The Board of Regents of the University of Texas System

Patent Trials and Appeals Board

Apr 8, 2020

15264551 - (D) (P.T.A.B. Apr. 8, 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.
15/264,551 09/13/2016 Gabriel LOPEZ-BERESTEIN UTSC.P0986US.D1 2879
108197 7590 04/08/2020
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
Austin, TX 78746
EXAMINER
POPA, ILEANA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
04/08/2020 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@phiplaw.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
_________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
_________________

Ex parte GABRIEL LOPEZ-BERESTEIN and ANIL K. SOOD,

_________________

Appeal 2019-003723
Application 15/264,551
Technology Center 1600
_________________

Before DEBORAH KATZ, JOHN E. SCHNEIDER, and
MICHAEL A. VALEK. Administrative Patent Judges.

KATZ, Administrative Patent Judge.

DECISION ON APPEAL

Appellant1 seeks our review2, under 35 U.S.C. § 134(a), of the
Examiner’s decision to reject claims 39, 41, 42, 44–48 and 62–65. We have
jurisdiction under 35 U.S.C. § 6(b). We AFFIRM.

1 We use the word “Appellant” as defined in 37 C.F.R. § 1.42. Appellant
identifies the real party-in-interest as Board of Regents, The University
of Texas System. (Appeal Br. 3.)
2 We consider the Specification filed September 13, 2016 (“Spec.”) Final
Office Action issued April 19, 2018 (“Final Act.”), the Appeal Brief filed
October 9, 2018 and the Response to Non-compliant Brief filed November
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Appellant’s Specification explains that the enhancer of the Zeste
homologue 2 (EZH2) gene has been implicated in the progression and
metastasis of several cancers. (Spec. 2:1–7.) Appellant’s Specification
discusses the use of small interfering RNA (siRNA)-based treatments that
can specifically target genes, including EZH2. (See id. at 2:8–15.) The
Specification explains that chitosans (CHs), naturally occurring
polysaccharides, have been used as carriers for nanoparticle drugs. (See id.
at 2:16–22.) Appellant reports that the present invention provides for drug
delivery particles that include a chitosan and a polyphosphate for effective
delivery of therapeutic agents, such as siRNA directed to EZH2, into tissues
of a subject. (See Spec. 3:7–11.)
Appellant’s claim 39 recites:
A method of treating a subject with ovarian cancer,
comprising administering to the subject with ovarian cancer a
pharmaceutically effective amount of a composition
comprising:
(a) a chitosan; and
(b) an siRNA that inhibits expression of a gene that
encodes EZH2; and a nucleic acid component comprising a
nucleic acid that inhibits the expression of a gene that encodes
EZH2,
(c) a polyphosphate anion of formula (I):

19, 2019 (“Appeal Br.”), the Examiner’s Answer issued on February 15,
2019 (“Ans.”), and the Reply Brief filed April 10, 2019 (“Reply Br.”), in
reaching our decision.
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wherein the weight ratio of the chitosan to the polyphosphate is
2.5:1 to 3.5:1 and the weight ratio of the polyphosphate to
therapeutic RNA is less than 15:1.

(Appeal Br. 21.)
Rejection over Katas, Lu, Birmingham, and Gan
The Examiner first rejects claims 39, 62, 63, and 65 under 35 U.S.C.
§ 103(a) as being unpatentable over Katas3, Lu4, Birmingham5, and Gan6.
(See Ans. 3–5.) Appellant does not argue for the separate patentability of
any of these claims. We focus on claim 39 in our review. See 37 C.F.R.
§ 41.37(c)(1)(iv).
Appellant does not dispute the Examiner’s finding that Katas teaches
nanoparticles for siRNA delivery comprising chitosan ionically cross-linked
by sodium tripolyphosphate (“TPP”), which includes formula I of claim 39,
with “n” as 2. (See Ans. 4; see Katas abstract.) Appellant also does not
dispute the Examiner’s finding that Liu teaches that EZH2 is overexpressed
in endothelial cells associated with ovarian cancer or that Liu teaches

3 Katas and Alpar, “Development and characterisation of chitosan
nanoparticles for siRNA delivery,” J. Controlled Release, 115: 216–25
(2006).
4 Lu et al., “Gene Alterations Identified by Expression Profiling in
Tumor-Associated Endothelial Cells from Invasive
Ovarian Carcinoma,” Cancer Res., 67: 1757–68 (2007).
5 Birmingham, et al., “A prototol for designing siRNAs with high
functionality and specificity,” Nature Protocols, 2:2068–78 (2007).
6 Gan et al., “Modulation of surface charge, particle size morphological
properties of chitosan-TPP nanoparticles intended for gene delivery,”
Colloids and Surfaces B: Biointerfaces, 44:65–73 (2005).
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silencing of EZH2 with siRNA to block endothelial cell migration and tube
formation in vitro. (See Ans. 4; see Liu abstract, 1763, Figs. 3B and C.)
Although Katas teaches nanoparticles of chitosan and the
polyphosphate TPP for siRNA delivery, Katas does not teach nanoparticles
having chitosan to TPP in the weight ratio of 2.5:1 to 3.5:1, as required in
Appellant’s claim 39. Instead, Katas teaches reducing the weight ratio of
chitosan to TPP from 6:1 to 5:1 by lowering the pH ratio of the chitosan
solution. (See Katas 223.) Katas teaches further:
Generally, particle size of chitosan-siRNA complexes or
nanoparticles was highly dependent on the molecular weight,
type and concentration of chitosan used. However, in the case
of ionic gelation, other factors like weight ratio of chitosan to
TPP and pH of the chitosan solution were also shown to affect
the particle size.

(Katas 223 (emphasis added).) Thus, Katas supports the Examiner’s finding
that the weight ratio of chitosan to TPP affects the particle size. (See Ans.
5.) Katas teaches that the weight ratio of chitosan to TPP is a result effective
variable for particle size.
Gan teaches ways to control and modulate the properties of chitosan-
TPP nanoparticles, including particle size and density of surface charge,
which are reported to be central to gene transfection efficiency. (See Gan
66.) Gan teaches:
The effect of chitosan to TPP weight ratio on particle size was
also very prominent (Fig. 4), showing a linear increase of size
with increasing chitosan to TPP weight: ratio within the tested
chitosan to TPP ratio range. These linear relationships provide a
simple processing window for manipulation and optimizing the
nano size for intended applications.

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(Gan 68.) Thus, like Katas, Gan teaches that the chitosan to TPP weight
ratio is a result effective variable for the size of the nanoparticle. (See Gan
68, Fig. 4.)
As the Examiner finds, Gan teaches, further:
Particle size is one of the most significant determinant in mucosal and
epithelial tissue uptake of nanoparticles and in the intracellular
trafficking of the particles . . . . Smaller size nanoparticles (~ 100 nm)
demonstrated more than 3-fold greater arterial uptake compared to
larger nanoparticles (~27 5 nm) in an ex vivo canine carotid artery
model . . . as the smaller nanoparticles were able to penetrate
throughout the sub-mucosal layers while the larger size nanoparticles
were predominantly localized in the epithelial lining.

(Gan 68 (citations omitted); see Ans. 5.) This correlation between particle
size, a feature affected by the weight ratio of chitosan to polyphosphate,
supports the Examiner’s finding that “[i]t would have been obvious to one of
skill in the art to use routine experimentation and obtain nanoparticles
having a chitosan to TPP ratio of 3:1 with the reasonable expectation of
obtaining small chitosan nanoparticles exhibiting enhanced transfection
efficiency.” (Ans. 5.)
Appellant’s arguments begin by addressing Katas alone. (See Appeal
Br. 4–16.) Appellant argues that Katas does not teach a weight ratio of
chitosan to polyphosphate of 2.5:1 to 3.5:1 as required in claim 39, citing
the teaching in Katas of a chitosan:TPP ratio from 4:1 to 6:1. (See Appeal
Br. 4–5.) According to Appellant, Katas teaches that as the relative weight
of chitosan increases, the surface charge decreases and the particles become
smaller, which is more desirable for therapeutic applications. (See Appeal
Br. 5, citing Katas 219.) Thus, according to Appellant, Katas teaches
reducing the size of chitosan-TPP nanoparticles by increasing the weight
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ratio of chitosan:TPP – in contrast to the claimed lower ratio of 2.5:1 to
3.5:1. (See Appeal Br. 5.)
We are not persuaded by Appellant’s argument because the
Examiner’s rejection is not based on the teachings of Katas alone. Katas
teaches that particles size is affected by the weight ratio of chitosan to TPP
and Gan teaches that particle size is a significant determinant in mucosal and
epithelial tissue uptake of nanoparticles and in the intracellular trafficking of
the particles. (See Gan 68 and Katas 223.) The Examiner’s rejection is
based on the determination that one of ordinary skill would have known to
optimize the ratio to achieve the best size for efficient uptake from these
teachings of the prior art. (See Ans. 5.) Appellant’s assertions about the
chitosan to TPP weight ratios taught in Katas do not address the Examiner’s
rejection because they do not address the teachings of Gan7 as well or how
those of ordinary skill would have understood these teachings. “Non-
obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references.” In re Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Appellant argues that the composition recited in claim 39, with a
weight ratio of chitosan: polyphosphate of 2.5:1 to 3.5:1, has a substantially
lower zeta potential than particles with a weight ratio of either 5:1 or 7:1 and
a somewhat higher encapsulation efficiency. (See Appeal Br. 5, citing Spec.
Fig. 1B and C, and 11A–D.) Appellant also argues that EZH2 siRNA at a
3:1 weight ratio of chitosan:polyphosphate exhibited good tumor reduction

7 We note that in Figure 4 of Gan provides a data point for chitosan and TPP
in a weight ratio of 3, which is within the scope of Appellant’s claim 39.
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with two human ovarian tumor cell lines. (See Appeal Br. 6.) According to
Appellant, Katas provides no efficacy data or guidance about adjusting the
chitosan to polyphosphate ratio to affect the physical properties of the
particles. (See Appeal Br. 6.) Appellant cites to the Declaration of inventor
Gabriel Lopez-Berestein submitted under 37 C.F.R. § 1.132 on August 12,
2018 (“First Lopez Decl.”) in support of these arguments. (See Appeal Br.
6–8, citing First Lopez Decl. ¶¶ 4–5.)
We are not persuaded by these arguments. First, Katas expressly
teaches that the “weight ratio of chitosan to TPP and pH of the chitosan
solution were also shown to affect the particle size.” (Katas 223.) Thus,
Appellant’s argument that Katas provides no guidance on adjusting the
chitosan to polyphosphate level to affect physical properties is not supported
by the record. Whether other parameters also affect particle size, as
Appellant argues, does not change the teaching in Katas that the chitosan to
TPP weight ratio affects the physical property of particle size. (See Reply
Br. 2.)
Appellant cites to Dr. Lopez’s testimony regarding the balance
between stability (measured by zeta potential) and the encapsulation
efficiency achieved with a chitosan to polyphosphate ratio of 1:3. (See
Appeal Br. 5 and 7–8, citing First Lopez Decl. ¶ 5.) Claim 39 does not
recite specific zeta potential, encapsulation efficiency, stability, or tumor
reduction ability. To the extent these features are not inherent in the
limitations that are recited in claim 39, they need not be taught in the prior
art for the method to have been obvious.
Dr. Lopez also testifies to other advantages of the claimed method and
the composition recited in claim 39, but none of these advantages are recited
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in claim 39. For example, the method of claim 39 does not recite a specific
level of “knock down” or other efficacy achieved with the recited
composition. Thus, Dr. Lopez’s testimony regarding results of experiments
showing such advantages is not persuasive. (See First Lopez Decl., ¶¶ 7 and
9.)
In general, neither Dr. Lopez in his declarations, nor Appellant in the
Appeal Brief, address the contribution of the statement in Katas that “in the
case of ionic gelation, other factors like weight ratio of chitosan to TPP and
pH of the chitosan solution were also shown to affect the particle size” to the
Examiner’s obviousness rejection. (Katas 223.) Neither addresses the
statement in Gan that “[p]article size is one of the most significant
determinant in mucosal and epithelial tissue uptake of nanoparticles and in
the intracellular trafficking of the particles” or the teaching that smaller
nanoparticles demonstrate greater arterial uptake than larger nanoparticles,
as well as being able to penetrate throughout the sub-mucosal layers better.
(See Gans 68.) Thus, Appellant does not address why the claimed method
would not have been obvious over the prior art.
In the Reply Brief, Appellant argues that a weight ratio of chitosan to
TPP of 3:1 produces an “unexpected” increase in encapsulation efficiency
for the particles. (See Reply Br. 8.) Appellant does not direct us to evidence
that one of ordinary skill in the art would have considered this result to be
unexpected. Without such evidence, Appellant’s argument is unsupported.
Dr. Lopez testifies further that the results of studies on different ratios
of chitostan to TPP “demonstrated that significant transfection was achieved
at a CH:TPP ratio of 3:1, 3.75:1 and 5:1 but that a significant decrease in
efficiency was seen at ratios greater than 5:1 (i.e., at a 7:1 ratio[]).
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Significantly, the highest level of the transfection efficiency was seen at a
ratio of 3.75:1.” (Lopez Decl. ¶ 8; see also id. at ¶¶ 9, 10.) Because ratios
outside of the range recited in claim 39, for example 5:1 and 3.75:1, appear
to have the same effect as the range recited in the claim (2.5:1 to 3.5:1),
Appellant has not sufficiently demonstrated that the claimed range is critical.
Furthermore, because Katas teaches a ratio of chitosan to TPP of 5:1 (see
Katas 223), and Dr. Lopez testifies that this ratio produced results similar to
ratios within the claimed range, we agree with the Examiner that the record
fails to show any results of the claimed range that would not have been
expected from the prior art. (See Ans. 9 and 15–17.)
In light of the Dr. Lopez’s testimony about the effects of chitosan to
TPP ratios of 5:1 and 3.75:1, we are not persuaded by his opinion that “these
results are very surprising, highly unexpected and could not have been
predicted based on the very limited disclosure provided by the Katas
reference cited in the Office Action.” (Lopez Decl., ¶ 11; see Ans. 17.)
Appellant argues further that the claimed method would not have been
obvious because Katas fails to teach the weight ratio of polyphosphate to
therapeutic RNA of “less than 15:1” recited in claim 39. Appellant
calculates a weight ratio of “16.8,” which we understand to mean 16.8:18,
for the composition taught in Katas. (See Appeal Br. 12.) This calculation
is supported by a second declaration by Dr. Lopez submitted under 37
C.F.R. § 1.132 on September 3, 2018 (“Second Lopez Decl.”) at paragraph
four.

8 Appellant also refers to the ratio calculated from Katas as being “16.6:1.”
(Appeal Br. 14.)
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Appellant cites to Dr. Lopez’s testimony to argue that Katas “later
refers to reducing the ratio [of chitosan to TPP] to 5:1, but only when the pH
of formation was changed from 6 to 4.5. Although not stated, the ratio of
polyphosphate to siRNA in the 5:1 composition necessarily either stayed the
same or increased.” (Second Lopez Decl. ¶ 4 (emphasis added).) Dr. Lopez
fails to explain why reduction of a ratio of chitosan:TPP of 5:1 would
necessarily mean that the amount of siRNA, and thus the TPP:siRNA ratio,
would be the same. Neither Dr. Lopez nor Appellant directs us to evidence
that one would not consider it obvious to increase the relative amount of
siRNA when the ratio of chitosan:TPP is reduced to 2.5:1 to 3.5:1 as
claimed. Instead, we agree with the Examiner that increasing the amount of
siRNA in nanoparticles, and thus decreasing the polyphosphate:RNA ratio,
would have been obvious to one of ordinary skill in the art because the
purpose would be to obtain a more therapeutic composition, that is, more
siRNA. (See Ans. 18.)
In the Reply Brief, Appellant argues further that Katas provides no
motivation to produce particles with a polyphosphate to RNA ratio lower
than 16.8 and that:
On the contrary, turning to Figure 4C and the associated text
(paragraph bridging pages 219 and 220) it is stated that complete
binding was achieved with a ratio of chitosan-PP-siRNA of 100:1. If
these particles employed a chitosan to PP ratio of 5, then the ratio of
PP:siRNA would be 20. If the particles employed a chitosan to PP
ratio of 6, then the ratio of PP:siRNA would be about 16.6. We
contend that since Katas teaches that the ratio of chitosan-PP-siRNA
of 100:1, with a chitosan:PP ratio of either 5 or 6, is not only outside
of the scope of the claims, it is implicitly taught by Katas that, to
achieve 100% encapsulation, the ideal ratio is that set forth in Figure
4C and explained in the text. Furthermore, if one were to employ the
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preferred ratios of Katas in the context of Appellant’s claimed 3.5:1
ratio of chitosan to PP, one then arrives at a ratio of PP to therapeutic
RNA of 20:1, the exact opposite direction from what is claimed!

(Reply Br. 12 (emphasis added).)
We are not persuaded by these arguments because we are not
persuaded that the TPP:siRNA ratio extrapolated from the amounts of
components taught in Katas are necessarily “the ideal ratio” as Appellant
asserts. Katas teaches only that “all tested chitosans show complete binding
of siRNA for chitosan-TPP nanoparticles with entrapped siRNA”
referencing Figure 4C, which provides a weight ratio of chitosan-TPP to
siRNA of 100:1. (See Katas 219–220, Fig. 4C.) Katas does not report the
binding of any other chitosan-TPP to siRNA ratio. Therefore, it is not clear
whether a lower chitosan-TPP to siRNA ratio would also exhibit complete
binding of the siRNA and, thus, a lower TPP to siRNA ratio. The discussion
of complete siRNA binding in Katas is not sufficient to persuade us that the
Examiner erred in determining that it would have been obvious to one of
ordinary skill in the art to increase the amount of siRNA to obtain a more
therapeutic composition.
Appellants argues further, relying on Dr. Lopez’s testimony, that the
formulation taught in Katas has the disadvantage of being less stable. (See
Appeal Br. 13, citing Second Lopez Decl. ¶ 6.) Dr. Lopez provides data in
an Exhibit A to his second declaration, stating: “There it can be seen that at
ratios of chitosan to TPP of 3.75:1 and a ratio of TPP to RNA of greater than
about 8, the RNA remained fully intact even after 24 hours incubation in
50% serum!” (Second Lopez Decl., ¶ 6.) We are not persuaded by this
testimony or evidence because it relates to a composition with a weight ratio
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of chitosan to TPP of 3.75:1, which is outside of the range of 2.5:1 to 3.5:1
recited in Appellant’s claim 39. (See Ans. 18.) Thus, Dr. Lopez’s testimony
about any surprising and unexpected stability in serum is not persuasive
evidence of non-obviousness of the present claims.
Appellant argues further that Gan fails to contribute to the
obviousness of the method of claim 39 because it presents studies of
chitosan-polyphosphate complexes that are free of nucleic acid, rather than
studies of siRNA-chitosan-polyphosphate. (See Appeal Br. 17; see Reply
Br. 4.) According to Appellant, there would be no basis for equating the
effects of siRNA particles and DNA particles because each has a different
structure. (See Appeal Br. 17.) Appellant argues further:
One of skill would never equate the physicochemical attributes
of a chitosan-polyphosphate-DNA complex with a chitosan-
polyphosphate-siRNA complex for several reasons. For one,
genes are typically very large molecules with an average length
of around 8000 base pair residues. In contrast, siRNAs are quite
small, on the order of 20-24 bases. While these molecules are
initially double-stranded they become single stranded when
they exert their biological effect.

(Appeal Br. 17–18.) In the Reply Brief, Appellant cites to the statement in
Katas “that siRNA bind to chitosan in a different manner from that observed
with pDNA,” to argue that Katas is not combinable with Gan. (Reply Br. 3,
citing Katas 223.)
We are not persuaded by these arguments because they do not address
the teachings of Katas and Gan regarding the size of the nanoparticle and its
uptake by tissues. Although there may be differences between siRNA and
DNA, Appellant does not direct us to evidence that one of ordinary skill in
the art would have considered the difference in size or in any other feature of
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DNA and siRNA molecules to have an effect on the size of chitosan/TPP
nanoparticles and the resulting transfection efficacy.
In general, we are not persuaded by Appellant’s arguments that Gan is
irrelevant to the teachings of Katas or to transfection because it does not
present data with particles loaded with nucleic acid. (See Appeal Br. 17;
Reply Br. 4.) This narrow reading of Gan fails to consider that the main
focus of Gan is on gene delivery. The abstract of Gan states that the work
provided
demonstrates that ionic gelation of cationic chitosan molecules offers
a flexible and easily controllable process for systemically and
predictably manipulating particle size and surface charge with are
important properties in determining gene transfection efficacy if the
nanoparticles are used as non-viral vectors for gene delivery, or as
carriers for protein molecules.

Gan is relevant to the teachings of Katas because it is directed to the same
field – transfection of nucleic acids with chitosan/TPP nanoparticles.
Because we are not persuaded by Appellant’s arguments that the
Examiner erred, we affirm the rejection of claim 39, and of claims 62, 63,
and 65 over Katas, Lu, Birmingham, and Gan.
Other Rejections
The Examiner also rejected Appellant’s claims 39 and 62–65 under 35
U.S.C. § 103(a) as being obvious over Katas, Lu, Birmingham, Gan, and Ji9.
(See Ans. 6.) Claim 64 recites the method of claim 39 “wherein the siRNA
is a combination of EZH2 Mm siRNA and EZH2 Hs siRNA.” (Appeal Br.

9 Ji et al., “Enhanced gene silencing by the application of multiple specific
small interfering RNAs,” FEBS Lett., 552:247–42 (2003).
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22.) Ji was cited for its teaching of to use two or more siRNAs directed to
different sites on the same gene to achieve enhanced silencing compared to
single siRNA. (See id., citing Ji abstract, p. 251.)
Appellant argues that Ji is irrelevant because it does not have any
disclosure of EZH2 Hs siRNA or EZH2 Mn SiRNA or a combination of
both. (See Appeal Br. 18.) We are not persuaded by this argument because
Appellant’s Specification indicates that Mm siRNA and Hs siRNA were
commercially available at the time. (See Spec. 61:29–3i (“Nonsilencing
control siRNA and EZH2 Hs siRNA were purchased from Qiagen, and
EZH2 Mm siRNA was purchased from Dharmacon (Chicago, IL).”)
Appellant’s argument focuses on Ji only, without addressing the entirety of
the Examiner’s rejection. See Merck, supra.
The Examiner rejected claims 39, 44–46, 48, 62, 63, and 65 under 35
U.S.C. § 103(a) as being obvious over Katas, Lu, Birmingham, Gan, and
Rubinfeld10. (See Ans. 6–7.) Appellant argues that “Rubinfeld is not
combinable with the primary references and do not cure the inadequacies of
Katas as discussed above.” (See Appeal Br. 18–19.) We are not persuaded
by Appellant’s argument because, as discussed above, we find no
inadequacies in the Examiner’s citation of Katas. Furthermore, Rubinfeld
was cited for its teaching of intravenous administration of anti-EZH2 siRNA
alone or in combination with a chemotherapeutic agent. (See Ans. 6–7,
citing Rubinfeld abstract, ¶¶ 56, 134, et al.) We are not persuaded that the
Examiner erred by combining the use of EZH2 siRNA as taught in

10 Rubinfeld, U.S. Patent Application Publication 2005/0059682 A1,
published March 17, 2005.
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Rubinfeld with the teachings of making siRNA nanoparticles in the other
cited references.
The Examiner rejected claims 39, 62, 63, and 65 under 35 U.S.C.
§ 103(a) as being obvious over Katas, Lu, Birmingham, Gan, and
Mahapatra11. (See Ans. 7.) The Examiner also rejected claims 39, 44–48,
62, 63, and 65 under 35 U.S.C. § 103(a) as being obvious over Katas, Lu,
Birmingham, Gan, Rubinfeld, and Spannuth12. (See id. at 8.) Appellant
argues that Mahapatra and Spannuth fail to disclose EZH2, chitosan/TPP, or
ratios of chitosan/TPP or TPP/siRNA. (See Appeal Br. 19–20.) Again, this
argument is not persuasive because it does not address the Examiner’s
rejection, which is based on a combination of the teachings of the cited prior
art, including the teachings in Katas, Lu, Birmingham, and Gan of the
effects of the ratio of the components of a chitosan/TPP nanoparticle and
targeting of EZH2.
Because we are not persuaded by Appellant’s arguments that the
Examiner erred, we affirm the Examiner’s other rejections under 35 U.S.C.
§ 103.
Conclusion
Upon consideration of the record and for the reasons given, we
AFFIRM the Examiner’s rejection.

11 Mohapatra, U.S. Patent Application Publication 2005/0266093, published
December 1, 2005.
12 Spannuth et al., “Angiogensis as a strategic target for ovarian cancer
therapy,” Nat. Clin. Pract. Oncol., 5:194–204 (2006).
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In summary:
Claims
Rejected
35 U.S.C. § Basis Affirmed Reversed
39, 62, 63, 65 103 Katas, Lu,
Birmingham,
Gan
39, 62, 63, 65
39, 44–46, 48,
62, 63, 65
103 Katas, Lu,
Birmingham,
Gan, Rubinfeld
39, 44–46,
48, 62, 63, 65

39, 62, 63, 65 103 Katas, Lu,
Birmingham,
Gan, Mohapatra
39, 62, 63, 65
39, 44–48, 62,
63, 65
103 Katas, Lu,
Birmingham,
Gan, Rubinfeld,
Spannuth
39, 44–48,
62, 63, 65

Overall
Outcome
39, 41, 42,
44–48, 62–65

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