Ex Parte Linder et al

Board of Patent Appeals and Interferences

Mar 30, 2009

10618443 (B.P.A.I. Mar. 30, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JAMES LINDER, MICHAEL COHENFORD,
ERIN COFFMAN and BRIAN B. LENTRICHIA
__________

Appeal 2008-2363
Application 10/618,443
Technology Center 1600
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Decided:1 March 30, 2009
__________

Before TONI R. SCHEINER, DEMETRA J. MILLS, and ERIC GRIMES,
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
1-23, 26-29, 36, and 37, all the claims pending. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).

Appeal 2008-2363
Application 10/618,443

STATEMENT OF THE CASE
“This invention relates to methods . . . useful in detecting target
substances in an alcoholic preservative solution, and for identifying sensors
useful for binding to such targets” (Spec. 1: 8-10). Independent claims 1 and
28 are representative of the subject matter on appeal:
1. An assay method comprising:
providing a sample that is suspected of containing a target;
providing a sensor that can bind to the target in an alcoholic
preservative solution that does not contain formamide, said sensor
conjugated to a chromophore;
contacting the sample with the sensor in the alcoholic preservative
solution that does not contain formamide under conditions in which the
sensor can bind to the target, if present;
applying a light source to the solution that can excite the
chromophore; and
detecting whether light is emitted from the target.

28. A method for identifying a sensor which specifically binds to a
desired target, comprising:
contacting a sample suspected of containing a target of interest with a
detectable sensor,
wherein said contacting takes place in a preservative solution
comprising an amount of one or more water-soluble alcohols effective to
preserve such solution against at least one contaminant and does not contain
formamide, and detecting whether said sensor has bound to said target.

The Examiner relies on the following evidence:
Ylikoski et al. US 5,256,535 Oct. 26, 1993
Shah et al. US 6,165,723 Dec. 26, 2000
Hyldig-Nielsen et al. US 6,280,946 B2 Aug. 28, 2001
Lorincz et al. US 6,969,585 B2 Nov. 29, 2005

Challberg et al. WO 93/10263 May 27, 1993

Kenji Fukasawa et al., Abnormal Centrosome Amplification in the Absence
of p53, 271 SCIENCE 1744-1747 (1996).
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Marcel Bruchez Jr., et al., Semiconductor Nanocrystals as Fluorescent
Biological Labels, 281 SCIENCE 2013-2016 (1998).

Ravindra Kumar et al., The First Analogues of LNA (Locked Nucleic Acids):
Phosphorothioate-LNA and 2'-Thio-LNA, 8 BIOORGANIC & MEDICINAL
CHEMISTRY 2219-2222 (1998).

The claims stand rejected as follows:
• Claim 28 under 35 U.S.C. § 102(e) as anticipated by Lorincz.
• Claims 1-4, 8-12, 14-16, 18, 19, 23, 26, and 27 under 35 U.S.C.
§ 103(a) as unpatentable over Lorincz and Shah.2

• Claims 20-22 under 35 U.S.C. § 103(a) as unpatentable over Lorincz,
Shah, and Challberg.

• Claim 29 under 35 U.S.C. § 103(a) as unpatentable over Lorincz and
Challberg.

• Claims 5, 7, 29, 36, and 37 under 35 U.S.C. § 103(a) as unpatentable
over Lorincz, Shah, and Hyldig-Nielsen.

• Claim 6 under 35 U.S.C. § 103(a) as unpatentable over Lorincz, Shah,
and Kumar.

• Claim 10 under 35 U.S.C. § 103(a) as unpatentable over Lorincz,
Shah, and Bruchez.

• Claim 13 under 35 U.S.C. § 103(a) as unpatentable over Lorincz,
Shah, and Ylikoski.

• Claim 17 under 35 U.S.C. § 103(a) as unpatentable over Lorincz,
Shah, and Fukasawa.

2 Both the Examiner and Appellants list claims 24 and 25 in this rejection,
but claims 24 and 25 have been canceled (App. Br. 2).
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Application 10/618,443

ISSUE: ANTICIPATION
The issue raised by this rejection on appeal is whether Appellants
have established that the Examiner erred in finding that Lorincz describes
contacting a sample suspected of containing a target of interest with a
detectable sensor, where contacting takes place in a water-soluble alcohol-
containing preservative solution.
FINDINGS OF FACT
FF1 The Examiner rejected claim 28 as anticipated by Lorincz.
Claim 28 is directed to a method for identifying a sensor which specifically
binds to a desired target. The method comprises contacting a sample
suspected of containing the target with a detectable sensor, “wherein said
contacting takes place in a preservative solution” comprising one or more
water-soluble alcohols in an amount effective to preserve the solution
against at least one (unspecified) contaminant (for an unspecified period of
time), and wherein the preservative solution does not contain formamide,
and detecting whether the sensor has bound to the target.
FF2 The Specification teaches that “the preservative solution
comprises a water-miscible alcohol . . . present in an amount sufficient to fix
sample cells or tissue while still permitting acceptable binding of the sensor
to its target. The alcohol . . . may be selected from the group consisting of
methanol, ethanol and isopropanol” (Spec. 22: 11-16).
In one embodiment of the invention, the alcohol is present
at a level sufficient for fixing and preserving the sample
component of interest, and may be present in an amount greater
than about 40% and less than about 60% . . . if the concentration
of alcohol in this embodiment is at 40% or below, the cells are
not sufficiently fixed for relatively long-term preservation . . . .
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In another embodiment of the invention, the alcohol is
present in an amount of at least approximately 20 percent by
solution. While this concentration of alcohol, as noted above,
does not enable long term preservation, (i.e., over two days), it
does sufficiently fix cells for subsequent analysis within that
time period.

(Spec. 22: 17-29.)
FF3 In Example 1 of the Specification, “a volume of 50 μl of PNA
[the sensor] is mixed into either a ThinPrep vial (Cytyc Corp.) or microfuge
tube containing [a cell sample in] a volume of PreservCyt® (Cytyc Corp.)
[the preservative solution] and the hybridization event takes place in
solution” (Spec. 25: 28 to 26: 1). Following hybridization, the cells are
separated from the preservative/sensor solution to remove unbound sensor,
suspended in wash buffer, transferred to a slide, and reviewed for a positive
reaction (id. at 26: 2-7).
FF4 Lorincz discloses several universal collection media (UCMs),
which “make[ ] it possible to conveniently collect and preserve cells and
their contents for assessment . . . from a single small patient sample, using
cytological assays, molecular assays, or both” (Lorincz, col. 4, ll. 24-28).
FF5 Lorincz describes several formulations suitable as UCMs,
including PreserveCyt® (Cytyc Corporation), which contains buffered
methanol, and a number of UCMs containing 20% ethanol. None of the
formulations contains formamide (Lorincz, col. 10, ll. 1-50).
FF6 Lorincz teaches that the UCMs permit “solution-based direct
analysis of biomolecules of interest” (Lorincz, col. 2, ll. 17-18), avoiding
“problems encountered in non-solution-based methods such as in situ
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hybridization or non-direct methods which require separation of the
biomolecule of interest from other cellular components before analysis” (id.
at col. 2, ll. 19-23), and “prior art methods [which] require several extra
steps, such as a separate concentration step, which . . . may result in many of
the molecular components of the cell being degraded” (id. at col. 8, ll. 3-6).
FF7 Lorincz’s UCMs are preservative solutions within the meaning
of the Specification and the claims (FF2, FF4, FF5).
FF8 Lorincz discloses “[an] assay for nucleic acids [which] follows
in general principle the method for detecting HIV [sic, HPV] RNA by the
Digene Hybrid Capture HIV [sic, HPV] Test, described in WO 93/10263”3
(Lorincz, col. 10, ll. 55-57). Lorincz’s description of the assay begins in the
middle of the Digene Hybrid Capture Test (i.e., the lysis step):
Briefly, following lysis, 50 μl of probe mix (containing DNA
biotinylated probe) [the sensor] was added to each well. The
plate was sealed and incubated . . . for hybridization to occur.
After hybridization, samples were transferred to a streptavidin-
coated microplate, and 25 μl of anti-hybrid antibody was added
to each well . . . a chemiluminescent substrate was added to
each well [and] . . . the plate was read . . .

(Lorincz, col. 10, l. 58 to col. 11, l. 1).
FF9 The Examiner finds that “[t]he steps prior to lysis are addressed
in Example 1 of WO93/10263 [Challberg] as comprising collection of
cervical specimens in a preservative solution, hydrolysis reagent is added
and following this lysis step, an [150 μl] aliquot was removed and added to
the probe mix containing the sensor” (Ans. 20-21) “without an intermediate

3 WO 93/10263 is the Challberg reference cited by the Examiner in the
obviousness rejection of claim 29.
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washing step” (id. at 21). “Therefore, the alcohol present in the original
preservative solution is maintained in the aliquot and the hybridization
reaction occurs in some ‘amount of’ alcohol . . . meeting the limitation of the
method as claimed” (id.).
FF10 Appellants acknowledge the Examiner’s finding (on page 18 of
the Office Action dated October 13, 2006) that there is “‘…no indication
that the original preservative solution in which the sample was maintained
. . . was no longer present in the sample following the hydrolysis step.
Therefore . . . the contacting does take place in a composition comprising the
preservative solution.’” (App. Br. 7.) Appellants “disagree with the
Examiner” on this point (id.), but do not specifically point out any error in
the Examiner’s finding.
PRINCIPLES OF LAW
“To anticipate a claim, a prior art reference must disclose every
limitation of the claimed invention, either explicitly or inherently.” In re
Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997).
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).
Nevertheless, “courts must not ‘import[ ] limitations from the
specification into the claim.’ . . . [I]t is improper to ‘confin[e] the claims to
th[e] embodiments’ found in the specification . . . .” In re Trans Texas
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Holdings Corp., 498 F.3d 1290, 1299 (Fed. Cir. 2007) (citations omitted,
bracketed text in internal quotes in original).
ANALYSIS
The Examiner finds that Lorincz describes universal collection media
“which comprise . . . alcoholic preservative solution[s]” (Ans. 4), and “a
method for identifying a sensor which specifically binds to a desired target”
(id. at 3). The Examiner finds that Lorincz’s Examples 1 and 3-5, where
probes and “samples were incubated and hybridized in UCM formulations”
(id. at 4), comprise contacting a sample suspected of containing the target
with the sensor “in a preservative solution comprising an amount of one or
more water soluble alcohols effective to preserve such solution against at
least one contaminant” (id.), and therefore meet all the limitations of claim
28.
Appellants dispute that “contacting a sample with a sensor in the
presence of a preservative solution is the same as contacting a sample with a
sensor in a preservative solution” (App. Br. 8 (emphasis added)). Appellants
contend that “[t]he method taught in [Lorincz and] WO 93/10263 . . . clearly
requires that ‘…after hydrolysis, a 150μl aliquot was removed from the
sample tube and added to 50μl of a probe diluent containing Probe A, B, or
C’ (emphasis added [by Appellants]) . . . . Thus, in Lorincz et al., the
contacting of a target of interest with a detectable sensor does not take place
in a preservative solution as specified by the current claims” (id. at 6).
Appellants contend that “[a]ll Examples described in Lorincz et al. . . .
require the manipulation of preserved cells outside of the original solution in
which the cells are collected. Whether the manipulation takes place on a
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slide or in a separate well of a microplate, the cells are no longer in the
original collection solution and no further hybridizations, bindings or other
experimental protocols takes place in that solution” (id. at 8).
Appellants’ arguments are not persuasive. The evidence of record
supports the Examiner’s finding that Lorincz removes a 150 μL aliquot from
a larger volume of UCM (i.e., the preservative solution) containing the lysed
cell sample, mixes that aliquot with 50 μL of a solution containing the
sensor, and the hybridization reaction proceeds in that mixture (FF8, FF9),
and Appellants have not established or argued otherwise. The fact that the
150 μL aliquot might have been removed from a larger volume in the
original sample collection vial does not change its composition – the 150 μL
aliquot still contains the UCM (i.e., preservative solution) when it is
combined with the sensor for hybridization. Appellants have not established,
or even argued, that the sample is separated from the UCM before
hybridization takes place (FF10).
To the extent Appellants contend that Lorincz does not anticipate the
claimed invention because the contacting step must take place in the original
collection vial, the claims neither recite nor require that the contacting take
place in the original collection vial.
CONCLUSION(S) OF LAW
Appellants have not established that the Examiner erred in finding that
Lorincz describes contacting a sample suspected of containing a target of
interest with a detectable sensor, where the contacting takes place in a water-
soluble alcohol-containing preservative solution. Accordingly, the rejection
of claim 28 as anticipated by Lorincz is affirmed.
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Appeal 2008-2363
Application 10/618,443

ISSUE: OBVIOUSNESS
There are eight separate obviousness rejections of remaining claims
1-23, 26, 27, 29, 36, and 37, as set forth above in the Statement of the
Rejection, but each of the rejections is based on the teachings of Lorincz,
relied on as in the anticipation rejection, together with the teachings of one
or more secondary references.
The issue raised by each of the obviousness rejections is the same
issue raised by the anticipation rejection: Have Appellants established that
the Examiner erred in finding that Lorincz describes contacting a sample
suspected of containing a target of interest with a detectable sensor, where
contacting takes place in a water-soluble alcohol-containing preservative
solution?
ANALYSIS
Appellants essentially reiterate their arguments with respect to
Lorincz in response to each of the eight obviousness rejections. For
example, in response to the rejection of claims 1-4, 8-12, 14-16, 18-19, 23,
26, and 27 as unpatentable over Lorincz and Shah, Appellants contend that
Lorincz “does not teach or suggest contacting a sample with a sensor in an
alcoholic preservative solution that does not contain formamide under
conditions in which the sensor can bind to the target” (App. Br. 10).
Appellants contend that “[t]his deficiency cannot be overcome by Shah”
(id.), thus, “[t]he Examiner has not pointed with specificity to any teaching
or suggestion in Lorincz et al. or Shah et al., either alone or in combination
that recites all the limitations of claim 1” (id.).
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Similarly, in response to the rejection of claims 20-22 as unpatentable
over Lorincz, Shah, and Challberg, Appellants contend that “[t]he Examiner
has not pointed with specificity to any teaching or suggestion in Lorincz et
al. or Shah et al., either alone or in combination that recites all the
limitations of claim 1” (id. at 11) and “[t]his deficiency cannot be overcome
by Challberg” (id.).
Appellants make analogous arguments in response to the rejection of
claims 5, 7, 29, and 36-37 over Lorincz, Shah, and Hyldig-Nielsen (id. at
12-13); the rejection of claim 6 over Lorincz, Shah, and Kumar (id. at 13-
14); the rejection of claim 10 over Lorincz, Shah, and Bruchez, Jr. (id. at 14-
15); the rejection of claim 13 over Lorincz, Shah, and Ylikoski (id. at 15-
16), and the rejection of claim 17 over Lorincz, Shah, and Fukasawa (id. at
15-16).
Finally, in response to the rejection of claim 29 as unpatentable over
Lorincz and Challberg, Appellants contend “[t]he Examiner has not pointed
with specificity to any teaching or suggestion in Lorincz et al. that recites all
the limitations of claim 28” (id. at 12) and “[t]his deficiency cannot be
overcome by Challberg” (id.).
Appellants do not identify any error in the Examiner’s reasoning with
respect to Lorincz beyond the arguments already addressed, and those
arguments are not persuasive for reasons discussed above.
CONCLUSIONS OF LAW
Appellants have not established that the Examiner erred in finding that
Lorincz describes contacting a sample suspected of containing a target of
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interest with a detectable sensor, where contacting takes place in a water-
soluble alcohol-containing preservative solution.
SUMMARY
• The rejection of claim 28 under 35 U.S.C. § 102(e) as anticipated by
Lorincz is affirmed.

• The rejection of claims 1-4, 8-12, 14-16, 18, 19, 23, 26, and 27 under
35 U.S.C. § 103(a) as unpatentable over Lorincz and Shah is affirmed.

• The rejection of claims 20-22 under 35 U.S.C. § 103(a) as
unpatentable over Lorincz, Shah, and Challberg is affirmed.

• The rejection of claim 29 under 35 U.S.C. § 103(a) as unpatentable
over Lorincz and Challberg is affirmed.

• The rejection of claims 5, 7, 29, 36, and 37 under 35 U.S.C. § 103(a)
as unpatentable over Lorincz, Shah, and Hyldig-Nielsen is affirmed.

• The rejection of claim 6 under 35 U.S.C. § 103(a) as unpatentable
over Lorincz, Shah, and Kumar is affirmed.

• The rejection of claim 10 under 35 U.S.C. § 103(a) as unpatentable
over Lorincz, Shah, and Bruchez is affirmed.

• The rejection of claim 13 under 35 U.S.C. § 103(a) as unpatentable
over Lorincz, Shah, and Ylikoski is affirmed.

• The rejection of claim 17 under 35 U.S.C. § 103(a) as unpatentable
over Lorincz, Shah, and Fukasawa is affirmed.

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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)(1)(iv)(2006).

AFFIRMED

Ssc

CYTYC CORPORATION
DARRY PATTINSON, SR. IP PARALEGAL
250 CAMPUS DRIVE
MARLBOROUGH, MA 01752

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