Kaohsiung Chang Gung Memorial Hospital of the C.G.M.F et al.

Patent Trials and Appeals Board

Jul 29, 2020

15485026 - (D) (P.T.A.B. Jul. 29, 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.
15/485,026 04/11/2017 Hsien-Yuan LANE 10016-002CON 5570
74603 7590 07/29/2020
IPC Intellectual Property Connections, INC.
3346 Ramona Street
Palo alto, CA 94306
EXAMINER
CHONG, YONG SOO
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
07/29/2020 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):
mingsaun@aol.com
mingsaun@gmail.com
mingsaun@ipcintel.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte HSIEN-YUAN LANE and CHIEH-HSIN LIN
Appeal 2020-000229
Application 15/485,026
Technology Center 1600
Before ERIC B. GRIMES, LINDA M. GAUDETTE, and
FRANCISCO C. PRATS, Administrative Patent Judges.
GAUDETTE, Administrative Patent Judge.
DECISION ON APPEAL1
The Appellant2 appeals under 35 U.S.C. § 134(a) from the Examiner’s
decision finally rejecting claims 6–24 under 35 U.S.C. § 103 as obvious over
Tsai (WO 2010/085452 A1, published July 29, 2010) in view of Good (US

1 This Decision includes citations to the following documents: Specification
filed April 11, 2017 (“Spec.”); Final Office Action dated March 29, 2019
(“Final”); Appeal Brief filed August 17, 2019 (“Appeal Br.”); Examiner’s
Answer dated September 18, 2019 (“Ans.”); and Reply Brief filed October
9, 2019 (“Reply Br.”).
2 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. The Appellant identifies the real parties in interest as
Kaohslung Chang Gung Memorial Hospital of the C.G.M.F. and China
Medical University. Appeal Br. 2.
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2003/0032070 A1, published February 13, 2003) and Kelleher (US
2010/0150839 A1, published June 17, 2010).3
We AFFIRM.
BACKGROUND
“Dementia is the progressive decline in cognitive function due to
damage or disease in the brain beyond what might be expected from normal
aging.” Tsai ¶ 24. “Dementia . . . includes mild cognitive impairment (MCI
. . .) which is a diagnosis given to individuals who have cognitive
impairments beyond that expected for their age and education, but that do
not interfere significantly with their daily activities. It is considered to be the
boundary or transitional stage between normal aging and dementia.” Id.
According to the Specification, “[p]eople with MCI have been found to be
impaired in neuropsychological functions such as speed of processing,
working memory, and verbal learning and memory.” Spec. 12:27–28.
The Specification discloses that MCI, “particularly amnestic mild
cognitive impairment (aMCI), is a risk factor and might be a prodromal
stage of AD [(Alzheimer’s Disease)].” Spec. 1:12–14; see also Tsai ¶ 24
(“[I]ndividuals tend to progress to probable Alzheimer’s disease at a rate of
approximately 10% to 15% per year.”). “The term ‘Alzheimer’s Disease’
refers to a progressive mental deterioration manifested by memory loss,
confusion and disorientation beginning in late middle life and typically
resulting in death in five to ten years.” Tsai ¶ 23. According to the
Specification, acetylcholine esterase inhibitor (AChEI), the main-stream

3 We have jurisdiction under 35 U.S.C. § 6(b).
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treatment for mild and moderate AD, “does not show convincing efficacy
for MCI.” Spec. 1:14–16.
Alzheimer’s disease and dementia are neuropsychiatric disorders,
meaning that they are diseases having a pathophysiological component of
attenuated N-methyl-D-aspartate (NMDA) receptor-mediated
neurotransmission. Spec. 1:18–19, 6:16–18; see also Tsai ¶ 20. “Recent data
indicate that aging is related to reduced D-serine levels and thereby impaired
NMDAR [(NMDA receptor)] transmission.” Spec. 2:14–15. The
Specification discloses that an “avenue[] to enhance NMDA activation . . . is
inhibiting the activity of DAAO [(D-amino acids oxidase)], a flavoenzyme
of peroxisomes responsible for degrading D-serine and D-alanine, . . .
thereby raising levels of the D-amino acids that are the neurotransmitters for
the coagonist site of the NMDAR.” Id. at 2:11–14. According to the
Specification, a recent study showed that sodium benzoate, a DAAO
inhibitor, benefited neurocognitive function in patients with schizophrenia
when administered in a dose of 1000 mg/day. Id. at 2:6–8; see also Tsai
¶ 129 (“In this pilot, placebo-control, randomized, double blind trial (not yet
published), we found that 1000-mg/day sodium benzoate adjunctive therapy
(n=18) can significantly improve positive and negative symptoms and
quality of life than placebo (n=18) in schizophrenia patients . . . .”).
Schizophrenia is also a neuropsychiatric disorder. Spec. 6:16–18; see also
Tsai ¶ 20.
CLAIMED SUBJECT MATTER
The inventors are said to have discovered a method of using sodium
benzoate to improve cognitive and overall function in patients with early-
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phase AD. Spec. 13:17–18. Claim 9, reproduced below, is illustrative of the
claimed subject matter:
9. A method of improving processing speed, memory and
learning in a human dementia patient, comprising:
administering to the human dementia patient a
therapeutically effective amount of benzoic acid, a salt, an ester,
or a derivative thereof to improve the processing speed,
memory and learning in the human dementia patient;
optionally concurrently administering an acetylcholine
esterase inhibitor but not administer[ing] any other
neuropharmaceutical to the human dementia patient.
Appeal Br. 11 (Claims Appendix). Claims 18 and 19 depend from claim 9
and specify, respectively, that “the patient is afflicted with Alzheimer
disease or mild cognitive impairment,” and that “the patient is afflicted with
an early phase Alzheimer disease or amnestic mild cognitive impairment.”
Id. at 12–13.
Like claim 9, the other independent claims (claims 6 and 7), recite
methods of improving processing speed, memory and learning in a human
dementia patient that include a step of administering to the patient “a
therapeutically effective amount of benzoic acid, a salt, an ester, or a
derivative thereof” “to improve the processing speed, memory and learning”
in the human dementia patient. Appeal Br. 11 (Claims Appendix).
OPINION
The Appellant argues the claims as a single group. See generally
Appeal Br. 3–9. Accordingly, we decide the appeal as to claims 6–24 on the
basis of independent claim 9. See 37 C.F.R. § 41.37(c)(iv) (2018).
The Examiner rejected claims 6–24 over Tsai, Good, and Kelleher.
See generally Final 3–7. The Examiner relies on Good and Kelleher solely
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for teachings of limitations found in independent claim 7 and various
dependent claims. See id. at 5. Accordingly, we focus our discussion on the
Appellant’s and the Examiner’s respective positions regarding Tsai’s
disclosure. See Appeal Br. 5 (arguing that Good and Kelleher do not cure the
deficiencies of Tsai).
The Appellant argues that the Examiner reversibly erred in finding
that the ordinary artisan reasonably would have expected that administering
sodium benzoate to an Alzheimer’s disease or dementia patient would
improve the patient’s processing speed, memory, and learning deficit
symptoms. See, e.g., Appeal Br. 4, 7. The Appellant contends that Tsai’s
teaching is very generic because the term “neuropsychiatric disorders”
encompasses “a wide variety of diseases and each type of neuropsychiatric
disorder can have many different neuropsychiatric symptoms,” and “Tsai
does not teach which symptoms of the dementia or Alzheimer’s disease
could be treated or improved/mitigated by benzoate.” Id. at 7. The Appellant
further argues that the Examiner’s finding that the symptoms of Alzheimer’s
disease are well-documented and known is insufficient to support a finding
that the ordinary artisan would have had a reasonable expectation of success
that administering benzoate to Alzheimer’s disease patients would improve
these symptoms. Id.; see also Reply Br. 4 (“Just because symptoms are well
documented and known does not mean one of ordinary skill in the art would
be able to reasonably predict which of the symptoms, would and could be
improved by benzoate.”).
In support of its arguments, the Appellant cites Tsai’s working
example in which Tsai found that “benzoate administration as an adjunct in
human schizophrenia patients resulted in improvement in positive and
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negative symptoms,” but did not report an improvement in the cognitive
symptoms of schizophrenia. Appeal Br. 8. The Appellant also cites its own
experimental data as “demonstrat[ing] that the same sodium benzoate
administration did not improve cognitive flexibility and attention, but
improved processing speed, memory and learning, of the patients with
Alzheimer’s disease.” Id. at 9. The Appellant argues that Tsai’s example (as
well as its own test results) “demonstrate[] that improving cognitive
symptoms by benzoate treatment in a patient with any neuropsychiatric
disorder is entirely unpredictable.” Id. at 8 (emphasis omitted); see id. at 9
(“Without conducting the clinical trial on the patients with Alzheimer’s
disease, even a skilled artisan would not have been able to reasonably
predict the outcome of benzoate treatment in the patient with dementia or
Alzheimer’s disease.”).
The Appellant’s arguments are not persuasive for the reasons stated in
the Final Office Action and the Answer. See generally Final 7–9; Ans. 6–9.
We add the following.
Tsai discloses “methods for mitigating one or more symptoms of a
neuropsychiatric disorder.” Tsai ¶ 9. Tsai discloses that “the treatment
methods of the invention entail administering to a subject in need thereof
(e.g., a patient diagnosed as having or at risk for a neuropsychiatric disorder)
one or more a pharmaceutical compositions containing a therapeutically
effective amount(s) of (i) an NMDA (N-methyl-D-aspartate)-Enhancer,
and/or (ii) a glycine transporter inhibitor, and/or (iii) a D-amino Acid
Oxidase Inhibitor (DAAOI).” Id. ¶ 80; see also id. claim 24. According to
Tsai, “the use of a DAAOI alone, especially a benzoic acid, benzoic acid
salt, benzoic acid ester or other benzoic acid derivative . . . can result in
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unexpected and surprising improvement in subjects diagnosed with a
neuropsychiatric disorder[].” Id. ¶ 60. Tsai includes Alzheimer’s disease,
dementia, and mild cognitive impairment in an exemplary list of
neuropsychiatric disorders that are treatable with benzoic acid. Id. Tsai
describes “Alzheimer’s Disease [as] a form of dementia that typically
involves progressive mental deterioration, manifested by memory loss,
confusion, and disorientation.” Id. ¶ 3. According to Tsai, “[m]ost of the
neuropsychiatric disorders present with cognitive deficits, behavioral and
mental symptoms[, and] [t]he various treatment strategies . . . can be applied
to most if not all of them including, for example, . . . Alzheimer’s Disease,
. . . dementia, [and] mild cognitive impairment.” Id. ¶ 79.
“[A] reasonable expectation of success, not absolute predictability”
supports a conclusion of obviousness. In re Longi, 759 F.2d 887, 897 (Fed.
Cir. 1985). The above-cited disclosure in Tsai supports the Examiner’s
finding that the ordinary artisan would have administered a benzoic acid,
benzoic acid salt, benzoic acid ester or other benzoic acid derivative to a
human dementia patient, as taught by Tsai, with a reasonable expectation of
successfully mitigating at least one symptom of the disease, for example,
“memory loss, confusion, [or] disorientation” (Tsai ¶ 3; see Tsai ¶ 79). See
also Tsai claims 24, 50, 51 (“A method of mitigating one or more symptoms
of a neuropsychiatric disorder, said method comprising administering to a
subject in need thereof a benzoic acid, benzoic acid salt, or benzoic acid
derivative . . . wherein said neuropsychiatric disorder is characterized by a
loss in cognition and/or neurodegeneration[,] . . . wherein said
neuropsychiatric disorder is selected from the group consisting of benign
forgetfulness, mild cognitive impairment, dementia and Alzheimer’s
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disorder.”). The fact that the ordinary artisan’s reasons for administering a
benzoic acid (or a salt or derivative thereof) might not have been for the
specific purpose of “improving processing speed, memory and learning,” as
recited in the claims, is not relevant to the obviousness determination. The
“motivation to modify a prior art reference to arrive at the claimed invention
need not be the same motivation that the patentee had.” Alcon Research, Ltd.
v. Apotex Inc., 687 F.3d 1362, 1368 (Fed. Cir. 2012) (citing KSR Int’l Co. v.
Teleflex, Inc., 550 U.S. 398, 420 (2007) (stating that it is error to look “only
to the problem the patentee was trying to solve”)).
The record evidence also supports the Examiner’s finding that
administering a benzoic acid (or a salt or derivative thereof) to a human
dementia patient in the manner suggested by Tsai necessarily would have
resulted in an improvement in processing speed, memory, and learning,
because “all the elemental steps are essentially the same as that for the
claimed invention.” Ans. 8. Tsai discloses the following: “[F]or human
patients, the effective unit dose of typical compounds include: DAAOI (e.g.,
benzoate, range of 50 mg–150 grams).” Tsai ¶ 81. “For a normal human
adult having a body weight of about 70 kilograms, it is estimated that a
dosage in the range of about 0.01 to about 100 mg per kilogram of body
weight per day is sufficient. . . . [T]he specific dose level for any particular
patient will depend upon a variety of factors . . . .” Id. ¶ 82. “[A]ppropriate
dosages of the active agent(s) can readily be determined by those of ordinary
skill in the art of medicine by monitoring the patient for signs of disease
amelioration or inhibition, and increasing or decreasing the dosage and/or
frequency of treatment as desired.” Id. ¶ 83. “Generally, treatment continues
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for at least one week and can continue for several years or life-long as
needed to control the subject’s symptoms.” Id. ¶ 85.
By comparison, the Specification describes clinical testing of 60
patients satisfying criteria for probable AD or for an aMCI of a presumably
degenerative nature. Spec. 7:21–27. The patients received a 24-week
treatment of sodium benzoate or placebo in a double-blind manner. Id. at
8:9–10. Patients receiving the sodium benzoate were administered mean
doses of 275.0 ± 76.3 mg/day, 525.0 ± 100.6 mg/day, and 716.7 ± 182.6
mg/day, at weeks 8, 16, and 24, respectively. Id. at 10:17–18. “The result
showed that sodium benzoate had better efficacy than placebo in improving
ADAS-cog score, additional cognition composite (consisting of speed of
processing, working memory, and verbal learning and memory), and global
function in all subjects as a whole.” Spec. 11:24–26. Thus, the Specification
instructs that administering sodium benzoate to a human dementia patient, in
the same amounts and time periods utilized by Tsai, necessarily results in
improved processing speed, memory and learning. See In re Kubin, 561 F.3d
1351, 1357 (Fed. Cir. 2009) (“Even if no prior art of record explicitly
discusses the . . . [limitation], [Appellant’s] application itself instructs that
[the limitation] is not an additional requirement imposed by the claims on
the [claimed invention], but rather a property necessarily present in [the
claimed invention].”); Ex parte Obiaya, 227 USPQ 58, 60 (BPAI 1985)
(“The fact that appellant has recognized another advantage which would
flow naturally from following the suggestion of the prior art cannot be the
basis for patentability when the difference would otherwise have been
obvious.”).
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“[W]hen the prior art evidence reasonably allows the [US]PTO to
conclude that a claimed feature is present in the prior art, the evidence
‘compels such a conclusion if the applicant produces no evidence or
argument to rebut it.’” In re Crish, 393 F.3d 1253, 1259 (Fed. Cir. 2004)
(quoting In re Spada, 911 F.2d 705, 708 n.3 (Fed. Cir. 1990)). The
Appellant has not met this burden. See Ans. 8 (“Appellant has been asked to
show a side-by-side comparison showing that ‘improving processing speed,
memory and learning’ did not occur according to the Tsai reference, and did
occur in the claimed invention, however no side-by-side comparison has
been given.”); Reply Br. 8 (“[S]ince Tsai teaches nothing about the
limitations regarding improving processing speed, memory and learning, the
Applicant is not required to show side-by-side comparison.”).
Any arguments made by the Appellant, but not discussed in this
decision, have been fully addressed by the Examiner and are unpersuasive
for the reasons stated in the Final Office Action and the Answer.
CONCLUSION
The Appellant has not identified reversible error in the Examiner’s
determination that claims 6–24 would have been obvious over the
combination of Tsai, Good, and Kelleher. Accordingly, we sustain the
rejection of claims 6–24 under 35 U.S.C. § 103.
DECISION SUMMARY
Claims
Rejected
35 U.S.C. § Reference(s)/Basis  Affirmed Reversed
6–24 103 Tsai, Good, Kelleher 6–24

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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).
AFFIRMED