Irina Aizman

Patent Trials and Appeals Board

Aug 19, 2019

12734855 - (D) (P.T.A.B. Aug. 19, 2019)

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.
12/734,855 08/23/2010 Irina Aizman SNBINZ00800 7570
63453 7590 08/19/2019
SANBIO, INC.
c/o LEVINE BAGADE HAN LLP
2400 GENG ROAD
SUITE 120
PALO ALTO, CA 94303
EXAMINER
BERKE-SCHLESSEL, DAVID W
ART UNIT PAPER NUMBER
1651
MAIL DATE DELIVERY MODE
08/19/2019 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte IRINA AIZMAN1
____________

Appeal 2019-002228
Application 12/734,855
Technology Center 1600
____________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
FRANCISCO C. PRATS, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
The claim in this appeal is directed to method for producing an
isolated extracellular matrix. The Examiner rejected the claim under
35 U.S.C. § 103 as obvious. Pursuant to 35 U.S.C. § 134, Appellant appeals
the Examiner’s determination that the claim is unpatentable. We have
jurisdiction for the appeal under 35 U.S.C. § 6(b). The Examiner’s decision
is reversed.
STATEMENT OF THE CASE
The Examiner finally rejected claim 1 under pre-AIA 35 U.S.C.
§ 103(a) as obvious in view of Naughton (U.S. Patent No. 5,830,708, issued

1 The Appeal Brief (“Appeal Br.” entered May 10, 2018) lists SanBio, Inc.
as the Real Party in Interest. Br. 1.
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Nov. 3, 1998) and Mari Dezawa et al., (Specific induction of neuronal cells
from bone marrow stromal cells and application for autologous
transplantation, 113(12) J. CLIN. INVESTIG. 1701–1710 (2004)) (“Dezawa”)
as evidenced by A. Alovskaya et al., (Fibronectin, Collagen, Fibrin -
Components of Extracellular Matrix for Nerve Regeneration in 3 TOPICS IN
TISSUE ENGINEERING (N. Ashammakhi, R. Reis & E. Chiellini, eds., 2007)
(“Alovskaya”). Final Act. 10–11.
Claim 1 is reproduced below:
1. A method for producing an isolated extracellular matrix,
the method comprising culturing differentiation-restricted
descendents of marrow adherent stromal cells (DRCs) on a
culture surface and isolating the extracellular matrix deposited
on the culture surface;
wherein the DRCs are produced by transfection of a
culture of marrow adherent stromal cells (MASCs) with a
nucleic acid comprising sequences encoding a Notch
intracellular domain, further wherein the isolated extracellular
matrix stimulates the growth of neural cells.

REJECTION
Claim 1 is directed to a method of producing isolated extracellular
matrix (“ECM”). The method comprises two steps: 1) “culturing
differentiation-restricted descendents of marrow adherent stromal cells
(DRCs) on the culture surface” and 2) “isolating the extracellular matrix
deposited on the culture surface.”
The claim requires the DRCs to be “produced by transfection of a
culture of marrow adherent stromal cells (MASCs) with a nucleic acid
comprising sequences encoding a Notch intracellular domain.”
The Examiner found Naughton discloses producing ECM from
stromal cells, but not from descendents of DRCs transfected with a Notch
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intracellular domain as required by the claim. Ans. 3. To meet this
deficiency, the Examiner cited Dezawa as teaching “a method of transfecting
marrow derived stromal cells with a sequence for coding for a notch
intracellular domain (NICD) in order to force the marrow derived stromal
cells into a neural precursor lineage.” Ans. 4. The Examiner stated that it
would have been obvious to one of ordinary skill in the art “to modify the
cell transfection taught by Naughton with the specific transfection method
for producing NICD expression in marrow derived stromal cells taught by
Dezawa because Naughton teaches that certain cell types produce ECM that
enhance proliferation of specific cells grown on that ECM.” Id. The
Examiner also found that the skilled worker would have been motivated to
use Dezawa’s cells because Naughton teaches “that the ECM secreting cells
can further be transfected to enhance the secretion of specific ECM
molecules, or for a specific differentiation (transformation). See column 11,
lines 2-4.” Id.
With respect to step 2) of isolating ECM, the Examiner found that the
skilled worker “would recognize that NICD transfected cells of Dezawa
(induced to differentiate into neural stem cells) is one suitable cell type to
produce neural specific ECM taught by Naughton.” Ans. 5. The Examiner
also cited Alovskaya as teaching that neural cells produce ECM. Id.

DISCUSSION
The issue in this rejection is whether it would have been obvious to
have utilized Dezawa’s cells transfected with the Notch intracellular domain
(NICD) in Naughton’s method. The Examiner found it would have been
obvious to do so because Naughton discloses using transfected cells “to
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promote certain cellular expressions/differentations [differentiation]” and
that “ECM secreting cells can further be transfected to enhance the secretion
of specific ECM molecules.” Ans. 4.
The Examiner’s findings are not supported by a preponderance of the
evidence.
Naughton does not disclose enhancing the production of ECM by
transfection of cells. The specific disclosure in Naughton cited by the
Examiner to establish this fact is reproduced below:
The three-dimensional extracellular matrix producing
culture of the present invention affords a vehicle for introducing
gene products in vivo. In certain situations, it may be desirable
to prepare an extracellular matrix containing a foreign gene
product, growth factor, regulatory factor, etc. In such cases, the
cells may be genetically engineered to express the gene product,
or altered forms of the gene product that are immobilized in the
extracellular matrix laid down by the stromal cells. For
example, using recombinant DNA techniques, a gene of interest
can be placed under the control of an inducible promoter. . . .
First, since the culture comprises eukaryotic cells, the gene
product will be properly expressed and processed in culture to
form an active product. Second, the number of transfected cells
can be substantially enhanced to be of clinical value, relevance,
and utility.
Naughton 10:59–11:11.
This disclosure from Naughton, cited by the Examiner, does not
describe modifying stromal cells to enhance ECM production, but rather
refers to genetically engineering the cells with a gene of interest, where the
gene produces a gene product that is expressed and subsequently
immobilized in the ECM manufactured by the stromal cells. The subsequent
disclosure in Naughton at column 11, lines 15–22, refers to controlling
expression of the gene and the ability to secrete the gene product, but makes
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no mention of enhancing ECM production by genetic modification. Thus,
we do not find that the disclosure in Naughton cited by the Examiner
supports the Examiner’s finding that the skilled worker would have been
motivated to use Dezawa’s cells in Naughton’s method based on the finding
that Naughton teaches “ECM secreting cells can further be transfected to
enhance the secretion of specific ECM molecules.” Ans. 4. The finding is
erroneous.
The Examiner also found it would have been obvious to use Dezawa’s
cells in Naughton’s method because Naughton teaches “that certain cell
types produce ECM that enhance proliferation of specific cells grown on that
ECM,” making it obvious to choose Dezawa’s cells which the Examiner
found would have been reasonably expected to produce ECM. Ans. 4, 7.
The Examiner did not establish that Dezawa’s cells produce ECM or
would have been reasonably expected to do so at the time of the invention.
Dezawa discloses:
Here we demonstrate a highly efficient and specific induction
of cells with neuronal characteristics, without glial
differentiation, from both rat and human MSCs [mesenchymal
stem cells] using gene transfection with Notch intracellular
domain (NICD) and subsequent treatment with bFGF,
forskolin, and ciliary neurotrophic factor.
Dezawa 1701 (Abstract).
The Examiner did not identify disclosure in Dezawa that the NICD
transfected cells produce ECM. Rather, the Examiner cited Alovskaya to
establish that these cells produce ECM. The Examiner summarized
Alovskaya as follows:
Alovskaya shows known ECM compounds of neural cells,
including stem/progenitor cells. See “Abstract” section; page 1,
last paragraph; page 5, first [incomplete] paragraph and
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“Inhibitory molecules in the glial scar” section; page 6, first
[incomplete] paragraph; page 17, first paragraph; page 19, last
[full] paragraph. In particular, Alovskaya specifically indicates
that neural progenitor cells express NG2, which can become
integrated in the ECM. See page 6, first [incomplete] paragraph.
Ans. 5.
We have reviewed the sections cited by the Examiner, and are in
agreement with Appellant that Alovskaya does not describe the production
of ECM by neural cell precursors, let alone the NICD transfected “cells with
neuronal characteristics” described by Dezawa. Appeal Br. 6. Appellant
addressed each of the disclosures cited by the Examiner and established that
none of the cited passages teach that ECM is produced by neural precursor
cells as found by the Examiner. Id. at 17–21.
The Examiner also makes specific mention of NG2 disclosed by
Alovskaya. Ans. 5. The Examiner cited the following disclosure from
Alovskaya as disclosing that NG2 “can become integrated in the ECM.” Id.
Alovskaya teaches:
NG2 [neuron-glia antigen 2] is a major component of
CSGP [Chondroitin sulfate proteoglycans] expression after SCI
[spinal cord injury], thereby potentially exerting an important
role in limiting axonal regeneration. It is a high molecular
weight CSPG that was first identified as a cell surface antigen
of neural tumour-derived cell lines that had properties
intermediate between neurons and glial cells. Adult Schwann
cells, which do not express NG2, support the extensive growth
of neurites from adult DRG cells. By contrast, Schwann cells
transfected to express NG2 on their surfaces are not very
supportive of neurite growth and cells extend mainly short
branching neurites with stubby brunches. This suggests that,
after injury, centrally projecting axons of damaged sensory
neurons would be unable to grow through accumulated NG2.
Oligodendrocyte progenitors are among several cell types that
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react rapidly and express NG2 after injury. Macrophages have
also been identified as another cell type which contributes
strongly to NG2 deposition after spinal injury.
Alovskaya 5–6 (citations numerals omitted; emphasis added)
Alovskaya identifies oligodendrocyte progenitors and macrophages as
a source of NG2, but not neural precursor cells as asserted by the Examiner.
Moreover, the Examiner did not establish that the production of the single
matrix molecule, NG2, is the same as the production of extracellular matrix.
For example, Naughton teaches that the extracellular matrix also comprises
collagens, hyaluronic acid, and various glycosaminoglycans and growth
factors. Naughton 3:66–col, 4, l. 2.
Harvey2 was additionally cited by both the Examiner and Appellant as
additional evidence, but this journal article was published in 2013, which is
after the priority date of the instant application. The Examiner stated that
this reference “unequivocally” shows “that the cells of Dezawa will
inherently produce ECM, and said ECM is inherently neuro-stimulatory.”
Ans. 16. The Examiner did not establish that this information about the
properties of Dezawa’s cells was known at the time of the invention.
Inherency cannot be used to establish obviousness because one of ordinary
skill in the art would not have known at the time of the invention that
Dezawa’s NICD transfected cells produced ECM.
“An examiner bears the initial burden of presenting a prima facie case
of obviousness.” In re Huai-Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir.
2011). Because the Examiner did not meet the burden of establishing claim

2 Adam Harvey et al., Proteomic Analysis of the Extracellular Matrix
Produced by Mesenchymal Stromal Cells: Implications for Cell Therapy
Mechanism, 8(11) PLOS One 1–11 (e79283) (2013).
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1 would have been obvious to one of ordinary skill in view of Naughton,
Dezawa, and Alovskaya, the rejection is reversed.

REVERSED