Karl Deisseroth et al.

Patent Trials and Appeals Board

Jun 23, 2020

13882566 - (D) (P.T.A.B. Jun. 23, 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.
13/882,566 12/02/2013 Karl Deisseroth STAN-902 4723
77974 7590 06/23/2020
STANFORD UNIVERSITY OFFICE OF TECHNOLOGY LICENSING
BOZICEVIC, FIELD & FRANCIS LLP
201 REDWOOD SHORES PARKWAY
SUITE 200
REDWOOD CITY, CA 94065
EXAMINER
WILSON, MICHAEL C
ART UNIT PAPER NUMBER
1632
NOTIFICATION DATE DELIVERY MODE
06/23/2020 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@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte KARL DEISSEROTH, VIKAAS SOHAL, and LISA GUNAYDIN
__________

Appeal 2019-006462
Application1 13/882,566
Technology Center 1600
__________

Before RICHARD M. LEBOVITZ, FRANCISCO C. PRATS, 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 identifying a candidate compound for treating psychosis, which have been
rejected for non-enablement. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
Schizophrenia involves psychotic behavior and impaired cognition.
(Spec. 1.) “It is widely believed that dysfunction of the prefrontal cortex
(PFC) underlies many of the most debilitating aspects of schizophrenia.”

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 The Board of
Trustees of the Leland Stanford Junior University. (Appeal Br. 3.)
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(Id.) “Identifying and understanding the neural pathways linked to
psychosis-related patterns of activity within the PFC region may aid in the
discovery of pharmacological therapies to treat patients with schizophrenia.”
(Id.) “[T]here remains a need for a useful animal model system for
schizophrenia that would allow for identification of these intricate neural
pathogenic pathways.” (Id.) Such a model “would allow for screening and
identification of pharmacological therapies that improve the pathogenic
patterns of neural activity that contribute to the symptoms of schizophrenia.”
(Id.) Appellant’s invention is directed to an animal model for psychosis and
its use in screening a compound that may be used for treating psychosis.
(Id.)

Claims 13–16, 51, 52, 54–61, and 63–69 are on appeal. Claim 13 is
representative and reads as follows:
13. A method of identifying a candidate compound for treating
psychosis, the method comprising:
a) exposing layer V pyramidal neurons in the prefrontal
cortex of a rat or mouse to light, wherein a subset of layer V
pyramidal neurons express on their cell membrane a light-
responsive depolarizing opsin, wherein the light-responsive
depolarizing opsin comprises an amino acid sequence having at
least 90% amino acid sequence identity with the amino acid
sequence set forth in one of SEQ ID NOs: 1-7, and wherein
exposure of the subset of layer V pyramidal neurons to light
induces depolarization of the membrane and induces a
psychotic state in the rat or mouse;
b) administering the compound to the rat or mouse
having the induced psychotic state; and
c) measuring a psychotic state of the rat or mouse before
and after administering the compound, wherein a decrease in
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the psychotic state indicates that the compound is a candidate
for treating psychosis.
(Appeal Br. Claims Appendix i.)

The following ground of rejection by the Examiner is before us on
review:
Claims 13–16, 51, 52, 54–61, and 63–69 under 35 U.S.C. § 112 first
paragraph as not being enabled.
DISCUSSION
The Examiner finds that Appellant’s Specification enables
“identifying a compound that decreases depolarization of the membrane of a
layer V pyramidal neuron in the prefrontal cortex” where the method
employs “a mouse that expresses an exogenous nucleic acid sequence
encoding a channel rhodopsin 2 (ChR2) on the membrane of a layer V
pyramidal neuron in the prefrontal cortex” where “the ChR2 has an amino
acid sequence that is at least 90% identical to the amino acid sequence of
SEQ ID NO: 1[–]7.” (Ans. 3.) The Examiner asserts that the Specification
does not provide enablement for
1) exposing the mouse/rat to light such that psychosis is
induced,
2) using the mouse/rat to screen for compounds that treat any
symptom of psychosis other than the depolarization of the
pyramidal neuron membrane,
3) making/using any layer V pyramidal neurons in the
prefrontal cortex of a mouse or rat that express a light
responsive opsin having any structure as broadly encompassed
by claim 13 other than genetically modified mice made by
transgenesis or gene therapy,
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4) the specific combination of “light-responsive depolarizing
opsin” and “exposure to light” encompassed by claim 13 that
“induces psychosis” or
5) using the method to study the role of ChR2 or any other
light-sensitive opsin in psychosis or depolarization.
(Ans. 4 (paragraphing added).)
Regarding categories 1, 2, 4, and 5, as to the term “psychosis,” the
Examiner finds it:
is as narrow as decreased socialization in an open field test (a
behavioral measurement as in claim 15) or depolarizing neurons
of the prefrontal cortex (a cellular measurement as in claim 15).
The concept encompasses causing hallucinations, breaks with
reality, a change personality, delusions, violence, or paranoia -
or all of the aforementioned symptoms in the rat/mouse. The
concept of “inducing psychosis” is also a broad umbrella for
inducing schizophrenia, bipolar disorder, or drug use.
(Ans. 5 (emphasis omitted).)
In arriving at the conclusion of non-enablement as to the claimed
animal model for psychosis, the Examiner reviewed the state of the art of
rat/mouse models in optogenetics and concluded that of the five articles that
were considered, they
did not teach the rats/mice had psychosis, symptoms associated
with psychosis, schizophrenia, bipolar disorder, drug use,
decreased polarization of neurons in the prefrontal cortex,
decreased exploration in an open field test, or any other cellular
or behavioral measurements associated with psychosis.
(Ans. 5–7.)
The Examiner further finds that “[i]t was unpredictable how to obtain
a rat/mouse that models the genus of psychosis, or the species of
schizophrenia or bipolar disorder within the genus of psychosis.” (Id. at 7.)
The Examiner arrives at this conclusion primarily because
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a) one prior art article indicated that “the precise etiologies of the
human schizophrenia” are not yet understood and “[j]ust as patients do no
[sic] not manifest every possible symptom of the disease, an animal model
will not necessarily exhibit all symptoms of the disease,” and
b) a second prior art article, which studied depolarization of the
membrane of layer V pyramidal neurons in prefrontal cortex of guinea pigs,”
although finding “the prefrontal cortex was associated with psychosis . . . did
not teach depolarization of neurons in the prefrontal cortex was equivalent to
a psychotic state.” (Id. at 8 (emphasis omitted).)
The Examiner further finds that it was “unpredictable how to use a
rat/mouse that has any behavioral or cellular abnormality, specifically
decreased exploration in an open field test and depolarized neurons in the
prefrontal cortex, as a model of psychosis, or of schizophrenia or bipolar
disorder within the genus of psychosis.” (Ans. 9.) The Examiner arrives at
this conclusion because the Examiner concludes that “decreased exploration
in an open field test and depolarized neurons in the prefrontal cortex” does
not meet the standard in the prior art of “obtaining a reasonable number of
features of psychosis.” (Id.) The Examiner points to prior art that “shows
that a behavioral response such as decreased exploration in an open field test
is generic and may be caused by ‘altered expectations of reward or
punishment.’” (Id. at 10.) Thus, the Examiner finds that “[d]ecreased social
exploration is generic to numerous disorders that affect motor function,
cognitive function, neuropsycho pathways” and “does not represent the
genus of ‘psychosis’ required in claim 13.” (Id. at 12.)
Against that backdrop, the Examiner then addresses the teachings in
the Specification. (Ans. 11.) The Examiner notes that the Specification
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exemplifies a single mouse model: a transgenic mouse that expresses ChR2.
(Id.) The Examiner further finds that “[t]he specification asserts the mice
have psychotic behavior (pg 31, line 29) and can be used to model
schizophrenia (pg 33, line 12).” (Id.) The mice in Example 1 were found to
have “decreased exploration in open field testing (pg 33, lines 1-4)” and
depolarization assays were performed. (Id.)
The Examiner finds that Example 2 of the Specification describes
measuring the effect of a compound on depolarization or open field tests on
mice after exposing their prefrontal neurons to light. (Ans. 11.) As to
Example 3, the Examiner finds similar measurements to Example 2 were
carried out, but were made after administering PCP to the mouse and
exposing the prefrontal neurons to light and then administering compounds
to determine the effect of the compound. (Id.)
Further, regarding Example 3, the Examiner finds “applicants fail to
correlate the mouse to psychosis, specifically psychosis found after drug use
as encompassed by claim 13.” (Ans. 13.)
The Examiner finds that while “[p]aragraph[s] 84, 109, [and] 111
assert disrupting social exploration in an open field test correlates to
psychosis or schizophrenia,” those paragraphs:
(a) “fail to provide adequate guidance that the decreased exploration
in an open field test observed in Examples 1 or 3 is a result of psychosis and
not a result of expectations of reward or punishment” (Ans. 13),
(b) “fail to provide adequate guidance that the decreased exploration
in an open field test observed in Examples 1 or 3 correlates to a reasonable
number of symptoms of psychosis as required by claim 13” (id.),
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(c) “fail to provide adequate guidance that administering PCP and
observing decreased exploration in an open field test observed in Example 3
correlates to a reasonable number of symptoms of psychosis as required by
claim 13” (id.), and
(d) “fail to correlate decreased exploration in an open field test to
hallucinating, breaking with reality, changing personality, delusions,
violence, paranoia” (id. at 13–14).
The Examiner concludes that Appellant’s Specification “fail[s] to
provide adequate guidance that the decreased exploration in an open field
test observed in Examples 1 or 3 is a result of psychosis and not a result of
expectations of reward or punishment.” (Ans. 12.) The Examiner further
concludes that Appellant’s Specification “fail[s] to provide adequate
guidance that the decreased exploration in an open field test and the
depolarization of prefrontal neurons observed in Examples 1 or 3 correlates
to a reasonable number of symptoms of [any] psychosis as required by claim
13.” (Id.) Consequently, the Examiner concludes that “[t]he claims should
be limited to assaying the depolarization of prefrontal neurons.” (Id. at 14.)
The Examiner also finds that the lack of correlation, combined “with the
unpredictability in art at the time of filing, the field of optogenetics, and the
limited teachings in the specification,” that the Specification “does not
enable measuring any ‘psychotic state’ in the rat/mouse or identifying
compounds that treat any symptom of psychosis other than the
depolarization of the pyramidal neuron membrane as broadly encompassed
by the claims.” (Id. at 14–15.)
Regarding lack of enablement category 3 (i.e., expression of an opsin
having at least 90% identity to the claimed sequences on the membrane of
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the neurons in the prefrontal cortex), the Examiner finds the following.
First, the Examiner finds that the claim requires “that at least some of the
neurons [in layer V pyramidal neurons in the prefrontal cortex] express a
light responsive depolarizing opsin that is at least 90% identical to SEQ ID
NO: 1–7 on their cell membrane.” (Ans. 16.) The Examiner also finds that
the claims include a rat/mouse that endogenously expresses the opsin. (Id.)
The Examiner finds that the prior art “was limited to a rat/mouse with
neurons comprising an exogenous sequence” encoding ChR2, and Appellant
“do[es] not teach any endogenous rat/mouse proteins” that meet the claimed
limitations. (Ans. 18.) According to the Examiner, the prior art teaches that
“the promoter required to obtain the desired expression of ChR2 in the
desired target neuron was unpredictable.” (Id. at 10.) And the Examiner
finds Appellant “do[es] not teach how to express an opsin having at least
90% identity to algae ChR2 of SEQ ID NO: 1-7 on the membrane of the
neurons in the prefrontal cortex of rats/mice without genetic modification.”
(Id. at 18.)
Regarding lack of enablement category 4 (the specific combination of
“light-responsive depolarizing opsin” and “exposure to light” encompassed
by claim 13 that “induces psychosis”), the Examiner finds that the
Specification lacks an adequate description of the “claimed model psychosis
upon exposure to any ‘light’.” (Ans. 19–20.) The Examiner further finds
that Appellant has
left those of skill to determine the specific combination of opsin
expressed by the Thy1 promoter and light conditions required
to induce psychosis or the amount of opsin, promoter
specificity and light conditions required to induce psychosis as
claimed . . . [and] left those of skill to determine other
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promoters (if any) that provide adequate expression levels and
tissue specificity required to induce psychosis.
(Id. at 20.)
We agree with the Examiner that the full scope of Appellant’s claims
are not enabled. However, we agree only as to a narrow point raised by the
Examiner regarding the scope of Appellant’s claims, namely, that Appellant
has not enabled the method without the use of the transgenic mouse
described in Example 1 of the Specification.
The Specification
“To quantify cognitive impairment and negative symptoms
characteristic of schizophrenia,” Example 1 of the Specification describes
optical stimulation of a mouse that has been transgenically modified to
express channel rhodospins-2 (ChR2) in layer V pyramidal neurons within
the prefrontal cortex. (Spec. 32 (Example 1 (“the well-established
Thy1::ChR18 transgenic mice”).) The optical stimulation “was achieved by
unilateral optical fiber placement above the infralimbic prefrontal cortex.”
(Id.) And “[t]o quantify cognitive impairment and negative symptoms
characteristic of schizophrenia, social exploration was measured in these
mice and for assessment of positive-like symptoms, disorganized or
catatonic behavior including stereotyped movements and rigidity were
measured.” (Id.)
The Specification reports that “relatively modest optical stimulation
(470 nm, 0.4 mW, 5 msec @ 10 Hz) was sufficient to markedly disrupt
social exploration without affecting normal locomotion.” (Spec. 32.) In
addition, it is reported that “[i]ncreasing the frequency of stimulation (470
nm, 0.4 mW, 2.5 msec @ 40 Hz) almost completely abolished social
behavior and elicited a variety of catatonic like behaviors,” namely
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“increased time spent in a catatonic-like rigid posture” as well as “increased
time spent engaging in repetitive side-to-side head movements.” (Id. at 32–
33.) The Specification indicates that “[t]hese results further validate the idea
that aberrant activity in layer V pyramidal neurons in the PFC can contribute
to schizophrenia-like behaviors” and “demonstrate that optical stimulation of
ChR2-expressing layer V pyramidal neurons in the Thyl::ChR2-EYFP
mouse line allows this mouse to be used as an animal model for
schizophrenia.” (Id. at 33.)
Example 2 of the Specification describes analysis of Thy1::ChR2
mice prefrontal brain slices for “network activity evoked by light in the
presence or absence of quinpirole [a dopamine receptor 2 agonist] followed
by treatment with known D2 [dopamine receptor 2] antagonists.” (Spec.
33.) It is noted that “D2 receptors play a key role in schizophrenia, and the
D2 agonist quinpirole, elicits schizophrenia-like behaviors in animals.” (Id.)
The experiments were undertaken “[t]o explore processes by which
pharmacologic manipulations relevant to schizophrenia could affect these
layer V pyramidal neurons in the PFC.” (Id.) The neurons were monitored
by electrophysiological recordings for cellular responses to trains of light
flashes. (Id.) It was found that “the effects of D2 agonists and antagonists
appeared to reflect effects on repetitive action potentials.” (Id. at 34–35.) In
particular, “D2 activation with quinpirole (purple trace) enhanced the spike
afterhyperpolarization” whereas “D2 blockade with sulpiride [D2
antagonist] widened action potentials.” (Id. at 35.) It was confirmed that the
activity dependent depolarization was mediated by D2 receptors because it
could be elicited with various doses of the D2 agonist quinpirole and
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blocked by using the antipsychotic haloperidol, as well as the D2 antagonist
sulpiride. (Id. at 36.)
In addition, in Example 3, it was determined that L-type Ca2+ ion
channels were involved in the activity-dependent depolarization. (Spec. 36–
38.) In that Example, PCP activity-dependent depolarization effects were
not blocked by the D2 antagonist sulpiride, but were blocked by the L-type
Ca2+ channel antagonist nifedipine. (Id. at 38.) It was also noted that PCP
produced a similar range of effects via the activity-dependent depolarization
as did quinpirole. (Id.) It was also found in social behavior testing of the
mouse that nifedipine alone impaired sociability in a dose-dependent fashion
and nifedipine ameliorated social deficits induced by PCP with a similar
dose-dependence. (Id. at 39.) In addition, it was found that nifedipine
“reduced the incidence of catatonic-like behaviors, e.g. circling and rigidity,
elicited by PCP alone.” (Id.) The Specification concluded “that the D2
agonist quinpirole and the psychotomimetic phencyclidine, which produce
schizophrenia-like behaviors in humans and animals but act via different
receptors, converge upon a novel activity-dependent depolarization
phenotype in a subset of layer V pyramidal neurons in the PFC” which
involve the Ca2+ L-type channel. (Spec. 31.) Thus, the Specification
describes the discovery that the schizophrenic-like behaviors induced by
dopamine agonists and PCP converge on this calcium channel.
Appellant’s Response Re: Mouse Model and Psychosis
In the Reply Brief, Appellant explains how the Specification
adequately enables the claimed method. Of particular note is the
explanation that PCP is a known psychotomimetic that impairs social
exploration and the Specification describes experiments that demonstrate the
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correlation of cellular responses of pyramidal V neurons to depolarizing
current in the presence and absence of PCP, which acts on L-type Ca 2+,
“with behavioral measurements indicative of psychosis, and found that mice
expressing a depolarizing light-responsive opsin, in response to light,
showed ‘significantly decreased social exploration of a novel juvenile in 6 of
6 Thy1::ChR2-EYFP animals tested’.” (Reply Br. 7–8.)
Appellant further explains that it was known in the prior art that D2
receptors play a key role in schizophrenia and the D2 agonist quinpirole
elicits schizophrenia-like behaviors in animals. (Reply Br. 6–8.) Appellant
further explains that the Specification describes measuring a psychotic state
in brain slices of Thy1::ChR2 mouse, which mouse expresses ChR2 in layer
V pyramidal neurons in the PFC, through electrical recordings of network
activity evoked by light in the presence of and absence of quinpirole
followed by treatment with known D2 antagonists. (Id.)
Appellant provides further explanation, that one of ordinary skill in
the art would have understood the foregoing to provide adequate guidance
that decreased exploration in the open field test was a result of psychosis,
consistent with the three criteria set forth in the prior art for validating
mouse models of psychiatric disease, construct validity, face validity, and
predictive validity. (Reply Br. 14–19.) In particular, Appellant explains that
the examples of the Specification indicate “that there is an activity-
dependent depolarization phenotype in layer V pyramidal neurons in the
prefrontal cortex associated with phenotypes of psychosis.” (Id. at 14.)
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Additionally, explains Appellant, Chadman2 “discloses that measuring social
behavior using an open field assay and sensorimotor gating are valuable in
schizophrenia-related behavioral tests in mouse models.” (Id. at 15–16.)
And, the Specification describes that with optical stimulation of the
transgenic mouse Thy1::Chr18, optical stimulation at 10 Hz disrupted social
exploration without affecting normal locomotion and at 40 Hz almost
completely abolished social behavior and elicited catatonic like behaviors.
(Id. at 16–17.) Furthermore, explains Appellant, the Specification examples
provide predictive validity of the model where the catatonic-like behaviors
elicited by the known psychotomimetic, PCP, were reduced with the L-type
Ca 2+antagonist, nifedipine. (Id. at 17–18.)
Appellant also explains, that the Specification enables that the
exploration in open field tests in the described mouse model, depolarization
of neurons of the PFC, as well as catatonic-like behaviors are correlated with
psychosis. (Reply Br. 18–19.) Appellant notes that prior art states: “that
‘validity of a mouse model for schizophrenia is greatest when phenotypes
relevant to two or more of the symptoms appear.’” (Id. at 19.)
Appellant addresses two of the primary prior art references cited by
the Examiner in support of non-enablement and explains how they do not
lead to finding non-enablement of the claimed animal model of psychosis in
light of the foregoing. (Reply Br. 21–22.) We agree with Appellant’s
assessment. That one of these references indicated in 2006 that an “ideal

2 Kathryn K. Chadman et al., Criteria for Validating Mouse Models of
Psychiatric Diseases, 150B(1) Am. J. Med. Genet. B Neuropsychiatr. Genet.
1–11 (2009). We reviewed the Author manuscript provided by Appellant
with the Reply Brief.
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animal model” for schizophrenia does not exist because the “precise
etiologies” of the disorder is not understood (Ans. 7–8), does not establish
that the model set forth in the Specification, which describes how the model
“recapitulates some features” of psychosis (id. at 8), is not an appropriate
model. Furthermore, that another reference “did not teach depolarization of
neurons in the prefrontal cortex was equivalent to a psychotic state” (id. at 8)
(emphasis omitted) is simply beside the point. The studies presented in
Appellant’s Specification, discussed above, demonstrate the relationship of
depolarization of V pyramidal neurons to psychosis. Also, that a third
reference did not have sufficient data to establish that the “[c]hanges in the
animals’ preference for the open field or the sheltered periphery may be
caused by artificially altered expectations of reward or punishment” (id. at
10) (emphasis omitted), is also beside the point. The studies presented in
Appellant’s Specification, discussed above, demonstrate that exploration in
open field tests in the described mouse model, depolarization of neurons of
the PFC, as well as catatonic-like behaviors are correlated with psychosis.
We find that the Appellant has adequately explained why the
Examiner’s cited references do not cast doubt on the enablement of the
Thy1::CHR18 mouse model for use in inducing psychosis by light as
exemplified in the Specification. Thus, we disagree with the Examiner’s
categories 1, 2, 4, and 5 of non-enablement noted above.
Generically Claimed Mouse Model
We turn to Appellant’s response to the category 3 non-enablement
position by the Examiner, i.e., enablement of other mouse or rat models that
have a subset of layer V pyramidal neurons in the PFC that express on their
cell membrane a light-responsive depolarizing opsin that are not the
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Thy1::ChR2 transgenic mouse described in Example 1 of the Specification.
(Ans. 18, 19–20.)
Appellant argues that “[t]he manner in which the light-responsive
opsin is introduced into the mouse or rat is not relevant to the presently
claimed screening method.” (Appeal Br. 9.) According to Appellant “an
expression construct can be administered to the prefrontal cortex of the rat or
mouse, where the expression construct comprises a nucleotide sequence
encoding a depolarizing opsin, and where the depolarizing opsin is then
expressed on the cell membrane of at least a subset of pyramidal V neurons
of the prefrontal cortex.” (Id. at 8–9.)
Appellant explains in the Reply Brief that the “specification describes
how an expression vector encoding a light-activated opsin can be introduced
into a non-human mammal” such as by being “‘delivered directly to the
pyramidal neurons of the prefrontal cortex of an animal using a needle,
catheter, or related device, using neurosurgical techniques known in the art,
such as by stereotactic injection.’ (PCT Publication, page 16, lines 16–24).”
(Reply Br. 9–10) (emphasis omitted).) The Appellant further explains that
“genetically modifying cells in any of a variety of non-human mammals
using recombinant viral vectors was a routine matter” as of the time the
application was filed. (Id. at 10 (citing prior art).) In addition, the Appellant
explains that “genetically modifying cells in various non-human mammals to
express light-activated opsins had been achieved,” such as by using adeno-
associated virus (AAV) vectors and lentiviral vectors. (Id. at 10–11 (citing
prior art).)
We find that the Specification adequately enables the use of a
Thy1::ChR2 transgenic mouse, such that the neurons functionally express a
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light-responsive protein that when exposed to light induce depolarization of
the neuronal membrane. However, we do not agree that the art and the
guidance in the Specification provide enablement for any other manner of
modifying layer V pyramidal neurons of a rat or mouse in the prefrontal
cortex such that the neurons functionally express a light-responsive protein
that when exposed to light would induce membrane depolarization. That the
Specification describes methods for delivery of a viral vector construct
directly to the neurons in the prefrontal cortex, or that AAV vectors have
been used in optogenetic studies does not establish enablement because
existence of methods to deliver a gene to cells does not provide evidence
that the specific V pyramidal neurons in the brain would express the opsin in
an effective amount to induce psychosis upon depolarization.
We note in this regard that Cardin,3 the article cited by Appellant in
support of broad enablement, states: “[s]uccessful use of optogenetic
techniques relies on sufficient expression levels of the light-activated
channels.” (Cardin 3.) Cardin notes that “[t]he most commonly used
strategy to date for the expression of ChR2 in brain tissue is through viral
transduction.” (Id. at 2.) Cardin notes that AAV has provided “extensive
spatial spread [to brain regions] and high expression levels” and lentiviral
vectors have been used in the cortex “but do not appear to spread as
effectively as AAV vectors.” (Id.) However, Cardin notes “targeting
expression to cell types” is more problematic. (Id. at 3.) In particular,

3 Jessica A. Cardin et al., Targeted optogenetic stimulation and recording of
neurons in vivo using cell-type-specific expression of Channelrhodopsin-2,
5(2) Nature Protocols 247–54 (2010). We rely on the Author manuscript
submitted by Appellant with the Reply Brief paginated 1–16.
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Cardin explains that “[i]n most cases, cellular promoters are not yet
identified or are incompatible for use in viruses because of size limitations.”
(Id.) And Cardin further notes “[c]ellular promoters may also fail to render
enough specificity or sufficient expression levels for meaningful optogenetic
studies.” (Id.) The claim, however, is not restricted as to what promoter is
used, while the experiments described in the Specification utilized only a
single promoter.
Cardin describes a method to “circumvent issues of specificity and
expression levels.” (Id.) However, Appellant does not cite that as
knowledge in the prior art (Reply Br. 10–11).
In light of the foregoing only, we agree with the Examiner that
Appellant’s claims on appeal are not enabled for their full scope. In re
Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993) (“[T]o be enabling, the
specification of a patent must teach those skilled in the art how to make and
use the full scope of the claimed invention without ‘undue
experimentation.’”)
Thus, we affirm the Examiner’s rejection of claims 13–16, 51, 52, 54–
61, and 63–69 under 35 U.S.C. § 112 first paragraph as not being enabled.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
13–16, 51,
52, 54–61,
63–69
112 Enablement 13–16, 51,
52, 54–61,
63–69

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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). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED