Preethi H. Gunaratne et al.

Patent Trials and Appeals Board

Nov 4, 2019

13136498 - (D) (P.T.A.B. Nov. 4, 2019)

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.
13/136,498 08/02/2011 Preethi H. Gunaratne UHOU.P0028US 7175
108197 7590 11/04/2019
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
11/04/2019 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 PREETHI H. GUNARATNE, LALITHYA C. JAYARATHNE,
and MATTHEW L. ANDERSON

Appeal 2019-004170
Application 13/136,498
Technology Center 1600
Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
JOHN G. NEW, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1, 5, 9–11, 13–15, 17, 26, and 28–30.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42(a). Appellant identifies the real party in interest as the University of
Houston and Baylor College of Medicine. Appeal Br. 3.
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STATEMENT OF THE CASE
The claims stand finally rejected by the Examiner as follows:
1. Claims 1, 5, 9, 10, and 14 under pre-AIA 35 U.S.C. § 103(a) as
obvious in view of Tomalia et al. (US 2006/0177376 A1, published Aug. 10,
2006) (“Tomalia”), Lee et al. (Bioconjug. Chem., 2003, 14: 1214–1221)
(“Lee-BC”), Giljohann et al. (J. Am. Chem. Soc., online January 2009, 131:
2072–2073) (“Giljohann”), Lee et al. (Int. J. Pharm., 2008, 364: 94–101)
(“Lee-IJP”), and Lieberman et al. (US 2010/0310583 A1, published Dec. 9,
2010) (“Lieberman”). Final Act. 3.
2. Claims 1, 5, 9, 10, 13, and 14 under pre-AIA 35 U.S.C. § 103(a) as
obvious in view of Tomalia, Lee-BC, Lee-IJP, and Lieberman, and further
view of Beezer et al. (Tetrahedron, 2003, 59: 3873–3880) (“Beezer”). Final
Act. 6.
3. Claims 1, 5, 9–11, 13, 14, 26, and 28–30 under pre-AIA 35 U.S.C.
§ 103(a) as obvious in view of Tomalia, Lee-BC, Lee-IJP, Lieberman, and
Beezer, and further view of Mizuarai et al. (Molecular Cancer, June 2009, 8:
1–12). Final Act. 7.
4. Claims 1, 5, 9, 10, 14, 15, and 17 under pre-AIA 35 U.S.C.
§ 103(a) as obvious in view of Tomalia, Lee-BC, Lee-IJP, Lieberman, and
Beezer, and further view of Shi et al. (Small, 2007, 3: 1245–1252, Abstract).
Final Act. 7–8.

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CLAIMED SUBJECT MATTER
Independent claim 1 is representative of the rejected claims. Claim 1
is reproduced below (bracketed numbering added for reference);
1. A nanoparticle platform, consisting of:
[1] a gold nanoparticle conjugated to [2] a plurality of
internally quaternized thiolated hyperbranched dendrons, said
hyperbranched dendrons comprising chemically-modifiable
surface groups, interior groups and nano-cavities within the
hyperbranched structure;
[3] a microRNA duplex consisting of a non-thiolated
sense strand and an antisense strand with one non-thiolated end
and [4] one thiolated end that is [5] covalently conjugated via a
disulfide bond to a thiolated polyethylene glycol [PEG] or to a
thiolated oligoethylene glycol [OEG], said microRNA duplex
[6] electrostatically conjugated at the nonthiolated ends directly
to the interior groups of the plurality of internally quaternized
thiolated hyperbranched dendrons;
[7] one or more therapeutic agents [8] conjugated to the
chemically-modifiable surface groups on the plurality of
internally quaternized thiolated hyperbranched dendrons; and
[9] one or both of a thiolated oligoethylene glycol or a
thiolated polyethylene glycol [10] covalently conjugated via a
disulfide bond directly to uncovered surface areas on the
nanoparticle surface.

To illustrate the claimed nanoparticle platform, we provide the
following drawing. The drawing is for illustrative purposes only. The
dendron particle drawing is from Tomalia (Fig. 2).
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The drawing shows [1] the “gold nanoparticle” conjugated to [2] the
plurality of dendrons. The [3] microRNA, shown as red line, is shown as
“[5] covalently conjugated via a disulfide bond to a thiolated polyethylene
glycol [PEG] or to a thiolated oligoethylene glycol [OEG]” (orange
rectangle) at the [4] thiolated end of the miRNA (“miRNA”). The [7]
therapeutic agent (show as a yellow rhombus) of the claim is [8] is
conjugated to the [2] dendrons on “chemically-modifiable surface groups.”
The claims requires a [9] thiolated PEG or OEG [shown as blue rectangle] to
be “[10] covalently conjugated via a disulfide bond directly to uncovered
surface areas on” the [1] gold nanoparticle.” The thiolated PEG or OEG is
shown as a blue rectangle.
REJECTION 1
The Examiner found that Tomalia describes [1] gold nanoparticles
stabilized by [2] dendrons as required by claim. Final Act. 3.
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The Examiner also found that the gold nanoparticle dendrons were
used for nucleic acid delivery as they are in claim 1. Id.
The Examiner found that Tomalia does not describe “quaternized
interior groups” as recited in the claim, but found that Lee-BC does, and
provided a reason for making this modification to Tomalia’s dendron. Id. at
3–4.
The Examiner further found that neither Tomalia nor Lee-BC describe
coupling the nucleic acid to PEG or OEG ([4] and [5]). Id. at 4.
However, the Examiner that Giljohann and Lee-IJP describe attaching
siRNA, a nucleic acid, via OEG and PEG ([4], [5]), respectively, to achieve
controlled delivery of the siRNA, meeting the corresponding limitation of
the claims. Id.
The claim also requires that [9] OEG or PEG is [10] “covalently
conjugated via a disulfide bond directly to uncovered surface areas on the
nanoparticle surface.” The Examiner found that Lee-IJP and Giljohann
teach this configuration. Id.
With respect to the requirement of the claim that the microRNA
duplex is [6] electrostatically conjugated at the non-thiolated ends” (purple
triangle in drawing) to the “internally quaternized” dendron, the Examiner
found that such configuration would “necessarily” result by electrostatic
interactions when the groups on the microRNA are exposed to the internally
quaternized groups of the dendron. Ans. 10; Final Act. 5.
The Examiner acknowledged that the Tomalia, Lee-BC, Lee-IJP, and
Giljohann publications do not describe a therapeutic agent conjugated to the
dendron as required in [7] and [8] of the claim, but found that Lieberman’s
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teaching of utilizing miRNA and cisplatin in combination would make the
claim limitations obvious to make. Final Act. 5.

DISCUSSION
We address Appellant’s arguments below.
A. Claim interpretation
Appellant states that claim 1 comprises “an arrangement in which the
microRNA component is exclusively conjugated within the quaternized
inner core of the internally quaternized hyperbranched dendron-AuNP [gold
nanoparticle]” and “the therapeutic agents are exclusively conjugated on the
exterior surface of the internally quaternized hyperbranched dendron-
AuNP.” Appeal Br. 9–10.
We do not agree with Appellant’s interpretation of the claims.
Appellant has not identified language in the claim which would require the
microRNA and therapeutic agent to be “exclusively conjugated” (Appeal Br.
9) to the respective locations on the dendrons. While the claims require the
microRNA and therapeutic agent to be conjugated to these positions on the
dendrons, Appellant has not identified language in the claim that would
exclude them from being located at other locations on the dendron, as well.
See Ans. 10. Thus, as discussed in more detail below, the claim recites that
the miRNA is “[6] electrostatically conjugated at the nonthiolated ends
directly to the interior groups of the plurality of internally quaternized
thiolated hyperbranched dendrons”; however, the claim does not exclude the
thiolated PEG or thiolated OEG of limitation [5] from also being attached to
another and additional position on the nanoparticle.

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B. Attachment of miRNA to gold nanoparticle; thiolated PEG or thiolated
OEG attached to the nanoparticle surface.
To reach the limitation of the thiolated PEG or thiolated OEG
attached to the nanoparticle surface as in [9], the Examiner relied on the
teachings in Lee-BC and Giljohann in which the miRNA is attached to the
gold particle surface by the thiolated PEG or thiolated OEG. Final Act. 4.
Appellant argues that the suggestion from Giljohann to covalently
attach OEGylated- or PEGylated- nucleic acids directly to the surface of the
Au atom in Tomalia’s gold nanoparticle (limitations [9] and [10]) would be
“modifying away from Tomalia’s nanoparticle (Fig. 2), wherein the core
material for the nanoparticle is a gold atom which is dendronized for
potential attachment of deliverable biologically active material.” Appeal Br.
10.
While it is true that Tomalia describes attaching molecules to the
dendron (Tomalia ¶¶ 54–57), Tomalia does not exclude attaching nucleic
acids directly to the gold nanoparticle. This configuration is expressly
disclosed in Lee-IJP and Giljohann as established by the disclosures
reproduced below:
Gold nanoparticles chemically modified with primary amino
groups were developed as intracellular delivery vehicles for
therapeutic small interfering RNA (siRNA). The positively
charged gold nanoparticles could form stable polyelectrolyte
complexes through electrostatic interactions with negatively
charged siRNA-polyethylene glycol (PEG) conjugates having a
cleavable di-sulfide linkage under reductive cytosol condition.
Lee-IJP 94 (Abstract).

Duplexes composed of a 27-base RNA strand, and 25-base
complement terminated with an ethylene glycol spacer and
alkylthiol, were hybridized and added to the RNase-free Au
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NPs, where they were allowed to chemisorb via the thiol-gold
bond.
Giljohann 2072 (second column).
Thus, both Lee-IJP and Giljohann disclose ways of attaching a nucleic
acid to a gold nanoparticle. It would have been obvious to one of ordinary
in the art to have used these techniques to attach the nucleic acid to a gold
particle as an alternate and known nucleic acid delivery system. As held in
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007):
[I]f a technique has been used to improve one device, and a
person of ordinary skill in the art would recognize that it would
improve similar devices in the same way, using the technique is
obvious unless its actual application is beyond his or her skill.
Appellant states that the way in which the nanoparticle platform is
manufactured would exclude the nucleic acid from being attached to the
gold nanoparticle. Specifically, Appellant explains that the claimed
nanoparticle platform is made by conjugating the gold to the internally
quaternized hyperbranched dendrons and then “conjugating PEG-microRNA
or OEG-microRNA with the pre-formed internally quaternized
hyperbranched dendron-AuNP.” Appeal Br. 11. Thus, Appellant contends
that “the possibility of alternative embodiments of nucleic acids such as
direct attachment of the PEG-microRNA or OEG-microRNA to the gold
atom as suggested by Giljohann et al. does not arise.” Id.
This argument does not persuade us that the Examiner erred.
The claims are directed to a product, the nanoparticle platform, and
not a method of making it. Therefore, even if the way the particles are made
in the Specification would preclude the nucleic acid from being conjugated
to the particle surface as in [9], the particle is not limited to this method of
fabrication.
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As discussed by the Examiner, when the microRNA-PEG/OEG
conjugate is added to the gold particle dendron, the ends of the microRNA-
PEG/OEG conjugate would interact with the gold particle when it is
modified as described in Lee-BC and Giljohann. Final Act. 9. We agree
with Appellant that the claim does not require nor recite that the PEG/OEG
end of the miRNA is conjugated to anything (“[4] one thiolated end [of the
miRNA] that is [5] covalently conjugated via a disulfide bond to a thiolated
polyethylene glycol [PEG] or to a thiolated oligoethylene glycol [OEG]”)
(see drawing above; orange rectangle); however, we have not been pointed
to any language in the claim which excludes the PEG/OEG end from being
attached to the nanoparticle gold surface.
In addition, although the claim does not recite that [9] the thiolated
oligoethylene glycol or a thiolated polyethylene glycol (see drawing above;
blue rectangle) is bound to anything other than the gold nanoparticle surface
(“[9] one or both of a thiolated oligoethylene glycol or a thiolated
polyethylene glycol [10] covalently conjugated via a disulfide bond directly
to uncovered surface areas on the nanoparticle surface,” the claim does not
exclude it from being the same PEG or OEG attached to the miRNA ([6]
orange rectangle). While this embodiment is not described in the
Specification, limitations from the Specification (in the instant case, the
embodiment depicted in Fig. 5J-L) are not read into the claims. See In re
Van Geuns, 988 F.2d 1181 (Fed. Cir. 1993).

C. Attachment of therapeutic agent
Claim 1 recites “[7] one or more therapeutic agents [8] conjugated to
the chemically-modifiable surface groups on the plurality of internally
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quaternized thiolated hyperbranched dendrons.” The Examiner found this
limitation to be rendered obvious by Lieberman and Tomalia.
Appellant states that Lee-IJP “provides a suggestion to attach
OEGylated- or PEGylated- nucleic acids by electrostatic conjugation to an
exterior surface and/or an interior core in Tomalia's nanoparticle with no
guidance however, on attachment of therapeutic agents.” Appeal Br. 10–11.
This argument is not persuasive because Tomalia teaches that
different substances maybe attached to the surface of the dendron:
The polyvalent surfaces of these quantum dot-core dendritic
shell structures are used for the targeted delivery with antibody
attachments, receptor directed targeting groups such as folic,
biotin/avidin, and the like.

Tomalia ¶ 56. Thus, one of ordinary skill in the art would have had
reason to attach a therapeutic agent to the dendron surface.
Appellant also argues that while Lieberman discloses “using
microRNA and therapeutic agents together,” it does not teach “how they
may be arranged in Tomalia’s nanoparticle.” Appeal Br. 11. Appellant
states:
Consequently, making Applicant’s nanoparticle platform based
on the combination requires taking recourse from the instant
specification which describes a nanoparticle platform with a
configuration such that the therapeutic agents are attached
ONLY (Applicant’s emphasis) to the exterior surface groups
and the nucleic acids are attached ONLY to the quaternized
groups in the interior core. This is however contrary to 35
U.S.C. § 103.
Id.
This argument is not persuasive. The [7] therapeutic agent of
Appellant’s claimed nanoparticle platform is conjugated to [8] “to the
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chemically-modifiable surface groups on the plurality of internally
quaternized thiolated hyperbranched dendrons.” (Emphasis added to
claimed langauge.)
Tomalia expressly teaches surface functional groups:
Contemplated within the scope of this invention are
functional groups on the surface of the dendrimers/dendrons
that are certain hydrophilic, hydrophobic, reactive or passive
groups that include, by way of example such groups as:
hydroxyl, amino, carboxylic, sulfonic, sulfonato, mercapto,
amido, phosphino, –NH–COPh, –COONa, alkyl, aryl, ester,
heterocylic, alkynyl, alkenyl, and the like.
Tomalia ¶ 41.
The ability to functionalize this unique dendritic
sheathing with the unlimited examples of dendritic polymeric
surfaces functionality allows one to produce very versatile,
polyvalent functional surfaces groups on a side variety of
metallic quantum dots that includes both metals as well as
metal salt or derivatives that may exhibit a wide variety of
properties, such as semi-conductivity, paramagnetic, magnetic,
fluorescing, electrotumescent, and the like.
Tomalia ¶ 54.
These disclosures, coupled with the disclosure in paragraph 56 which
teaches attachment of molecules to the dendron surface for targeted delivery,
would have reasonably suggested to one of ordinary skill in the art to attach
a therapeutic agent to the dendron surface. It is true that Tomalia does not
expressly teach [8] therapeutic agents as required by claim 1. However, one
of ordinary skill in that would have recognized that the teaching of
antibodies and receptor targeting groups (¶ 56) and the general functionality
of the surfaces (¶54), establishes the function of the gold nanoparticle
dendron as a carrier for various desired agents. In fact, the purpose of
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functionalizing the surface groups in Tomalia is so that they can serve as
carriers. Therefore, attaching a therapeutic agent to the gold nanoparticle
dendron is using Tomalia’s nanoparticle for its known and expected purpose.
For the foregoing reasons, the rejection of claim 1 is affirmed. Claims
5, 9, 10, and 14 fall with claim 1 because separate reason for their
patentability were not provided. 37 C.F.R. 41.37(c)(1)(iv).

REJECTIONS 2–4
Rejections 2–4 are based on the same combination of publications
cited in Rejection 1 – Tomalia, Lee-BC, Giljohann, Lee-IJP, and
Liebermann – and cite additional publications to reach further limitations
cited in dependent claims. The Examiner explained how the newly cited
publications meet the limitations recited in the dependent claims. Final Act.
6–8. Appellant discusses the newly cited publications, but argues that they
did not meet the deficiency in the rejection based on Tomalia, Lee-BC,
Giljohann, Lee-IJP, and Liebermann. Br. 13, 18, 20. Consequently,
rejections 2–4 are affirmed for the same reasons as rejection 1. None of the
claims, in each separately argued rejection, were argued separately.

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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 5, 9, 10,
14
103 Tomalia, Lee-BC,
Lee-IJP, Lieberman
1, 5, 9, 10,
14

1, 5, 9, 10,
13, 14
103 Tomalia, Lee-BC,
Lee-IJP, Lieberman,
Beezer
1, 5, 9, 10,
13, 14

1, 5, 9–11,
13, 14, 26,
28–30
103 Tomalia, Lee-BC,
Lee-IJP, Lieberman,
Beezer, Mizuarai
1, 5, 9–11,
13, 14, 26,
28–30

1, 5, 9, 10,
14, 15, 17
103 Tomalia, Lee-BC,
Lee-IJP, Lieberman,
Beezer, Shi
1, 5, 9, 10,
14, 15, 17

Overall
Outcome
1, 5, 9–11,
13–15, 17,
26, 28–30

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).
AFFIRMED