Ex Parte Saito et al

Board of Patent Appeals and Interferences

Jan 22, 2008

10253967 (B.P.A.I. Jan. 22, 2008)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte KATSUYUKI SAITO, JAR-HOW LEE, and LINDLEY BLAIR
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Appeal 2007-2363
Application 10/253,967
Technology Center 1600
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Decided: January 22, 2008
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Before TONI R. SCHEINER, DONALD E. ADAMS, and
LORA M. GREEN, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON REQUEST FOR REHEARING
Appellants have requested rehearing of the decision entered
September 11, 2007 (hereinafter “Decision”). That decision affirmed a
rejection under 35 U.S.C. § 102(b) as to claims 1-6, 8 and 20, but reversed
as to claims 9-19. After careful review and consideration of the arguments
presented, we decline to make any substantive change in our previous
opinion.
Appeal 2007-2363
Application 10/253,967

Appellants argue that “the Board affirmed the rejection on a new
ground relying upon a rationale that was different from that used by the
Examiner in the Final Rejection.” (Req. Reh’g 3.) Because of such,
Appellants assert that fairness requires that they have an opportunity to
respond (id. at 4).
While we affirmed the rejection based on anticipation of claim 1 by
Guo, which is the same rejection made by the Examiner, we understand
Appellants’ argument that the basis of the affirmance may have differed
from that of the Examiner. Thus, we address Appellants’ arguments made in
the Request for Rehearing below.
Appellants argue that in the method of Guo, when “the target is an
allelic variant of the control sequence, base-pair duplexes will not be formed
at the location of the true mismatch and the Guo probe will not stably
hybridize to the variant sequence.” (Req. Reh’g 10.)
According to Appellants, that
is a very different mechanism from that described by
Appellants’ claims wherein neither the first nor the second
probe region is intended to hybridize with an “intervening
sequence” on the target polynucleotide. Those first and second
probe regions are intended to form base pairs with and
hybridize to target regions on the (control) target but will not
form base-pair duplexes at the location of true mismatches
when the target polynucleotide is an allelic variant of the
control. Such true mismatches can be substitution mismatches
such as those disclosed in Guo Fig. 2 and relied upon in the
Final Rejection (see Fig., middle column) or they can be
insertion mismatches such as relied upon in the Board Decision
(see Fig., right-hand column).

(Id.)
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Appeal 2007-2363
Application 10/253,967

Appellants assert that “in contrast to the construction urged in the
Board Decision there exists an intervening sequence in both the control
target and the allelic variant” in the claimed invention, which is not
disclosed by Guo (id. at 12). Therefore, according to Appellants, the
“practice of the Guo method does not anticipate the claimed method because
the ‘true mismatch’ does not create an intervening sequence on the target.”
(Id.)
Appellants’ arguments have been carefully considered, but are not
found to be convincing as they are not commensurate with the claimed
invention. Appellants’ claim 1 is drawn to:
A method for detecting the presence of a target nucleic acid sequence
on a sample nucleic acid strand comprising the steps of:
contacting a sample suspected of containing said target nucleic acid
sequence with a diagnostic probe under hybridizing conditions;
wherein the nucleotide sequence of said diagnostic probe comprises
(1) a first probe region at its 5'-end that is substantially complementary to a
first target region characteristic of said target nucleic acid sequence, and (2)
a second probe region, located 3' to said first probe region, where the second
probe region is substantially complementary to a second target region
characteristic of said target nucleic acid sequence on the target nucleic acid
strand wherein the first and second probe regions on the diagnostic probe
may be separated by a spacer region of nucleic acid, and further there exists
an intervening sequence between the first and second target regions on the
target nucleic acid strand;
wherein when said first and second probe regions are separated by a
spacer region then said spacer region forms a non-self-hybridized loop under
said selected conditions;
whereby for said selected hybridization conditions the first and second
probe regions are such that the diagnostic probe is only stably hybridized to
the target nucleic acid strand to form a detectable probe:target hybrid when
the first probe region is substantially complementary to the first target region
and the second probe region is substantially complementary to the second
target region,
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Appeal 2007-2363
Application 10/253,967

but wherein for said selected hybridization conditions the diagnostic
probe is not stably hybridized to the target nucleic acid strand to form a
probe:target hybrid detectable above a threshold indicative of stable
hybridization when either the first probe region is not substantially
complementary to the first target region or the second probe region is not
substantially complementary to the second target region; and
detecting the presence or absence of the stable probe:target hybrid in
the absence of elongation of the probe:target hybrid as an indication of the
presence of the target nucleic acid sequence in the sample.

As to the requirement that wherein the nucleotide sequence of said
diagnostic probe comprises (1) a first probe region at its 5'-end that is
substantially complementary to a first target region characteristic of said
target nucleic acid sequence, and (2) a second probe region, located 3' to
said first probe region, where the second probe region is substantially
complementary to a second target region characteristic of said target nucleic
acid sequence on the target nucleic acid strand wherein the first and second
probe regions on the diagnostic probe may be separated by a spacer region
of nucleic acid, there is no requirement that there be a spacer region in the
probe. (See Decision 7.) That is, the first probe region may be contiguous
with the second probe region. In addition, there is no requirement that the
probe regions be completely complementary to the target sequence, and the
introduction of the artificial mismatch would read on a probe region that is
“substantially complementary” to a region characteristic of the target nucleic
acid sequence. (See id. at 7-8.)
As to the limitation that there exists an intervening sequence between
the first and second target regions on the target nucleic acid strand, as we
indicated in the Decision, that limitation is met when the variant, i.e., the
true mismatch (pointed symbol), is an insertion of additional nucleotides in
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Appeal 2007-2363
Application 10/253,967

the target sequence. That is, the portions of the target flanking the insertion
read on “a first target region characteristic of said target nucleic acid
sequence,” and “a second target region characteristic of the target nucleic
acid sequence.” The insertion then reads on the “intervening sequence
between the first and second target regions on the target nucleic acid strand.”
(See id. at 6.)
As to the argument that when the target is an allelic variant of the
control sequence, base-pair duplexes will not be formed at the location of the
true mismatch and the Guo probe will not stably hybridize to the variant
sequence, when the allelic variant is an insertion, the probe of Guo also will
not form base pair duplexes at the location of the true mismatch. As to
“stable hybridization,” all that is required by claim 1 is that
for said selected hybridization conditions the first and second probe
regions are such that the diagnostic probe is only stably hybridized to the
target nucleic acid strand to form a detectable probe:target hybrid when the
first probe region is substantially complementary to the first target region
and the second probe region is substantially complementary to the second
target region,
but wherein for said selected hybridization conditions the diagnostic
probe is not stably hybridized to the target nucleic acid strand to form a
probe:target hybrid detectable above a threshold indicative of stable
hybridization when either the first probe region is not substantially
complementary to the first target region or the second probe region is not
substantially complementary to the second target region;

The claim does not specify any particular hybridization conditions,
and Appellants have not explained why, when the allelic variant of Guo is an
insertion, which reads on the intervening sequence between the first and
second target regions on the target nucleic acid strand, and each method has
a probe containing a first and second probe regions that are substantially
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Appeal 2007-2363
Application 10/253,967

complementary to the first and second target regions and the first and second
probe regions are contiguous, why stable hybridization would occur using
the method of claim 1 and not in the method of Guo.
As to the argument that, in contrast to the construction urged in the
Board Decision, there exists an intervening sequence in both the control
target and the allelic variant in the claimed invention, which is not disclosed
by Guo, that argument is not understood as claim 1 does not require a
“control target.” As already explained, all that is required by claim 1 is a
target nucleic acid sequence and a diagnostic probe. As to the target nucleic
acid sequence, the claim specifies that the target region contains a first target
region and a second target region, wherein there is an intervening sequence
between the two target regions. The target nucleic acid sequence of Guo
reads on the target nucleic acid sequence of claim 1 when the allelic variant
is an insertion. As to the probe, claim 1 requires that the probe contain a
first probe region that is substantially complementary to the first target
region, and also contain a second probe region that is substantially
complementary to the second target region, wherein the two probe regions
may or may not be separated by a spacer. The probe of Guo reads on the
probe of claim 1 when the probe does not contain a spacer, that is, when the
two probe regions are contiguous to one another. Thus, Guo teaches a
method that meets all of the limitations of claim 1, and we decline to make
any substantive changes to our previous opinion.

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Appeal 2007-2363
Application 10/253,967

CONCLUSION
We have considered Appellants’ Request for Rehearing, but decline to
make any substantive change in our previous opinion.

REHEARING DENIED

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