Ex Parte McMichael et al

Board of Patent Appeals and Interferences

Jun 25, 2009

10624328 (B.P.A.I. Jun. 25, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JOHN MCMICHAEL and KENNETH A. UNICE
__________

Appeal 2009-0027091
Application 10/624,328
Technology Center 1600
__________

Decided:2 June 25, 2009
__________

Before DONALD E. ADAMS, LORA M. GREEN, and
FRANCISCO C. PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

1 The real party in interest is Milkhaus Laboratory, Inc.
2 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).

Appeal 2009-002709
Application 10/624,328

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of alleviating symptoms of a psychological condition. The Examiner has
entered two rejections for obviousness. We have jurisdiction under
35 U.S.C. § 6(b).
We affirm one obviousness rejection, but reverse the other.
STATEMENT OF THE CASE
Claims 1, 2, 4, 5, 8-18, and 20-24 are pending and on appeal (App. Br.
5). Claims 1 and 15, the independent claims, are representative and read as
follows:
1. A method of alleviating symptoms of a
psychological condition selected from the group consisting of
depression, anxiety disorders, panic attacks, premenstrual
dysphoric disorder (PMDD), and premenstrual syndrome
(PMS) comprising administering to a subject in need thereof
nerve growth factor in an amount effective to treat one or more
symptoms of said psychological condition.

15. A method of alleviating symptoms of a
psychological condition selected from the group consisting of
sleep disorders, tension headaches, and constipation comprising
administering to a patient in need thereof nerve growth factor in
an amount effective to treat one or more said symptoms.

The Examiner cites the following documents as evidence of
unpatentability:
Siuciak US 5,599,560 Feb. 4, 1997
Frey, II et al. US 2003/0072793 A1 Apr. 17, 2003

THE MERCK MANUAL OF DIAGNOSIS AND THERAPY, 1525-1539, 1932-
1933 (Mark H. Beers, M.D., & Robert Berkow, M.D., eds., 17th ed. 1999).

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The following rejections are before us for review:
Claims 1, 2, 4, 5, 8-18, and 20-24 stand rejected under 35 U.S.C.
§ 103(a) as being obvious in view of Frey and The Merck Manual (Ans. 4-
7).
Claims 1, 2, 4, 5, 11-15, and 20-24 stand rejected under 35 U.S.C.
§ 103(a) as being obvious in view of Siuciak and The Merck Manual (Ans.
7-10).
OBVIOUSNESS -- FREY AND THE MERCK MANUAL
ISSUE
The Examiner cites Frey as teaching “the administration of nerve
growth factor [‘NGF’] for the treatment of disorders or diseases of the
central nervous system (Paragraphs 50, 51, and 169)” (Ans. 4). The
Examiner notes that Frey lists nerve growth factor among its preferred
neurologic agents, and teaches “the treatment of central nervous system
disorders, particularly affective disorders and anxiety disorders (Paragraph
169)” (id. at 4-5).
The Examiner cites The Merck Manual as teaching that depression
“falls under a broad class of mood or affective disorders (Page 1525),” that
“individuals with mixed anxiety-depression possess conditions of symptoms
that have both anxiety and depression (page 1529),” and that “a patient with
the condition of premenstrual syndrome [‘PMS’] is characterized, inter alia,
by anxiety and depression (page 1932)” (id. at 5).
The Examiner urges that although Frey is “silent to the use of NGF to
treat the psychological conditions of PMS, anxiety disorders, and panic
attacks, Frey . . . do[es] in fact teach and provide the artisan with the
necessary motivation to use nerve growth factor in the treatment of affective
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and anxiety disorders (Paragraph 169)” (id.). Based on the references’
teachings, the Examiner finds that an ordinary artisan would have
recognized that treating depression and anxiety “would also be treating and
alleviating the symptoms of related conditions and ailments that have
depression and anxiety as symptoms, namely anxiety disorders, PMS, and
depression associated with menustration [sic] and anxiety associated with
panic attacks, most especially in view of the teaching of the Merck Manual”
(id.). Thus, the Examiner concludes, “Frey . . . in view of the Merck
Manual make obvious the claimed subject matter” (id. at 6).
Appellants contend that Frey “discloses a laundry list of more than
forty (40) potential agents for delivery to the CNS of a subject by a
particular mode of drug administration, but fails to disclose or suggest that
any one of the forty-plus agents disclosed therein is for the treatment of any
one disorder” (App. Br. 10). Rather, Appellants urge, “most of the forty-
plus agents listed would not be expected to be therapeutic for most of the
seventeen or more conditions listed in paragraph [0169]” (id.).
For example, Appellants argue, an ordinary artisan “would not expect
that an ‘anti-cancer agent’ (Frey II, paragraph [0045]) would be therapeutic
for an anxiety disorder (Frey II, paragraph [0169]). Similarly, one would not
expect that cisplatin, an anti-viral agent, (Frey II, paragraph [0043]) would
be therapeutic for attention deficit disorder (Frey II, paragraph [0169])” (id.).
Thus, Appellants contend, because Frey does not “specifically
correlate any particular agent as a therapeutic for a specific disorder, one of
skill in the art would not know which of the many agents disclosed in Frey .
. . could be used for the treatment of, for example, affective disorders” (id. at
11). Therefore, Appellants argue, “one of skill in the art would not be
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motivated upon review of Frey II to use NGF for the treatment of any
disorder, much less the psychological disorders or symptoms recited in
independent claims 1 and 15, respectively” (id.).
Appellants further contend that The Merck Manual does not remedy
Frey’s shortcomings because it does not mention the use of NGF in treating
any neurological disorder (id.). Thus, Appellants argue, “the combined
disclosure of Frey II and Beers fails to disclose or suggest the claimed
invention. Accordingly, there can be no prima facie case of obviousness”
(id.).
In view of the positions advanced by Appellants and the Examiner,
the issue with respect to this rejection is whether Appellants have shown that
the Examiner failed to make a prima facie case that a person of ordinary skill
in the art would have been prompted by the cited references to administer
nerve growth factor to a patient in order to treat the disorders recited in
claims 1 and 15.
FINDINGS OF FACT (“FF”)
1. Claim 1 recites a method in which nerve growth factor is administered
to alleviate symptoms of a psychological condition. The nerve growth factor
is administered to alleviate symptoms of depression, anxiety disorders, panic
attacks, premenstrual dysphoric disorder (PMDD), or premenstrual
syndrome (PMS).
2. Claim 15 also recites a method in which nerve growth factor is
administered to alleviate symptoms of a psychological condition. The nerve
growth factor is administered to alleviate sleep disorders, tension headaches,
or constipation.
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3. Frey discloses “a method for transporting or delivering an agent to a
central nervous system of a subject. The method employs administration of
the agent to a tissue outside the subject’s nasal cavity and innervated by the
trigeminal nerve” (Frey [0006]).
For example, “[i]n one embodiment, the method administers the agent
through the mucosa or epithelium of the tongue, mouth, skin, or conjunctiva.
In another embodiment, the method includes administering a composition of
the agent under the tongue, to the skin, or to the conjunctiva of the subject”
(id.).
4. Frey discloses that its methods are advantageous in that
“[a]dministration of agents by the method of the invention can more
effectively deliver the agent to the CNS, brain and/or spinal cord, can
decrease the amount of agent administered outside the CNS, brain and/or
spinal cord, and, preferably, can decrease the undesirable systemic effects of
the agent” (Frey [0039]).
5. Frey discloses:
The present method can administer a variety of different
agents to the central nervous system. In general, the method of
the invention can administer an agent that can be employed for
diagnosis, prevention, or treatment of a disease or disorder
affecting the CNS, brain, and/or spinal cord; that can nourish or
maintain a cell or tissue in the CNS, brain, and/or spinal cord;
that can prevent or inhibit degradation of a cell or tissue in the
CNS, brain, and/or spinal cord; that can alter gene expression in
a cell or tissue in the CNS, brain, and/or spinal cord; that can
regulate a functional activity of a cell or tissue in the CNS,
brain, and/or spinal cord; that can regulate growth of a cell or
tissue in the CNS, brain, and/or spinal cord; or the like.

(Frey [0037].)
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6. Frey discloses that the “agent can be an organic pharmaceutical, an
inorganic molecule, a peptide, a peptoid, a protein, a lipid, or carbohydrate, a
nucleic acid, or the like” (Frey [0041]). According to Frey:
An organic pharmaceutical can be a stimulant, a sedative,
an hypnotic, an analgesic, an anticonvulsant, an
antihypertensive, an antiemetic, an anxiolytic, an
antidepressant, a tranquilizer, a cognition enhancer, a narcotic
antagonist or agonist, a vitamin or nutrient, an enzyme
inhibitor, an antioxidant, a free radical scavenger, a metal
chelating agent, an agent which can alter the activity of an ion
channel, an antineoplastic, an anti-inflammatory, or a
combination thereof. Advantageously, an organic
pharmaceutical modulates a functional activity of an enzyme,
receptor, cell, or tissue in the CNS, brain, and/or spinal cord. A
preferred agent that can regulate a functional activity includes,
for example, a neurotransmitter, a neuromodulator, a nootropic,
a receptor agonist or antagonist, or a combination thereof.

(Id. at [0042].)
7. Frey also discloses:
The organic pharmaceutical can be an antiviral, an
antibacterial, an antiparasitic, an antifungal, or a combination
thereof. Preferred agents for diagnosis, prevention or treatment
of an infection of the CNS, brain, and/or spinal cord include an
antibacterial, an antiparasitic, and/or an antifungal agent.
Preferred antiviral agents include agents that stop or inhibit the
replication or spread of viruses such as adenoviruses,
arboviruses, enteroviruses, rabies viruses, and HIV.

(Frey [0043].)
8. Frey discloses that an “inorganic agent can be an antioxidant or an
anti-cancer agent (e.g. cisplatin)” [0045].
9. Frey discloses:
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Neurologic agents are one preferred category of agents
that can be administered according the present invention. A
neurologic agent employed in the method of the present
invention can be any substance that promotes the function or
survival of neurons and prevents the loss or further loss of
nerve cells. For example, a preferred neurologic agent can
promote nerve or glial cell growth, promote survival of
functioning cells, augment the activity of functioning cells,
enhance the synthesis of neurotransmitter substances, augment
the activity of naturally occurring nerve growth promoting
factors, act as a nerve growth promoting factor, prevent
degeneration of neurons, induce regrowth of dendrite and axon,
have more than one of these properties, or the like. A preferred
neurologic agent is a neurotrophic and/or neuritogenic factor
that is similar to a naturally occurring nerve growth promoting
substance. Numerous of such neurologic agents are known to
those of skill in the art.

(Frey [0050].)
10. Frey discloses:
Among the preferred neurologic agents are proteins,
growth factors, and neurotrophins such as nerve growth factor
(NGF), neurotrophins 3, 4, and/or 5 (NT-3, NT-4 and/or NT-5),
brain-derived neurotrophic factor (BDNF), fibroblast growth
factors (FGFs, e.g., basic fibroblast growth factor), insulin,
insulin-like growth factors (IGFs, e.g., IGF-I and/or IGF-II),
ciliary neurotrophic factor (CNTF), glia-derived neurotrophic
factor (GDNF), glia-derived nexin, combinations thereof, and
the like.

(Frey [0051].)
11. Frey discloses that “[n]erve growth factor [NGF] stimulates mitosis
and growth processes associated with cell, particularly nerve cell,
development” (Frey [0097]). Also, the “biological activities of NGF include
increasing levels of choline acetyl transferase” (id. at [0099]).
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12. Frey discloses that a “preferred embodiment of the present
composition includes an effective amount of NGF with a pharmaceutically-
acceptable liquid carrier containing an appropriate amount of micelles
included of GM-1 ganglioside. GM-1 is thought to act synergistically with
nerve growth factor (NGF) to protect neurons and promote nerve
regeneration and repair” (Frey [0134]).
13. Frey discloses:
The present method can be employed to deliver agents to
the brain for diagnosis, treatment or prevention of disorders or
diseases of the CNS, brain, and/or spinal cord. These disorders
can be neurologic or psychiatric disorders. These disorders or
diseases include brain diseases such as Alzheimer’s disease,
Parkinson’s disease, Lewy body dementia, multiple sclerosis,
epilepsy, cerebellar ataxia, progressive supranuclear palsy,
amyotrophic lateral sclerosis, affective disorders, anxiety
disorders, obsessive compulsive disorders, personality
disorders, attention deficit disorder, attention deficit
hyperactivity disorder, Tourette Syndrome, Tay Sachs, Nieman
Pick, and other lipid storage and genetic brain diseases and/or
schizophrenia. The method can also be employed in subjects
suffering from or at risk for nerve damage from cerebrovascular
disorders such as stroke in the brain or spinal cord, from CNS
infections including meningitis and HIV, from tumors of the
brain and spinal cord, or from a prion disease. The method can
also be employed to deliver agents to counter CNS disorders
resulting from ordinary aging (e.g., anosmia or loss of the
general chemical sense), brain injury, or spinal cord injury.

(Frey [0169].)
14. The Merck Manual discloses that depression can include symptoms of
anxiety (see, e.g. Merck Manual 1529 (Table 189-2)). The Merck Manual
also discloses that Premenstrual syndrome can include symptoms of
depression (id. at 1932).
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PRINCIPLES OF LAW
In KSR Int' l Co. v. Teleflex Inc., 550 U.S. 398, 415 (2007) the
Supreme Court rejected a “rigid approach” to the analysis under 35 U.S.C. §
103, and instead emphasized that, “[t]hroughout this Court’s engagement
with the question of obviousness, our cases have set forth an expansive and
flexible approach . . . .” The Court also noted, however, that
[I]t can be important to identify a reason that would have
prompted a person of ordinary skill in the relevant field to
combine the elements in the way the claimed new invention
does . . . because inventions in most, if not all, instances rely
upon building blocks long since uncovered, and claimed
discoveries almost of necessity will be combinations of what, in
some sense, is already known.

Id. at 418-419 (emphasis added); see also id. at 418 (requiring a
determination of “whether there was an apparent reason to combine the
known elements in the fashion claimed by the patent at issue”) (emphasis
added).
The court advised that in determining whether the prior art supplied a
reason for practicing the claimed subject matter, the analysis “need not seek
out precise teachings directed to the specific subject matter of the challenged
claim, for a court can take account of the inferences and creative steps that a
person of ordinary skill in the art would employ.” Id. at 418; see also id. at
421 (“A person of ordinary skill is . . . a person of ordinary creativity, not an
automaton.”).
The Court further advised, however, that “rejections on obviousness
grounds cannot be sustained by mere conclusory statements; instead, there
must be some articulated reasoning with some rational underpinning to
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support the legal conclusion of obviousness.” Id. at 418 (quoting In re
Kahn, 441 F.3d 977, 988, (Fed. Cir. 2006) (emphasis added).
In KSR, the Supreme Court also addressed the “obvious to try” issue:
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that it was obvious under § 103.

Id. at 421.
Thus, as our reviewing court has stated, “[o]bviousness does not
require absolute predictability of success. . . . For obviousness under § 103,
all that is required is a reasonable expectation of success.” In re O’Farrell,
853 F.2d 894, 903-04 (Fed. Cir. 1988).
[T]o have a reasonable expectation of success, one must be
motivated to do more than merely to “vary all parameters or try
each of numerous possible choices until one possibly arrived at
a successful result, where the prior art gave either no indication
of which parameters were critical or no direction as to which of
many possible choices is likely to be successful.” Similarly,
prior art fails to provide the requisite “reasonable expectation”
of success where it teaches merely to pursue a “general
approach that seemed to be a promising field of
experimentation, where the prior art gave only general guidance
as to the particular form of the claimed invention or how to
achieve it.”
Medichem S.A. v. Rolabo S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006)
(quoting O’Farrell, 853 F.2d at 903-04).

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ANALYSIS
We agree with Appellants that the Examiner did not make a prima
facie case of obviousness with respect to claims 1 and 15.
Frey discloses that administering CNS-acting therapeutic agents to
tissue innervated by the trigeminal nerve is advantageous in that the agents
are more effectively delivered to the CNS and less drug is delivered outside
the CNS, thus decreasing undesirable systemic side effects (FF 3-4). Frey
discloses that a number of different types of drugs, with widely varying
chemical makeups and therapeutic properties, are amenable to the disclosed
administration techniques (FF 6-7). NGF is among the preferred agents
deliverable by Frey’s techniques (FF 10).
Frey also discloses that its administration techniques can be used to
treat a wide variety of neurological disorders, ranging from psychological
disorders, such as affective and anxiety disorders, to actual physical damage,
such as caused by stroke, viral or bacterial infection, or from tumors (Frey
[0169] (FF 13)). However, while the Examiner urges that paragraph [0169]
discloses treating anxiety disorders with NGF, that paragraph simply sets
forth a list of disorders that are amenable to the disclosed treatment methods,
and does not explicitly state which of the many and varied therapeutic agents
listed should be used to treat those disorders (see FF 13).
Given the extensive variety of therapeutic agents amenable to its
techniques (FF 6-7), combined with the wide variety of treatable disorders
and diseases with vastly different etiologies (FF 13), we do not agree with
the Examiner that a person of ordinary skill in the art would have considered
the lists in Frey as amounting to a disclosure that any of the cited drugs were
useful in treating any of the named ingredients. Rather, in our view, an
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ordinary artisan would have viewed Frey as simply providing separate lists
of the disorders and drugs amenable to its techniques.
We therefore do not agree with the Examiner that a person of ordinary
skill in the art would have been prompted by Frey to treat anxiety disorders
with NGF. Nor do we agree with the Examiner that Frey would have
provided an ordinary artisan with a reasonable expectation that all of the
drugs listed would be useful in treating anxiety disorders.
We note that Frey discloses that NGF stimulates nerve cell growth
and development, increases choline acetyl transferase, and can be used to
protect neurons and promote nerve regeneration and repair (FF 11-12).
However, the Examiner has not explained how any of these activities would
have led a person of ordinary skill in the art to treat the disorders recited in
claims 1 and 15 with nerve growth factor.
As noted above, “rejections on obviousness grounds cannot be
sustained by mere conclusory statements; instead, there must be some
articulated reasoning with some rational underpinning to support the legal
conclusion of obviousness.” KSR, 550 U.S. at 418 (quoting In re Kahn, 441
F.3d at 988 (emphasis added)).
Thus, we agree with Appellants that Frey does not disclose, or suggest
with sufficient specificity, using nerve growth factor to treat depression,
anxiety disorders, panic attacks, premenstrual dysphoric disorder (PMDD),
or premenstrual syndrome (PMS) as recited in claim 1, or sleep disorders,
tension headaches, or constipation as recited in claim 15. We also agree
with Appellants that The Merck Manual does not remedy Frey’s
shortcomings in this respect. We therefore reverse the Examiner’s rejection
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of claims 1 and 15, and their dependent claims, as obvious over Frey and
The Merck Manual.
OBVIOUSNESS -- SIUCIAK AND THE MERCK MANUAL
ISSUE
Claims 1, 2, 4, 5, 11-15, and 20-24 stand rejected under 35 U.S.C. §
103(a) as being obvious in view of Siuciak and The Merck Manual (Ans. 7-
10).
The Examiner cites Siuciak as teaching that “it is known in the art that
nerve growth factor (Col. 6, lines 16-31) is used for the treatment of
depression as well as panic disorders (Col. 6, lines 44- 65)” (id. at 7). As in
the previous rejection, the Examiner cites The Merck Manual as teaching
that depression “falls under a broad class of mood or affective disorders
(Page 1525),” that “individuals with mixed anxiety-depression possess
conditions of symptoms that have both anxiety and depression (page 1529),”
and that “a patient with the condition of premenstrual syndrome [‘PMS’] is
characterized, inter alia, by anxiety and depression (page 1932)” (id. at 7-8).
The Examiner urges that although Siuciak is “silent to the use of NGF
to treat the psychological conditions of PMS, anxiety disorders, and panic
attacks, Siuciak does in fact teach and provide the artisan with the necessary
motivation to use nerve growth factor in the treatment of affective and
anxiety disorders (Col. 6, lines 44-65)” (id. at 8). Based on the references’
teachings, the Examiner finds that an ordinary artisan would have
recognized that treating depression and anxiety “would also be treating and
alleviating the symptoms of related conditions and ailments that have
depression and anxiety as symptoms, namely anxiety disorders, PMS, and
depression associated with menustration [sic] and anxiety associated with
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panic attacks, most especially in view of the teaching of the Merck Manual”
(id.). Thus, the Examiner concludes, “Siucuak [sic] in view of the Merck
Manual make obvious the claimed subject matter” (id. at 8).
Appellants contend that the Examiner’s conclusion of obviousness is
erroneous because “NGF is a different protein with different properties than
BDNF, NT-3 and NT- 4 disclosed by Siuciak for treatment of depression”
(App. Br. 12). In fact, Appellants argue, “Siuciak itself emphasizes that
NGF lacks some of the biological properties of BDNF, NT-3 and NT-4 (col.
3, lines 11-14) contradicting the Examiner’s apparent assertion that all
members of the neurotrophin family can be used interchangeably” (id.; see
also Reply Br. 5). In support of the proposition that NGF has different
biological properties than BDNF, NT-3, and NT-4, Appellants cite the
Friedman3 article (App. Br. 12; see also 21 (Appendix B (Exhibit C))).
Because NGF has different properties than other members of the
neurotrophin family, Appellants argue, an ordinary artisan “would not have
concluded from Siuciak that NGF could be used as a therapeutic in disorders
normally treated with BDNF, NT-3 or NT-4 and would not be motivated
upon review of Siuciak to use NGF to alleviate the symptoms of the
psychological disorders or any other disease” (App. Br. 12). Appellants
argue that The Merck Manual fails to remedy Siuciak’s shortcomings in this
regard (id).
Thus, Appellants urge, the Examiner’s conclusion of obviousness is
based on hindsight reasoning, and the Examiner therefore “has failed to

3 W.J. Friedman et al., Differential Actions of Neurotrophins in the Locus
Coeruleus and Basal Forebrain, 119 EXPERIMENTAL NEUROLOGY 72-78
(1993).
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establish a prima facie case of obviousness for the subject matter of any of
[the] claims” (id. at 13).
Appellants do not argue the claims subject to this ground of rejection
separately. We select claim 1 as representative of the rejected claims. See
37 C.F.R. § 41.37(c)(1)(vii).
In view of the positions advanced by Appellants and the Examiner,
the issue with respect to this rejection is whether Appellants have shown that
the Examiner erred in finding that an ordinary artisan would have been
prompted by the teachings of Siuciak and The Merck Manual to administer
nerve growth factor to alleviate symptoms of depression, anxiety disorders,
panic attacks, premenstrual dysphoric disorder (PMDD), or premenstrual
syndrome (PMS), as recited in claim 1.
FINDINGS OF FACT
15. Siuciak discloses a “method for treating depression which involves
the use of neurotrophic factors, specifically the NGF family of
neurotrophins. Although not wishing to be bound by theory, these
neurotrophins are believed to be active for the treatment of depression based
on their ability to alter serotonin turnover in the brain” (Siuciak, col. 4, ll.
16-22).
16. Siuciak discloses that “animal models used to predict the
antidepressant activity of test agents indicate that neurotrophins that alter
serotonin levels appear to have such activity” (Siuciak, col. 4, ll. 28-31).
17. Siuciak discloses:
One group of compounds that have recently been found
to be active in altering serotonin turnover in the brain are the
neurotrophins. The neurotrophin family includes brain-derived
neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and
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neurotrophin-4 (NT-4), all of which have recently been
molecularly cloned and shown to be members of the nerve
growth factor (NGF) family by virtue of their sequence
homology.

(Siuciak, col. 2, ll. 47-55.)
18. Siuciak discloses:

Studies involving the in vivo actions of the
neurotrophins, in particular the neurotrophin BDNF, have
confirmed their actions in maintaining the survival and
regulating the function or phenotype of various neuronal cells. .
. . A recent report described the in vitro survival effect of NT-3
and NT-4 (but not NGF) on locus ceruleus neurons (Friedman,
et al. Exp. Neurol 119: 72-78 (1993).

(Siuciak, col. 2, l. 66, through col. 3, l. 14.)
19. Siuciak discloses that “[i]n a preferred embodiment of the invention,
BDNF and/or NT-3 are delivered into the midbrain tegmentum, near the
periaqueductal gray and the dorsal raphe, areas of the brain which contain an
abundance of serotonergic neurons. In a preferred embodiment, the
neurotrophin BDNF is used to reduce depression” (Siuciak, col. 5, ll. 6-11).
20. Friedman discloses a study comparing “different neurotrophins in the
regulation of neuronal survival and function using dissociated embryonic
cell cultures from two brain regions, the basal forebrain (BF) and locus
coeruleus (LC)” (Friedman 72 (abstract)).
21. Friedman found that “[s]pecific neurotrophins such as NT-3 and NT-4
enhanced survival of both neuronal populations. NGF, which has no effect
on LC neurons, influenced the BF by increasing cholinergic function but not
survival, in contrast to BDNF, NT-3, and NT-4” (Friedman 76).
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22. Friedman discloses that NGF, BDNF, NT-3, and NT-4 all increased
choline acetyl transferase in BF cells (Friedman 72 (abstract)).
23. Friedman concluded that the “discovery that neuronal survival in both
the basal forebrain and locus coeruleus is affected by common target-derived
trophic factors provides a possible mechanism by which these distinct
populations undergo necrosis in a single degenerative disorder such as
Alzheimer’s disease” (Friedman 76-77).
PRINCIPLES OF LAW
It is well settled that, “in a section 103 inquiry, ‘the fact that a specific
[embodiment] is taught to be preferred is not controlling, since all
disclosures of the prior art, including unpreferred embodiments, must be
considered.’” Merck & Co. Inc. v. Biocraft Laboratories, Inc., 874 F.2d
804, 807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750
(CCPA 1976)); see also In re Mills, 470 F.2d 649, 651 (CCPA 1972) (“All
the disclosures in a reference must be evaluated, including nonpreferred
embodiments, and a reference is not limited to the disclosure of specific
working examples.” (citations omitted)).
ANALYSIS
Appellants’ arguments do not persuade us that the Examiner erred in
finding that an ordinary artisan would have been prompted by Siuciak and
The Merck Manual to administer nerve growth factor to alleviate symptoms
of depression, anxiety disorders, panic attacks, premenstrual dysphoric
disorder (PMDD), or premenstrual syndrome (PMS), as recited in claim 1.
We note that Siuciak discloses BDNF and NT-3 as being the preferred
members of the NGF family for treating depression (FF 19). However, as
noted above, a reference must be evaluated for all it teaches, not just its
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preferred embodiments. See Merck v. Biocraft, 874 F.2d at 807; see also In
re Mills, 470 F.2d 649, 651.
Thus, in the instant case, Siuciak explicitly discloses that members of
the NGF family are useful in treating depression (FF 15). Given this
teaching, we agree with the Examiner that a person of ordinary skill in the
art would have reasoned that any of the proteins in the related NGF family
(FF 17) would have been suitable to treat the disorder.
We further note that Siuciak and Friedman provide evidence that
unlike NT-3 and BDNF, NGF does not promote survival of certain neuronal
populations (see FF 18, 21). However, Appellants fail to point to any
specific scientific principle suggesting that NGF’s failure to promote
neuronal survival would have led an ordinary artisan to consider it
unsuitable as a treatment for depression despite Siuciak’s generic disclosure.
Moreover, Friedman discloses that NGF shares with NT-3 and BDNF
the capacity to increase choline acetyl transferase activity in certain neuronal
populations (FF 22). Siuciak also notes that the preferred agents, BDNF and
NT-3, share sequence homology with other members of the NGF family of
proteins (FF 17). Thus, while NGF may be different from other members of
its family in some respects, it also shares properties with the other members,
including Siuciak’s preferred treatment agents.
Therefore, in contrast to the other appealed rejection, we do not agree
with Appellants that Siuciak’s generic disclosure amounts to an invitation to
vary numerous parameters, try numerous possibilities, or follow a promising
suggestion with only vague or general guidance. See Medichem v. Rolabo,
437 F.3d at 1165. Rather given Siuciak’s generic disclosure of using NGF
family members to treat depression, and the fact that the family is disclosed
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Application 10/624,328

as consisting of only a few related proteins (FF 17), the instant situation is
more akin to that described in KSR:
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that it was obvious under § 103.

KSR, 550 U.S. at 421. We again note that “[o]bviousness does not require
absolute predictability of success. . . . For obviousness under § 103, all that
is required is a reasonable expectation of success.” In re O’Farrell, 853
F.2d at 903-04.
In sum, because we are not persuaded that the Examiner failed to
make a prima facie case of obviousness with respect to claim 1, we affirm
the Examiner’s rejection of that claim as being obvious over Siuciak and
The Merck Manual.
Claims 2, 4, 5, 11-15, and 20-24 fall with claim 1. See 37 C.F.R.
§ 41.37(c)(1)(vii).
SUMMARY
We reverse the Examiner’s rejection of claims 1, 2, 4, 5, 8-18, and 20-
24 under 35 U.S.C. § 103(a) as being obvious in view of Frey and The
Merck Manual.
However, we affirm the Examiner’s rejection of claims 1, 2, 4, 5, 11-
15, and 20-24 under 35 U.S.C. § 103(a) as being obvious in view of Siuciak
and The Merck Manual.

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Appeal 2009-002709
Application 10/624,328

TIME PERIOD
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-IN-PART

cdc

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