Ex Parte Wang

Patent Trials and Appeals Board

Jun 20, 2019

13872733 - (D) (P.T.A.B. Jun. 20, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/872,733 04/29/2013 Yanming Wang
68705 7590 06/24/2019
TAROLLI, SUNDHEIM, COVELL & TUMMINO, LLP
1300 EAST NINTH STREET
SUITE 1700
CLEVELAND, OH 44114
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.
CWR-021321US CIP 1030
EXAMINER
DONOHUE, SEAN R
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
06/24/2019 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):
rkline@tarolli.com
docketing@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YANMING WANG
Appeal2019-000814
Application 13/872,733
Technology Center 1600
Before ULRIKE W. JENKS, TIMOTHY G. MAJORS, and
MICHAEL A. VALEK, Administrative Patent Judges.
VALEK, Administrative Patent Judge.
DECISION ON APPEAL
Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving
claims to a method of detecting myelin in a tissue of interest. We have
jurisdiction under 35 U.S.C. § 6(b ).
We AFFIRM.
STATEMENT OF THE CASE
Claims 1, 4-10, and 16-22 are on appeal and can be found in the
Claims Appendix of the Appeal Brief. Claims 1 and 10 are the only
1 Appellant identifies the real party in interest as Case W estem Reserve
University. App. Br. 2. Herein we refer to the Final Office Action mailed
Feb. 21, 2018 ("Final Act."), Appeal Brief filed July 23, 2018 ("App. Br."),
Examiner's Answer mailed Sept. 6, 2018 ("Ans."), and Reply Brief filed
Nov. 6, 2018 ("Reply Br.").
Appeal2019-000814
Application 13/872,733
independent claims. Claim 1 is representative and provides as follows:
Claim 1 (Finally Rejected): A method of detecting myeHn in a tissue of interest of a
subjf-?Ct tho method comprising:
(i) administering to the tissue of lnterest of the central nervous system and/or
peripheral nervous system of the subject a molecular probe including the general
formula:
v1lherein Ri and R2 are each independently selected from the group
consisting of H, F, Cl, Br. I, a lo'\:ver alkyl group, N0.2, NH2., NHCH::1, N(CIH,:t)2, (CH2)r,OB'
(wherein n"'1, 2, or 3}, CF:i, CH2-CH2X, O-CH2-CH2X, CH2-CHrCH2X, O-CH2-CH2X, O-
CHrCH~,-O~CH2-CHrO-CHrCH2X (wherein X,,,F, C!, Br, or !), CN, C,,,O, (C,,,0)-R',
N(R')2, N02, (C,,,O)N(R'h, O{CO)R, OR', SR',. COOR", Rpff, Cff,,,CR'-R.oh, GR/-CR2'-R.1..':11
(wherein Rp,, represents an unsubstituted or substituted phenyl group, wt1erein R' is H or
a lower alkyl group}, and alkyl derivat!ves thereof, aJkoxy derivatives thereof; or a
pharmaceutically acceptable salt thereof, and
(ii) detecting the amount or distribution of the molecular probe in the
tissue of interest of the subject, wherein the amount or distribution of the c.1etected
molecular probe in the tissue of interest is indicative of the amOLmt or distribution or
rnyelin in the Ussue of interest.
App. Br. 13. Appellant does not argue dependent claims 4-9 and 16-22
separately from claims 1 and 10 so those claims stand or fall with claims 1
and 10. 37 C.F.R. § 41.37 (c)(l)(iv).
Appellant seeks review of Examiner's rejection of claims 1, 4-10, and
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Appeal2019-000814
Application 13/872,733
16-22 under 35 U.S.C. § 103 as unpatentable over Wang2 in view of Zhang. 3
App. Br. 7.
The issue is: Does the preponderance of evidence of record support
Examiner's conclusion that the cited prior art renders obvious the claimed
method?
Findings of Fact
FF 1. Wang teaches the detection of myelin by administering "molecular
probes that readily enter the brain and selectively localize in the myelinated
regions." Wang ,-J 3. According to Wang, "[t]he molecular probes can bind
to myelin membrane" and are "readily visualized using conventional
visualization techniques to indicate myelinated regions of the brain, central
nervous system, and peripheral nervous system." Id. at ,-J 27. Accordingly,
Wang teaches both "a method of detecting a level of myelination in vivo in a
subject" and "a method of detecting a myelin related disorder in a subject."
Id.; see also id. ,-i 51 ( explaining that the probes can be "radio labelled" and
"used for positron emission tomography to detect and quantify myelin
contents in vivo").
FF2. Wang teaches the use of a "fluorescent trans-stilbene derivative or a
pharmacophore thereof' as a molecular probe to detect myelin. Wang ,-J 28.
According to Wang, these trans-stilbene derivatives have the "following
formula:
2 Yanming Wang et al., WO 2010/039815 Al, published April 8, 2010
("Wang").
3 Wei Zhang et al., 18F-labeled Styrylpyridines As PET Agents For Amyloid
Plaque Imaging, Nucl. Med. Biol., Vol. 34, 89-97 (2006) ("Zhang").
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Appeal2019-000814
Application 13/872,733
wherein R1 and R2 are each independently selected from the group consisting
ofH, N02, NH2, NHCH3, N(CH3)2, OH, OCH3, COOCH3, SH, SCH3, and
alkyl derivatives thereof or a pharmaceutically acceptable salt thereof." Id. at
iJ 45.
FF3. Zhang teaches the use of radiolabeled stilbene and styrylpyridine
derivatives as molecular probes to detect and image B-amyloid plaques.
Zhang Abst. Zhang Fig. 1 ( copied in part below) depicts the chemical
structure of two of these probes.
Id. at 90. As shown in this Figure, the styrylpyridine derivative has a
"different backbone structure" because "one of the benzene rings of
stilbene" has been replaced with "one pyridine ring." Id. at 89-90.
FF4. Zhang teaches that the use of a styrylpyridine derivative may "lead to
different profiles of in vivo kinetics and metabolism, which may enhance the
signal between target and nontarget regions" as compared to stilbene probes.
Zhang 90. In particular, Zhang reports that the styrylpyridine probe in Figure
1 "appeared to show better stability toward microsomal degradation, as
compared to [18FJFPEGN3-stilbene" in in vitro testing. Id. at 96. Zhang
teaches that "[a] slower metabolic degradation of [the styrylpyridine probe]
in human microsomal fraction suggests that it is a promising tracer for in
vivo plaque detection." Id.
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Appeal2019-000814
Application 13/872,733
Analysis
Examiner finds that "Wang teaches all of the limitations of the instant
claims except for the use of a compound having aryl C-H unit replaced by
N." Ans. 6; Final Act 4 ("The only difference between the compounds in
Wang [is that] the compounds of the instant claims have a ring Nin place of
the ring C-H unit in the Wang compounds."). According to Examiner,
Zhang teaches "that benzene and pyridine rings are bioisosteric
replacements" and that "styrylpryridines advantageously enabled reduced
metabolism and improved pharmacokinetic properties." Ans. 7. Examiner
determines that a skilled artisan would be motivated to "use styrylpyridines
instead of styrylbenzenes in the methods of Wang in order to gain the
advantages of reduced metabolism and improved pharmacokinetic
properties." Id.
Appellant argues that claims 1 and 10 are not obvious for two reasons.
App. Br. 8. First, Appellant contends Wang and Zhang "do not teach or
suggest a method of detecting myelin, lipid or lipid matter" comprising the
step of administering a molecular probe with a styrylpyridine backbone. Id.
at 8-10. Second, Appellant urges that "one [of] ordinary skill in [the] art
would not have a reasonable expectation of success ... that the
styrylpyridine derivatives of Zhang et al. could bind to and/or be used to
detect myelin or lipid matter of the central or peripheral nervous system."
Id. at 8. In particular, Appellant argues it would not be obvious to replace
the phenyl ring in Wang's probes with a pyridinyl ring as shown in Zhang
because Zhang does "not teach or suggest that such compounds could be
used to detect anything but B-amyloid plaques of the brain." Id. at 10.
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Application 13/872,733
We determine that the preponderance of the evidence supports
Examiner's rejection and are not persuaded by Appellant's arguments to the
contrary. As our reviewing court has explained, "structural similarity
between claimed and prior art subject matter, proved by combining
references or otherwise, where the prior art give reason or motivation to
make the claimed compositions, creates a prima facie case of obviousness,
and ... the burden (and opportunity) then falls on an applicant to rebut that
primafacie case." In re Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990) (en
bane). As explained below, the record here demonstrates a prima facie case
of obviousness based on structural similarity and related prior art teachings
that Appellant has not overcome.
Wang teaches the use of stilbene derivatives as molecular probes to
detect myelin in the brain, central nervous system, and peripheral nervous
system. FF l -FF2. Indeed, the detection methods taught in Wang differ
from those in claims 1 and 10 only in that Appellant's claims recite the use
of probes with a styrylpyridine, as opposed to a stilbene or styrylbenze,
backbone. As shown in the table below, Appellant's claims recite probes
with a structure that is similar to the probes taught in Wang.
Wang's stilbene probes Claimed styrylpyridine probes
/"""'',. ~>-~ \ I~""'"' ¢""">'" ,:: . . ...• L___jt R,-v ······N "'"=··· .........
The only difference between the two is that the claimed probes have a
nitrogen atom instead of a carbon-hydrogen at the three position in one of
the aromatic rings.
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Application 13/872,733
Moreover, Zhang provides a reason and motivation to use a probe
with a styrylpyridine backbone in Wang's methods. Specifically, Zhang
teaches that probes with a styrylpyridine backbone exhibited improved
metabolic and kinetic properties as compared to their stilbene analongs.
FF4. At least some of those properties, e.g., slower metabolic degradation
by the liver, are not specific to the use of such probes to bind B-amyloid and
would also benefit the use of such probes in Wang's methods to detect
myelin. Accordingly, Examiner has demonstrated a prima facie obviousness
case based on the close structural similarity of the prior art probes and
Zhang's teaching that styrylpyridine derivatives display properties that are
useful for in vivo molecular probes.
We are not persuaded by Appellant's argument that the cited prior art
does not teach the use of a styrylpyridine probe in a method to detect myelin.
See App. Br. 8-10. "[N]on-obviousness cannot be established by attacking
references individually where the rejection is based upon the teachings of a
combination of references." Soft Gel Techs., Inc. v. Jarrow Formulas, Inc.,
864 F.3d 1334, 1341 (Fed. Cir. 2017) (quoting In re Merck & Co., 800 F.2d
1091, 1097 (Fed. Cir. 1986)). The rejection here is premised on the use of a
styrylpyridine probe, as taught in Zhang, as the molecular probe in Wang's
methods to detect myelin. Appellant's argument that Wang only discloses
stilbene probes, whereas Zhang only teaches styrylpyridine probes to detect
B-amyloid, does not distinguish the stated combination of those references.
We are likewise unpersuaded by Appellant's argument that a skilled
artisan would not reasonably expect a probe with a styrylpyridine backbone
to bind to myelin or other lipid matter in the nervous system. See App. Br.
10-11. The structural similarity between stilbene and styrylpyridine
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provides an expectation that the two will display similar properties. See
Otsuka Pharma. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280, 1293 (Fed. Cir.
2012) ("It is sufficient to show that the claimed and prior art compounds
possess a sufficiently close relationship to create an expectation, in light of
the totality of the prior art, that the new compound will have similar
properties to the old.") (internal quotations and citations omitted). This is
particularly true here because, in addition to the close structural similarity of
its stilbene backbone, Wang teaches pyridine as an additional substituent on
that backbone. See Wang ,-J,-J 29, 40 ( teaching "pyridnyl" as an example of a
"heteroaromatic" or "heteroaryl" ring substituent on its probes). Thus,
Wang affirmatively suggests that the addition of a pyridine ring will not
adversely affect myelin binding. Moreover, Zhang demonstrates that
"replacing one of the benzene rings of stilbene with one pyridine ring" did
not adversely affect the binding of the biological target in the case of B-
amyloid. See Zhang 89-90.
We disagree with Appellant that there would be no expectation of
success absent an affirmative teaching "that styrylpyridines and
styrylbenzenes function similarly in binding to myelin, lipids, or lipid
matter." Reply Br. 4. "Obviousness does not require absolute predictability
of success." In re O 'Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988). Here, the
close structural similarity, coupled with the teachings noted above, are
sufficient to provide one of skill in the art with a reasonable expectation that
a styrylpyridine probe could be successfully used in Wang's methods to
detect myelin in the central and peripheral nervous system.
For these reasons, we determine that the preponderance of the
evidence supports Examiner's rejection. Accordingly, we affirm.
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Application 13/872,733
SUMMARY
We affirm the rejection of claims 1, 4-10, and 16-22 under 35 U.S.C.
§ 103 as unpatentable over Wang in view of Zhang.
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. § l .136(a).
AFFIRMED
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