Ravi Bellamkonda et al.

Patent Trials and Appeals Board

Oct 15, 2021

2021000060 (P.T.A.B. Oct. 15, 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.
13/814,009 02/28/2013 Ravi V. Bellamkonda 47381.2 6361
21130 7590 10/15/2021
BENESCH, FRIEDLANDER, COPLAN & ARONOFF LLP
ATTN: IP DEPARTMENT DOCKET CLERK
200 PUBLIC SQUARE
SUITE 2300
CLEVELAND, OH 44114-2378
EXAMINER
MCNEIL, STEPHANIE A N
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
10/15/2021 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte RAVI V. BELLAMKONDA and ANJANA JAIN
__________

Appeal 2021-000060
Application 13/814,009
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
JAMIE T. WISZ, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims to a system
for treatment of cancer. The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We reverse.

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 Georgia
Tech Research Corporation and Children’s Healthcare of Atlanta (see
Appeal Br. 3). We have considered the Specification filed Feb. 4, 2013
(“Spec.”); Final Rejection of May 28, 2019 (“Final Act.”); Appeal Brief
filed Jan. 22, 2020 (“Appeal Br.”); and Examiner’s Answer filed July 24,
2020 (“Ans.”).
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Statement of the Case
Background
“Medulloblastomas are highly invasive tumors of the cerebellum and
the most common childhood malignant brain tumor, constituting 20-40% of
all pediatric brain tumors. Treatment of these invasive intracranial brain
tumors in children provides significant challenges” (Spec. 1:12–15). There
is a “need to preserve as much non-cancerous, ‘normal’ tissue as possible to
avoid long-term cognitive dysfunction. In such cases surgery is complicated
and chemotherapy is prone to major side effects” (id. at 1:15–18). Similarly,
malignant gliomas “are among the most aggressive and least successfully
treated types of cancer with few patients surviving longer than a year
following diagnosis” (id. at 1:20–21).
“[T]he present application relates to systems and methods for
directing cancer cell migration in order to remove, relocate or manage the
growth of tumors, including tumors that would otherwise be inoperable or
lead to a recurrence of the tumor” (Spec. 1:8–11).
The Claims
Claims 45, 46, 49, 50, and 59–67 are on appeal. Claim 45 is an
independent claim, is representative and reads as follows:
45. A system comprising:
a first scaffold having a length and including a substrate
film formed of aligned biocompatible polymeric nanofibers, the
film having an elongated configuration with a length reaching
from a first end portion to a second end portion remote from the
first end portion, with the nanofibers oriented lengthwise of the
film in uniaxial alignment with a longitudinal axis of the film,
and further having cues for directing tumor cell migration
lengthwise of the film from the first end portion to the second
end portion, whereby the first scaffold is configured for
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directing tumor cell migration away from the first end portion
of the film at a tumor site to a distal location of the second end
portion of the film remote from the tumor site, the first scaffold
being free of a cytotoxic agent;
a second scaffold that has a length less than the length of
the first scaffold, is free of aligned biocompatible nanofibers,
and is separate from the first scaffold and thereby configured
for surgical implantation and resection separately from the first
scaffold, adjacent the second end portion of the film, whereby
the second scaffold is configured to receive tumor cells
migrated from the first end portion of the film at a tumor site to
the second end portion of the film at a distal location remote
from the tumor site; and
a cytotoxic agent tethered or conjugated to the second
scaffold to contact and kill the migrated tumor cells received at
the second scaffold.

The Rejections
A. The Examiner rejected claims 45, 46, 49, 50, and 59–67 under 35
U.S.C. § 102(b) as anticipated by Blaha2 (Final Act. 3–4).
B. The Examiner rejected claims 45, 46, 49, 50, and 59–67 under 35
U.S.C. § 103(a) as obvious over Barron3 and Johnson4 (Final Act. 4–6).

A. 35 U.S.C. § 102(b) over Blaha
The Examiner finds “Blaha teaches an implantable stent with a
coating of aligned nanofibers that allow for cell migration along the

2 Blaha et al., US 2009/0043380 A1, published Feb. 12, 2009.
3 Barron et al., US 2010/0159008 A1, published June 24, 2010.
4 Johnson et al., Quantitative Analysis of Complex Glioma Cell Migration on
Electrospun Polycaprolactone Using Time-Lapse Microscopy, 15 Tissue
Engineering: Part C 531–40 (2009).
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nanofibers” where “the fibers are uniform longitudinally along the central
axis of the lumen of the tubular stent” (Final Act. 3). The Examiner finds
“Blaha teaches regions between the aligned fibers form reservoirs for
antiproliferative drugs” where “teaches the drug is embedded, trapped, in the
reservoirs” and is paclitaxel (id.). The Examiner finds “Blaha teaches the
aligned nanofibers comprise grooves for directing cell growth along the
fibers” (id. at 4).
Appellant contends in “claim 45, the first scaffold is ‘free of a
cytotoxic agent.’ The Blaha stent is not free of a cytotoxic agent. Instead,
the Blaha stent includes an antiproliferative drug such as paclitaxel” (Appeal
Br. 11). Appellant contends “Blaha does not disclose a second scaffold.
The Office Action asserts that Blaha’s reservoirs correspond to the claimed
second scaffold, yet the reservoirs are nothing more than open grooves
etched into the stent” and “are not separate from or configured for surgical
implantation and resection separately from a first scaffold” (id. at 12;
emphasis omitted). Appellant contends “[e]ven if the Blaha grooves were
considered to be a scaffold separate from the stent, which they simply
cannot, such a scaffold would not be free of nanofibers” (id. at 13).
Appellant contends “[t]here is no disclosure of paclitaxel on a second
scaffold that is both separate from the stent and free of nanofibers” (id.).
The issue with respect to this rejection is: Does a preponderance of the
evidence of record support the Examiner’s conclusion that Blaha anticipates
the claims?
Findings of Fact
1. Blaha teaches “biodegradable layer is designed to act as a
switch to turn on the release of antiproliferative drug (i.e.[,] rapamycin,
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paclitaxel) once enough proliferation has occurred to encapsulate the stent
strut” (Blaha ¶ 26).
2. Blaha teaches
The present invention controls tissue encapsulation of the
stent and of injured tissue in at least three ways: biologically,
geometrically, and chronologically.
Biologically, aligned nano/microfibers with or without
aligned nano/microgrooves therein (or alternatively, aligned
grooves formed within a non-fibrous material) facilitate
functional endothelization by encouraging a uniform orientation
in any cell growth that occurs (whether of true endothelial cells
or artificial endothelial cells).
(Blaha ¶ 67).
3. Blaha teaches
geometric control is the alignment of fibers/grooves and all
growth thereupon whether it be endothelial cells, smooth
muscle cells, proteins, matrix fibers, or collagen fibers. Due to
the structure supplied by the fibers/grooves, all subsequent in
vivo growth, migration, and/or proliferation is necessarily
aligned to correspond to the template set by the fibers/grooves.
(Blaha ¶ 68).
4. Blaha teaches
the inner surface of the stent strut can have micro/nano-grooves
etched on it longitudinally (parallel to axis of stent). ECs
[endothelial cells] will tend to grow into these grooves. . . . The
longitudinally aligned micro/nano-grooves may also be used as
reservoirs or longitudinal wells for storing therapeutic drugs
within the aligned fiber layers.
(Blaha ¶ 64).
Principles of Law
Anticipation under 35 U.S.C. § 102 requires that “each and every
element as set forth in the claim is found, either expressly or inherently
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described, in a single prior art reference.” In re Robertson, 169 F.3d 743,
745 (Fed. Cir. 1999).
Analysis
We do not agree with the Examiner’s finding that “Blaha teaches
regions between the aligned fibers form reservoirs for antiproliferative drugs
(reads on second scaffold free of aligned nanofibers that is less than the
length of the first scaffold)” (Final Act. 3). As Appellant correctly points
out, the Examiner provides no persuasive evidence that the reservoirs in
Blaha are a separate component or that the reservoirs are free of aligned
biocompatible nanofibers, both requirements of the second scaffold recited
in claim 45.
Indeed, the evidence in Blaha appears to suggest that the reservoirs
are within aligned fibers, teaching “longitudinally aligned micro/nano-
grooves may also be used as reservoirs or longitudinal wells for storing
therapeutic drugs within the aligned fiber layers” (FF 4). The Examiner
does not identify, and we do not find, any specific teaching in Blaha
suggesting that the reservoirs meet any of the requirements of the second
scaffold of claim 45. Blaha does not provide guidance on the length of the
reservoirs, so it is uncertain if the reservoirs have a length less than that of a
first scaffold. Blaha teaches the reservoirs are in grooves within the aligned
fiber layers (FF 4) and therefore are not separate from the first scaffold or
free of aligned nanofibers. Because Blaha does not teach all of the required
elements of claim 45, we reverse this rejection.
Conclusion of Law
A preponderance of the evidence of record does not support the
Examiner’s conclusion that Blaha anticipates the claims.
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B. 35 U.S.C. § 103(a) over Barron and Johnson
The Examiner finds “Barron teaches a system comprising a polymeric
hydrogel that can be implanted at the site of a tumor, wherein the hydrogel is
configured to actively migrate cancer cells into the core of the hydrogel
where the cells become trapped” and that “the hydrogel contains a cell
killing agent” that may be tethered (Final Act. 4). The Examiner
acknowledges that “Barron does not teach the system further contains a
scaffold comprising a plurality of aligned polymeric nanofibers . . . or that
they contain [grooves]” (id. at 5).
The Examiner finds “Johnson teaches an elongated nanofiber scaffold
composed of aligned nanofibers that form a surface on which glioma cells
can migrate” (Final Act. 5). The Examiner finds it obvious “to combine
Barron with Johnson to include both tumor cell mobility devices together in
a system” “because both are individually taught to be used for experiments
on tumor cells, and therefore could be packaged together for use in labs
studying tumor cells” (id.).
Appellant contends “Barron perfectly exemplifies ‘teaching away’
from the claimed invention. Appellant’s invention provides and promotes
directionally controlled tumor cell migration along a path leading away from
the tumor site. Barron provides and promotes controlled tumor cell
migration in an opposite direction along a path leading into the tumor site”
(Appeal Br. 18). Appellant contends
the rejection goes on to combine Barron with Johnson in a
strained attempt to derive Appellants’ dual scaffold system
from the prior art. The Johnson device employs aligned
nanofibers only to ‘mimic’ tumor cell migration for assay
purposes in vitro. . . . There is no intention to kill the migrating
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cells in the assay process, yet the Examiner asserts that a person
of ordinary skill in the art would have ‘a reasonable expectation
of success’ in using the Barron and Johnson devices together in
a system.
(id. at 19). Appellant contends “[b]y simultaneously driving cells both into
and away from the tumor, success for one would certainly ensure failure for
the other. There is no reconciliation between the two conflicting references”
(id.). Appellant contends a “solution cannot be attributed to Barron and
Johnson without the impermissible use of hindsight to identify Appellants’
sought-after success, which is irrelevant to the success sought by either
Barron or Johnson” (id. at 20).
The issue with respect to this rejection is: Does a preponderance of the
evidence of record support the Examiner’s conclusion that the combination
of Barron and Johnson render the rejected claims obvious?
Findings of Fact
5. Barron teaches:
the implanted hydrogel may limit metastasis by one or more of
the following: (1) releasing these potent signaling moieties
(growth factors such as SDF-1 or EGF) to attract migratory
cancer cells; (2) presenting adhesion moieties within or upon
the hydrogel implant, so that cancer cells actively migrate into
the hydrogel, (3) patterning a higher density of integral or
adhesion peptides near the core of the hydrogel, trapping
individual cancer cells via the formation of a high density of
focal adhesions, and/or (4) releasing chemotherapeutic drugs,
polypeptides, or polypeptoids that are able to bind to, penetrate,
and kill cancer cells with some specificity relative to normal
cells, within a small radius of the hydrogel core.
(Barron ¶ 49).
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6. Barron teaches a
certain selectivity of killing for cancer as opposed to normal
mammalian cells can be achieved either by the inherent cancer
specificity of the drug itself, or by the highly localized nature of
the delivery of the chemotherapeutic drug. By initially
attracting and sequestering cancer cells into a localized system,
the design of the hydrogel can be employed as a preparation
that could boost the efficacy of other therapies.
(Barron ¶ 50).
7. Barron teaches “the hydrogel can be a hybrid synthetic material
incorporating synthetic polymers such as poly(ethylene glycol) in addition to
biosynthetically derived, repetitive proteins. Embodiments of the hydrogel
can include high-molar mass protein polymers” (Barron ¶ 58).
8. Barron teaches the “killing substrates can be tethered to the
hydrogel, or directly mixed into the hydrogel, or pre-formulated into
polymeric microparticles/nanoparticles and then mixed into hydrogel”
(Barron ¶ 83).
9. Johnson teaches:
a tissue engineering approach to develop a physiologically
relevant model of glioma cell migration. This revealed that
glioma cells display dramatic differences in migration when
challenged by random versus aligned electrospun poly-ε-
caprolactone nanofibers. Cells on aligned fibers migrated at an
effective velocity of 4.2 ± 0.39 mm=h compared to 0.8 ± 0.08
µm/h on random fibers.
(Johnson 531, abstract).
10. Johnson teaches “cells seeded on aligned fibers maintained an
elongated morphology (except during division) and displayed decisive
motion, that is, consistent motility along the fiber axis” (Johnson 534, col.
1).
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11. Figure 1, panel B of Johnson is reproduced below:

“FIG. 1. SEM of . . . aligned PCL fibers (B)” (Johnson 534).
Principles of Law
A prima facie case for obviousness “requires a suggestion of all
limitations in a claim,” CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333,
1342 (Fed. Cir. 2003) and “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’l Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007).
Analysis
We agree with Appellant that the Examiner has not provided a
persuasive reason for the ordinary artisan to combine the hydrogel of Barron
with the aligned nanofibers of Johnson. In particular, we are not persuaded
by the Examiner’s logic to combine “because both are individually taught to
be used for experiments on tumor cells, and therefore could be packaged
together for use in labs studying tumor cells” (Final Act. 5). This generic
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statement is not a particular reason that would have prompted a skilled
artisan to combine the hydrogel of Barron and the nanofibers of Johnson.
Instead, the Examiner’s reasoning would generically apply to any two
products whatsoever. The Examiner does not identify any improvement in
either product based on the combination, does not identify a known or
obvious problem that would be solved by combining the two products, any
design need or market pressure, or any equivalence with another product.
We agree with Appellant that the rejection appears to be based on hindsight
and we reverse this obviousness rejection.
Conclusion of Law
A preponderance of the evidence of record does not support the
Examiner’s conclusion that the combination of Barron and Johnson render
the rejected claims obvious.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
45, 46, 49,
50, 59–67
102 Blaha 45, 46, 49,
50, 59–67
45, 46, 49,
50, 59–67
103 Barron, Johnson 45, 46, 49,
50, 59–67
Overall
Outcome
45, 46, 49,
50, 59–67

REVERSED