-linked stimuli-
responsive polymer, the scaffold having a plurality of
interconnected pores that each has a volume that changes in
relation to a phase transition event, wherein the phase transition
event is initiated by an effective stimulus to the cross-linked
stimuli-responsive polymer,
wherein the cross-linked stimuli-responsive polymer
comprises a random copolymer backbone comprising stimuli-
responsive portions and biodegradable portions, and the
crosslinked stimuli-responsive polymer is configured to fully
biodegrade in vivo to yield oligomeric units that can be excreted
or otherwise biologically cleared from the body.
Br. 27 (Claims App’x).
The following rejection is on appeal:
Claims 1—5, 7, 8, 10-18, and 33—35 stand rejected under 35 U.S.C.
§ 103(a) over Chang,2 Chaterji,3 Stayton,4 You,5 and Zhang.6 Ans. 2—7.
2 Cong Chang et al., Fabrication of Thermosensitive PCL-PNIPAAm-PCL
Triblock Copolymeric Micelles for Drug Delivery, 46 J. Poly. Sci. 3048—57
(2008) (“Chang”).
3 Somali Chaterji et al., Smart Polymeric Gels: Redefining the Limits of
Biomedical Devices, 32 Prog. Polym. Sci. 1083—122 (2007) (Author
Manuscript, paginated 1—58) (“Chaterji”).
4 U.S. Pat. App. Pub. No. US 2007/0224241 Al (pub. Sept. 27, 2007)
(“Stayton”).
5 Ye-Zi You et al., Dually Responsive Multiblock Copolymers via RAFT
Polymerization: Synthesis of Temperature- and Redox-responsive
Copolymers ofPNIPAMand PDMAEMA, 40 Macromolecules 8617-24
(2007) (Author Manuscript, paginated 1—19) (“You”).
6 Youwei Zhang et al., A Novel Route to Thermosensitive Polymeric Core-
Shell Aggregates and Hollow Spheres in Aqueous Media, 15 Adv. Funct.
Mater. 695-99 (2005) (“Zhang”).
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Application 13/090,999
FINDINGS OF FACT
We identify the following findings of fact to highlight certain
evidence of record.
FF1. Chaterji discloses, “development and applications of
smart polymeric gels, especially in the context of biomedical devices”
and “[sjmart polymeric gels constitute a new generation of
biomaterials that are now being developed at a prolific pace for use in
a range of applications including . . . scaffolds for tissue engineered
prostheses.” Chaterji 1 (Abstract and Introduction); see also Ans. 2,
5, 7, 8, 10 (discussing Chaterji).
FF2. Chaterji discloses, “[sjome of the potential biomedical
applications of smart hydrogels . . . include: temporally and spatially
controlling delivery of therapeutics (e.g., glucose sensitive phase
reversible gels for insulin delivery . . . [and] engineering scaffolds for
cell culture and tissue reconstruction (e.g., thermo-responsive surfaces
for cell detachment, MMP-sensitive biodegradable polymers for
ECM-mimicry).” Chaterji 25; see also Ans. 2, 5, 7, 8, 10 (discussing
Chaterji).
FF3. Chaterji identifies, “poly(A-isopropylacrylamide-co-
acrylamide) (poly(NIPAM-AM))” as a “temperature-sensitive
swelling,” superporous hydrogel (SPH), which “have large
interconnected pores” and can be, e.g., “mechanically strengthened
second generation SPHs.” Chaterji 4—5; see also Ans. 2, 5, 7, 8, 10
(discussing Chaterji).
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Application 13/090,999
FF4. Chaterji discloses, “[t]he temperature dependent
switching characteristic of poly(NIPAM) surface coatings . . . has
been useful in both in vitro cell culturing and in fabricating layered
constructs for engineering novel tissues.” Chaterji 16; see also Ans.
2, 5, 7, 8, 10 (discussing Chaterji).
FF5. Chaterji discloses that there are advantages to “designing
biodegradable [smart polymeric gels]” and identifies e-caprolactone as
a biocompatible monomer for synthesizing new polymers “with this
concept in mind.” Chaterji 7, 8; see also Ans. 2, 5, 7, 8, 10
(discussing Chaterji).
FF6. Chaterji discloses forming hydrogels “by the use of a
crosslinker” and explains that “[wjithout such crosslinking-based or
supramolecular assembling-based entanglements, polymers would
react to stimuli by cycling between the sol and the gel states, rather
than oscillating between the swollen and the collapsed states.”
Chaterji 3; see also Ans. 2, 5, 7, 8, 10 (discussing Chaterji).
FF7. Chang disclosed, “thermosensitive ABA type triblock
poly(e-caprolactone)-/)-poly(A-isopropylacrylamide)-/)-poly(e-
caprolactone) (PCL-PNIPAAm-PCL) copolymers with different
molecular weights were synthesized by the combination of ring
opening polymerization and reversible addition-fragmentation chain
transfer (RAFT) polymerization,” which formed micellular drug
delivery particles “with good biocompatibility and degradability,”
“demonstrating] both thermoresponsive and biodegradable
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Application 13/090,999
properties.” Chang 3048^49; see also Ans. 2—5, 7—11 (discussing
Chang).
FF8. Stayton discloses, “[pjolymer systems that undergo phase
transitions in response to environmental stimuli such as temperature
and pH have been widely investigated . . ., especially poly(N-
isopropylacrylamide) (pNIPAAm) [hydrogel], which undergoes a
sharp coil-globule transition and phase separation at its lower critical
solution temperature (LCST).” Stayton 13; see also Ans. 2—4, 7—11
(discussing Stayton).
FF9. Stayton discloses, “[s]ome copolymer hydrogels of
NIPAAm and acidic (e.g., acrylic acid, methacrylic acid) or basic
comonomers are known to be both pH-sensitive and temperature-
sensitive. These dual pH/temperature responsive hydrogels have a
variety of applications in many fields including controlled drug
delivery systems [and] cell culture.” Stayton | 6; see also Ans. 2-4,
7—11 (discussing Stayton).
FF10. Stayton discloses, “copolymeriz[ation] with NIPAAm
using traditional free radical polymerization techniques to form
random copolymers with both temperature- and pH-responsive
properties,” including forming copolymers of NTPAAm-co-PAA by
RAFT and by cross-linking. Stayton, inter alia, 14, 9-16, 150-155
(Example 1), 156—160 (Example 2); see also Ans. 2-4, 7—11
(discussing Stayton).
FF11. Stayton discloses, “[fjaster swelling response of
hydrogels can also be achieved by changing the gel structure or the
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Application 13/090,999
gel morphology to a porous inhomogeneous network structure.”
Stayton till; see also Ans. 2-4, 7—11 (discussing Stayton).
FF12. You discloses, “temperature- and redox-responsive
multiblock copolymers [prepared] by reversible addition-
fragmentation chain transfer (RAFT) polymerization,” including
“poly(N-isopropylacrylamide) (PNIPAM).” You 1; see also Ans. 2—
3, 8—9, 11 (discussing You).
FF13. Further to the preceding finding of fact and FF7, You
discloses, “[mjultiblock copolymers consist of two or more different
blocks of monomers arranged in a random or alternating sequence”
and “the experimental and theoretical studies of these systems show
that multiblock copolymers often can provide more advantageous
properties compared with corresponding diblock or triblock
copolymers.” You 1; see also Ans. 2—3, 8—9, 11 (discussing You).
FF14. You also discloses synthesizing multiblock copolymers
using poly(e-caprolactone) (PCL). You 2; see also Ans. 2—3, 8—9, 11
(discussing You).
DISCUSSION
“[W]hen a patent claims a structure already known in the prior art that
is altered by the mere substitution of one element for another known in the
field, the combination must do more than yield a predictable result.” KSR
Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (citing U.S. v. Adams,
383 U.S. 39, 50-51 (1966)). “The combination of familiar elements
according to known methods is likely to be obvious when it does no more
than yield predictable results.” Id. As to motivation to combine separately
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disclosed subject matter, ‘“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 Fulton, 391 F.3d 1195, 1200 (Fed. Cir.
2004) (citation omitted). Also, “where a rejection is predicated on [several]
references each containing pertinent disclosure ... we deem it to be of no
significance, but merely a matter of exposition, that the rejection is stated to
be on A in view of B instead of on B in view of A, or to term one reference
primary and the other secondary.” In re Bush, 296 F.2d 491, 496 (CCPA
1961).
We find, under the above precedent, the Examiner has established a
prima facie case that claim 1 would have been obvious over Chaterji, Chang,
Stayton, You, and Zhang. For example, the Examiner determined:
According to Chaterji et al., it is well known in the art that the
“smart” polymers (i.e. stimuli-responsive polymers) are used in
a range of applications including templates for nanoscale and
other biomedical devices, scaffolds for tissue engineered
prosthesis, and biosensors and actuators according to Chaterji et
al. (see Introduction at p.1083 [1]). Thus, it would have been
obvious to a person skilled in the art to use the crosslinked
random copolymers of PNIPAAm and PCL taught by Chang et
al. in view of Stayton et al. for a scaffold for tissue engineered
prosthesis as taught by Chaterji et al.
Ans. 7; see also FF1—FF14 (highlighting certain evidence supporting
obviousness). Appellants have not produced evidence showing, or
persuasively argued, that the Examiner’s determinations are incorrect. Only
those arguments made by Appellants in the Briefs have been considered in
this Decision. Arguments not presented in the Briefs are waived. See 37
C.F.R. § 41.37(c)(l)(iv) (2015). We address Appellants’ arguments below.
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Appellants’ arguments focus on the contention that Chang’s disclosed
micelles would not have been modified in view of the other cited prior art.
For example, Appellants argue the claimed porous scaffolds have no relation
to Chang’s micelles (Br. 14); Chang’s polymers are triblock copolymers and
are not random copolymers, which would not be well-suited for forming
micelles {id. at 15—16), Chaterji does not provide a reason to modify Chang
to use a random copolymer {id. at 17), You does not describe the subject
matter of claim 1 {id. at 18), Stayton does not provide a reason for changing
Chang’s well-defined triblock polymer to be random {id.), and Zhang
teaches crosslinking only PNIPAAm {id. at 18—19). Further, Appellants
argue the skilled artisan would never have looked to Chang in developing a
scaffold in the first place and, even if one did, the other cited references do
not cure Chang’s deficiencies. Id. at 20. These arguments are not
persuasive.
As taught by Chaterji, the use of smart polymer gels as tissue
scaffolds is not new, and it was known that poly(A-isopropylacrylamide)
(PNIPAAm) is a superporous hydrogel that is thermo-responsive and that
8- caprolactone (PCL) is a biodegradable polymer used in synthesizing
biodegradable smart polymer gels. FF1—FF5. Chaterji also teaches that
such smart polymers should be synthesized by crosslinking. FF6. In view
of these teachings, one of ordinary skill in the art would reasonably produce
a porous scaffold of crosslinked, randomly copolymerized PNIPAAm and
PCL. The details on how to go about doing so and further advantages of
these materials are disclosed in Chang, Stayton, and You (and Zhang, also),
such that the skilled artisan would look to these references, which are each
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related to such smart polymers, for their teachings regarding the suitability
of pairing PNIPAAm and PCL, the advantages of random copolymerization,
and methods of synthesis/copolymerization. FF7—FF14. Therefore, we are
not persuaded by Appellants’ arguments and affirm the obviousness
rejection. Appellants present the same arguments for all claims on appeal,
thus, all claims fall with claim 1.
SUMMARY
The obviousness rejection is affirmed.
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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