MULTIPLE SCLEROSIS RESEARCH CENTER OF NEW YORK

Patent Trials and Appeals Board

Jul 31, 2020

14525903 - (D) (P.T.A.B. Jul. 31, 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.
14/525,903 10/28/2014 Saud A. SADIQ 22484ZY 3308
23389 7590 07/31/2020
SCULLY SCOTT MURPHY & PRESSER, PC
400 GARDEN CITY PLAZA
SUITE 300
GARDEN CITY, NY 11530
EXAMINER
MACFARLANE, STACEY NEE
ART UNIT PAPER NUMBER
1649
NOTIFICATION DATE DELIVERY MODE
07/31/2020 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@SSMP.COM
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte SAUD A. SADIQ and VIOLAINE K. HARRIS1
____________

Appeal 2019-006719
Application 14/525,903
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies Multiple Sclerosis Research Center of
New York as the real party-in-interest. App. Br. ii.

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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 16–25 as unpatentable under 35 U.S.C.
§ 101 as being directed to nonstatutory subject matter.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s invention is directed to mesenchymal stem cell-derived
neural precursor cells. Spec. p. 6, ll. 1–4.

REPRESENTATIVE CLAIM
Claim 16 is representative of the claims on appeal and recites:
16. Isolated neural precursor cells, prepared by a process
comprising the steps of:

(a) expanding mesenchymal stem cells isolated from a human
subject,

(b) culturing a portion of the expanded mesenchymal stem
cells obtained in step (a) in a neural progenitor basal medium
(NPBM) supplemented with epidermal growth factor (EGF),
basic fibroblast growth factor (bFGF), and neural cell survival
factor-1 (NSF-1),

(c) collecting floating cell clusters from the culture of step (b),

(d) measuring, in a test portion of the collected cells,
expression of nestin, glial fibrillary acidic protein (GFAP),
neurofilament-M (NF-M), and alpha smooth muscle (αSM)
actin, and Vimentin, relative to expression of nestin, GFAP, NF-
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M, and αSM actin and Vimentin in a test portion of the expanded
mesenchymal stem cells obtained from step (a), and

(e) selecting the remaining portion of the collected cells as
neural precursors based on increased expression of nestin,
GFAP, and NF-M, decreased expression of Vimentin and
decreased expression of αSM actin in said test portion of the
collected cells, relative to the expression of nestin, GFAP, NF-
M, and αSM actin in said test portion of the expanded
mesenchymal stem cells, wherein the selected neural precursors
exhibit 2–4 fold increase in the amount of nestin, 5–15 fold
increase in the amount of NF-M, 7–10 fold increase in the
amount of GFAP, and 0.4–0.7 fold decrease in Vimentin.

App. Br. xvi.

ISSUES AND ANALYSIS
We agree with, and expressly adopt, the Examiner’s findings,
reasoning, and conclusion that the claims are directed to nonstatutory subject
matter. We address below the arguments raised by Appellant.

Issue
Appellant argues the claims recite mesenchymal stem cell-derived
neural progenitor cells produced by an artificial culturing process that are
markedly different from mesenchymal stem cells or neural precursor cells
found in vivo. See App. Br. iv–v.

Analysis
The Examiner concludes that claim 16 is directed to a judicial
exception, without reciting significantly more. Ans. 3. The Examiner finds
the claims recite a product of nature or natural phenomenon, “specifically, a
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product-by-process isolated neural precursor cell.” Id. The Examiner finds
that the claimed isolated neural precursor cells are not markedly different
from mesenchymal stem cells or neural precursor cells found in nature. See
id.
Appellant argues that the claimed product is isolated mesenchymal
cell-derived neural progenitor cells (“MSC-NPCs”) that do not exist in
nature. See App. Br. iv. Appellant argues that “the MSC-NPCs have been
derived artificially by driving MSC differentiation toward neural progenitors
in a non-natural, ex vivo environment that induces increased expression of
nestin, GFAP and NF-M and decreased expression of αSM actin.” Id. at v.
In performing an analysis of patentability under Section 101, we
follow the framework set forth by the Supreme Court in Mayo Collaborative
Servc’s v. Prometheus Labs., Inc., 566 U.S. 66 (2012). We are also mindful
of, and guided by, the United States Patent and Trademark Office’s 2019
Revised Patent Subject Matter Eligibility Guidance, 84(4) Fed. Reg. 50–57
(January 7, 2019) (the “Guidance”).
Following the first step of the Mayo framework, we find that claim 16
recites a composition of matter and therefore falls into one of the broad
statutory categories of patent-eligible subject matter under 35 U.S.C. § 101.
In the next step of the Mayo analysis, we determine whether the claim
at issue is directed to a nonstatutory, patent-ineligible concept, i.e., a law of
nature, a phenomenon of nature, or an abstract idea. Mayo, 566 U.S. at 70–
71; Guidance 54 (step 2A, Prong 1). If we determine that the claim recites a
judicial exception, we then determine whether the limitations of the claim
reciting the judicial exception are integrated into a practical application. Id.
(Step 2A, Prong 2). Finally, if we determine that the claim is directed to a
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judicially-created exception to Section 101, we evaluate the claims under the
next step of the Mayo analysis, considering the elements of each claim both
individually and “as an ordered combination” to determine whether
additional elements “transform the nature of the claim” into a patent-eligible
application. Mayo, 566 U.S. at 78–79; 2019 Guidance at 56 (Step 2B).
Appellant’s claim 16 recites: “[i]solated neural precursor cells,
prepared by a process.” App. Br. xvi. The claim further includes product-
by-process limitations, viz., steps of expanding, culturing, collecting,
measuring, and selecting. Id. “[E]ven though product-by-process claims are
limited by and defined by the process, determination of patentability is based
on the product itself.” In re Thorpe, 777 F.2d 695, 697 (Fed. Cir. 1985).
Accordingly, we evaluate the patentability of the claim, including under
Section 101, based on the product.
Appellant argues the claimed process steps are limiting on the claimed
product. See Reply Br. 3–4. For example, Appellant argues that “the
claimed NPCs are collected from ‘floating neural precursor clusters’ after
MSCs have been induced to differentiate, and have a spherical morphology.”
Id. (citing Spec. p. 19, ll. 11–22)(emphasis omitted). However, the claims
do not recite any specific morphology, and “limitations are not to be read
into the claims from the specification.” In re Van Geuns, 988 F.2d 1181,
1184 (Fed. Cir. 1993). Appellant also argues that the claimed “expression
pattern” in the selecting step “is defined by relative changes of a
combination of markers as compared to the starting MSCs.” Id. at 5
(emphasis omitted). However, selecting neural precursor cells from a mixed
population of cells based on an expression pattern merely exploits the
natural characteristic of the cells in response to extraneous stimuli used to
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isolate the natural product. In other words, the cells are doing what they
would naturally do under the circumstances to which they are subjected to
by Appellant. Because the process steps themselves are not limiting on the
claim, claim 16 recites an isolated natural product, i.e., isolated neural
precursor cells.
Isolating a natural product and thereby creating a non-naturally
occurring material does not necessarily result in patent-eligible subject
matter. See Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569
U.S. 576, 593 (2013). In Myriad, the Supreme Court held claims directed to
isolated DNA were not “saved by the fact that isolating DNA from the
human genome severs chemical bonds and thereby creates a nonnaturally
occurring molecule.” 569 U.S. at 593. Rather, to be patent eligible, a
“nonnaturally occurring manufacture or composition of matter” must
possess “markedly different characteristics from any found in nature.” Id. at
590–591 (citing Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980)).
Appellant argues that the claimed cells are markedly different from
naturally-occurring neural progenitor cells because: (1) “[t]he claimed MSC-
NPCs are produced by an artificial culturing process,” (2) “[t]he claimed
MSC-NPCs behave differently from naturally-occurring neural precursors,”
and (3) “[t]he claimed MSC-NPCs demonstrate specific expression marker
characteristics as recited.” App. Br. v, vi, ix (emphasis omitted). We do not
find these arguments persuasive for the reasons set forth below.
Appellant first argues that the claimed cells are markedly different
from naturally-occurring cells because the claimed cells are produced by an
artificial culturing process. App. Br. v. Appellant argues that different
artificial culture conditions generate neural precursor cells with different
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phenotypes. See id. Appellant cites C. S. Padovan et al., Expression of
Neuronal Markers in Differentiated Marrow Stromal Cells and CD133+
Stem-Like Cells, 12 CELL TRANSPLANTATION 839–848 (2003) (“Padovan”),
as evidence that culturing mesenchymal stem cells using different known
protocols results in different cells. See id.
Padovan teaches that mesenchymal stem cells “are capable of
differentiating into cells that express the neural stem cell marker nestin as
well as neuronal proteins resembling immature neurons when cultured in
conditions appropriate for neural stem cells.” Padovan 845. Rather than
support Appellant’s argument, Padovan supports the conclusion that
mesenchymal stem cells have the natural ability to differentiate toward
neural precursor cells when cultured in the appropriate conditions. See id.
In other words, the cells are performing their natural function depending
upon the artificial environment in which they are cultured.
We can distinguish these claims from those in Chakrabarty. In
Chakrabarty, the Supreme Court held that claims directed to a genetically
altered Pseudomonas bacterium, which was thereby rendered capable of
digesting crude oil, were directed to patentable subject matter. 447 U.S. at
305. The Court held that genetically modifying the bacterium rendered it: “a
nonnaturally occurring manufacture or composition of matter-a product of
human ingenuity ‘having a distinctive name, character [and] use.’” Id. at
310 (quoting Hartranft v. Wiegmann, 121 U.S. 609, 615 (1887)). In this
instance, the cells are not genetically altered, but merely subjected to a
regime that causes them to respond in a manner that is consonant with no
more than their natural capabilities.
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Second, Appellant submits evidence to support their argument “that
neural progenitors derived from MSCs, prepared using the same methods
described in the present application, are markedly different from neural
precursors that exist in vivo.” App. Br. vi. Appellant cites V. K. Harris et
al., Clinical and pathological effects of intrathecal injection of mesenchymal
stem cell-derived neural progenitors in an experimental model of multiple
sclerosis, 313 J. NEUROLOGICAL SCI. 167–177 (2012) (“Harris”),2 to
demonstrate the properties of the claimed cells in an experimental
autoimmune encephalomyelitis (“EAE”) model. See Harris at *1. Appellant
argues that Harris teaches that “MSC-NPCs initially display higher nestin
expression as compared to the MSCs they were derived from,” but “lose
nestin expression as early as 2 weeks after engraftment.” App. Br. vi.
Appellant contrasts endogenous neural progenitor cells, which do not lose
nestin positivity. Id. Appellant further argues that Harris demonstrates
“MSC-NPCs locate to the inflammatory foci and act to regulate immune
responses by reducing T-cell infiltration” and “increase the association of
endogenous progenitor cells in vivo.” Id. (emphasis omitted).
In response to Appellant’s argument, the Examiner cites A. M. Parr et
al., Bone marrow-derived mesenchymal stromal cells for the repair of
central nervous system injury, 40 BONE MARROW TRANSPLANTATION 609–
619 (2007) (“Parr”), which summarizes the art regarding transplantation of
MSCs in vivo. Ans. 12. Parr teaches “[m]uch of the interest surrounding the
use of stromal cells in [central nervous system] injury began with the

2 We cite to Appellant’s submitted “article in press” version of Harris.
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discovery that MSCs from both rats and humans give rise to cells with
neuronal morphology in vitro, and may also express neuronal or astrocytic
markers in vitro.” Parr 609. Parr teaches that “it has also been shown that
continued expression of neuronal markers … may depend on the
continuation of specific, nonphysiological environmental conditions in
vitro.” Id. at 609–610. With respect to the behavior of the cells after
administration, Parr teaches that, “human MSCs can improve neurological
functional recovery in mice with experimental autoimmune encephalitis
(EAE), possibly via reduction of inflammatory infiltrates and areas of
demyelination, stimulation of oligodendrogenesis and by elevating [brain-
derived neurotrophic factor] expression.” Id. at 613. Although Parr does not
specifically describe neural precursor cells as claimed, Parr teaches that
MSCs may express neuronal markers in vitro, stop expressing neuronal
markers absent artificial conditions, and act to regulate the immune response
in EAE. Accordingly, the claimed neural precursor cells do not appear to
behave markedly differently from similar cells administered for similar
conditions.
Appellant also submits two Declarations by Dr. Harris. App. Br. vii.
Appellant argues that the Harris Declaration submitted October 16, 2017
(“Harris Declaration 1”) establishes that “mouse MSC-derived neural
precursors actually did not fully differentiate into neural cells types in the
brain” and thus are different from naturally-occurring neural precursor cells.
Id. (emphasis in original). Appellant argues that the Harris Declaration
submitted April 20, 2018 ( “Harris Declaration 2”) establishes that “unlike
isolated human MSCs, the claimed MSC-NPCs do not proliferate and do not
demonstrate self-renewal properties in vitro.” Id. (emphasis omitted).
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We agree with the Examiner that the Declarations are not persuasive
evidence of markedly different characteristics of the isolated neural
precursor cells as compared to their naturally-occurring counterparts. See
Ans. 11–13. The Declarations state that isolated neural precursors cells may
not share the identical characteristics of naturally-occurring cells in
particular situations, e.g., endogenous neural precursors cells in vivo or
MSCs in vitro. Harris Decl. 1 ¶¶ 8–11; Harris Decl. 2 ¶¶ 5–6. However,
neither Declaration presents evidence of the behavior of naturally-occurring
isolated neural precursors cells or isolated MSCs administered in an EAE
model. See generally, Harris Decls. 1, 2. Given the Examiner’s findings in
Parr that MSCs share similar characteristics to the claimed isolated neural
precursor cells, the burden shifts to the Appellant to show a difference
between the naturally-occurring cells and the claimed cells. The PTO lacks
the resources to do comparisons. See in re Best, 562 F.2d 1252, 1254–1255
(C.C.P.A. 1977).
Third, Appellant argues that “[t]he claimed MSC-NPCs display
specific fold differences of the expression of the recited markers as a result
of an artificial culturing process.” App. Br. ix. Appellant argues that the
references cited by the Examiner do not represent naturally-occurring cells,
but rather cells that have been manipulated in cell culture. Id. at x.
We agree with the Examiner that “[t]here is no evidence that
alterations in the relative levels of marker proteins constitutes a marked
difference — either structurally or functionally — over naturally-occurring
counterparts.” Ans. 10. The references cited by the Examiner indicate that
naturally-occurring neuronal precursor cells will express different markers,
e.g., nestin, GFAP, NF-M, Vimentin, and αSM, at different levels when
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exposed to artificial culture conditions. See id. at 15–17. As discussed
supra, the claimed cells naturally function to express different phenotypes
due to environmental conditions. Appellant’s manipulation of the
environmental conditions does not alter the cells from performing their
natural function, and thus the claimed isolated neural precursor cells are not
markedly different from their naturally-occurring counterparts.
Consequently, we find that the claims recite a judicial exception, i.e., a
product of nature.
We next determine whether the judicial exception is integrated into a
practical application. See 2019 Guidance at 55 (Step 2A, Prong 2). For
example, integration may include using the natural product in a particular
treatment or prophylaxis for a medical condition or a particular manufacture
that is integral to the claims. Id.
As discussed supra, the claims recite a product-by-process including
steps for preparing the claimed product. The claims do not include any
particular treatment or prophylaxis for a medical condition. Because the
patentability of product-by-process claims centers on the product itself, we
are not presented with the question whether the method of culturing and
selecting neural precursor cells is patentable. See Funk Bros. Seed Co. v.
Kalo Inoculant Co., 333 U.S. 127, 130 (1948). Accordingly, we determine
that the recited natural product is not integrated into a practical application,
and claim 16 is directed to a judicial exception.
Finally, we evaluate whether additional elements in the claims recite
“an inventive concept —i.e., an element or combination of elements that is
sufficient to ensure that the patent in practice amounts to significantly more
than a patent upon the [ineligible concept] itself.” Ariosa Diagnostics, Inc.
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v. Sequenom, Inc., 788 F.3d 1371, 1375 (Fed. Cir. 2015). Particularly, we
evaluate whether the claims include specific limitations that are not “well-
understood, routine, conventional activity previously engaged in by
scientists who work in the field.” Mayo, 566 U.S. at 79. Apart from the
process limitations, which are not considered for patentability, the claims
include isolated MSCs and an artificial culture including NPBM, EGF,
bFGF, and NSF-1. See App. Br. xvi. MSCs are naturally occurring
materials. The Specification describes the artificial culture medium as
Neural Progenitor Maintenance Medium (NPMM) commercially sold by
Lonza. Spec. p. 15, ll. 28–33. There is no evidence of record that the claim
includes other, unconventional elements, either alone or in combination. See
In re Marco Guldenaar Holding B.V., 911 F.3d 1157, 1161 (Fed. Cir. 2018).
We therefore conclude that claim 16 recites no additional elements
that amount to significantly more than a patent on the ineligible concept
itself. See Ariosa, 788 F.3d at 1378. Because the claim is directed to a
judicial exception and the additional recited elements do not transform the
judicial exception into a patent-eligible invention, we sustain the Examiner’s
rejection upon this ground.
Appellant does not argue present separate arguments with respect to
the dependent claims. Accordingly, we sustain the Examiner’s rejection of
claims 16–25.

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CONCLUSION
The rejection of claims 16–25 as unpatentable under 35 U.S.C. § 101
is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1).

AFFIRMED

Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
16–25 101 Eligibility 16–25