Ex Parte Dalvit

Board of Patent Appeals and Interferences

Apr 26, 2010

10454898 (B.P.A.I. Apr. 26, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte CLAUDIO DALVIT
__________

Appeal 2009-005013
Application 10/454,898
Technology Center 1600
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Decided: April 26, 2010
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Before CAROL A. SPIEGEL, TONI R. SCHEINER, and LORA M. GREEN,
Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 from the rejection of claims
1-11 and 13-17, directed to a method of identifying a ligand to a target
molecule. The claims have been rejected under 35 U.S.C. § 103(a) as
obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
Appeal 2009-005013
Application 10/454,898

STATEMENT OF THE CASE
Claim 1 is representative of the subject matter on appeal:
1. A method of identifying a ligand to a target molecule, the
method comprising:
providing a reference compound that interacts with the target
molecule;
collecting a first WaterLOGSY nuclear magnetic resonance spectrum
of the reference compound in the presence of the target molecule;
providing a test sample comprising at least one test compound;
collecting a second WaterLOGSY nuclear magnetic resonance
spectrum of the reference compound in the presence of the test sample and
the target molecule; and
comparing the first and second WaterLOGSY spectra to determine if
at least one test compound interacts with the target molecule by displacing
the reference compound.

The Examiner rejected claims 1-11 and 14-17 under 35 U.S.C.
§ 103(a) as unpatentable over Boguslaski1 and Stockman.2 In addition, the
Examiner rejected claim 13, which depends from claim 1, under 35 U.S.C. §
103(a) as unpatentable over Boguslaski, Stockman, and Jarrett.3
ISSUE
The claimed invention is directed to a competitive binding assay for
identifying a ligand of a target molecule by determining whether a test
compound (i.e., a potential ligand) can displace a reference compound from
the target molecule. The method comprises acquiring a WaterLOGSY4
nuclear magnetic resonance spectrum of the reference compound in the

1 US 4,383,031, issued May 10, 1983 to Boguslaski et al.
2 International Application WO 01/23330 A2 of Stockman et al, published
April 5, 2001.
3 US 4,687,808, issued August 18, 1987 to Jarrett et al.
4 Water-Ligand Observation with Gradient SpectroscopY).
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presence of the target molecule, and comparing it with a spectrum of the
reference compound acquired in the presence of the target molecule and the
test compound (claim 1). According to the Specification, a change in sign or
signal reduction of the reference compound resonance spectrum in the
presence of the test compound is an indication that the test compound is able
to bind the target molecule with greater affinity than the reference
compound, thereby displacing the reference compound from the target
molecule (Spec. 8).
According to the Examiner, Boguslaski discloses the claimed method
except that displacement of the reference compound by a test compound is
detected by a change in enzymatic activity, rather than by comparing
WaterLOGSY nuclear magnetic resonance spectra. However, the Examiner
finds that Stockman discloses that WaterLOGSY NMR can detect binding to
target molecules at very low levels of the target molecules, and concludes
that it would have been obvious “to employ WaterLOGSY NMR . . . as the
means of collecting and analyzing specific binding data in the method of
Boguslaski . . . in order to provide a detection method that can operate with
extremely low levels of target molecule[s]” (Ans. 5).
Appellant concedes that Boguslaski discloses “a related competitive
displacement assay,” but contends that Boguslaski doesn’t “teach or suggest
a reference compound as a spectroscopic probe . . . within a competitive
displacement assay method” (App. Br. 6), but measures a change in the
activity of a “reactant” that is “separate from,” and doesn’t meet the
functional requirements of the “reference compound” required by the claims
(id. at 10). Appellant contends that neither Stockman nor Jarrett makes up
for this deficiency.
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The Examiner’s position is that the claims use open transitional
language, and “fail to recite a particular structure or chemical composition
that must be possessed by the reference compound. Therefore, the claims
would not rule out reference compounds that include multiple components
or elements, such as the reactant component of the reference probe (ligand-
reactant conjugate) used by Boguslaski” (Ans. 9). The Examiner finds that
Boguslaski’s “reactant” reads on the “reference compound” required by the
claims because the reactant is part of a ligand-reactant conjugate which
binds the target molecule, and the activity of the reactant changes when the
ligand-reactant conjugate is displaced from the target molecule (id. at 4).
The issue raised by both of the rejections on appeal is whether the
evidence of record supports the Examiner’s finding that the reactant
component of Boguslaski’s ligand-reactant conjugate satisfies the functional
requirements of the “reference compound” required by the claimed method.
FINDINGS OF FACT
FF1 The method of claim 1 requires “a reference compound that
interacts with the target molecule,” wherein the reference compound can be
displaced from the target molecule by a competing test compound that also
“interacts” with the test compound.
FF2 According to the Specification:
The reference compound is one that interacts with the
selected target molecule with a binding affinity sufficiently low
that it gives rise to a readily observed, positive-intensity
WaterLOGSY signal in the presence of the target molecule.
Preferably, a weakly binding reference compound is used.
Relatively weakly binding reference compounds are typically
defined as those having a dissociation binding constant KD of at
least about 10 micromolar or higher.

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(Spec. 10: 1-10.)
FF3 “The test compounds that can be evaluated can be any of a wide
variety of compounds, which potentially have a wide variety of binding
affinities to the target” (Spec. 10: 11-13). “[T]he lower limit in affinity
strength for the detection can be tuned by properly selecting the reference
compound (i.e., different KD) and/or different . . . ratios” (id. at 11: 9-11).
FF4
[C]omparing the WaterLOGSY spectra to determine if at least
one test compound interacts with the target molecule involves
evaluating at least one reference compound resonance for a
change in sign (i.e., by virtue of the opposite sign of their
water-ligand nuclear Overhauser effects (NOEs)) . . . [or]
evaluating at least one reference compound resonance for a
reduction in signal intensity (i.e., by virtue of a decreased
fraction of bound reference compound).

(Spec. 8: 24-30.)
FF5 Boguslaski discloses:
[A] homogeneous specific binding assay method and system
based on the use of, as labeling substance, a substance which
exhibits given reactant activity as a constituent of a
predetermined reaction, such substance being referred to herein
as the reactant. The method is based, in part, on the fact that
the reaction between a ligand and a specific binding partner
thereof to one of which the reactant is coupled alters the activity
of the reactant in the predetermined reaction, which reaction
thus serves as a means for monitoring the specific binding
reaction. . . . The preferred . . . schemes are the direct binding
technique and the competitive binding technique.

(Boguslaski, col. 3, l. 62 to col. 4, l. 10 (emphasis added).)
FF6 “A variation of the competitive binding technique is the
displacement binding technique wherein the conjugate is contacted first with
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the specific binding partner of the ligand and thereafter with the liquid
medium. Competition for the specific binding partner then occurs.”
(Boguslaski, col. 6, ll. 34-39.)
FF7 “[T]he activity of the conjugated reactant on contact with the
liquid medium varies directly with the extent of binding between the ligand
in the liquid medium and the specific binding partner.” (Boguslaski, col. 6,
ll. 8-11.)
FF8 Boguslaski’s “monitoring reaction preferably is enzyme-
catalyzed” (Boguslaski, col. 4, ll. 36-37).
PRINCIPLES OF LAW
During examination, the PTO must interpret terms in a claim using
“the broadest reasonable meaning of the words in their ordinary usage as
they would be understood by one of ordinary skill in the art, taking into
account whatever enlightenment by way of definitions or otherwise that
may be afforded by the written description contained in the applicant’s
specification.” In re Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997).
ANALYSIS
The Examiner’s position is that the claims use open transitional
language, and “fail to recite a particular structure or chemical composition
that must be possessed by the reference compound. Therefore, the claims
would not rule out reference compounds that include multiple components
or elements, such as the reactant component of the reference probe (ligand-
reactant conjugate) used by Boguslaski” (Ans. 9).
Appellant contends that Boguslaski measures a change in the activity
of a “reactant” that is part of a ligand-reactant conjugate, and the reactant
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doesn’t meet the functional requirements of the “reference compound”
required by the claims (id. at 10).
We agree with Appellant that the “reactant” monitored by Boguslaski
doesn’t have the functional properties required by the “reference compound”
monitored in the claimed methods. The claims require “providing a
reference compound that interacts with the target molecule” and then
“determin[ing] if at least one test compound interacts with the target
molecule by displacing the reference compound” (claim 1). When read in
light of the Specification, the broadest reasonable interpretation of this
language is that the reference compound specifically binds the target
molecule and may be displaced by a test compound that also specifically
binds the target molecule. (FF2, FF3.) Given this interpretation,
Boguslaski’s “specific binding partner” corresponds to the present “target
molecule,” and Boguslaski’s “ligand” corresponds to the present “reference
compound.” Rather than monitoring the activity of the ligand, however,
Boguslaski monitors the activity of the “reactant” component of a ligand-
reactant conjugate. In Boguslaski’s method, the reactant is merely a passive
label carried by the ligand, and there is no indication that the reactant itself
binds the specific binding partner. (FF5-FF7.)
Because the Examiner has not established that Boguslaski monitors a
“reference compound,” or otherwise explained why it would have been
obvious to do so, we cannot affirm the rejections of record.
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CONCLUSIONS OF LAW
The evidence of record does not support the Examiner’s finding that
the reactant component of Boguslaski’s ligand-reactant conjugate satisfies
the functional requirements of the “reference compound” required by the
claimed method.
The rejection of claims 1-11 and 14-17 under 35 U.S.C. § 103(a) as
unpatentable over Boguslaski and Stockman is reversed. The rejection of
claim 13 under 35 U.S.C. § 103(a) as unpatentable over Boguslaski,
Stockman, and Jarrett is reversed as well.

REVERSED

cdc

PETER I. BERNSTEIN
BERNSTEIN.SCULLY, SCOTT MURPHY & PRESSER
400 GARDEN CITY PLAZA
GARDEN CITY, NY 11530
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