California Institute of Technology

Patent Trials and Appeals Board

Jun 29, 2020

2019005787 (P.T.A.B. Jun. 29, 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.
14/120,309 05/14/2014 DEVIN WILEY 101465.000137 / CIT-6566 7873
23377 7590 06/29/2020
BakerHostetler
Cira Centre 12th Floor
2929 Arch Street
Philadelphia, PA 19104-2891
EXAMINER
ROGERS, JAMES WILLIAM
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
06/29/2020 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):
eofficemonitor@bakerlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte DEVIN WILEY, ANDREW CLARK, and
MARK E. DAVIS
____________

Appeal 2019-005787
Application 14/120,309
Technology Center 1600
____________

Before DEBORAH KATZ, JOHN G. NEW, and
RYAN H. FLAX, Administrative Patent Judges.

FLAX, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims to a method of delivering enhanced levels of a therapeutic agent to a
brain parenchyma of a subject having a neurological brain disorder.
Appellant appeals the Examiner’s rejection of claims 1–8, 18–23, 28–36,
38–41, 46–49, 52–54, and 56–60 under 35 U.S.C. § 103(a) and for
obviousness-type double patenting.1 We have jurisdiction under 35 U.S.C.
§ 6(b).
We affirm.2

1 “Appellant” herein refers to the “applicant” as defined by 37 C.F.R. § 1.42.
Appellant identifies “California Institute of Technology,” as the real party-
in-interest. Appeal Br. 1.
2 A hearing was conducted on May 6, 2020. The transcript (“Hr’g Tr.”) of
the hearing is a part of the record on appeal.
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RELATED MATTERS
Appellant indicates that there are no related appeals, interferences, or
trials with respect to the appealed claims. Appeal Br. 1.
STATEMENT OF THE CASE
The application includes one independent claim, claim 1, which is
reproduced below:
1. A method of delivering enhanced levels of a
therapeutic agent to a brain parenchyma of a subject having a
neurological brain disorder, the method comprising:
systemically administering nanoparticles to the subject
having the neurological brain disorder and in need of delivery of
an enhanced level of the therapeutic agent across a blood-brain
barrier to the subject’s brain parenchyma, each nanoparticle
comprising a nanoparticle core having a surface comprising a
cationic mucic acid polymer (cMAP), a poly(lactic-co-glycolic
acid) (PLGA), chitosan, polyethyleneimine, iron oxide, or gold;
wherein
the nanoparticle further comprises (a) the therapeutic
agent and (b) a targeting agent, the targeting agent comprising a
targeting ligand attached to the surface of the nanoparticle core
by a linker;
the targeting ligand having an affinity for binding to a
receptor expressed by endothelial cells of the blood-brain barrier;
and
the linker comprising a polyethylene glycol (PEG)
polymer moiety that is conjugated to the surface of the
nanoparticle core by a pH sensitive linkage selected from the
group consisting of diamino ketal, orthoester, nitrophenyl
boronic ester, acetal, ketal, imine, and hydrazone or an
enzymatically cleavable disulfide or polypeptide bond; and
wherein
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each nanoparticle has a size in a range of from about 40
nm to 100 nm and a zeta potential in a range of from about- 0.5
mV to -10.0 mV; and wherein
the therapeutic agent is effective against a neurological
disorder; and
the enhanced level of the therapeutic agent delivered by
the nanoparticles to the brain parenchyma is an amount that is
greater than is delivered using otherwise equivalent
nanoparticles that do not contain the cleavable linker under the
same conditions.
Appeal Br. 21 (Claims Appendix).
The Specification states that “[c]hronic diseases of the central nervous
system (CNS) are a major cause of morbidity and mortality in the developed
world,” and lists conditions such as Alzheimer’s disease, Huntington’s
disease, Parkinson’s disease, and multiple sclerosis. Spec. ¶ 3. The
Specification further states that “[a] major reason for the lack of progress in
treating these diseases is due to the presence of the blood-brain barrier
(BBB). The BBB is a physical barrier between the CNS parenchyma and
vasculature that plays a critical role in maintaining homeostasis within the
CNS.” Id. ¶ 4.
In view of this issue, the Specification provides Figure 2, reproduced
below, which illustrates how the components of the claimed invention, noted
above, allow the crossing of the BBB for a drug-delivering nanoparticle:
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Spec., Fig. 2. Figure 2, above, shows:
Transit of targeted nanoparticle through the blood-brain
barrier (BBB) facilitated by targeting molecules falling off the
nanoparticle. (1) Targeted nanoparticle in the blood reaches the
BBB luminal surface. (2) Nanoparticle ligand [e.g., transferrin]
binds to its receptor on the blood side of the BBB.
(3) Internalization of the receptor-nanoparticle complex.
(4) Chemical and/or physical changes experienced by the
nanoparticle as it crosses the BBB cause detachment of the ligand
from the rest of the nanoparticle. (5) The untargeted nanoparticle
reaches the brain side of the BBB. (6) The nanoparticle diffuses
into the CNS. Components of the nanoparticle are identified in
the inset key on the left of the figure. Terms in the brackets on
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the right side of the figure indicate relative compartments
involved in this sequence.
Id. ¶ 13 (addition identifies specifically claimed components providing the
described functionality); see also id. ¶¶ 37–38, 52–53 (describing the
claimed targeting ligand and transferrin as a suitable protein for such
purpose).
The following rejections by the Examiner are appealed:
Claims 1–8, 18–23, 28–36, 38, 40, 41, 46–49, 53, 54, 56, 57, and 59
stand rejected under 35 U.S.C. § 103 over Davis ’5563 and Lam.4 Final
Action 4.
Claims 1–8, 18–23, 28–36, 38–41, 46–49, 52–54, and 56–60 stand
rejected under 35 U.S.C. § 103 over Davis ’556, Lam, and Pratt.5 Id. at 6–7.
As apparent from a comparison of the rejections, this rejection adds claims
39, 52, 58, and 60.
Claims 1–8, 18–23, 28–36, 38–41, 46–49, 51–54, and 56–60 stand
rejected on the ground of non-statutory, obviousness-type double patenting
over claims 1–30 of Davis ’097.6 Id. at 9.
DISCUSSION
I. LEGAL STANDARDS
Arguments made by Appellant in the Appeal Brief and properly
presented in the Reply Brief have been considered; arguments not so-
presented are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2017); see also Ex

3 US 2010/0040556 A1 (published Feb. 8, 2010) (“Davis ’556”).
4 WO 2012/158622 A2 (published Nov. 22, 2012) (“Lam”).
5 US 8,367,116 B2 (issued Feb. 5, 2013) (“Pratt”).
6 US 9,132,097 B2 (issued Sept. 15, 2015) (“Davis ’097”).
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parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) (“Any
bases for asserting error, whether factual or legal, that are not raised in the
principal brief are waived.”).
“The combination of familiar elements [or steps] according to known
methods is likely to be obvious when it does no more than yield predictable
results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). The test
for obviousness is “whether the teachings of the prior art, taken as a whole,
would have made obvious the claimed invention.” In re Gorman, 933 F.2d
982, 986 (Fed. Cir. 1991). “What matters is the objective reach of the claim.
If the claim extends to what is obvious, it is invalid under § 103.” KSR, 550
U.S. at 419.
“[T]he law of obviousness-type double patenting looks to the law of
obviousness generally. As . . . explained in Amgen, ‘[t]his part of the
obviousness-type double patenting analysis is analogous to an obviousness
analysis under 35 U.S.C. § 103.’” AbbVie Inc. v. The Mathilda & Terrence
Kennedy Inst. of Rheumatology Trust, 764 F.3d 1366, 1378 (Fed. Cir. 2014)
(second alteration in original) (citing Amgen Inc. v. F. Hoffman-La Roche
Ltd., 580 F.3d 1340, 1661 (Fed. Cir. 2009); see also In re Braithwaite, 379
F.2d 594, 600 n.4 (CCPA 1967) (A nonstatutory double patenting rejection
is “analogous to the non-obviousness requirement of 35 U.S.C. 103,” except
that only the claims of, not the disclosure of, the reference patent underlying
the double patenting rejection is considered prior art.).
With these standards in mind and in view of the Findings of Facts set
forth above, we address the Examiner’s rejections and Appellant’s
arguments there-over.
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II. OBVIOUSNESS
We address both obviousness rejections together, because the same
facts and arguments are determinative for each. Appellant likewise argues
both obviousness rejections simultaneously and asserts a singular argument
for both.
In the first obviousness rejection, the Examiner determined that the
claimed method and particles used therein of, e.g., claim 1, were disclosed
by the combination of Davis ’556 and Lam, where Davis ’556 teaches the
nanoparticles of mucic acid polymer, with PEG and phenyl boronic acid
linker, bound to a transferrin targeting agent, used to systemically administer
therapeutic and imaging agents in the nanoparticles. Final Action 4–5
(citing Davis ’556 ¶¶ 41, 63, 67–68, 72, 115, 119, 163, 176, 192, claims 1, 6,
8, 17, 24, Figs. 2, 5, 6, 14 15). The Examiner stated, “[t]he nanoparticle [of
Davis ’556] additionally comprised therapeutic agents and imaging agents,
including Cu-64 (meeting claim 41 ), and were useful in treating mental
disorders, considered to read on treating a neurological disorder of the brain
as now recited in claim 1.” Id. at 4. The Examiner cited Lam for teaching
nitrophenyl boronic acid, as a part of nanoparticles, which the Examiner
determined was predictably interchangeable with Davis ’556’s phenyl
boronic acid as a linker component. Id. at 5–6 (citing Lam 47 (example
11)). In the second obviousness rejection directed most specifically to
dependent claims 39, 52, 58, and 60, the Examiner adds Pratt to the
aforementioned prior art combination for teaching the use of dopamine with
nanoparticles as a therapeutic agent suitable to treat brain injury, cancer, and
Alzheimer’s disease. Id. at 6–7 (citing Pratt claims 1, 13, 22, 25, 27, 30).
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Appellant’s arguments focus only on whether Davis ’556’s discussion
of treating mental disorders is sufficient to teach or suggest delivering drugs
across the BBB. Appeal Br. 13–19. Appellant agues “Davis [’556] teaches
a variety of nanoparticle compositions for drug delivery applications, but
Davis [’556] nowhere discloses crossing the blood-brain barrier, or even
mentions the brain, the brain parenchyma, or any neurological condition”
and that Davis ’556’s disclosure of treating mental disorders would not
render its claimed method, including crossing the BBB, obvious. Id. at 14,
16.
We are unpersuaded by Appellant’s arguments. As the Examiner
points out, “Davis [’556] teaches [its] nanoparticles were useful in treating
mental disorders, considered to read on treating a neurological disorder of
the brain.” Answer 4; see also Davis ’556 ¶ 172 (“Exemplary conditions
include but are not limited to injuries, disabilities, disorders (including
mental and physical disorders) . . .”). As the Examiner also points out, and
Appellant concedes, Davis ’556’s disclosed administration of the therapeutic
agent and its carrier nanoparticles is systemic (e.g., “orally, parenterally,
topically, or rectally.”). See Answer 3; Appeal Br. 14; Davis ’556 ¶ 163. If
Davis ’556’s systemically administered therapeutic agent is to treat a
“mental disorder,” i.e., a disorder of the mind or brain, the brain must be
treated and the BBB must be traversed by the drug. Appellant’s unsupported
assertions to the contrary are not persuasive. Davis ’556’s omitting any
discussion of this specific path to the brain does not indicate, or even
support, that it would not be required. Appellant’s assertions to the contrary
are not persuasive.
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Davis ’556 specifically identifies transferrin as a preferred targeting
agent for its nanoparticles, which is the same targeting agent of focus in
Appellant’s Specification. Davis ’556 Fig. 12; Spec. ¶¶ 37–38. “[I]t is
beyond argument that no utility need be disclosed for a reference to be
anticipatory of a claim to an old compound. The compound appellants are
attempting to patent is not new.” In re Schoenwald, 964 F.2d 1122, 1124
(Fed. Cir. 1992). Here, as in Schoenwald, it is not disputed that Davis ’556
discloses the same compound (a pharmaceutical nanoparticle with a
transferrin targeting agent) as claimed (once its liker is modified as taught by
Lam). However, unlike Schoenwald, here Davis ’556 actually teaches using
this same nanoparticle in the same way as claimed, that is, by systemically
administering it to treat a mental/brain disorder. Thus, Davis ’556’s
transferrin targeting agent would necessarily function to transport the
nanoparticle across the BBB, just as it would for the claimed invention. See,
e.g., Spec. ¶¶ 7, 13, 37–38, 52–54, 68 (transferrin is “a ligand for targeting
brain endothelial cell”). Thus, the claimed method would have been
obvious.
III. OBVIOUSNESS-TYPE DOUBLE PATENTING
Under the doctrine of obviousness-type double patenting, the
Examiner determined that the claimed invention would have been obvious
over the claims of Davis ’097, without further elaboration. Final Action 9.
Appellant argues:
The claims of the 097 patent recite various nanoparticle
compositions, as well as methods of administering those
nanoparticles such as “the method comprising administering to
the individual the nanoparticle . . . .” None of the claims of the
097 patent refer to the blood-brain barrier in any way (or even
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“mental disorders”). As such, it is unclear why the examiner
believes that the 097 patent claims would render obvious or be
patentably indistinct from the process claimed in this application.
Appeal Br. 19.
Upon review, we do not observe that the claims of Davis ’097 recite a
targeting ligand having an affinity for binding to a receptor expressed by
endothelial cells of the BBB, for example, transferrin. Davis ’097, 85:38–
93:10. We also do not observe that these claims recite a size for the
nanoparticles, the zeta potential of the nanoparticles, or whether any claimed
therapeutic agents are for treating neurological disorders. Id. Thus, it
appears that there are substantial differences between the Davis ’097 claims
and the appealed claims that remain unaccounted for by the Examiner’s
rejection. The Examiner has not accounted for these differences in his
rejection. For this reason, we find the Examiner has not established a prima
facie case that the appealed claims would have been obvious over the claims
of Davis ’097 and, therefore, we reverse the rejection.
CONCLUSION
In summary:
Claims
Rejected 35 U.S.C. §
Reference(s)
/Basis Affirmed Reversed
1–8, 18–23,
28–36, 38,
40, 41, 46–
49, 53, 54,
56, 57, 59
103 Davis ’556, Lam
1–8, 18–23,
28–36, 38,
40, 41, 46–
49, 53, 54,
56, 57, 59

1–8, 18–23,
28–36, 38–
41, 46–49,
52–54, 56–60
103 Davis ’556, Lam, Pratt
1–8, 18–23,
28–36, 38–
41, 46–49,
52–54, 56–60

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Claims
Rejected 35 U.S.C. §
Reference(s)
/Basis Affirmed Reversed
1–8, 18–23,
28–36, 38–
41, 46–49,
51–54, 56–60
Obviousness-
type double
patenting
Davis ’097
1–8, 18–23,
28–36, 38–
41, 46–49,
51–54, 56–60
Overall
Outcome
1–8, 18–23,
28–36, 38–
41, 46–49,
52–54, 56–60

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)(1)(iv).

AFFIRMED