Ex Parte Wang et al

Patent Trial and Appeal Board

Dec 20, 2018

13806795 (P.T.A.B. Dec. 20, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/806,795 04/03/2013 Yanming Wang
26294 7590 12/25/2018
TAROLLI, SUNDHEIM, COVELL & TUMMINO L.L.P.
1300EASTNINTH 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-019297US PCT 9920
EXAMINER
PERREIRA, MELISSA JEAN
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
12/25/2018 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@tarolli.com
rkline@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte Y ANMING WANG and CHANGNING WANG 1
Appeal2017-008298
Application 13/806, 795
Technology Center 1600
Before TONI R. SCHEINER, ERIC B. GRIMES, and
CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.
SCHEINER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) from the non-final
rejection of claims directed to a method of detecting myelin in a subject's
tissues. The claims have been rejected on the grounds of anticipation and
obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
1 Appellants identify the real party in interest as Case W estem Reserve
University. Br. 2.
Appeal2017-008298
Application 13/806,795
BACKGROUND
"In the vertebrate nervous systems, myelination is one of the most
fundamental biological processes [and] provide[s] a unique structure that
fosters rapid and efficient conduction of impulses along axons." Spec. ,r 5.
"Destruction or changes in myelination have been considered as a causative
event in numerous neurological diseases such as multiple sclerosis (MS)."
Id.
This application relates to molecular probes that ... can
specifically or selectively bind to, localize with, and/or label
myelinated regions of the nervous system, including the central
nervous system and peripheral nervous system, and ... can be
imaged, using, for example, fluorescence or near-infrared
imaging techniques, to detect, measure, and/ or quantify the
amount, level, and/ or distribution of myelin in the tissue being
imaged.
Id. ,I 63.
Further according to the Specification, "the phrase 'molecular probe'
refers to a compound that specifically binds to a biomarker (e.g., myelin)"
(id. ,r 59), and "a molecular probe exhibits 'specific binding' or 'selective
binding' to myelin if it associates more frequently with, more rapidly with,
for a longer duration with, or with greater affinity to, myelin than with
tissues not containing myelin" (Id. ,r 55).
The Specification discloses a series of molecular probes comprising
cyanine dyes, and evaluates the myelin-binding properties of two in
particular: 3 ,3 '-diethylthiatricarbocyanine iodide ( CNIR) and 3 ,3 '-di(2-
meoxylbenzyl)-thiatricarbocyanine bromide (CNP). Id. ,r 115.
The myelin-binding properties of CNIR and CNP were
first examined by fluorescent tissue staining of wild-type mouse
brain sections. For comparison, immunohistochemical staining
with myelin-specific antibody was also conducted. At 1 µM
2
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Application 13/806,795
concentration, CNIR selectively labeled intact myelin sheaths
presented in the whole mouse brain, particularly in the corpus
callosum and striatum (Fig. 2A). The pattern of myelin sheaths
stained by CNIR was virtually identical to the pattern stained
by [myelin basic protein (MBP)] antibody (Fig. 2B). Similar
results were observed with CNP (Figure 2C, D). These
observations indicated that CNIR and CNP bind specifically to
myelin sheaths in vitro.
Spec. ,r 127.
STATEMENT OF THE CASE
Claims 11-17, 21, 23, 74--79, 81, and 82 are on appeal. 2 Claims 11
and 74 are independent. Claim 11 is representative of the subject matter on
appeal and reads as follows:
11. A method of detecting myelin in vivo in a subject's
tissue, the method comprising:
(i) administering to the subject a molecular probe
including a compound having the general formula selected from
the group consisting of:
wherein n is an integer from 1 to 10; A, Beach
independently represent CR'2, 0, S, NH, CH2CH2, CH=CH; R1,
R2, R', and Z each independently represent H, alkyl, alkenyl,
2 Claims 1-10 and 24--73 have been canceled; claims 18, 20, and 22 have
been withdrawn from consideration, and claims 19 and 80 have been
objected to.
3
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Application 13/806,795
alkynyl and/or an aryl group; X and Y each independently
represent
""~
)(<),
[ :: .-'' ,,, ~ J •'·
'-../' ""'
~J , wherein R" = H, alkyl, alkenyl, alkynyl or
an aryl group; and pharmaceutically acceptable salts thereof;
and
(ii) detecting the location, distribution, and/or amount
of the compound that is bound to the myelin to detect the
myelin in the tissue.
The claims stand rejected as follows:
Claims 11-17, 23, 74--79, and 82 under pre-AIA 35 U.S.C. § I02(b)
as anticipated by Horan3 (Ans. 2-3);
Claims 11-17, 21, 23, 74--79, 81, and 82 under pre-AIA 35 U.S.C.
§ I03(a) as unpatentable over Horan and Licha4 (Ans. 3-5); and
3 Horan et al., U.S. Patent 4,762,701, issued August 9, 1988.
4 Licha et al., U.S. Patent 6,534,041 Bl, issued March 18, 2003.
4
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Application 13/806,795
Claims 11-17, 21, 23, 74--79, 81, and 82 under pre-AIA 35 U.S.C.
§ I03(a) as unpatentable over Kilgore, 5 Horan, and Licha (Ans. 5-7).
ANTICIPATION
Claims 11-17, 23, 74--79, and 82 stand rejected under 35 U.S.C.
§ 102(b) as anticipated by Horan.
Horan
Horan discloses "procedures for tracking cells in vivo and for
determining in vivo cell lifetime." Horan 1 :53-54. "[C]ells first are labelled
with a cyanine dye and then are injected into a subject and the cyanine dye is
used to locate the cells." Id. at 1 :56-58. In addition, "cell lifetime is
determined by measuring the rate of disappearance of labelled cells." Id. at
1:59---60.
According to Horan, "any viable cell can be labelled with cyanine
dyes ... includ[ing] nucleated eukaryotic cells such as white blood cells,
various tumor cells, other mammalian cells, ... yeast; and non-nucleated
cells such as red blood cells and platelets." Id. at 2:66-3 :4. Moreover, in
vivo "data combined with data from tissue culture showing no transfer of
dye from labelled to unlabelled cells demonstrates that the cells are stably
labelled with the dyes." Id. at 6:37--40.
Horan discloses several examples where a patient's condition is
determined by labeling in vitro the patient's lymphocytes, neutrophils, or
platelets with cyanine, injecting the labeled cells into the patient, and
5 Kilgore, U.S. Patent Application Publication US 2006/0073541 Al,
published April 6, 2006.
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tracking the labeled cells in vivo. For instance, localization of cyanine-
labeled cells is used to detect imminent or ongoing transplant rejection
(Example 13), or to diagnose multiple sclerosis (Example 14), as follows:
EXAMPLE 13
Rapid Determination of Transplant Rejection
Lymphocytes, neutrophils or platelets each play an
important part in transplant or organ rejection. Patient cells are
removed and labelled ... with the radio-isotopic or NMR
imaging form of the molecule. Labelled cells are reinjected and
sequential imaging done on the patient. At or prior to the time
of impending rejection, there is increased localization of the
injected cell type in the transplant which is detected by this
methodology.
Id. at 14:49---60.
EXAMPLE 14
Diagnosis of Multiple Sclerosis
This application has the same methodology as Example
13, except that localization of cells in the region of the spinal
cord or other regions high in myelin is determined.
Id. at 14:61---68.
Discussion
With respect to independent claims 11 and 74, 6 the Examiner finds
that Horan discloses "in vivo cellular tracking wherein cells are labelled with
cyanine dyes" and detecting the cells "by measuring fluorescence or by
detecting nuclear magnetic resonance probes included in the cyanine dyes."
Ans. 2. According to the Examiner, "[t]he cells are tracked ... for the
6 Claim 7 4 is similar to claim 11, except that the choice of cyanine dyes is
narrower.
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diagnosis of multiple sclerosis by detecting the localization of cells in
regions high in myelin." Id. at 3 (citing Horan, Example 14).
Appellants contend that the Examiner's analysis of Horan's teachings,
including Example 14, is incorrect. Br. 10. Appellants contend, in relevant
part:
The fact that "localization of cells in ... regions [ of] high
myelin is determined" does not teach the cells localize to
myelin just that presence of the cells in such regions is
determined. Notably, the detected cyanine dye-labeled cells are
not administered to detect myelin in a subject's tissue; they are
administered and detected to determine whether cells are
present in the high myelin regions.
There is nothing in Horan et al. that teaches that cyanine
labeled cells bind myelin or localize to myelin; nor does the
Examiner provide any evidence that the cyanine labeled cells
would localize to a greater or lesser extent to a region high in
myelin let alone bind to myelin as recited in claim[s] 11 and 74.
Id. at 10-11.
The Examiner disagrees, arguing that the Specification "states that
selective binding or specific binding includes association," and Horan
"explicitly teaches that the cyanine dye labeled cells localize in the regions
high in myelin." Ans. 10. The Examiner contends that Horan's
"localization to regions high in myelin ... anticipates the association of the
instant disclosure" because "[l]ocalizing inherently includes [the situation
where] the cyanine dye labeled cells are brought into relation with the region
high in myelin and thus are associated with myelin." Id.
We are not persuaded that the evidence of record supports the
Examiner's assertions.
As discussed above, according to the Specification, "the phrase
'molecular probe' refers to a compound that specifically binds to ...
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myelin" (Spec. ,r 59); and "a molecular probe exhibits 'specific binding' or
'selective binding' to myelin if it associates more frequently with, more
rapidly with, for a longer duration with, or with greater affinity to, myelin
than with tissues not containing myelin" (id. ,r 55). Similarly, the
Specification teaches that the subject molecular probe "can specifically or
selectively bind to, localize with, and/or label myelinated regions of the
nervous system" upon administration to a patient (id. ,r 63). Thus, to
establish that Horan anticipates the claimed subject matter, the Examiner
must show that, once cells labeled ex vivo with cyanine dye are reinjected
into a patient, either the cyanine dye itself or the labeled cells associate more
frequently, more rapidly, for a longer duration, or with greater affinity, to
myelin than with tissues not containing myelin.
Turning to Example 14 of Horan-the only portion of the reference
that mentions myelin-we find that Appellants' assertions are consistent
with the evidence relied on by the Examiner. Example 14 is based on "the
same methodology as Example 13, except that localization of cells in the
region of the spinal cord or other regions high in myelin is determined."
Horan 14:65---68. Accordingly, in Example 14, as in Example 13,
lymphocytes, neutrophils, or platelets are removed from a patient and
labeled. Id. at 14:52-55. The labeled cells are subsequently reinjected into
the patient. Id. at 14:56-57. Horan also teaches that cells labeled as
disclosed therein are stably labeled and the cyanine dye does not transfer
from labelled to unlabeled cells (id. at 6:37--40); thus, the evidence does not
show that the dye specifically or selectively binds to myelin itself, or to
other cells in myelin-rich regions, when the labeled cells are reinjected into
the patient. Nor has the Examiner pointed to any evidence in Horan that
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labeled cells, once reinjected, associate more frequently, more rapidly, for a
longer duration, or with greater affinity, to tissues containing myelin. That
is, Horan simply discloses that known myelin rich regions, e.g., the spinal
cord, are examined by sequential imaging for the presence of reinjected
cyanine-labeled cells. Id. at 14:56-57, 66-68.
We find that the Examiner has not established that Horan's cyanine-
labeled cells constitute "molecular probe[ s ]" that bind myelin or selectively
localize to myelin or to myelin-rich regions as required by the claims.
Accordingly, we reverse the rejection of claims 11 and 74 as anticipated by
Horan, as well as the rejection of dependent claims 12-17, 23, 75-79, and
82, which necessarily include the same limitations.
OBVIOUSNESS
Horan and Licha
Claims 11-17, 21, 23, 74--79, 81, and 82 stand rejected under
35 U.S.C. § 103 as unpatentable over Horan and Licha.
Overview of Licha
Licha discloses "acid-labile and enzymatically cleavable compounds
for in-vivo and in-vitro diagnosis with near-infrared radiation," and the use
of the compounds as "as optical diagnostic agents." Licha 1:9-14. Such
compounds include cyanine dyes. Id. at 1:11-17.
Discussion
Claim 21 depends from claim 11, and recites that the cyanine
compound "is detected using in vivo imaging modality comprising a near-
infrared fluorescence imaging modality." Claim 81 depends from claim 7 4,
and recites the same limitation.
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The Examiner acknowledges that Horan does not disclose near-
infrared fluorescence imaging, and cites Licha as evidence that cyanine dyes
are suitable labels for near-infrared fluorescence imaging. The Examiner
concludes that it would have been obvious for one of ordinary skill in the art
to detect Horan's cyanine dyes using near-infrared fluorescence imaging
because Licha "teaches that cyanine dyes that are similar in structure and
function are detected via near-infrared imaging." Ans. 4--5.
For the reasons discussed above, we find that the Examiner has not
established that Horan's cyanine-labeled cells constitute "molecular
probe[ s ]" that bind myelin or selectively localize to myelin or to myelin-rich
regions, and Licha does not cure this deficiency.
Accordingly, we reverse the rejection of claims 11-17, 21, 23, 7 4--79,
81, and 82 as unpatentable over Horan and Licha.
Kilgore, Horan, and Licha
In addition, claims 11-17, 21, 23, 74--79, 81, and 82 stand rejected
under 35 U.S.C. § 103 as unpatentable over Kilgore, Horan, and Licha
Overview of Kilgore
Kilgore discloses "methods [ of] selectively stain[ing] myelin in a
sample, typically a tissue section that has been immobilized on a glass
surface." Kilgore ,r 59. Kilgore teaches that "[a] wide range of lipophilic
dyes ... can be used with the present methods," and appropriate dyes
"include, but are not limited to, cyanine dyes." Id. ,r,r 59, 60.
Briefly, Kilgore' s method is as follows:
The present lipophilic dyes, in the form of a staining
solution, are contacted with the sample to form a labeling
mixture. The sample is typically a tissue section that is
believed to comprise myelin ... [e.g.,] a brain tissue section ...
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prepared in such a way as to facilitate contact between the
myelin and the staining solution. In this instance, the tissue
sections are typically immobilized on a solid or semisolid
support, such as ... a polymeric membrane, within a
polyacrylamide gel, within an agarose gel, on a polymeric
membrane, on a glass slide or on a microarray.
Id. ,I,I 104--105.
The labeling mixture is incubated for a sufficient amount
of time to allow the present dye to associate with the present
myelin. . . . In one aspect the sample and staining solution are
incubated less than about 1 hour and in a further aspect the
sample and staining solution are incubated about 20 minutes.
Id. ,I 106.
At any time after or during staining, the sample is
illuminated with a wavelength of light selected to give a
detectable optical response, and observed with a means for
detecting the optical response.
Id. ,I 115.
The optical response is optionally detected by visual
inspection, or by use of any of the following devices: CCD
cameras, video cameras, photographic film, laser-scanning
devices, fluorometers, photodiodes, quantum counters,
epifluorescence microscopes, scanning microscopes,
fluorescence microplate readers, or by means for amplifying the
signal such as photomultiplier tubes.
Id. ,I 116.
Discussion
The Examiner finds that Kilgore discloses a method for selectively
detecting myelin in tissue samples using lipophilic dyes, including certain
cyanine dyes. Ans. 6. The Examiner acknowledges that Kilgore "does not
explicitly disclose the compounds of the instant claims, [ or an] in vivo
method or parenteral administration." Id. Nevertheless, the Examiner,
relying on Horan and Licha as discussed above, concludes that it would have
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been obvious for one of ordinary skill in the art "to substitute the cyanine
dyes of Kilgore for the cyanine dyes of Horan et al. and utilize them for in
vivo methods of detecting myelin" because "Horan et al. teaches of the use
of cyanine dyes comprising lipophilic chains for in vivo methods of
detecting cells in regions high in myelin and Kilgore teaches of using
lipophilic cyanine dyes for the method of selectively detecting myelin." Id.
at 6-7. According to the Examiner, "[ t ]he combination of prior art elements
according to known methods yields predictable results, such as the in vivo
detection of myelin." Id. at 7.
We are not persuaded that the evidence relied on by the Examiner
supports the Examiner's assertions.
Appellants contend, in relevant part, that "Kilgore discloses lipophilic
dyes that can stain myelin in vitro," but "does not teach molecular probes
having the presently claimed formula or that the disclosed probes could be
used to detect myelin in vivo." Br. 19. Appellants further contend Kilgore's
and Horan' s compounds "are not even used for the same purpose, let alone
substitutable for each other" (id. at 21 ), i.e., Horan "label[ s] cells, not
myelin, and the cyanine dye is located in the cells when used for in vivo
cellular tracking, which can be used to determine if the cells can localize to
regions high in myelin; while Kilgore discloses compounds that selectively
bind myelin in vitro" (id. at 22).
We agree with Appellants that the Examiner has not established that
Horan's cells, labeled with cyanine dyes ex vivo, bind myelin or selectively
localize to myelin or to myelin-rich regions when reinjected into a subject.
Moreover, although Kilgore teaches that its cyanine dyes-which are not the
same cyanine dyes required by the claims-selectively bind myelin in vitro,
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there is nothing in either Kilgore or Horan to indicate that replacing Horan's
dyes with Kilgore's dyes in Horan's method would result in labeled cells
that bind myelin or selectively localize to myelin or to myelin-rich regions.
Nor would substituting Horan' s dyes for Kilgore' s dyes in Kilgore' s method
satisfy the limitations of the claims, because Kilgore does not disclose using
its dyes to detecting myelin in vivo. Rather, Kilgore merely discloses
staining a prepared tissue sample in vitro, and says nothing at all about the
fate or distribution of its dyes in vivo.
Accordingly, we reverse the rejection of claims 11-17, 21, 23, 7 4--79,
81, and 82 as unpatentable over Kilgore, Horan, and Licha.
DECISION
The rejection of claims 11-17, 23, 74--79, and 82 under 35 U.S.C.
§ 102(b) as anticipated by Horan is reversed;
The rejection of claims 11-17, 21, 23, 74--79, 81, and 82 under
35 U.S.C. § 103(a) as unpatentable over Horan and Licha is reversed; and
The rejection of claims 11-17, 21, 23, 74--79, 81, and 82 under
35 U.S.C. § 103(a) as unpatentable over Kilgore, Horan, and Licha is
reversed.
REVERSED
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