Beverly A. Rzigalinski et al.

Patent Trials and Appeals Board

May 19, 2020

2019001476 (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.
12/252,905 10/16/2008 Beverly A. Rzigalinski VCOM-021299 US CIP 8293
26294 7590 05/19/2020
TAROLLI, SUNDHEIM, COVELL & TUMMINO L.L.P.
1300 EAST NINTH STREET, SUITE 1700
CLEVELAND, OH 44114
EXAMINER
LIU, SUE XU
ART UNIT PAPER NUMBER
1616
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):
docketing@tarolli.com
rkline@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BEVERLY A. RZIGALINSKI, NEERAJ SINGH, and
COURTNEY A. COHEN1
Appeal 2019-001476
Application 12/252,905
Technology Center 1600

Before DONALD E. ADAMS, ERIC B. GRIMES, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of treatment, which have been rejected as obvious and lacking
adequate written description. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM the rejection for lack of adequate written description.
STATEMENT OF THE CASE
The Specification states that “Alzheimer’s and Parkinson’s diseases,
neuromuscular disorders, and mitochondrial diseases are associated with
increased oxidative stress, production of free radicals, and/or destruction of

1 Appellant identifies the real parties in interest as “the inventors Beverly A.
Rzigalinski, Neeraj Singh, and Courtney A. Cohen.” Appeal Br. 3. We use
the word Appellant to refer to “applicant” as defined in 37 C.F.R. § 1.42(a).
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mitochondria.” Spec. ¶ 4. The Specification also states that “[i]t has
previously been shown that cerium oxide nanoparticles (CeONP) decrease
oxidative stress, reduce free radical production, and extend cell and
organism longevity.” Id. The Specification discloses that “cerium oxide
nanoparticles (CeONP) can be used to treat or prevent neurodegenerative
diseases, including for example Alzheimer’s Disease, Parkinson’s Disease,
Huntington’s Disease, AIDS-related dementia, ALS, . . . , as well as
mitochondrial diseases.” Id. ¶ 15.
Claims 1, 8, 9, 11, and 15–17 are on appeal. Claims 1 and 8,
reproduced below, are the independent claims:
1. A method of treating a subject for Alzheimer’s Disease,
Huntington’s Disease, Parkinson’s Disease, or amyotrophic
lateral sclerosis (ALS), said method comprising:
administering a non-agglomerating composition
comprising cerium oxide nanoparticles having an average
particle diameter size of about 10 nm to about 20 nm in an
amount sufficient to provide a therapeutically effective dose of
about 10 ng, 50 ng, 100 ng, 500 ng, 1 μg, 5 μg, 10 μg, or 50 μg
per kg body mass to a subject having Alzheimer’s Disease,
Huntington’s Disease, Parkinson’s Disease, or amyotrophic
lateral sclerosis (ALS).

8. A method of treating a subject for a mitochondrial disease or
the suffering from the effects of a mitochondrial toxin,
comprising:
administering a non-agglomerating composition
comprising cerium oxide nanoparticles having an average
particle diameter size of about 10 nm to about 20 nm in an
amount sufficient to provide a therapeutically effective dose of
about 10 ng, 50 ng, 100 ng, 500 ng, 1 μg, 5 μg, 10 μg, or 50 μg
per kg body mass to a subject having mitochondrial disease or
suffering from the effects of a mitochondrial toxin.
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The claims stand rejected as follows:
Claims 1, 8, 9, 11, and 15–17 under 35 U.S.C. § 112, first paragraph,
for lack of adequate written description (Final Action2 5) and
Claims 1, 8, 9, 11, and 15–17 under 35 U.S.C. § 103(a) as obvious
based on McGinnis,3 Chinopoulos,4 and Wang5 (Final Action 11).
OPINION
Written Description
Claims 1, 8, 9, 11, and 15–17 stand rejected for “failing to comply
with the written description requirement,” because
[t]he claims have been amended to claim doses of 10 ng, 50 ng,
100 ng, 500 ng, 1 mg, 5 mg, 10 mg, or 50 mg per kg body
mass. The Applicant cites to paragraph 0055 of the 11/993,260
application (which entire disclosure is incorporated by
reference by the present Specification (see paragraph 0001 of
the Specification) as support for the claimed dosage range but
. . . the incorporation by reference is not proper as the US
Patent Application Publication must be cited. As such, the
dosage range lacks written description support.
Final Action 5.
Appellant argues that “37 CFR l.57(d) . . . corresponds to the situation
in the present case, where incorporation by reference was present in

2 Final Office Action mailed February 23, 2018.
3 McGinnis et al. (US 7,347,987 B2; iss. Mar. 25, 2008).
4 Christos Chinopoulos & Vera Adam-Vizi, Mitochondria Deficient in
Complex I Activity are Depolarized by Hydrogen Peroxide in Nerve
Terminals: Relevance to Parkinson’s Disease, J. Neurochem. 76:302–306
(2001).
5 Jinsheng Wang et al., Protective Effect of Cerium on Mitochondria Wheat
Under Salinity Stress, Zhongguo Xitu Xuebao 17:187–190 (abstract only)
(1999).
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paragraph [0001] of the application.” Appeal Br. 8. Appellant argues that
“the application satisfies the requirements of 37 CFR l.57(d).” Id.
As the Examiner has pointed out, however, “37 CFR 1.57 (d) clearly
requires reference to a US Patent or US Patent Application Publication.”
Ans. 4. Currently, and in relevant part, the instant Specification states that
“this application is a continuation-in-part application of U.S. Patent
Application No. 11/993,260, filed December 20, 2007 . . . , the disclosure[]
of which [is] incorporated herein by reference.” Spec. ¶ 2.
There is no dispute that the incorporation by reference of the ’260
application is required to provide support for the dosages recited in the
claims. Thus, Appellant seeks to incorporate by reference essential material
from the ’260 application, and 37 C.F.R. § 1.57(d) applies. See Appeal Br. 8
(“37 CFR l.57(d) . . . corresponds to the situation in the present case.”) That
rule states that “‘[e]ssential material’ may be incorporated by reference, but
only by way of an incorporation by reference to a U.S. patent or U.S. patent
application publication.” 37 C.F.R. § 1.57(d) (emphasis added).
The instant Specification does not refer to the U.S. patent application
publication number, but only to the application serial number, and therefore
does not comply with 37 C.F.R. § 1.57(d). As the Examiner has pointed out,
the ’260 application “was published on July 1, 2010 as US Patent
Application Publication US 2010/0166821 A1. As such, the Appellants need
only amend the Specification to also cite said US Patent Application
Publication in order to comply with 37 CFR 1.57 (d).” Ans. 4 (emphasis
added).
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At present, however, the incorporation by reference of the ’260
application is improper and the dosages recited in the claims lack adequate
written support in the instant Specification. We therefore affirm the rejection
of claims 1, 8, 9, 11, and 15–17 under 35 U.S.C. § 112, first paragraph, for
lack of adequate written description.
Obviousness
Claims 1, 8, 9, 11, and 15–17 stand rejected as obvious based on
McGinnis, Chinopoulos, and Wang. The Examiner finds that McGinnis
“disclose[s] a method of promoting the longevity of retinal neuron[s] by
administering cerium oxide particles having a diameter range between about
1 nanometer and about 10 nm to the eye . . . at a dosage of about 3
nanomolar to about 50 nanomolar.” Final Action 11.
The Examiner finds that McGinnis discloses “that the cerium oxide
particles can be used to inhibit neurodegeneration, e.g. Alzheimer’s,
Parkinson’s, dementia and amyotrophic lateral sclerosis, by destroying toxic
product of metabolism known as reactive oxygen species.” Id. The Examiner
also finds that McGinnis describes an experiment “in which 2 microliters of
cerium oxide nanoparticles at a concentration of 0.1 to 1.0 micromolar is
injected into rats which protected retinal cells from damage due to reactive
oxygen species.” Id.
The Examiner finds that Chinopoulos “disclose[s] that deficiency of
mitochondrial complex I activity is believed to be a critical factor in the
development of Parkinson’s disease” and that “mitochondria have increased
vulnerability to hydrogen peroxide induced oxidative stress when the
activity of complex I is reduced to a similar extent as found in Parkinson’s
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disease by rotenone.” Id. at 12. The Examiner finds that Wang “disclose[s]
that that cerium reduced levels of O2 [O2] and OH thereby normalizing lipid
hydroperoxide and fluidity of the mitochondria membrane . . . such that the
function of mitrochondria [sic] is on relatively normal levels.” Id.
The Examiner concludes that “nanoceria[6] within the claimed size
range and dosages have been used in the treatment of retinal neuron
degeneration due to reactive oxygen species. As the nanoceria have shown
to be effective as an antioxidant, one of ordinary skill in the art would expect
that they can be used as an antioxidant in patients.” Id. at 13. The Examiner
also concludes that “one of ordinary skill in the art would have expected that
nanoparticles of cerium oxide can be administered to subjects having
Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis and
mitochondrial disease . . . where the mitochondrial dysfunction is due to
inhibition of mitochondrial complex I.” Id.
Appellant argues that the claims have been amended “to recite
providing a ‘therapeutically effective’ dose. Because the claims recite use of
an effective dosage, . . . Applicants respectfully request that the rejection of
claims 1, 8, 9, 11, 15, 16, and 17 for obviousness be reversed.” Appeal Br.
19. More specifically, Appellant argues that McGinnis “describe[s]
administering a concentration of cerium oxide nanoparticles in a range
between 3 nanomolar and 50 nanomolar.” Reply Br. 7. Appellant argues that
such concentration values do not provide therapeutically useful
dosage information, since the amount administered can vary
widely from the concentration used for administration, and it is

6 Cerium oxide nanoparticles are also referred to as nanoceria. See, e.g.,
McGinnis 1:13–17, 2:42–45.
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the amount administered compared to the size of the subject
that is important. The claimed dosage amounts, on the other
hand, are provided in nanograms or micrograms per kilogram
of body mass.
Id. Appellant argues that “the claimed dosages are non-obvious in view of
the cited prior art.” Id.
We agree with Appellant that the Examiner has not adequately shown
that the dosages recited in the claims would have been obvious based on the
cited references. Both claim 1 and claim 8 recite administering specific
dosages of “10 ng, 50 ng, 100 ng, 500 ng, 1 μg, 5 μg, 10 μg, or 50 μg per kg
body mass to a subject.”
The Examiner cites McGinnis as disclosing “a dosage of about 3
nanomolar to about 50 nanomolar.” Final Action 11. However, as Appellant
has pointed out, “nanomolar” is a unit of concentration; specifically,
nanomoles per liter—not a dosage of nanograms per kilogram of body mass.
A composition having a particular concentration of an active agent does not
teach or suggest any specific dosage of that agent, because any desired
dosage can be administered by varying the volume of the composition that is
administered.
With regard to Appellant’s argument that the claims require a
“therapeutically effective dose,” the Examiner reasons that “the claims do
not define the therapeutic effect. As such, the claims do not require that
doses be effective to treat Alzheimer’s Disease, [etc.,] . . . only that the
subject treated with the cerium oxide nanoparticles have said diseases and/or
conditions.” Ans. 4.
We do not agree with the Examiner’s reasoning. First, the claims
recite a method of “treating” specific conditions by administering a
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“therapeutically effective dose” of cerium oxide nanoparticles. A dose of a
drug is not “therapeutically effective” unless it is effective to treat the
condition being treated. The claims therefore do require that the dosage of
cerium oxide nanoparticles is effective to treat the specified disease or
disorder.
In addition, the claims go on to define what a “therapeutically
effective dose” is: “10 ng, 50 ng, 100 ng, 500 ng, 1 μg, 5 μg, 10 μg, or 50 μg
per kg body mass to a subject.” Claims 1, 8. In order to support a prima facie
case of obviousness, therefore, the cited references must teach or suggest
one of the specific dosages recited in the claims. The Examiner has not
shown that they do so, and because this burden was not met, we reverse the
rejection of claims 1, 8, 9, 11, and 15–17 under 35 U.S.C. § 103(a).
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 8, 9, 11,
15–17
112, first
paragraph
Written Description 1, 8, 9, 11,
15–17

1, 8, 9, 11,
15–17
103(a) McGinnis,
Chinopoulos, Wang
1, 8, 9, 11,
15–17
Overall
Outcome
1, 8, 9, 11,
15–17

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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) (2017).
AFFIRMED