Ex Parte Wang et al

Patent Trial and Appeal Board

Nov 15, 2017

13121742 (P.T.A.B. Nov. 15, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/121,742 03/30/2011 Yanming Wang CWR-018645US PCT 1537
68705 7590 11/17/2017
TAROLLI, SUNDHEIM, COVELL & TUMMINO, LLP
1300 EAST NINTH STREET
SUITE 1700
CLEVELAND, OH 44114
EXAMINER
DONOHUE, SEAN R
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
11/17/2017 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 and CHUNYING WU1
Appeal 2016-005768
Application 13/121,742
Technology Center 1600
Before RICHARD J. SMITH, TAWEN CHANG, 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 directed to a method of detecting myelin in vivo in an animal. Claims
9-12, 15-17, 19, and 32 are on appeal as rejected under 35 U.S.C. § 103(a).2
We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
1 Appellants identify the Real Party in Interest as “Case Western Reserve
University.” Br. 2.
2 Claims 1-8, 13, 14, 18, and 20-31 are cancelled. Br. 2.
Appeal 2016-005768
Application 13/121,742
STATEMENT OF THE CASE
The Specification states, “[mjyelin is a specialized membrane that
ensheathes neuronal axons, promoting efficient nerve impulse transmission,”
and “[d]ue to its important biological functions in the normal central nervous
system (CNS) and its vulnerability in disease, several techniques have been
developed to visualize and characterize myelin histopathology.” Spec. ^ 4.
The Specification further states, “[although [known] myelin-staining
techniques are widely used in vitro, none can be applied in vivo due to
impermeability of the blood-brain barrier (BBB). The lack of in vivo
molecular probes has limited the progress of myelin imaging and hindered
efficacy evaluation of novel myelin repair therapies during their
development.” Id.
Claim 9, the sole independent claim, is representative, and is
reproduced below:
9. A method of detecting myelin in vivo in an animal, the method
comprising:
(i) administering to the animal a molecular probe including the
general formula:
.0
wherein Ri and R2 are each independently selected from the
group consisting of H, N02, NH2, NHCH3, N(CH3)2, OH, OCH3,
2
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Application 13/121,742
COOCH3, SH, SCH3, alkyl derivatives thereof, a halo group, a
radiolabel, a chelating group, and a near infrared imaging group
or a pharmaceutically acceptable salt thereof;
(ii) detecting the molecular probe in the animal using an in vivo
imaging modality to determine myelinated regions in the animal,
wherein the detected molecular probe is indicative of myelinated
regions of the animal.
Br. 16 (Claims App’x).
The following rejection is on appeal:
Claims 9-12, 15-17, 19, and 32 stand rejected under 35 U.S.C.
§ 103(a) over Nakayama,3 Wu,4 Stankoff,5 Kung,6 and Jacobs.7 Final Action
3; see also Office Action dated June 20, 2014 (cited in the Final Action as
detailing the rationale of the rejection).
DISCUSSION
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant.” In re Rijckaert, 9F.3dl531, 1532 (Fed.
Cir. 1993). When a prima facie case of obviousness has not been
3 EP 1 815 872 A1 (published Aug. 8, 2007) (“Nakayama”).
4 Chunying Wu et al., A Novel Fluorescent Probe That Is Brain Permeable
and Selectively Binds to Myelin, 54 J. Histochem. & Cytochem. 997-1004
(2006) (“Wu”).
5 Bruno Stankoff et al., Imaging of CNS Myelin by Positron-emission
Tomography, 103 PNAS 9304-09 (“Stankoff’).
6 US 2003/0149250 Al (published Aug. 7, 2003) (“Kung”).
7 Russell E. Jacobs & Simon R. Cherry, Complementary Emerging
Techniques: High-resolution PET and MRI, 11 Current Op. Neurobio.
621-29 (2001) (“Jacobs”).
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Appeal 2016-005768
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established, the rejection must be reversed. In re Fine, 837 F.2d 1071, 1075
(Fed. Cir. 1988). “[Dependent claims are nonobvious if the independent
claims from which they depend are nonobvious.” In re Fritch, 972 F.2d
1260, 1266 (Fed. Cir. 1992).
We conclude that, under the above precedent and on the record before
us, the balance of evidence supports Appellants’ contention that:
(i) Nakayama et al., Wu et al., Stankoff et al., Kung et al., and
Jacobs et al., alone or in combination, do not teach a probe
including the formula recited in claim 9 can be detected to
determine myelinated regions of an animal; (ii) one of ordinary
skill in the art would not have found it predictable and/or had a
reasonable expectation of success in view of Nakayama et al.,
Wu et al., and Stankoff et al., that the molecular probes of
Nakayama et al. could be used to determine myelinated regions
in an animal; and (iii) the Office Action has failed to provide a
reasonable rationale to combine the teachings of the cited prior
art to teach the invention recited in claim 9.
Br. 5-6.
The crux of the Examiner’s obviousness determination is expressed in
the Final Rejection as follows:
Nakayama was relied on to teach that the compounds discussed
above exhibit high-bindability to amyloid (3-protein. Stankoff
and Wu were relied on to provide teachings that amyloid 13-
protein and MBP in myelin are structurally similar. In addition,
Stankoff and Wu go so far as [to] experimentally demonstrate
binding of known amyloid (3-protein binding compounds to
myelin. Thus, Stankoff and Wu motivate one of ordinary skill
with a reasonable expectation of success to combine the
teachings of Nakayama by administering instant coumarin
derivatives, and detecting the molecular probe in an animal using
an in vivo imaging modality to determine myelinated regions in
the animal because it would advantageously enable diagnosis
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Application 13/121,742
and treatment of subjects exhibiting myelin related abnormalities
in vivo, such as MS.
Final Act. 6-7. The above-referenced compound of Nakayama is
reproduced below, from Nakayama’s Figure 8:
R: OHt OMe, NHMe, NMeg
Nakayama Fig. 8. The Examiner determined that the above-reproduced
chemical compound of Nakayama taught the following chemical compound
within the scope of claim 9:
Final Act. 5. The Examiner does not indicate that the above chemical
structure image was reproduced from any specific source; it is our
understanding that it is the Examiner’s creation in consideration of the
limitations of claim 9. While there are significant similarities between the
two above-reproduced chemical structures, it is apparent that they are not
5
Appeal 2016-005768
Application 13/121,742
identical. The Examiner concedes “Nakayama [] do[es] not expressly teach
a method comprising the administration to an animal [of] a molecular probe
of formula represented by [the claimed chemical structure] and detecting the
molecular probe in the animal using an in vivo imaging modality to
determine the myelinated regions in the animal.” Ans. 5.
Wu, relied upon by the Examiner for its teaching of the binding
properties between a chemical probe and myelin proteins, discloses the
following chemical compound, called BDB, that Wu teaches is a stilbenzene
derivative and stains myelin:
Wu Fig. 1. Stankoff, also relied upon by the Examiner for its teaching of the
binding properties between a chemical probe and myelin proteins, discloses
the following chemical compound, called BMB, which Stankoff discloses to
be a Congo red derivative that is useful as a probe to image myelin:
OM&
OMe
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Application 13/121,742
Stankoff 9308 (Scheme 1). We note the substantial similarity between the
Wu and Stankoff molecular probes reproduced above (Wu adds a methoxy
group to the central ring, but they are otherwise identical).
Appellants argue (Br. 7, 12) that the compounds disclosed by
Nakayama and Wu/Stankoff have different structures, which Nakayama
expressly distinguishes, which calls into question the Examiner’s
determination of obviousness, and Appellants direct our attention to
Nakayama’s paragraphs 3-5, which state:
Senile plaque is a cerebral lesion that is the most
characteristic of AD, and the main constituent thereof is an
amyloid (3 protein having a (3 sheet structure. It is considered that
imaging of such senile plaque from outside the body results in
the establishment of an effective diagnostic method for AD.
However, for such imaging, a probe compound that []
specifically binds to such an amyloid/?protein is necessary. To
date, several derivatives having congo red or thioflavine T as a
base structure have been reported (Patent Documents 1 and 2,
and Non-Patent Document 1). However, such compounds have
been considerably problematic in terms of low binding
specificity to an amyloid /?protein, low permeability to a blood-
brain barrier, slow clearance caused by non-specific bond in
brain, and the like. Therefore, the reported compounds have not
yet been practically used in the diagnosis of diseases that are
associated with accumulation of amyloid under the present
circumstances. . . .
The present invention has been made under the technical
background as stated above. It is an object of the present
invention to provide a compound, which has high binding
specificity to an amyloid/?protein, high permeability to a blood-
brain barrier, and ability to rapidly disappear from sites other
than cerebral senile plaque.
As a result of intensive studies directed towards achieving
the aforementioned object, the present inventors have found that
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Application 13/121,742
a flavone derivative, a chalcone derivative, a styrylchromone
derivative, and a coumarin derivative, which have a structure
completely differing from those of congo red or thioflavine T,
have a superior property as a probe compound for imaging an
amyloid (3 protein, thereby completing the present invention
based on such findings.
Nakayama 3-5 (emphasis added). This disclosure in Nakayama compels
a reversal of the obviousness rejection.
The chemical compounds disclosed in Nakayama, which are similar,
but not identical to those claimed, are explained by the reference to be
completely different from the chemical congo red, to provide high
specificity for binding to senile plaques, and to characteristically rapidly
disappear from sites other than cerebral senile plaques. Therefore, it is not
reasonable to equate the binding properties of the congo red-derivative
compounds of Wu and Stankoff to the compounds of Nakayama. Further,
the compounds of Nakayama are probes specific to senile plaques and
nothing else, as explicitly explained by the reference. As Nakayama
describes them, its compounds would rapidly disappear from the myelin of
the CNS / brain where not associated with a senile plaque, thus being of no
apparent use in identifying myelin in vivo.
Therefore, we conclude the claimed method, directed to using a
molecular probe to detect myelin in vivo in an animal, would not have been
obvious in view of the cited prior art combination (the Examiner does not
explain how Kung and Jacobs overcome the above-identified shortcomings
of the discussed prior art).
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SUMMARY
The obviousness rejection is reversed.
REVERSED
9