SALK INSTITUTE FOR BIOLOGICAL STUDIES

Patent Trials and Appeals Board

May 19, 2020

2019005153 (P.T.A.B. May. 19, 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.
14/783,633 10/09/2015 Fred H. Gage 082700.0131 1031
21003 7590 05/19/2020
BAKER BOTTS L.L.P.
30 ROCKEFELLER PLAZA
44TH FLOOR
NEW YORK, NY 10112-4498
EXAMINER
CORDAS, EMILY ANN
ART UNIT PAPER NUMBER
1632
NOTIFICATION DATE DELIVERY MODE
05/19/2020 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):
DLNYDOCKET@BAKERBOTTS.COM
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte FRED H. GAGE and CEDRIC BARDY
_________________

Appeal 2019-005153
Application 14/783,633
Technology Center 1600
_________________

Before DEBORAH KATZ, JOHN G. NEW, and RYAN H. FLAX,
Administrative Patent Judges.

KATZ, Administrative Patent Judge.
DECISION ON APPEAL
Appellant1 seeks our review2, under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 1–193. (Appeal Br. 1.) We have
jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party-in-interest as Salk Institute for Biological Studies.
(Appeal Br. 2.)
2 We consider the Final Office Action issued July 27, 2018 (“Final Act.”),
the Appeal Brief filed February 28, 2019 (“Appeal Br.”), the Examiner’s
Answer issued on April 24, 2019 (“Ans.”), the Reply Brief filed June 24,
2019 (“Reply Br.”) and the oral argument held on May 6, 2020, in reaching
our decision.
3 Claims 20–24 have been withdrawn and claim 25 was canceled. (See
Appeal Br. 19–20.)
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Application 14/783,633

2
The Examiner rejected claims 1, 2, 5–16, 18, and 19 under 35 U.S.C.
§ 103 over Brewer4, Zeiger5, and Spiliotopoulos.6 (Ans. 4–8.)
Appellant’s specification is directed to culture conditions for growing
brain cells in vitro. (Spec. 1:20–25.)
Appellants’ claim 1 recites:
A cell medium comprising:
(a) Sodium chloride at a concentration of between about 70 and
about 150 mM;
(b) a neuroactive inorganic salt at a concentration of between
about 0.000001 and about l0mM;
(c) Glycine at a concentration of between about 0.0001 and
about 0.05 mM;
(d) L-alanine at a concentration of between about 0.0001 and
about 0.05 mM; and
(e) L-serine at a concentration of between about 0.001 and
about 0.03 mM;
wherein (a) through (e) are each present at a concentration that
maintains the survival and in vivo-like neurophysiological function of
a neural cell cultured in the medium in vitro, wherein the in vivo-like
neurophysiological function comprises synaptic function, action
potential generation, energetic maintenance, or combinations thereof.

(Appeal Br. 16.) We note that the claimed ranges are quite broad. For
example Appellant’s claimed cell medium includes a neuroactive inorganic
salt in a range of concentrations on the order of 107.

4 Brewer, U.S. Patent Application Publication 2008/0160006 A1, published
July 3, 2008.
5 Zieger et al., “Assessing Neuronal Bioenergetic Status,” Methods in Mol.
Bol., 758:215–35 (2011).
6 Spiliotopoulos et al., “An optimized experimental strategy for efficient
conversion of embryonic stem (ES)-derived mouse neural stem (NS) cells
into a nearly homogeneous mature neuronal population,” Neurobiology of
Disease, 34:320–21 (2009).
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The Examiner finds that Brewer teaches a medium including the
components recited in claim 1. (See Ans. 4, citing Brewer ¶ 28.) Although
Brewer does not teach these components in exactly the same ranges recited
in claim 1, as the Examiner finds, it teaches them in ranges significantly
overlapping the recited concentrations. (See id.) The table below provides a
comparison of the concentrations of components taught in Brewer with the
concentrations recited in Appellant’s claim 1.
Component Concentration7 in
Brewer Table 1
Concentration in Claim 1
Sodium chloride 30.000-150.000 mM between about 70 and
about 150 mM
Potassium chloride
(neuroactive inorganic
salt)
2.500-10.000 mM between about 0.000001
and about 10 mM
Glycine 0-2.400 mM between about 0.0001
and about 0.05 mM
L-alanine 0-0.120 mM between about 0.0001
and about 0.05 mM
L-serine 0-2.400 mM between about 0.001 and
about 0.03 mM

Brewer teaches a cell medium with the components of the claimed
composition in ranges that significantly overlap those recited.
The Examiner also finds that Brewer teaches the medium promotes
the survival and regeneration of adult human neurons. (See Ans. 5, citing
Brewer ¶ 32.) Brewer teaches further that cultures could be maintained in
the medium for many weeks, long enough to demonstrate the appearance of

7 Concentrations converted to mM from the µM values provided in Brewer
Table 1.
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synaptic elements, such as synaptic boutons, synaptic vesicles, and
postsynaptic densities. (See id.) In addition, Brewer teaches that the culture
medium maintains and improves viability of exposed, injured and isolated
neural cells. (See Brewer ¶¶ 2, 12; see Ans. 5.)
The Examiner finds that one of ordinary skill in the art would have
recognized that all of the components of a culture medium are result-
effective variables and that the concentration of the components of a cell
medium would have been a matter of routine optimization, as evidenced by
Brewer. (See Ans. 5–6.) Brewer teaches further that media can be
formulated to optimize particular outcomes, such as improved survival of
embryonic rat hippocampal neurons. (See Brewer ¶ 4; Ans. 5–6.)
Appellant argues that the Examiner failed to establish a prima facie
case for obviousness by allegedly conceding that two of the three functional
properties recited in claim 1 are not disclosed in Brewer. (See Appeal Br. 6,
9.) Appellant also argues that the Examiner improperly shifted the burden to
Appellant to establish the criticality of the ranges claimed and failed to show
why it would have taken only routine optimization to arrive at the claimed
ranges. (See id.) Appellant cites In re Stepan Co., 868 F.3d 1342, 1348
(Fed. Cir. 2017), in support of the these arguments. (See id.)
We are not persuaded that the Examiner erred by ignoring the
functional properties recited in claim 1. At the outset, we disagree that the
Examiner conceded that the functional properties recited in claim 1 are not
taught in Brewer. (Contra Appeal Br. 6.) Contrary to Appellant’s
argument, the Examiner cites to paragraphs 2, 12, and 32 of Brewer as
evidence that the medium taught promotes the survival, viability, and
regeneration of neurons in culture, which would maintain the
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neurophysiological functions of the cells, rendering the claimed functional
properties inherent. (See Ans. 11–12.)
We also disagree that Stepan is controlling under the facts of this case.
According to Appellant, Stepan prohibits burden shifting when a claim
comprises functional properties in addition to overlapping ranges. (See
Appeal Br. 7–8, 10–11; see Reply Br. 2–3.) In Stepan, the prior art
composition had a cloud point of at least 50o C and ideally 60o C, which was
different than the claimed cloud point of at least 70o C. See Stepan, 868
F.3d at 1345. The Stepan court explained that the cloud point limited and
defined the scope of what surfactant combinations satisfied the claimed
composition. (See id. at 1348.) Thus, under the facts of Stepan, the effect of
the prior art composition was different from the effect of the claimed
composition.
In contrast, the Examiner points to portions of Brewer providing a
reasonable basis that the medium it teaches achieves the same results as the
claimed medium. Even though Brewer does not expressly state the
functional results recited in Appellant’s claim 1 (survival, synaptic function,
action potential generation, energetic maintenance), it does teach that the
medium promotes the survival and regeneration, and maintains the viability
of adult human neurons and maintains neural cells for many weeks. (See
Brewer ¶¶ 2, 12, 32.) Brewer teaches that such conditions allow for the
appearance of the synaptic elements, including synaptic boutons, synaptic
vesicles, and postsynaptic densities. (See id.) We are persuaded that these
teachings provide a sufficient basis for the Examiner to conclude the
medium of Brewer would produce the functional results recited in claim 1
because it is reasonable to find that one of ordinary skill would have
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considered the functions of neural cells to follow from the long-term culture
of neural cells that supports expression of typical synaptic structures.
Because the Examiner had a reasonable basis to conclude that the
functional properties recited in claim 1 would result from the medium taught
in Brewer, we are persuaded that the burden properly shifted to Appellant to
show otherwise. Contrary to Appellant’s argument in footnote 1 of the
Appeal Brief, In re Best, 562 F.2d 1252, 1255 (CCPA 1977), is controlling
because of the Examiner’s reasonable basis for finding the functional
properties of the claimed cell medium would be met by the mediums taught
in Brewer. In Best, the court explained:
Where, as here, the claimed and prior art products are identical or
substantially identical, or are produced by identical or substantially
identical processes, the PTO can require an applicant to prove that the
prior art products do not necessarily or inherently possess the
characteristics of his claimed product. See In re Ludtke, supra [441
F.2d 660 (CCPA 1971)]. Whether the rejection is based on
‘inherency’ under 35 USC 102, on “prima facie obviousness” under
35 USC 103, jointly or alternatively, the burden of proof is the same,
and its fairness is evidenced by the PTO's inability to manufacture
products or to obtain and compare prior art products. See In re Brown,
59 CCPA 1036, 459 F.2d 531, 173 USPQ 685 (1972).

(Id.) We are therefore persuaded that, because the effects of the medium of
Brewer are the same as the effects recited in claim 1, it is Appellant’s burden
to provide evidence showing that culture in the medium of Brewer would
not result in the functional characteristics recited in Appellant’s claims.
Appellant fails to direct us to this evidence.
Appellant also argues that the Examiner improperly relied on Ziegler
to show that the teaching in Brewer of improving cell viability would be
understood to be improving metabolic activity or energetic maintenance as
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recited in claim 1. (See Appeal Br. 9–10; see Reply Br. 4–5.) Appellant
argues that Zieger uses a specific assay (the MTT assay), which measures
cell viability, with a galactose challenge assay to measure cell respiration.
(See Appeal Br. 9.) According to Appellant cell viability is not a direct
measurement of cell respiration or energy maintenance. (See id.)
We are not persuaded by Appellant’s argument because Appellant
does not direct us to, and we do not find, a definition of the claim term
“energetic maintenance” that would not be met by viable cells. In the Reply
Brief, Appellant argues that “energetic maintenance is an aspect of
neurophysiological function that is independent of cell viability” (Reply Br.
5), but the portions of the Specification Appellant cites do not explain why
cell viability does not indicate “energetic maintenance.” Specifically,
Appellant cites page 34, lines 20–21 of the Specification, which states:
“DMEM and Neurobasal medium were specifically optimized to promote
the survival of cells in vitro.” (See Reply Br. 5.) This portion fails to
indicate anything about energy or to explain what is meant by the claim term
“energetic maintenance.”
Appellant argues further, citing the Specification at page 39:18–25,
that “energetic maintenance is suboptimal in neural cells cultured in DMEM
and Neurobasal media, where cells exhibit chronically open synaptic and
extra-synaptic passive ionotropic channels leading to the consumption of a
considerable amount of cellular energy.” (Reply Br. 5.) The Specification
indicates that “[i]f a large number of synaptic and extra-synaptic passive
ionotropic channels are chronically open, as reported here for DMEM and
Neurobasal, the pumps will fight against the gradients in vain, which is
likely to waste a considerable amount of cellular energy.” (Spec. 39:22–25.)
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Although this portion of the Specification refers to conditions in which
energy is wasted, it is still unclear how the claim term “energetic
maintenance” is defined. (See Ans. 15.) It is not clear from Appellant’s
Specification whether a cell can have some degree of energy “waste” and
still be in a state of “energetic maintenance” or whether the term requires
100% conservation of energy and how that would be achieved.
Furthermore, if the ionic pumps in the neural cell membrane “fight against
the gradients in vain,” as disclosed by the Specification, a person of ordinary
skill in the art would understand this to mean that cellular homeostasis
cannot be maintained under such circumstances, with the consequent
negative attendant effects on cell viability. Accordingly, we are not
persuaded by Appellant’s argument that the Examiner improperly relied on
Ziegler.
Furthermore, and more importantly, the portions of the Specification
cited by Appellant fail to indicate that the medium used in Brewer or the
conditions of its use to maintain viable cells as stated by Brewer –
maintenance in culture for many weeks, appearance of synaptic boutons,
synaptic vesicles, and post-synaptic densities – would be possible without
“energetic maintenance.” Accordingly, we are not persuaded that the
portions of the Specification cited by the Examiner indicate that there is not
a reasonable basis to conclude that the medium of Brewer would produce the
same functional results recited in claim 1.
Appellant argues further that the Examiner failed to provide sufficient
reasoning why only routine optimization is required to select the claimed
cell medium components and why there would have been a reasonable
expectation of success in doing so. (See Appeal Br. 10–12.) According to
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Appellant, the Examiner fails to provide sufficient reasoning for
optimization to achieve the recited properties of the claimed medium. (See
Appeal Br. 11.) Appellant acknowledges that paragraph 4 of Brewer teaches
adjusting certain components, but argues that such optimization would not
have provided any motivation to adjust a medium to achieve the recited
properties of cell survival and “in vivo-like neurophysiological function”
recited in claim 1. (See Appeal Br. 11–12.) According to Appellant, the
Examiner fails to explain why a person of ordinary skill would have had a
reasonable expectation of success in doing so. (See id. at 12.)
We are not persuaded by these arguments because, as explained
above, the teachings in Brewer of survival, regeneration, viability, and
neurophysiological features in cells cultured for many weeks would have
provided a reasonable basis for one of ordinary skill in the art to have
expected the functions recited in claim 1 to also be achieved with the
medium taught. Because Brewer also teaches that optimizing the
components of culture media to achieve different effects was known, we are
persuaded that one of ordinary skill would have considered it obvious to
have adjusted the concentrations of the components of the medium taught in
Brewer to optimize the claimed effects. (See Brewer ¶ 4; see Ans. 7.)
“Normally it is to be expected that a change in temperature, or in
concentration, or in both, would be an unpatentable modification,” absent a
showing that the claimed ranges claimed produce a new and unexpected
result which is different in kind and not merely in degree from the results of
the prior art. In re Aller, 220 F.2d 454, 456 (C.C.P.A. 1955). Appellant
fails to persuade us that the claimed concentrations produce new or
unexpected results from the results reported in Brewer.
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We are not persuaded by the arguments Appellant presents that the
Examiner erred in rejecting claim 1. Appellant does not present separate
arguments for the patentability of dependent claims 2, 5–16, 18, and 19 over
the Examiner’s obviousness rejection. Accordingly, we are not persuaded
that the Examiner erred in rejecting these claims.
The Examiner also rejected claims 3, 4, and 17 under 35 U.S.C. § 103
over Brewer, Zeiger, Spiliotopoulos, Espinosa, Espinosa del los Monteros8,
and Kido9. (Ans. 8–10.) Claims 3 and 4 provide further limitations of the
ranges of L-aspartic acid, L-glutamic acid, respectively. (See Appeal Br.
16–17.) Claim 17 recites cell medium further comprising the light sensitive
agent, HEPES. (See Appeal Br. 19.)
Appellant argues that combining the “disclosure of Espinosa de los
Monterose and Kido with Brewer fails to remedy the deficiencies of Brewer,
as neither Espinosa de los Monterose nor Kido disclose nor suggest a cell
culture medium comprising the claimed components in amounts effective to
produce the recited functional properties.” (Appeal Br. 13.) Because we
determine there is no deficiency in the Examiner’s rejection of claim 1 over
Brewer, Zieger, and Spiliotopoulos, we are not persuaded by Appellant’s
argument that the Examiner erred in rejecting claims 3, 4, and 17.

8 Espinoza de los Monteros and de Vellis, U.S. Patent Application
Publication 2012/0052577, published March 1, 2012.
9 Kido, U.S. Patent Application Publication 2012/0177614 A1, published
July 12, 2012.
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Conclusion
Upon consideration of the record and for the reasons given, we affirm
the Examiner’s rejection.
In summary:
Claims
Rejected
35 U.S.C. § Basis Affirmed Reversed
1, 2, 5–16,
18, 19
103 Brewer,
Zeiger,
Spiliotopoulos
1, 2, 5–16,
18, 19

3, 4, 17 103 Brewer,
Zeiger,
Spiliotopoulos,
Espinosa del
los Monteros,
Kido
3, 4, 17
Overall
Outcome
1–19

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.

AFFIRMED