Ex Parte Evers et al

Patent Trials and Appeals Board

Apr 26, 2019

14358512 - (D) (P.T.A.B. Apr. 26, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/358,512 05/15/2014 Toon Hendrik Evers
24737 7590 04/30/2019
PHILIPS INTELLECTUAL PROPERTY & STANDARDS
465 Columbus A venue
Suite 340
Valhalla, NY 10595
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.
2011P01417WOUS 5768
EXAMINER
COUNTS, GARY W
ART UNIT PAPER NUMBER
1641
NOTIFICATION DATE DELIVERY MODE
04/30/2019 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):
patti. demichele@Philips.com
marianne.fox@philips.com
katelyn.mulroy@philips.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TOON HENDRIK EVERS and MATHIAS FOURNIER
Appeal2018-008984
Application 14/358,512
Technology Center 1600
Before ULRIKE W. JENKS, TIMOTHY G. MAJORS, and
MICHAEL A. VALEK, Administrative Patent Judges.
VALEK, Administrative Patent Judge.
DECISION ON APPEAL
Appellants submit this appeal 1 under 35 U.S.C. § 134 involving
claims to a device for detecting a target molecule using a functionalized
magnetic particle that binds the target molecule and a sensor surface, which
have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b ).
We AFFIRM.
STATEMENT OF THE CASE
According to the Specification, a drawback to prior art devices is that
1 Appellants identify the real party in interest as KONINKLIJKE PHILIPS
N.V. App. Br. 2. Herein we refer to the Final Office Action mailed Oct. 6,
2017 ("Final Act."), Advisory Action mailed Dec. 22, 2017 ("Adv. Act."),
Appeal Brief filed April 5, 2018, 2018 ("App. Br."), Examiner's Answer
mailed July 19, 2018 ("Ans."), and Reply Brief filed Sept. 19, 2018
("Reply").
Appeal2018-008984
Application 14/358,512
"the binding of the functionalized particles having bound a target molecule
to the [sensor] surface is still very slow, rate-limiting and inefficient." Spec.
2, 11. 25-26. The Specification states that "surface contact and thus the
binding probability of magnetic nanoparticles can be increased by virtue of
putting a repulsive surface structure on the particles." Id. at 3, 11. 20-22.
The Specification explains that this is advantageous because it "lead[ s] to a
decrease of clustering of particles [ and] unspecific binding of particles to
each other" as well as to "pushing of the particles toward the surface without
the need to increase particle concentration." Id. at 3, 11. 22-28.
Claims 1, 3-12, and 15 are on appeal,2 and can be found in the Claims
Appendix of the Appeal Brief. Claim 1 is the only independent claim and is
representative of the claims on appeal. Claim 1 reads as follows:
1. A device for detecting a target molecule within a sample,
compnsmg:
(a) a sample container for measurement of the target
molecule within a sample;
(b) a magnetic particle, wherein said particle is
functionalized with
(i) a first binding molecule capable of specifically
binding to said target molecule, wherein said first binding
molecule is attached to the particle, and
(ii) a repulsive surface structure, which is directly
attached to the surface of said particle, wherein said
repulsive surface structure covers the surface of the
magnetic particle so as to result in a specific net charge
and/or steric repulsion of the magnetic particle; and
2 Appellants mistakenly identify claims 2 and 13 as also being on appeal.
App. Br. 2. Those claims were not elected in Appellants' response to
Examiner's restrict requirement and subsequently withdrawn. See Response
to Restriction Req. filed Jan. 16, 2017. In their reply brief, Appellants
acknowledge that the listing of claim 2 in their opening brief was an "error,"
but do not mention claim 13. See Reply 2.
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Application 14/358,512
( c) a sensor surface comprising a second binding
molecule, wherein said magnetic particles are capable of
binding said second binding molecule of the sensor surface
directly or indirectly, wherein the number of bound particles is
directly or inversely related to an amount of target molecules
present in the sample; and wherein said repulsive surface
structure conveys an electrostatic and/or steric pushing effect on
said magnetic particles towards said sensor surface.
App. Br. 12.
Appellants seek review of the following obviousness rejections: 3
I. Claims 1, 5-10, and 15 under 35 U.S.C. § 103 as unpatentable over
Masters4 and Xu. 5
II. Claims 3, 4, 11, and 12 under 35 U.S.C. § 103 as unpatentable over
Masters, Xu, and Ault-Riche. 6
Appellants group the two rejections together on appeal and do not argue any
claim separately from independent claim 1 so claims 3-12 and 15 stand or
fall with claim 1. 37 C.F.R. § 41.37 (c)(l)(iv).
3 Appellants do not seek review of the provisional obviousness-type double
patenting rejection of claims 1, 3-12, and 15 over claims 1-15 of co-pending
Patent Application No. 14/358,550. Reply 2; see also Final Act. 9-10. We
therefore summarily affirm this rejection. See MPEP § 1205.02 ("If a
ground of rejection stated by the examiner is not addressed in the appellant's
brief, appellant has waived any challenge to that ground of rejection and the
Board may summarily sustain it, unless the examiner subsequently withdrew
the rejection in the examiner's answer.").
4 Brett P. Masters et al., US 2006/0257945 Al, published Nov. 16, 2006
("Masters").
5 Xiaohong Nancy Xu et al., US 2009/0148863 Al, published June 11, 2009
("Xu").
6 Dana Ault-Riche et al., US 2004/0241748 Al, published Dec. 2, 2004
("Ault-Riche").
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Appeal2018-008984
Application 14/358,512
The issue is: Does the preponderance of evidence of record support
Examiner's conclusion that the cited prior art renders obvious the claimed
device?
Findings of Fact
FF 1. Masters teaches methods for detecting cardiac injury by detecting a
cardiac marker. Masters Abst. Masters teaches "[a] plurality of particles,
each of which is coated with a capture agent having an affinity for a cardiac
marker [that] is combined with the sample to form a plurality of analyte-
particle complexes" that are then exposed to a "sensor surface." Id. Masters
teaches that "[t ]he particles are magnetic" such that a magnetic field is
preferably applied adjacent to a sensor surface "to attract at least one of the
plurality of magnetic particles toward the sensing surface." Masters ,r 48; see
also id. at Abst.
FF2. Masters teaches that "the sensing surface is coated with a capture
agent (also referred to herein as a second capture agent) capable of binding
the analyte (e.g., a sandwich binding format) .... " Masters ,r 47. Masters
teaches that "in the sandwich assay formats" taught therein "the amount of
particles capable of binding to the sensing surface ... is proportional to the
amount of analyte present in the same." Id. Masters explains that the sensor
"produces a signal corresponding to an amount of analyte-particle complexes
that are bound to the sensor surface." Id. at Abst.
FF3. Xu teaches "functionalized nanoparticles having exceptional
combinations of properties including stability, brightness, binding specificity,
and ability to be imaged at single nanoparticle resolution over desired period
of time." Xu Abst. Xu teaches that such particles have "[m]any biological
applications" including in "sensors" and "diagnostics" because they allow for
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Application 14/358,512
both "quantitative detection" and detection of "trace amounts of analytes."
Id. ,I 122.
FF4. Xu teaches the coating of nanoparticles with a first monolayer
component that is used to bind a binding molecule such as an antibody and "a
second monolayer component, which is adapted to help expose the first
monolayer component on the surface." Xu Abst.; Fig. IA. Xu teaches that
the "second mono layer component is [also] adapted to provide a stability
against aggregation of nanoparticles when a collection of the nanoparticles is
dispersed in water." Id. ,r 11.
FF5. As a preferred embodiment, Xu teaches a silver nanoparticle coated
with 11-mercaptoundecanoic acid (MUA) as a first monolayer component
and 6-mercapto-1-hexanol (MCH) as a second monolayer component at a
mole ratio of 1:9. Xu ,r,r 38; 144; Fig. IA. Xu explains that because the
MCH is both "much shorter" and "more rigid" than MUA it does "not block"
and allows more effective linking of MUA to the antibody to functionalize
the particle. Id. ,r 144. In addition, Xu teaches that the MCH prevents
"aggregation of the Ag nanoparticles," which was previously "the major
problem in synthesis" of such particles. Id. According to Xu, this approach
allows for the preparation of "nanoparticles that are stable ... in aqueous
solution ... for months." Id.
Analysis
Examiner finds that Masters teaches all of the limitations of claim 1,
other than the "repulsive surface structure" limitation. Final Act. 3--4.
Examiner finds that Xu' s mixed mono layer, comprising a first and second
monolayer component, teaches the repulsive surface structure limitation. Id.
at 4--5. Examiner determines that it would be obvious for the skilled artisan
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"to incorporate mixed monolayers such as taught by Xu et al into the
magnetic particles, devices and methods of Masters et al because Xu et al
shows that this provides for particles having a stability against aggregation
and for use ... in sensors." Id. at 5.
Appellants do not dispute that it would be obvious to combine the
cited references, as articulated by Examiner, in their appeal briefing.
Instead, Appellants first contend that "the Office Action mentions nothing
about the relationship between the number of bound particles to target
molecules" and that Masters, in fact, "is directed to a different
proportionality [i.e., claim 1 's requirement that "the number of bound
particles is directly or inversely related to the amount of target molecules
present in the sample"] than that which is claimed." App. Br. 5---6. Second,
Appellants urge that claim 1 requires that "said repulsive surface structure
conveys an electrostatic and/or steric pushing effect on said magnetic
particles towards said sensor surface" and that Examiner has not shown this
requirement is met by the articulated combination of Masters and Xu. Id. at
7-9.
We are not persuaded by Appellants' arguments and agree with
Examiner's statement of the rejection and responses to Appellants'
arguments in both the Answer and Final Action, which we adopt and
incorporate by reference. We provide the following additional comments to
Appellants' arguments.
Both of Appellants' arguments arise from the last two wherein clauses
at the end of claim 1. In an Advisory Action after entry of the final
rejections appealed here, Examiner implied that it was unnecessary to
demonstrate the presence of these limitations for the obviousness rejection
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because these "limitations are intended use of the device ... not part of the
device" itself. Adv. Act. 2. Examiner has since clarified that both wherein
clauses are, in fact, taught by the cited references as articulated in
Examiner's rejections. See Ans. 12 (referring to Masters ,r 48 and Xu ,r,r 11-
21, 103-131, 144---all of which were previously cited by Examiner in the
Final Action). And Appellants have had sufficient opportunity to respond in
their Reply. Thus, we treat both of these wherein clauses as limiting and
affirm because we determine that a preponderance of the evidence supports
Examiner's finding that the stated combination of Masters and Xu teaches
these limitations. Accordingly, Examiner's suggestion in the Advisory
Action that these wherein clauses are not limiting is moot.
We are not persuaded by Appellants' argument that the cited prior art
does not teach the "directly or inversely related" limitation of claim 1.
Masters discloses a "sandwich assay format" in which the functionalized
particles form a complex with the analyte that subsequently binds to a
capture molecule on the sensor surface. FF1-FF2. Masters teaches that the
amount of particles capable of binding to the sensing surface is "proportional
to the amount of analyte present" in the sample. FF2. In other words,
Masters teaches that there is a direct relationship between the amount of
sensor bound particle-analyte complexes and the amount of analyte in the
sample. Contrary to Appellants' argument, this is exactly the type of
proportionality recited by claim 1 's requirement that "the number of bound
particles is directly or inversely related to an amount of target molecules
present in the sample."
We are likewise not persuaded by Appellants' argument that the cited
references fail to teach that the "repulsive surface structure conveys an
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electrostatic and/or steric pushing effect on said magnetic particles towards
said sensor surface." Appellants' Specification states that one way to
achieve the claimed steric pushing effect is by "providing a mesh of
molecules on the magnetic particles surface which may act as a steric
coating or barrier to prevent unspecific binding of unrelated molecules, or,
which keeps other molecules or magnetic particles in a certain distance."
Spec. 20, 11. 31-34. Xu teaches the application of such a "mesh of
molecules" to the surface of a magnetic particles. See FF4--FF5. In
particular, Xu teaches that the addition of MCH at a relatively high molar
ratio shifts the reaction to form the mixed monolayer on the surface of a
silver particle from a SNl to a SN2 mechanism. Xu ,r 144. The SN2
mechanism "prevents the aggregation of the Ag nanoparticles" because the
"noncharged short-chain" MCH forms a bond with the silver particle at the
same time the bond with the leaving group ( citrate in Xu' s example) is
dissolved. Id. Thus, instead of forming an aggregation-prone intermediate
via a unimolecular SNl mechanism, Xu teaches the skilled artisan to directly
substitute a rigid layer of uncharged MCH molecules at the surface of the
silver particles to push them apart and prevent aggregation. See id.
As such, we agree that the record supports Examiner's finding that
"the combination of Masters et al. and Xu teach the same magnetic particles,
binding molecules and sensor surface as instantly recited," i.e., the same
"mesh of molecules" described on page 20 of the Specification. Ans. 12.
Given the structural similarity, it is presumed that this combination will
"convey[] an electrostatic and/or steric effect on the magnetic particles
towards the sensor surface." Id.; see also In re Dillon, 919 F.2d 688, 692-93
(Fed. Cir. 1990) (en bane) ("[S]tructural similarity between claimed and
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prior art subject matter, proved by combining references or otherwise, where
the prior art gives reason or motivation to make the claimed compositions,
creates a prima facie case of obviousness and that the burden ( and
opportunity) then falls on an applicant to rebut that prima facie.") (emphases
omitted). Appellants offer no evidence, nor argument, to the contrary in
their briefs. Accordingly, we determine that a preponderance of the
evidence supports that Examiner presented a prima facie showing for this
element that Appellants have not rebutted.
For all these reasons, Appellants' arguments fail to persuade us that
Examiner erred in rejecting the claims and we therefore affirm.
SUMMARY
We affirm the rejection of claims 1, 5-10, and 15 under 35 U.S.C.
§ 103 as unpatentable over Masters and Xu.
We affirm the rejection of claims 3, 4, 11, and 12 under 35 U.S.C.
§ 103 as unpatentable over Masters, Xu, and Ault-Riche.
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).
AFFIRMED
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