Ex Parte Hardy et al

Patent Trial and Appeal Board

Mar 28, 2019

14491686 (P.T.A.B. Mar. 28, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/491,686 09/19/2014
24504 7590 04/01/2019
THOMAS I HORSTEMEYER, LLP
3200 WINDY HILL ROAD, SE
SUITE 1600E
ATLANTA, GA 30339
FIRST NAMED INVENTOR
John Hardy
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
222108-1895 9592
EXAMINER
HA YES, ROBERT CLINTON
ART UNIT PAPER NUMBER
1649
NOTIFICATION DATE DELIVERY MODE
04/01/2019 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):
uspatents@tkhr.com
ozzie. liggins@tkhr.com
docketing@thomashorstemeyer.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOHN HARDY and CHRISTINE E. SCHMIDT
Appeal2018-000406
Application 14/491,686 1
Technology Center 1600
Before ERIC B. GRIMES, TIMOTHY G. MAJORS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of delivering nerve growth factor to nerve tissue, which have been rejected
as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
The Specification explains that "[ w ]hen a peripheral nerve has a
defect of more than two centimeters, a biomaterial is needed to repair the
defect." (Spec. 1.) "Schwann cells are known to increase the production of
nerve growth factor when electrically stimulated, and nerve growth factor
1 Appellants identify the real party in interest as The University of Florida
Research Foundation. (Appeal Br. 3.)
Appeal2018-000406
Application 14/491,686
has been demonstrated to promote regeneration of nerve tissue." (Id.) The
invention is directed at delivering nerve growth factor "to nerve tissue by
implanting in the tissue a[ n electroactive] scaffold ... upon which Schwann
cells have been cultured, and electrically stimulating the Schwann cells."
(Id. at 2.)
Claims 1-9 and 18 are on appeal. Claim 18 is representative and
reads as follows:
18. A method of delivering nerve 1 growth factor to nerve
tissue, comprising the following steps:
a. culturing Schwann cells on an electroactive tissue
scaffold;
b. implanting the scaffold and cultured Schwann cells
into the peripheral nerve tissue to be repaired; and
c. electrically stimulating the Schwann cells by placing a
voltage across the scaffold
(Appeal Br. 17.)
The following ground of rejection by the Examiner is before us on
review:
Claims 1-9 and 18 under 35 U.S.C. § 103 as unpatentable over Hoke2
and Shastri. 3
DISCUSSION
The Examiner finds that Hoke teaches a method of implanting a nerve
guide scaffold onto injured peripheral nerve tissue where the scaffold
includes Nerve Growth Factor (NGF) and Schwann cells. (Final Action 3.)
2 Hoke et al., WO 2009/094225 A2, published July 30, 2009.
3 Shastri et al., US 6,569,654 B2, issued May 27, 2003.
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Application 14/491,686
The Examiner further finds that Hoke teaches the scaffold is a
biodegradable/bioerod[a]ble hydrogel-grafted scaffold that also includes a
polycaprolactone nanofiber layer. (Id. at 4.)
The Examiner notes that Hoke does not teach electrically stimulating
the Schwann cells by placing a voltage across the scaffold after
implantation, as claimed. (Id.) According to the Examiner, such stimulation
is rendered obvious from the teachings of Shastri. (Id.)
In particular, the Examiner finds that Shastri teaches a method of
"affecting cell activity, growth and/or function" that involves "attaching
stem cells which differentiate into Schwann cells (e.g., col. 10 (lines 14-27),
onto a biodegradable/bioerod[ a ]ble scaffold surface comprising a
polycaprolactone matrix," which scaffold also includes an electroactive
polymer, i.e., an aromatic poly(heterocyclic) polypyrrole polymer. (Final
Action 4.) The Examiner finds that Shastri "teach[es] implanting their nerve
guide scaffold onto injured [peripheral] nerve tissue (e.g., pp bridging cols.
3-4), and placing a voltage across the scaffold after implantation (e.g., col. 4;
as it relates to claim 18)." (Id., alteration in original.)
According to the Examiner, it would have been obvious to one of
ordinary skill in the art to "electrically stimulate Hoke's Schwann cells"
"after addition of Shastri' s electrochemically respons[ ive] poly(pyrrole)
polymer" because "Shastri also teach[ es] use of scaffolds comprising
cultured stem cells that differentiate into Schwann cells on a
polycaprolactone matrix to repair damaged peripheral nerve tissue." (Id.;
see also Ans. 4--5.) Thus, the Examiner also implicitly recognizes that Hoke
does not teach an electrochemically responsive polypyrrole polymer but
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Application 14/491,686
concludes that modifying Hoke to include such polymer would have been
obvious in light of the teachings of Shastri.
We disagree with the Examiner's factual findings regarding Shastri
and the Examiner's conclusion that the invention recited by claim 18 would
have been obvious. We agree with the Examiner that Shastri is reasonably
understood to teach using neuronal stem cells on a matrix that is implanted
for tissue healing. (Shastri 10:13-27 (noting that "[c]onstructs including
PPy [polypyrrole] and stem cells may be used in both tissue healing and
tissue regeneration applications" and "when the construct is implanted, the
environment will trigger differentiation of the cells into the proper
proportions for each cell type"), 5: 19-23 (noting that "[a] stem cell, for this
invention, refers to any pluripotent cell ... includ[ing] neural").)4 And thus,
we also agree with the Examiner that "both Shastri et al. and Hoke et al
teach implantation of neural cells to repair the same injured PNS tissue."
(Ans. 6.) However, as Appellants explain (Appeal Br. 10), Shastri teaches in
its neural stem cell embodiment that the electrical stimulation after
4 We do, however, agree with Appellants (Reply Br. 4), that the Examiner's
finding that "Shastri et al. further teach implanting their nerve guide scaffold
into injured [peripheral] nerve tissue ( e.g., pp bridging cols. 3-4)" (Ans. 3,
alteration in original) overstates Shastri's teachings. Nowhere in the cited
portion of Shastri is this stated. Column 3 of Shastri, however, does state:
A three-dimensional stimulant of one or more biological
activities of cells is also provided comprising an electroactive
substrate associated with or attached to a matrix and wherein
the electroactive substrate is associated with or attached to one
or more mammalian cells at a desired location.
(Shastri 3:15-20.) We determine, though, that, combined with other
disclosure at column 10 in Shastri, Shastri fairly suggests implanting
the nerve guide into injured nerve tissue.
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Application 14/491,686
implantation causes the neural stem cells to differentiate into the proper
proportion of each cell type for tissue repair. In other words, Shastri does
not teach that Schwann cells are reasonably likely themselves to be
stimulated.
While Shastri does teach that electrical stimulation will stimulate
biological activities within the cells, "including but not limited to, gene
expression, cell growth, cell differentiation, signal transduction, membrane
permeability, cell division, and cell signaling" (Shastri 4:5-15), it does not
indicate that stem cells differentiated into, e.g., Schwann cells are also
reasonably likely to be stimulated into gene expression, cell growth, cell
differentiation, signal transduction, membrane permeability, cell division, or
cell signaling on the described scaffolds of Shastri. Rather, Shastri explains
that:
According to the current hypothesis, while a particular stem cell
usually differentiates according to a specific pattern ( e.g.,
neural stem cells into some type of nerve cell), exposure to
appropriate growth factors or other environmental modification
may cause differentiation into a wide variety of cells.
(Id. 5:46-50.) Thus, while it may be true that Hoke and Shastri teach the use
of cells of the same class, e.g., neuronal as opposed to muscular, we disagree
with the Examiner that Shastri provides a motivation to apply electrical
stimulation to the Schwann cells of the scaffold taught by Hoke. There is no
evidence that the Schwann cells are undifferentiated cells that can be
manipulated into a wide variety of other cell types. Moreover, Shastri does
not appear to broadly teach electrical stimulation of any neural cells on a
scaffold will likely result in stimulating biological activities within the cell.
Consequently, we do not find that the combination is one of simple
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Application 14/491,686
substitution of one known equivalent element for another to obtain
predictable results, as the Examiner contends. (Ans. 6-7.)
Furthermore, even if it could be said that Shastri broadly suggests any
cell's biological activities would be stimulated on the type of scaffold it
teaches, the Examiner has not provided a reason that such a teaching would
have motivated one of ordinary skill in the art to substitute that scaffold into
Hoke and use electrical stimulation on the Schwann cells that Hoke teaches
to use on a scaffold for peripheral nerve regeneration. According to the
Examiner "adding an electrochemically responsive polymer to a
polycaprolactone matrix [ would] allow stimulation of biological activities
within cells by electromagnetic stimulation." (Ans. 7.) However, that
merely states a result that may be expected, not why one of ordinary skill in
the art would have combined the teachings with a desire for that result.
Hoke teaches including nerve growth factors in the hydro gel layer of the
scaffold. (Hoke 4:4--7.) Hoke teaches that the Schwann cells are included in
the nanofiber layer of the nerve guide scaffold of Hoke. (Hoke 5: 1-5.) The
nerve growth factors on the scaffold are neurotrophic factors that promote
neural regeneration. (See, e.g., Hoke 3:3-5, 10:21-24, 21:21-24.) The
Schwann cells are added "to enhance the regeneration outcomes." (See, e.g.,
Hoke 15: 1-8.) The Examiner has not explained why electromagnetic
stimulation to stimulate biological activity within the Schwann cell of the
Hoke scaffold, where the Schwann cell is there to simply enhance
regeneration outcomes, and the scaffold also includes NGF to promote
neural regeneration would have been sought by one of ordinary skill in the
art. "[R ]ejections on obviousness grounds cannot be sustained by mere
conclusory statements; instead, there must be some articulated reasoning
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Application 14/491,686
with some rational underpinning to support the legal conclusion of
obviousness." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,418 (2007). The
rational underpinning is missing here.
For the foregoing reasons, we do not sustain the Examiner rejection of
claims 1-9 and 18 as being obvious over Hoke and Shastri.
SUMMARY
We reverse the rejection of claims 1-9 and 18 under 35 U.S.C. § 103
as unpatentable over Hoke and Shastri.
REVERSED
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