Hui Xu et al.

Patent Trials and Appeals Board

Jul 8, 2020

2019006096 (P.T.A.B. Jul. 8, 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.
12/956,058 11/30/2010 Hui Xu 128196-05801 8679
145655 7590 07/08/2020
McCarter & English, LLP/LifeCell
265 Franklin Street
Boston, MA 02110
EXAMINER
MOLOYE, TITILAYO
ART UNIT PAPER NUMBER
1632
NOTIFICATION DATE DELIVERY MODE
07/08/2020 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):
docket@mccarter.com
mvaneman@mccarter.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte HUI XU, WENDELL SUN, CUNQI CUI, and HUA WAN
____________

Appeal 2019-06096
Application 12/956,058
Technology Center 1600
____________

BEFORE DONALD E. ADAMS, ELIZABETH A. LAVIER, and
TAWEN CHANG, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 17–21, 25–26, and 28–37 (Appeal Br. 2). 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 “LifeCell
Corporation” (Appellant’s January 17, 2019 Appeal Brief (Appeal Br.) 1).
Appeal 2019-06096
Application 12/956,058

2
STATEMENT OF THE CASE
Appellant’s disclosure relates to, inter alia, “a device for treating a
nerve . . ., comprising an arterial tissue matrix, wherein substantially all of
the native cells have been removed” (Spec. ¶ 5). Claim 17 is reproduced
below:
17. An implantable device for treating a nerve, comprising:
an arterial tissue matrix having substantially all of the
native cells removed, having exogenous mesenchymal stem
cells added to the arterial tissue matrix, wherein the exogenous
mesenchymal stem cells added to the arterial tissue matrix
improve repair, regrowth, and regeneration of nerve and muscle
tissue compared to arterial tissue matrix alone when the arterial
tissue matrix is implanted across a defect in a nerve;
wherein the shape of the arterial tissue matrix is a
conduit;
and wherein the implanted conduit is capable of allowing
a peripheral nerve to grow therethrough.
(Appeal Br. 16.)

Claims 17–21, 25, 26, and 28–37 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over the combination of McFetridge,2 Siemionow,3
Hadler,4 and Ayares.5

2 McFetridge, US 2006/0282173 A1, published Dec. 14, 2006.
3 Siemionow et al., WO 2009/124170 A1, published Oct. 8, 2009.
4 Hadler et al., Ultrastructure of a hyaluronic acid matrix, 79 Proc. Natl.
Acad. Sci. USA 307-09 (1982).
5 Ayares et al., US 2005/0260176 A1, published Nov. 24, 2005.
Appeal 2019-06096
Application 12/956,058

3
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. McFetridge discloses:
[A]n implantable device that includes a tissue graft comprising
a substantially decellularized umbilical vessel having a luminal
surface and an ablumenal surface. The substantially
decellularized umbilical vessel is prepared by an automated
dissection process and is not substantially cross-linked. The
substantially decellularized umbilical vessel may be capable of
having at least one cell type seeded on at least a portion of at
least one of the luminal and ablumenal surfaces thereof. The
umbilical vessel may be an umbilical vein or an umbilical
artery, and may be from a mammal, such as but not limited to, a
human.
(McFetridge ¶ 16; see id. ¶ 4 (McFetridge “relates to implantable devices for
tissue engineering, and more particularly but not by way of limitation, to
substantially decellularized grafts from umbilical cord vessels for use in
tissue engineering as a substantially acellular matrix and for use with cell
seeding methodology.”); Final Act. 5; see also Final Act. 6 (citing
McFetridge ¶¶ 91 and 134; Hadler 307) (Examiner finds that McFetridge
discloses that its arterial tissue matrix includes hyaluronic acid, a
glycosaminoglycan.).)
FF 2. McFetridge discloses:
The term “substantially decellularized” . . . mean[s] that
physical, chemical, or enzymatic means, or any combination
thereof, has substantially or completely removed the cellular
component of vascular tissue thereof. The remaining
substantially decellularized vascular tissue comprises the
extracellular matrix of the native vascular tissue and may
include, but is not limited to, elastin, collagen, fibrin, and other
Appeal 2019-06096
Application 12/956,058

4
extracellular proteins or non-proteinaceous compounds found in
vascular tissue, or any combination thereof known to one of
ordinary skill in the art.
(McFetridge ¶ 76; see Final Act. 6.)
FF 3. McFetridge discloses that its device may be seeded with “at least one
cell type on the substantially decellularized umbilical vessel, wherein the at
least one cell type is selected from the group consisting of smooth muscle
cells, fibroblasts, endothelial cells, keratinocytes, myogenic cells, stem cells,
muscle cells, epithelial cells, any other applicable cell type lineages, and
combinations thereof” (McFetridge ¶ 21; see id. ¶ 176 (McFetridge discloses
that “cells will be seeded inside a bioreactor on the ablumenal side, and
media will be flushed inside. Thus the cells will integrate the matrix and be
fed by the media diffusion through the scaffold from the lumen flow.”); id.
¶ 104; Final Act. 5 (Examiner finds that McFetridge’s implantable device
comprises “exogenous cells added to . . . [its] arterial tissue matrix.”); Final
Act. 5–6; Final Act. 7 (citing McFetridge ¶ 81) (Examiner finds that
McFetridge discloses the use of an “arterial tissue matrix is derived from a
pig,” i.e. exogenous (allogenic) cells.).
FF 4. McFetridge discloses that its implantable device can be used for,
inter alia, nerve regeneration (McFetridge ¶ 104; see Final Act. 5).
FF 5. McFetridge discloses that “[f]or peripheral nerve grafts a favorable
environment for nerve growth placed in the gap of the injury will permit
regeneration. The tubular structure of the scaffold along with nerve growth
factor and Schwann cells will promote the natural regeneration of the nerve
once implanted” (McFetridge ¶ 181; see Final Act. 5).
FF 6. McFetridge discloses that a “key component of . . . [peripheral nerve
regeneration] process is the choice of 3D scaffold with which tissue growth
Appeal 2019-06096
Application 12/956,058

5
is guided,” wherein “human umbilical artery (HUA) . . . because of its
vascular derivation, it presents surfaces that are conducive to cellular
attachment and subsequent [remodeling] processes” is “an excellent tubular
structure scaffold for peripheral nerve reconstruction” (McFetridge ¶¶ 182–
183; see Final Act. 5–6).
FF 7. Examiner finds that McFetridge fails to disclose that “the cells added
to the arterial tissue matrix are exogenous mesenchymal stem cells” (Final
Act. 7).
FF 8. Siemionow discloses that “[w]hen direct repair of the injured nerve
with epineural sutures is impossible, the defect between the nerve stumps
has to be bridged by a conduit of some kind, which will facilitate axonal
regeneration towards the distal nerve stump” (Siemionow 1:9–12; see Final
Act. 7).
FF 9. Siemionow discloses a “conduit material that causes minimal
inflammatory reaction, and can serve as a structural guide for regenerating,
or as a shield for protecting, nerve tissue (e.g., axons)” and “methods of
treating an injury to a (one or more) nerve or protecting a nerve in an
individual in need thereof,” wherein “[t]he methods employ all or a portion
of an isolated, naturally occurring epineural sheath, and can be used, for
example, to regenerate nerve tissue in an individual in need thereof”
(Siemionow 2:29–3:4; see id. at 18:32–19:2 (Siemionow discloses methods
that “comprise contacting the epineural sheath (e.g., filling the graft; coating
the sheath) with cells that aid and/or enhance regeneration of neural
tissue.”); id. at 19: 5–6 (Siemionow discloses that the seeded “cells can be
autologous, allogenic, isogenic, xenogenic or a combination thereof (e.g.,
chimeric cells.)”); see generally id. at 11:12–26; Final Act. 7).
Appeal 2019-06096
Application 12/956,058

6
FF 10. Siemionow discloses that its “epineural sheath can be filled with
different types of cells including[, inter alia,] . . . mesenchymal stem cells”
(Siemionow 21:16–18; see Final Act. 7).
FF 11. Examiner finds that although the combination of McFetridge,
Siemionow, and Hadler suggest the use of an “arterial tissue
matrix . . . derived from a pig,” the combination fails to disclose a pig
derived arterial tissue matrix that has been “genetically modified to have
reduced expression of α-1,3-galactose,” “lacks expression of α-
galactosyltransferase,” or “treated to remove α-1,3-galactose moieties” and
relies on Ayares to make up for these deficiencies in the combination of
McFetridge, Siemionow, and Hadler (Final Act. 7).
ANALYSIS
Based on the combination of McFetridge, Siemionow, Hadler, and
Ayares, Examiner concludes, inter alia, that, at the time Appellant’s
invention was made, it would have been prima facie obvious to a person of
ordinary skill in this art to combine: (1) McFetridge’s disclosure of an
implantable intact decellularized arterial tissue matrix, for treating a nerve,
that is in the shape of a conduit and seeded with exogenous cells with (2)
Siemionow’s disclosure of a method of treating a nerve injury in an
individual with a conduit material filled with exogenous mesenchymal stem
cells to regenerate nerve tissue (see Final Act. 9; see also FF 1–10). We find
no error in Examiner’s prima facie case of obviousness.
As Examiner explains, the recitation of the phrases “for treating a
nerve” and “wherein the exogenous mesenchymal stem cells added to the
arterial tissue matrix improve repair, regrowth, and regeneration of nerve
and muscle tissue compared to arterial tissue matrix alone when the arterial
Appeal 2019-06096
Application 12/956,058

7
tissue matrix is implanted across a defect in a nerve,” as set forth in
Appellant’s claim 17, are intended use limitations (see Final Act. 4–5).
“[T]he patentability of apparatus or composition claims depends on the
claimed structure, not on the use or purpose of that structure.” Catalina
Mktg. Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir.
2002). See Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464,
1468 (Fed. Cir. 1990) (“[A]pparatus claims cover what a device is, not what
a device does.”).
We acknowledge Appellant’s contention that “Examiner fails to make
the required factual determination of the level of skill in the art” (Appeal Br.
6–7 (emphasis omitted)). Appellant’s contention, however, is not persuasive
because the prior art relied upon by Examiner is representative of the level
of ordinary skill in this art (see Ans.6 6 (Examiner explains that the prior art
relied upon is representative of the level of ordinary skill in this art)). See
Okajima v. Bourdeau, 261 F.3d 1350, 1355 (Fed. Cir. 2001) (“[T]he absence
of specific findings on the level of skill in the art does not give rise to
reversible error ‘where the prior art itself reflects an appropriate level and a
need for testimony is not shown.”’ (quoting Litton Indus. Prods., Inc. v.
Solid State Sys. Corp., 755 F.2d 158, 163 (Fed. Cir. 1985))).
McFetridge discloses an implantable device that can be used for nerve
regeneration comprising a substantially decellularized umbilical vessel,
seeded with at least one cell type, such as stem cells (see FF 1–5).
Siemionow discloses an implantable device that can be used for nerve
regeneration comprising an epineural sheath seeded with cells that aid and/or

6 Examiner’s June 13, 2019 Answer.
Appeal 2019-06096
Application 12/956,058

8
enhance regeneration of neural tissue, such as exogenous mesenchymal stem
cells (see FF 8–10). Thus, a person of ordinary skill in this art, reading
McFetridge and Siemionow in combination, would have: (a) been
motivated, and (b) found it prima facie obvious, to use Siemionow’s
mesenchymal stem cells, which aid and/or enhance regeneration of neural
tissue, as the stem cells of McFetridge’s device (see e.g., Final Act. 9; see
also Ans. 10 (Examiner explains that “[t]he simple substitution of the stem
cells of McFetridge for the mesenchymal stem cells of Siemionow is nothing
more than the simple substitution of one known element for another to
obtain predictable results.”); Ans. 15 (Examiner explains that a “skilled
artisan would have found it prima facie obvious to substitute the generic
stem cells of McFetridge for the mesenchymal stem cells [of] Siemionow
because . . . Siemionow teaches mesenchymal stem cells . . . aid or enhance
the regeneration of nerve tissue.”) (quotation omitted)). See In re
Omeprazole Patent Litigation, 483 F.3d 1364, 1374 (Fed. Cir. 2007)
(“[T]his court finds no . . . error in [the] conclusion that it would have been
obvious to one skilled in the art to substitute one ARC [alkaline reactive
compound] for another.”). Therefore, we are not persuaded by Appellant’s
contention that “Examiner offers no motivation or rationale to combine the
teachings of McFetridge and Siemionow” (Appeal Br. 8 (citing Final Action
8–9); cf. Ans. 9–10). For the same reasons, we are not persuaded by
Appellant’s contention that Examiner’s “[m]otivation to combine
McFetridge and Siemionow could only arise through impermissible
hindsight” (Appeal Br. 13).
For the foregoing reasons, we find that the prior art relied upon by
Examiner provides a person of ordinary skill in this art with a reasonable
Appeal 2019-06096
Application 12/956,058

9
expectation of success in combining a decellularized umbilical vessel with
exogenous mesenchymal stem cells into an implantable device (see FF 1–10;
see Final Act. 10). Therefore, we are not persuaded by Appellant’s
contention that Examiner failed to establish a reasonable expectation of
success on this record (see Appeal Br. 9–12; see also Reply Br. 3–4; cf. Ans.
9–10).
For the foregoing reasons, we are not persuaded by Appellant’s
contention that Examiner suggests the combination of “mesenchymal stem
cell-filled epineural tube (decellularized conduit) of Siemionow with the
stem-cell-seeded umbilical vessel of McFetridge to facilitate peripheral
nerve regeneration” (Appeal Br. 13). As Appellant recognizes, such an
interpretation of Examiner’s prior art rejection “makes no sense” (id.).
The test for obviousness is not whether the features of a
secondary reference may be bodily incorporated into the
structure of the primary reference; nor is it that the claimed
invention must be expressly suggested in any one or all of the
references. Rather, the test is what the combined teachings of
the references would have suggested to those of ordinary skill
in the art.
In re Keller, 642 F.2d 413, 425 (CCPA 1981).
We are not persuaded by Appellant’s reliance on Keilhoff to support
an assertion that Appellant’s claimed product exhibits unexpected results
(see Appeal Br. 5, 7, 8, 10–11 (citing Keilhoff,7 110–112 ; Spec. ¶¶ 20, 21,
69, 71, 73, 80–82 and FIG. 3); Reply Br. 3–4; see also Reply Br.8 3
(Appellant contends that “Examiner does not give proper weight to Keilhoof

7 Keilhoff et al., Mesenchymal stem cells for peripheral nerve regeneration–
A real hope of just an empty promise?, 232 Experimental Neurology 110–
113 (2011).
8 Appellant’s August 12, 2019 Reply Brief.
Appeal 2019-06096
Application 12/956,058

10
in determining . . . the level of ordinary skill in the pertinent art.”). In order
to be persuasive of non-obviousness, “[e]vidence of secondary
considerations must be reasonably commensurate with the scope of the
claims.” In re Huai-Hung Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011). In
addition, “when unexpected results are used as evidence of nonobviousness,
the results must be shown to be unexpected compared with the closest prior
art.” In re Baxter-Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991).
Keilhoff addresses why a particular document was “accepted for
publication in Experimental Neurology” (Keilhoff 110). Specifically,
Keilhoff discloses:
Ladak et al. (2011) report on mesenchymal stem cells (MSCs),
isolated from rat bone marrow, which were stimulated towards
Schwann cell differentiation and then used to support peripheral
nerve regeneration in vitro and in vivo. Such a paradigm is an
interesting but not entirely new approach. . . . Nevertheless, the
study of Ladak and co-workers has been accepted for
publication in Experimental Neurology. Why?
(Id.) Keilhoff discloses that “Ladak and colleagues have consecutively
evaluated the efficiency of MSCs in supporting axonal regeneration in vivo
using a clinically available collagen nerve guide (Neurogen)” (id. at 111).
Keilhoff recognizes, however, that “[a]lthough . . . [Ladak’s] experimental
design is well conducted, a comparison of stem cell seeded guides[, i.e.
tubes,] with autografts is not quite accurate,” because, inter alia, “the tube is
different from the autograft” and “focus . . . [must be] on the physical
properties of the scaffold, i.e. the extracellular matrix” (id.).
Appellant fails to identify an evidentiary basis on this record to
support a conclusion that Keilhoff’s Neurogen, a collagen tube, is “similar to
the decellularized umbilizal vessel-based device of McFetridge,” “the
Appeal 2019-06096
Application 12/956,058

11
epineural tube of Siemionow,” or Appellant’s arterial tissue matrix (Appeal
Br. 10; see also id. at 16). “Attorney’s argument in a brief cannot take the
place of evidence.” In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974).
Thus, Appellant fails to establish an evidentiary basis on this record to
support a finding that Keilhoff discusses an implantable device that is both
commensurate in scope with Appellant’s claimed invention and provides a
comparison with the closest prior art.
Appellant’s contention regarding “a long felt but unsolved need,” was
presented for the first time in Appellant’s Reply Brief (Reply Br. 4) and,
therefore, was not properly presented to this panel for review. See Ex parte
Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) (Appellant fails
to “explain what ‘good cause’ there might be to consider the new argument.
On this record, Appellant’s new argument is belated.”).
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claim 17 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of McFetridge, Siemionow,
Hadler, and Ayares is affirmed. Claims 18–21, 25, 26, and 28–37 are not
separately argued and fall with claim 17.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
17–21, 25,
26, 28–37
103 McFetridge,
Siemionow,
Hadler, Ayares
17–21, 25,
26, 28–37

Appeal 2019-06096
Application 12/956,058

12
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