Ex Parte Dhar et al

Patent Trial and Appeal Board

Jan 17, 2019

14378813 (P.T.A.B. Jan. 17, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/378,813 08/14/2014
26813 7590 01/22/2019
MUETING, RAASCH & GEBHARDT, P.A.
P.O. BOX 581336
MINNEAPOLIS, MN 55458-1336
UNITED ST A TES OF AMERICA
FIRST NAMED INVENTOR
Shanta Dhar
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
235.02180101 1056
EXAMINER
CABRAL, ROBERTS
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
01/22/2019 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):
ptodocketing@mrgs.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SHANTA DHAR and SEAN M. MARRACHE
(APPLICANT: University of Georgia Research Foundation, Inc.)
Appeal2018-002932
Application 14/378,813 1
Technology Center 1600
Before DONALD E. ADAMS, RACHEL H. TOWNSEND, and
DAVID COTTA, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL
This Appeal under 35 U.S.C. § 134(a) involves claims 1, 3-24, and 28
(App. Br. 2). Examiner entered rejections under 35 U.S.C. § 103(a). We
have jurisdiction under 35 U.S.C. § 6(b ).
We REVERSE.
1 Appellants identify "University of Georgia Research Foundation, Inc." as
the real party in interest (Appellants' June 26, 2017 Appeal Brief (App. Br.)
2).
Appeal2018-002932
Application 14/378,813
STATEMENT OF THE CASE
Appellants' disclosure "relates to nanoparticles configured to traffic
agents to mitochondria and methods of use thereof, including diagnostic and
therapeutic uses" (Spec. ,r 3). Claim 1 is representative and reproduced
below:
1. A nanoparticle, comprising:
a hydrophobic nanoparticle core;
a hydrophilic layer surrounding the core; and
a mitochondria targeting moiety tethered to the core,
wherein the nanoparticle has a diameter of from about 10
nanometers to about 200 nanometers or less and has a zeta
potential of about O m V or greater.
(Appellants' August 16, 2017 Claims Appendix (Claims App.) (emphasis
added).)
Grounds of rejection before this Panel for review:
Claims 1, 3-8, 10-23, and 28 stand rejected under 35 U.S.C. § I03(a)
as unpatentable over the combination of Sung2 and Levy. 3
Claims 9 and 24 stand rejected under 35 U.S.C. § I03(a) as
unpatentable over the combination of Sung, Levy, and Skulachev. 4
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
2 Sung et al., US 8,449,915 Bl, issued May 28, 2013.
3 Levy et al., US 2007/0292353 Al, published Dec. 20, 2007.
4 Skulachev et al., US 2011/0245207 Al, published Oct. 6, 2011.
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Application 14/378,813
FACTUAL FINDINGS (FF)
FF 1. Sung discloses a "nanoparticle system for topical transcutaneous or
transdermal delivery or targeted epidermal delivery of the biodegradable
nanoparticles that encapsulate at least one bioactive agent of
protein/peptides, nucleic acid (for example pDNA, RNA, or siRNA) via
nanoparticle projectile bombardment or other transcutaneous/transdermal
means" (Sung 2: 54---60).
FF 2. Sung's "nanoparticles for transcutaneous or transdermal
bombardment delivery processes hav[ e] a mean particle size between about
50 and 500 nanometers" (id. at 13:36-39; see Ans. 3).
FF 3. Examiner finds that Sung discloses a nanoparticle having "zeta
potentials ranging from -34.6 to 27.6" (Ans. 3).
FF 4. Sung's nanoparticles comprise: (1) "a core portion comprised of
[(a)] hydrophobic poly (D,L-lactic-co-glycolic acid) (PLGA) and [(b )] a
detection-enhancing substance, and [(2)] a shell portion comprised of
positively charged chitosan adapted to cause no aggregation of nanoparticles
due to electrostatic repulsion between the positively charged nanoparticles"
(Sung, Abstract; see Ans. 3).
FF 5. Sung discloses that "[b ]y modifying the chitosan structure to alter its
charge characteristics, such as grafting the chitosan with ... polyethylene
glycol (PEG) ... the surface charge density (zeta potential) of the ...
nanoparticles may become more pH resistant or more hydrophilic" (Sung
21:62-22:2).
FF 6. Sung discloses the encapsulation of "rhodamine 6G ... in the PLGA
hydrophobic core of [the nanoparticles] as a fluorescent probe" to track the
nanoparticle "internalization pathway" (Sung 44:9-11; see Ans. 3).
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Application 14/378,813
FF 7. Although Examiner asserts that "rhodamine 6G reads on 'a
mitochondrial targeting moiety'," Examiner recognizes that Sung fails to
disclose a "mitrochondrial targeting moiety ... [] attached to the
[nanoparticle's] core" (Ans. 4). Examiner, therefore, relies on Levy to make
up for this deficiency in Sung (see id. at 4--5).
FF 8. Levy "relates to biocompatible composite nanoparticles, comprising:
[ ( 1)] a nucleus comprising at least one inorganic or organic compound
activatable by excitation, [(2)] optionally, a biocompatible coating, and [(3)]
at least one targeting molecule, preferably exposed at the particle surface,
displaying affinity for an intracellular molecule or structure" (Levy ,r,r 12-
15; id. ,r 1 (Levy "relates to composite particles comprising an intracellular
targeting element, which can generate a response when excited, and to the
uses thereof in the health field, particular in relation to human health").
FF 9. Levy's "particles comprise a nucleus comprising at least one
inorganic or organic compound which can be activated, in order to label or
alter cells, tissues or organs" (id. ,r 1)
FF 10. Levy's "nanoparticles ... can additionally comprise a coating ...
[that] preferably comprises one or more compounds selected [from] the
group consisting of slica (Si02), alumina, metals (Au, etc.), polyethylene
glycol (PEG) or dextran, optionally in mixture(s)" (id. ,r,r 46,49; see Ans. 4--
5).
FF 11. Levy's "targeting molecule is grafted to the optional coating or to
the nucleus of [Levy's] nanoparticle," wherein the "grafting can be achieved
for example via molecular hydrocarbon chains of variable length but also via
other types of molecules such as polysaccharides, polypeptides, DNA, etc."
(Levy ,r 61 (emphasis added)).
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Application 14/378,813
FF 12. Levy discloses the use of"[r]hodamine ... as [a] targeting
molecule" to target "nanoparticles to intracellular mitochondria" (Levy ,r 63;
see Ans. 4--5).
FF 13. Examiner finds that the combination of Sung and Levy fails to
disclose "triphenyl phosphonium ... or 2,4-DNP" and relies on Skulachev
to make up for this deficiency in the combination of Sung and Levy (Ans. 5-
6).
ANALYSIS
The rejection over the combination of Sung and Levy:
Appellants' claim 1 is reproduced above and requires, inter alia, a
mitochondrial targeting moiety tethered to the core of a nanoparticle ( Claims
App.). According to Appellants, "'targeting' a nanoparticle to mitochondria
means that the nanoparticle accumulates in mitochondria relative to other
organelles or cytoplasm at a greater concentration than [a] substantially
similar non-targeted nanoparticle" (Spec. ,r 55). In addition, Appellants'
disclose that "targeting moieties may be tethered to the core or components
that interact with the core" (id. ,r 37; see id. ,r 56 ("mitochondrial targeting
moieties may be tethered to the core in any suitable manner, such as binding
to a molecule that forms part of the core or to a molecule that is bound to the
core")).
Examiner finds that Sung discloses nanoparticles having a diameter of
from about 10 to about 200 nanometers or less and a zeta potential of about
0 m V or greater (see FF 2-3). Sung and Levy both suggest nanoparticles
that comprise (1) a nucleus or core and (2) a shell or coating (see FF 3, 7).
Sung and Levy both disclose a shell or coating comprising a hydrophilic
layer, which surrounds the core (see FF 4 (Sung discloses a coating
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Appeal2018-002932
Application 14/378,813
comprising a modified chitosan structure, wherein the coating is made more
hydrophilic by modifying the chitosan with PEG), FF 9 (Levy's coating may
comprise PEG)). In addition, Sung and Levy both disclose nanoparticles
comprising rhodamine, which Levy discloses as a targeting moiety, wherein
rhodamine is encapsulated in Sung's core or grafted to Levy's optional
coating or to the nucleus of Levy's nanoparticle (FF 5, 6, 10, 11).
Based on the combination of Sung and Levy, Examiner concludes
that, at the time Appellants' invention was made, it would have been prima
facie obvious to incorporate Levy's mitochondrial targeting moiety "into a
multifunctional nanoparticle as taught by Sung" (Ans. 5). In support of
Examiner conclusion, Examiner asserts that: (a) "one of ordinary skill in the
art confronted with the problem of improving and diversifying targeted
delivery to mitochondria," would have combined Sung and Levy, (b) such a
combination is nothing more than adding "known ingredients to [a] known
composition[] with the expectation of obtaining their known function," and
( c) a person of ordinary skill in this "art would have had a reasonable
expectation of success in the modification as Sung ... already teaches the
incorporation and/or use of rhodamine" (id.).
We are not persuaded that Examiner established an evidentiary basis
on this record that is sufficient to support a conclusion that the combination
of Sung and Levy discloses a nanoparticle, comprising a core, a layer
surrounding the core, and a mitochondria targeting moiety tethered to the
core, as is required by Appellants' claimed invention (see Claims App.).
Notwithstanding the requirements of Appellants' claimed invention,
Examiner has, at best, established that the combination of Sung and Levy
suggests a nanoparticle comprising a targeting moiety tethered to a
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Application 14/378,813
component of a hydrophilic layer surrounding the nanoparticle 's core not to
the nanoparticle' s core as required by Appellants' claimed invention (see
Ans. 4--5 ("PEG ... [meets] the limitation of the hydrophilic layer and
hydrophilic polymer moiety being attached to the core" and "the targeting
moiety would be attached to the core via hydrophilic polymer moiety"); cf
FF 11 (Levy's targeting molecule is attached to a nanoparticle's coating
when present or, in the absence of a coating, to a nanoparticle's nucleus (i.e.
core)); Spec. ,r 34 (Appellants' disclose that "targeting moieties may be
tethered to the core or components that interact with the core"); see also id.
,r 56 ("mitochondrial targeting moieties may be tethered to the core in any
suitable manner, such as binding to a molecule that forms part of the core or
to a molecule that is bound to the core"); see App. Br. 9 (Appellants'
"claims recite that the mitochondria targeting moiety is tethered to the
core"); see also App. Br. 11 ("Another relevant question is whether one
would consider the rhodamine to such a nanoparticle to be tethered to the
core")).
The rejection over the combination of Sung, Levy, and Skulachev:
Examiner finds that the combination of Sung and Levy fails to
disclose "triphenyl phosphonium ... or 2,4-DNP" and relies on Skulachev
to make up for this deficiency in the combination of Sung and Levy (FF 13).
Based on the combination of Sung, Levy, and Skulachev, Examiner
concludes that, at the time Appellants' invention was made, it would have
been prima facie obvious "to modify the combined teachings of Sung ...
and Levy ... with the teachings of Skulachev ... the modification being the
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Application 14/378,813
simple substitution of one mitochondrial targeting moiety for another to
obtain predictable results" (Ans. 6). We are not persuaded.
As Appellants' explain, Examiner failed to establish that Skulachev
makes up for the deficiencies in the combination of Sung and Levy
discussed above (App. Br. 13).
CONCLUSION
The preponderance of evidence relied upon by Examiner fails to
support a conclusion of obviousness. The rejection of claims 1, 3-8, 10-23,
and 28 under 35 U.S.C. § 103(a) as unpatentable over the combination of
Sung and Levy is reversed. The rejection of claims 9 and 24 under 35
U.S.C. § 103(a) as unpatentable over the combination of Sung, Levy, and
Skulachev is reversed.
REVERSED
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