Georgia State University Research of Foundation, Inc.

Patent Trials and Appeals Board

Apr 14, 2021

2020005199 (P.T.A.B. Apr. 14, 2021)

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.
14/400,846 11/13/2014 Gangli Wang GSURF 2012-11 8469
23579 7590 04/14/2021
PABST PATENT GROUP LLP
1545 PEACHTREE STREET NE
SUITE 320
ATLANTA, GA 30309
EXAMINER
LAMBERSKI, JENNIFER A
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
04/14/2021 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@pabstpatent.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte GANGLI WANG,
ZHENGHUA TANG, CECIL CONROY,
and TARUSHEE AHUJA

Appeal 2020-005199
Application 14/400,846
Technology Center 1600
____________

Before ERIC B. GRIMES, RICHARD M. LEBOVITZ, and
FRANCISCO C. PRATS, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
The Examiner rejected claims 1–16, 18–20, and 32–35 under 35
U.S.C. § 103 as obvious. Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals
from the Examiner’s decision to reject the claims. We have jurisdiction
under 35 U.S.C. § 6(b).
We REVERSE.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as Georgia State
University Research Foundation, Inc. Appeal Br. 2.
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STATEMENT OF THE CASE
The Examiner rejected claims 1–16, 18–20, and 32–35 in the Final
Office Action as follows:
1. Claims 1–4, 6–8, 12, 13, 16, and 32–34 under 35 U.S.C. § 103(a) as
obvious in view of Wang et al., J. Phys. Chem. B, 2006, 110, 20282–20289
(“Wang–1”). Final Act. 5.2
2. Claims 1–8, 11–13, 16, and 32–35 under 35 U.S.C. § 103(a) as
obvious over Wang–1, Lim et al., Nanotechnology, 20:405701, 2009
(“Lim”), and Liu et al., Sci. China Chem., 54: 1157–1176, 2011 (“Liu”).
Final Act. 8.
3. Claims 1–4, 6–10, 12, 13, 16, and 32–35 under 35 U.S.C. § 103(a)
as obvious in view of Wang–1 and Hostetler et al., J. Am. Chem. Soc.,
120:9396–9397, 1998 (“Hostetler”). Final Act. 9.
4. Claims 1–4, 6–8, 12–16, and 32–35 under 35 U.S.C. § 103(a) as
obvious in view of Wang-1, Jupally et al., J. Am. Chem. Soc., 133:20258–
20266, 2011 (“Jupally”), and U.S. Published Application No. US
2006/0286305 Al to Thies et al., published Dec. 21, 2006, (“Thies”). Final
Act. 10.
5. Claims 1–4, 6–8, 12, 13, 16, 18, 19, and 32–34 under 35 U.S.C. §
103(a) as obvious in view of Wang-1 and de la Fuente, et al., Langmuir,
22:3286–3293, 2006 (“Fuente”). Final Act. 10.
6. Claims 1–4, 6–8, 12, 13, 16, 20, and 32–34 under 35 U.S.C. §
103(a) as obvious in view of Wang-1 and Zhang et al., Bioorg. Med. Chem.,
18:5528–5534, 2010 (“Zhang”). Final Act. 11.

2 The alternative ground of this rejection under 35 U.S.C. § 102(b) was
withdrawn by the Examiner. Ans. 9.
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Claim 1, the only independent claim on appeal, is reproduced below:
1. Monolayer protected nanoclusters comprising clusters
and a monolayer comprising a plurality of ligands bound to the
clusters,
wherein the plurality of ligands comprises one or more
ligands selected from the group consisting of mercaptosuccinic
acid, tiopronin, dithiols, and combinations thereof, and
wherein the monolayer protected nanoclusters display
near-IR luminescence with a quantum efficiency that is greater
than 1%.

Appeal Br. 35 (Claims App.).
An oral hearing was held in this appeal on March 2, 2021. A transcript
of the hearing has been entered into the record.

REJECTIONS
Claim 1 is directed to a monolayer protected nanocluster, referred to
as an “MPC” throughout this decision and in the cited publications. The
claimed MPC comprises “clusters” and a “monolayer” of ligands bound to
the clusters. The claim requires the ligands to be one of three choices,
mercaptosuccinic acid (“MSA”), tiopronin, dithiols, and combinations
thereof. Each of these ligands comprises sulfur. The MPCs display near-IR
luminescence with a quantum efficiency (“QE”) that is greater than 1%.
The claim does not limit the type of “clusters” comprising the MPC
with the recited QE property, but dependent claim 3 lists the clusters as
comprising “metal atoms or mixtures of metal atoms, metal oxides, metal
atoms bridged by non-metallic elements, and combinations thereof” and
dependent claim 4 lists the metal as selected from “aluminum, tin,
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magnesium, gold, copper, nickel, iron, cobalt, magnesium, platinum,
palladium, iridium, vanadium, silver, rhodium, ruthenium, and combinations
thereof.”
The Specification does not provide a definition of quantum efficiency.
However, based on disclosure in the Specification, the prior art cited in this
appeal, and the Zheng Declaration,3 we understand that a high quantum
efficiency is desirable because it bears a relationship to the light emission
intensity of the MPC, and a high light emission intensity is a desirable
property of an MPC. Spec. 18:1, 34: 21–22; Wang-1, 20284 (right col., 1st
full para.), Zheng Decl. ¶ 8. The claimed MPCs are required by the claim to
display Near-infra red (“Near-IR”) luminescence which is defined in the
Specification as follows:
“Near-infra red” and “Near-IR” are used interchangeabl[y] and
refer to electromagnetic radiation having a wavelength from
about 650 nm to about 1400 nm, preferably about 700 nm to
about 1400 nm. In some embodiments, “near-IR” luminescence
refers to the emission maximum at a wavelength of about 700
nm or greater or a the [sic] total emission at greater than 50% is
at a wavelength of about 700 nm or greater.
Spec. 25:21–26.
The Specification explains that MPCs with these optical properties
“are highly favorable for biomedical applications because tissues are most
transparent within the spectrum range of about 650 to about 900 nm.” Spec.
1:13–15. The Specification discloses that MPCs with these properties can be
used in imaging and hyperthermia therapeutics. Spec. 1:15–17. Thus, the
recited nanoclusters with the recited “near-IR luminescence with a quantum

3 Appellant provided a declaration by Jie Zheng, Ph.D. (executed July 13,
2017) which is also referred to as the “Zheng Declaration” or “Zheng Decl.”
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efficiency that is greater than 1%” are useful in biomedical applications
because of their spectrum range and light emission intensity associated with
the quantum efficiency.
The Examiner rejected all the claims over Wang-1 alone, or in
combination with additional publications, depending on the type of cluster in
the MPC. Wang-1, which describes MPCs comprising gold (“Au”) clusters,
was cited by the Examiner for making it obvious to obtain MPCs that
“display near-IR luminescence with a quantum efficiency that is greater than
1%” as recited in claim 1. Ans. 3–4. The Examiner acknowledged that Wang
does not teach a QE greater than 1% as in claim, but found it would have
been obvious to have optimized Wang-1 to achieve a QE within the claimed
range. Ans. 4. The Examiner did not rely on the additionally cited
publications in Rejections 2–6 as evidence of the obviousness of achieving a
QE within the claim scope, but focused solely on Wang-1.
Appellant disagrees that such optimization would have been obvious
to one of ordinary skill in the art at the time the invention was filed. Appeal
Br. 20.
DISCUSSION
The Examiner found that it would have been obvious to a person of
ordinary skill in the art at the time the invention was made “to optimize the
QE of the gold MPCs of Wang to within known amounts, e.g., 0.1–10%” to
achieve a QE within the claimed range. Ans. 4. The Examiner found that
“QE is clearly a results effective parameter that a person of ordinary skill in
the art would routinely optimize.” Id. The Examiner explained:
Optimization of parameters is a routine practice that would be
obvious for a person of ordinary skill in the art to employ. It
would have been customary for an artisan of ordinary skill to
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determine the optimal QE needed to achieve the desired results.
As noted in Wang, the PL [luminescence emission intensity]
and QE are influenced by the nature of the surface ligand, the
number of ligands attached to the gold MPCs, and the size of
the gold MPCs, and QEs greater than 10% are quite impressive.
Thus one of ordinary skill would optimize the QE by adjusting
the nature of the surface ligand, the number of ligands attached
to the gold MPCs, and the size of the gold MPCs in order to
achieve the desired QE.
Ans. 4.
The dispute in this appeal is whether it would have been obvious to
one of ordinary skill in the art at the time the application was filed to have
optimized Wang-1 to have achieved MPCs which “display near-IR
luminescence with a quantum efficiency that is greater than 1%.” We begin
the analysis with Wang-1.
MPCs comprise a cluster of atoms and a monolayer of ligands bound
to the cluster. Wang-1 describes monolayer-protected Au38 and Au140
clusters comprising different ligands. Wang-1 Abstract. The monolayer-
protected Au clusters in Wang-1 are MPCs. Id. The values of 38 and 140 are
the number of Au atoms in the MPC core cluster. Wang-1 20282. Wang-1
discloses various sulfur containing ligands in the monolayer bound to the Au
clusters, including tiopronin (Wang-1 20283 (Table 1)), which is one of
three ligands recited in rejected claim 1.
The experiments described in Wang-1 involve the exchange, or
replacement, of one ligand for another ligand on an MPC comprising Au
clusters. Wang-1 20284 (right col.). Using this technique, Wang-1’s
experiments demonstrated that “near-infrared photoluminescence of
monolayer-protected Au38 and Au140 clusters (MPCs) is intensified with the
exchange of nonpolar ligands by more polar thiolate ligands,” the latter of
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which are sulfur-containing ligands, including the claimed tiopronin ligand.
Wang-1 Abstract.
Wang-1 describes the synthesis of the MPC, Au38(SC2Ph)24 which
served as the exchange MPC in Wang-1’s experiments. Wang-1 20283–
20284. This MPC was mixed with the thiols listed in Wang-1’s Table 1 and
measurements were made as the thiol ligands replaced the ligands on the
Au38(SC2Ph)24 MPC. Wang-1 20284, 20285. This process is referred to by
Wang-1 as “ligand exchange.” Wang-1 20283. Wang-1 reported QE
enhancement as a result of the ligand exchange “assuming that quantum
efficiency is proportional to emission intensity” (Wang-1 20284, 2nd col.)
and recorded it in Table 1 as “emission QE enhancement” (Wang-1 20283
(Table 1)). While the reported values in Table 1 are QE enhancement, the
measurements in Wang-1 are of luminescence intensity (“PL”). See Wang-1
Figs. 1–3; Table 1 (footnote a).
Based on this disclosure in Wang-1 the Examiner found that “QE is
optimizable based on the size of the MPCs, nature of the surface ligand, the
number of ligands attached to the MPCs.” Ans. 10. The Examiner cited the
following disclosures from Wang-1 to support her position (numbered herein
as W1–W4, where “W” is shorthand for Wang-1).
W1.
Quantum confinement effects become significant when the
dimensions of the metal object are greatly decreased, and
among other changed properties, luminescence becomes more
likely.
Wang-1 20282 (right col.).

W2.
The reason(s) for the discord among ligand types in the
nanoparticle size dependency of the Au MPC luminescence
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energy is unclear. Variations in Au nanoparticle luminescence
intensities are, on the other hand, more consistent; emission
intensities of both PAMAM- and thiolate-protected
nanoparticles increase with decreasing size, and at the smallest
sizes, attain quite impressive (>10%) quantum efficiencies.
Wang-1 20283 (left col.).

W3.
Figure 3 amplifies the linear correlation between exchanged
ligand number and emission intensity of Au38(SC2Ph)24 MPCs
for the thiophenolate series I-V by plotting them directly
against one another. These linear changes of luminescence
intensity with nanoparticle ligand count are remarkable and, as
far as we know, unprecedented among nanoparticle spectral
observations.
Wang-1 20286 (spanning left and right cols.).

W4.
Ligand exchange to the extent of ca. seven TMA ligands (after
product cleanup and NMR analysis) increases the QE to ~2 x
10-4, a roughly 10-fold increase. Exhaustive exchange of all of
the Au140 MPC thiolate ligands has not been achieved, but
extrapolation of the data predicts that a completely TMA-
ligated Au140 MPC should exhibit a quantum efficiency of ca.
10-3, or 0.1%.
Wang-1 20287 (left col.) (footnotes omitted).
The disclosures in Wang-1 cited by the Examiner establish that
emission intensity increases with decreasing size of the cluster (W2), that
ligand exchange with the thiolate ligands increased PL luminescence linearly
(W3), and that this ligand exchange also increased QE (W4). While this data
establishes that increasing the content of the thiolate ligands, including the
claimed ligand tiopronin, in MPCs also increases PL and QE, the question in
this appeal is narrower. Specifically, the question is whether Wang-1
describes the conditions necessary to optimize the production of an MPC
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having “near-IR luminescence with a quantum efficiency that is greater than
1%” with a reasonable expectation of success.
The Examiner found that the size of the cluster is one of the
optimizable parameters, namely decreasing the cluster atom size results in
increased PL and QE. Ans. 4, 10 (citing W1 at 20282 above). While it is
correct that Wang-1 describes a relationship between cluster size and
luminescence, the full passage on page 20282 of Wang-1 – not quoted by the
Examiner – gives a more complete understanding of its teachings:
Quantum confinement effects become significant when the
dimensions of the metal object are greatly decreased, and
among other changed properties, luminescence becomes more
likely. Luminescence of a variety of Au nanoparticles, nearly
all <5 nm diameter and with capping ligands ranging from
citrate to PAMAM dendrimer to thiolate, has been reported.
PAMAM Au nanoparticle luminescence energies are reported
to vary strongly with their size, from 3.2 to 1.4 eV for Au5 to
Au31. In contrast, thiolate-protected Au nanoparticle
luminescence energies vary more modestly with size, for
example that from glutathione-protected MPCs ranging in size
from Au10 to Au39 lies in the 1.4-1.7 eV range. The broad 1.1-
1.3 eV NIR [Near-IR] emission in a collection of Au13, Au38,
and Au140 MPCs having a variety of different thiolate
monolayers also varied scarcely at all. The reason(s) for the
discord among ligand types in the nanoparticle size dependency
of the Au MPC luminescence energy is unclear. Variations in
Au nanoparticle luminescence intensities are, on the other hand,
more consistent; emission intensities of both PAMAM- and
thiolate-protected nanoparticles increase with decreasing size,
and at the smallest sizes, attain quite impressive (>10%)
quantum efficiencies.
Wang-1 20282–20283 (underlining added, footnotes omitted).
The Examiner only cited the first sentence of this paragraph. The
remaining paragraph indicates that both ligand type and cluster size are
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factors in determining the luminescence of MPCs. As to the ligand type,
Wang-1 discloses that NIR emissions varied “scarcely at all” for different
thiolate ligands in a collection of Au MPCs for reasons that are “unclear.”
Thiolate ligands contain a sulfur atom. Spec. 3: 16–17. Therefore, based on
this disclosure from Wang-1 about the effect of ligands on MPCs, it cannot
be concluded that one of ordinary skill in the art on the application filing
date could have predicted the effect of one of three different ligands recited
in claim 1 on the near-IR luminescence of an MPC.
The same passage copied also, in describing the background to the
experiments in Wang-1, states that decreasing size of the cluster leads to
increased emissions intensities and quantum efficiencies. Wang-1 referenced
two publications, footnotes 3 and 32, respectively, to support this statement.
Footnote 3 is to the Zheng publication,4 a publication listing Dr. Zheng as
first author, the same Dr. Zheng who authored the Zheng Declaration.
Footnote is to 32 is to another Wang publication, Wang-2.5
In his declaration, Dr. Zheng states, with respect to his scientific
expertise, that he has “been working in the field of nanotechnology, single
molecule spectroscopy, and bioimaging for more than 15 years” and that he
has “performed research on the in vivo and in vitro luminescent properties of
metal nanoclusters that are encapsulated in organic molecules, such as
polymers.” Zheng Decl. ¶ 1. Dr. Zheng explains in his declaration that the
results in the Zheng publication are not applicable to gold MPCs. Dr. Zheng
explains:
[T]he statement of Wang-1 on page 20283 to the effect that
emission intensities of gold MPCs increase with decreasing size

4 Zheng et al., Phys. Review Lett., 93(7): 077402-1–077402-4, 2004.
5 G. Wang et al., J. Am. Chem. Soc., 127, 812–813, 2005.
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is not predictive of changes in emission intensities of the MPCs
described in the amended claim because the statement is based
on unrelated ligands with confounding features. Based on my
experience, those in the field of bioimaging involving MPCs
would not have any reason to expect that substituting the
PAMAM dendrimers in the MPCs of Zheng with the thiolate-
containing ligands described in the amended claims would
result in MPCs with a QE greater than 1%, at least because they
would have different relaxed midgap energy states.
Zheng ¶ 14.
Dr. Zheng’s statement about lack of predictability is also consistent
with Wang-1’s disclosure discussed above that NIR emissions varied
“scarcely at all” for different thiolate ligands in a collection of Au MPCs for
reasons that are “unclear.”
Wang-2, cited in Wang-1 for showing that the emission-intensity of
thiolate-protected nanoparticles increases with decreasing size of the cluster,
also shows in Figure 2B that the intensity increased as the number of Au
atoms in an Ag/Au-tiopronin MPC increased:
A similar quantitative dependence (Figure 2B) was observed in
core metal galvanic exchange reactions of tiopronin-coated Ag
MPCs with Au(I)[p-SCH2(C6H4)C(CH3)3, at various mole ratios
of the two . . . The final Au MPC-like emission increases
linearly with the reactant ratio of Au(I)[p-SCH2(C6H4)C(CH3)3]
to silver MPCs; analysis of the products reveals that the
increase is linear with the number of incorporated gold atoms
per MPC core.
Wang-2 812–813 (emphasis added).
Thus, it is not immediately predictable from this disclosure that
reducing the size of the Au cluster would increase emission intensity as
asserted by Wang-1 and the Examiner, because in the exchange experiment
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performed by Wang-2, the intensity increased in proportion to the number of
Au atoms.
The Examiner cited Wang-1 (W4) as showing it was obvious to
optimize the QE to the amount of greater than 1% as recited in claim 1. Ans.
4, 11. However, this disclosure in Wang-1 acknowledges that exhaustive
exchange of the thiolate ligand had not been achieved and that extrapolation
of the data in Wang-2 (footnote 32) would result in a QE of 0.1% for the
TMA ligand. This value is 10-fold below the claimed value of greater than
1%, indicating the opposite of what the Examiner asserts, namely, that if the
method of making the MPC is optimized to get full ligand exchange, a QE of
only about 0.1% would be achieved.
The Examiner also found that there is a relationship between
luminescence and quantum efficiency and that therefore increasing
luminescence would necessarily increase QE. However, while the disclosure
in Wang-1 may have led the Examiner to make such a statement, Appellant
provided additional evidence, a publication by Muhammed,6 that is
inconsistent with a strict relationship between the two. Muhammed, as
explained by Appellant in reference to Figure 4 of Muhammed,
“demonstrates that luminescence emission intensities are not correlated with
quantum efficiencies of MCPs.” Appeal Br. 17. Figure 4 of Muhammed
shows that “Au8 (Traces I and II) and Au25 (Traces III and IV) both display
very similar maximum PL [luminescence intensity] values of about 160, but
the observed quantum efficiencies of Au8 and Au25 were different, 15% and
0.19%.” Appeal Br. 17. Figure 4 of Muhammed is reproduced below:

6 M. A. H. Muhammed et al., Nano Res., 1: 333-340, 2008.
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Figure 4, copied above from Muhammed, shows a “Comparison of the
photoluminescence profiles of the clusters with Au@MSA.” Muhammed
336. “Traces I and II are the excitation and emission spectra of Au8,
respectively. Traces III and IV are the excitation and emission spectra of
Au25.” Id. Appellant’s statement about Muhammed is consistent with the
graph reproduced above, at least, that the emission intensity of Au8 and Au25
clusters with mercaptosuccinic acid (MSA), which is one of three claimed
ligands, have about the same emission intensity value of 160 (y-axis) at their
spectra peak (x-axis) (see traces II and IV). In this example, the emission
intensity did not change as the Au cluster size varied from Au8 to Au25.
Appellant also relied upon Muhammed as teaching MPCs that have
the same components but do not have the same quantum efficiencies. Appeal
Br. 15. As explained by Appellant, Muhammed shows that MSA Au25
exhibits near-IR luminescence,7 but its QE is 0.19%, while MSA Au8 has a

7 Near-IR has a wavelength “from about 650 nm to about 1400 nm,
preferably about 700 nm to about 1400 nm.” See Spec. 25:21–26.
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quantum efficiency of 15%,8 but it does not show near-IR luminescence. See
Muhammed, Figure 4, showing that II, associated with Au8, shows an
emission peak below the Near-IR, while IV, the emission spectrum of Au25,
has an emission peak in the near-IR. The claim requires that the cluster
display near-IR luminescence. Therefore, it is not predictable from
Muhammed that a MPC with Au and MSA would have near IR-
luminescence and a QE within the scope of claim 1. Muhammed was
originally cited by the Examiner in a § 103 rejection,9 but was withdrawn by
the Examiner upon Appellant making the same argument above.10 We could
not identify a response by the Examiner to this argument at that time, nor a
response to it when the same argument was made in the Appeal Brief.
Dr. Zheng states in the declaration that “it is not possible, as the
Examiner suggested, to calculate or predict the QE of an MPC from only the
maximum PL of the MPC or of another MPC.” Zheng Decl. ¶ 8. Dr. Zheng
showed an equation describing “the standard relationship of QE to intensity
(I), absorbance (A), and refractive index (ƞ),” explaining the QE cannot be
directly predicted from intensity, as asserted by the Examiner, because
absorbance and refractive indices are also factors affecting the QE of an
MPC. Zheng Decl. ¶ 10. Dr. Zheng’s testimony is also consistent with
Muhammad as discussed above.
Dr. Zheng states in his declaration that the Examiner was not correct
in concluding that “it is possible to optimize the QE of gold MPCs such as

8 “The quantum yields calculated for Au8 and Au25 were 0.15 and
1.9xl0-3, respectively, which are in agreement with the reported
values.” Wang-2 336 (left col.).
9 Office Action (dated Mar. 22, 2016) 7.
10 Response to Office Action (dated Aug. 16, 2016) 10–11.
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those of Wang-I to a desired QE within the range 0.1-10%.” Zheng Decl.
¶ 14. Dr. Zheng explains that the Examiner is incorrect “because the
relationship of the characteristics of MPCs and their QE were not
sufficiently known, direct, or predictable to allow for directed optimization.”
Id. Dr. Zheng, as explained above, explained why the results of MPCs with
PAMAM dendrimers would not be predictive of MPCs with the ligands
required by claim 1. Id.
Appellant’s own data in the Specification shows variability in
quantum efficiency. Table 1 contains entries for MSA-Au and tiopronin-Au
MCPs, both ligands encompassed by claim 1.
For MSA-Au MPC’s prepared with a 15x ligand:Au synthesis ratio,
three MPCs had QE’s less than 1% (0.4, 0.8, 0.6) and one MPC had a QE
greater than 1% (1.7).
For tiopronin-Au MCPs prepared with a 3x ligand:Au synthesis ratio,
one MPC was less than 1% (0.7) and the other was greater than 1% (1.8).
Thus, despite having the same components and prepared under the
same conditions, variability in QE was observed, consistent with
Muhammed and Dr. Zheng’s declaration that QE could not be routinely
optimized because the same conditions and components produce variable
results. Appellant addressed this issue in the Specification by using a
technique known as “etching” which increased all the MPCs in Table 1 to
above 1%. Spec. 19:6–20:1.11

11 “It is believed that the annealing process enhances the optical and/or
electrochemical properties of the nanoclusters by: (1) optimizing the ligand
arrangement; (2) favoring formation of more stable nanoclusters, and/or (3)
modifying less stable compositions and/or ligand attachments to improve
stability.”
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The Examiner correctly recognized that “the nature of the surface
ligand, the number of ligands attached to the gold MPCs, and the size of the
gold MPCs” are factors to be considered when producing MPCs with the
goal of increasing their luminescence and QE. Ans. 4. However, the
Examiner’s conclusion that QE could be routinely optimized based on these
factors is not supported by the evidence in this record. Specifically, as
discussed above, it is unclear how the ligand type would affect luminescence
(see Wang-1) and how the number of atoms in the MPC would affect
luminescence and therefore QE (see Wang-2). While Wang-1 provides
evidence that increasing ligand number also increases luminescence,12 there
is a lack of expectation of success that increasing the luminescence intensity
would predictably result in increased QE and Near-IR luminescence (see
Muhammed). Wang-1 refers to achieving “[e]xhaustive exchange” of
ligands to increase QE (Wang-1 20287, left col.), but the value cited by
Wang-1 is far less than the required value in claim 1. Even using the same
ligand, Muhammed shows that Near-IR luminescence is not always
obtained. While it is admitted by the inventors that “QE . . . increases with
the decrease of core size from about 2.2 nm” of an MPC,13 their own data, as
discussed above, shows the unpredictability of achieving a QE within the
scope of claim 1.

12 For tipronin, Wang-1 shows that as the number of exchanged ligands
increased, the PL increased, as well. Wang-1 20285–20286 (see Fig. 2(B)).
Wang-1 states that “All of the Au38(SC2Ph)24 MPC ligand exchanges using
the latter three thiol groups enhance the NIR emission intensities.” Wang-1
20286 (right col., second full para.).
13 Spec. 2:2–3.
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To establish obviousness under 35 U.S.C. § 103, one of ordinary skill
in the art must have a reasonable expectation that the prior art, when
combined, would succeed in making the claimed invention. In re Merck &
Co., Inc., 800 F.2d 1091 (Fed. Cir. 1986). Obviousness, however, does not
require “absolute predictability of success.” In re O’Farrell, 853 F.2d 894,
903–04 (Fed. Cir. 1988). In some cases, however, “the evidentiary basis for
an inference of reasonable expectation of success may be inadequate.”
Accorda Therapeutics, Inc. v. Roxane Laboratories, Inc., 903 F.3d 1310,
1333–34 (Fed. Cir. 2018). Here, we find that there is insufficient evidence to
establish a reasonable expectation of success. Accordingly, for the reasons
discussed above, we reverse the obviousness rejections 1–6 of claim 1, and
dependent claims 2–16, 18–20, and 32–35.

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Application 14/400,846

18
CONCLUSION
In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1–4, 6–8,
12, 13, 16,
32–34
103(a) Wang-1 1–4, 6–8,
12, 13, 16,
32–34
1–8, 11–
13, 16, 32–
35
103(a) Wang-1, Lim, Liu 1–8, 11–
13, 16, 32–
35
1–4, 6–10,
12, 13, 16,
32–54
103(a) Wang-1, Hostetler 1–4, 6–10,
12, 13, 16,
32–35
1–4, 6–8,
12–16, 32–
35
103(a) Wang-1, Jupally,
Thies
1–4, 6–8,
12–16, 32–
35
1–4, 6–8,
12, 13, 16,
18, 19, 32–
34
103(a) Wang-1, de la
Fuente
1–4, 6–8,
12, 13, 16,
18, 19, 32–
34
1–4, 6–8,
12, 13, 16,
20, 32–34
103(a) Wang-1, Zhang 1–4, 6–8,
12, 13, 16,
20, 32–34
Overall
Outcome
1–16, 18–
20, 32–35

REVERSED