Ex Parte Olson et al

Board of Patent Appeals and Interferences

Jun 30, 2009

09697028 (B.P.A.I. Jun. 30, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
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Ex parte JEFFREY OLSON, and VINCENT P. JR. STANTON
__________

Appeal 2008-006230
Application 09/697,028
Technology Center 1600
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Decided:1 June 30, 2009
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Before TONI R. SCHINER, DEMETRA J. MILLS, and LORA M. GREEN,
Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s final rejection of claims 10-16. We have jurisdiction under 35
U.S.C. § 6(b).

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 2008-006230
Application 09/697,028

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The claims are directed to a method for biasing a DNA amplification
reaction at a polymorphic site. Claim 10 is representative of the claims on
appeal, and reads as follows:
10. A method for biasing a DNA amplification reaction such that a first
nucleic acid molecule having a first nucleotide present at a polymorphic site
is amplified to a greater extent than a second nucleic acid having a second,
different nucleotide present at the polymorphic site, comprising
(a) contacting a sample of DNA comprising at least the first nucleic
acid molecule with two amplification primers that hybridize to both the first
nucleic acid molecule and the second nucleic acid molecule at locations
which flank the polymorphic site such that neither the first primer nor the
second primer hybridizes to the polymorphic site, one of the two primers
including a 5´ portion which, when incorporated into an amplification
product, will upon further amplification yield products that form a stable
stem-loop structure, the stem of which is perfectly matched and includes the
polymorphic site only when the second nucleotide is present at the
polymorphic site, but not when the first nucleotide is present at the
polymorphic site; and
b) carrying out an amplification reaction, whereby the first nucleic
acid molecule is amplified to a greater extent than the second nucleic acid
molecule.

The Examiner relies on the following evidence:
Whitcombe US 6,326,145 B1 Dec. 4, 2001
We reverse.

ISSUE
The Examiner finds that claims 10-16 are anticipated by Whitcombe.
Appellants contend that Whitcombe does not anticipate the claims on
appeal as the probes described in the reference do not include a 5´ portion
that is incorporated into an amplification product.
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Thus, the issue on appeal is: Have Appellants demonstrated that the
Examiner erred in finding that Whitcombe teaches the use of a primer
including a 5´ portion which, when incorporated into an amplification
product, will upon further amplification yield products that form a stable
stem-loop structure, the stem of which is perfectly matched and includes the
polymorphic site only when the second nucleotide is present at the
polymorphic site, but not when the first nucleotide is present at the
polymorphic site?

FINDINGS OF FACT
FF1 The claims on appeal “relate to DNA amplification methods that
cause differential amplification of two nucleic acid molecules that differ in
sequence at a polymorphic site.” (App. Br. 2.)
FF2 According to the Specification:
The method involves contacting a segment of DNA with two
primers encompassing the polymorphic site under amplification
conditions. One primer contains a region at its 5' end that is not
complementary to the target nucleic acid but which, when
incorporated into the amplification product, will cause the 3'
end of the strand complementary to this primer in the
amplification product to form a sufficiently stable hairpin loop
by hybridizing with the sequence including the polymorphic
site to inhibit further amplification only if the specific
nucleotide is present at the polymorphic site. The method also
involves determining whether the segment is amplified.
Amplification (or preferential amplification) of the segment is
indicative that the polymorphic site contains an alternative to
the specific nucleotide.

(Spec. 10.)
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FF3 The Examiner rejects claims 10-16 under 35 U.S.C. § 102(e) as being
anticipated by Whitcombe (Ans. 2).
FF4 The Examiner finds that Whitcombe teaches a method of “biasing
(enriching desired nucleic acid) a DNA amplification reaction such that a
first nuclei [sic] acid having a first nucleotide present at a polymorphic site
(allele 1) is amplified to a greater extent than a second nucleic acid having a
second, different nucleotide present at the polymorphic site (allele 2).” (Id.
at 3.)
FF5 The Examiner finds that Whitcombe teaches that “one of the two
primers include[es] a 5´ portion which, when incorporated into an
amplification product, will upon further amplification yield products that
form a stable-stem-loop structure (see col. 7, line 49-67, col. 8, line 1-11,
col. 9, line 2-24, indicate stem-loop structures when scorpion primers are
used, Figs. 9, 11-12, indicating stem loop structures), the stem of which is
perfectly matched and includes the polymorphic site only when the second
nucleotide is present at [the] polymorphic site (allele-specific) (see col. 9,
line 2-24, col. 10, line 53-67, col. 11, line 1-17, col. 13, line 45-52).” (Id.)
FF6 Whitcombe teaches “a tailed nucleic acid primer having a template
binding region and [a] tail comprising a linker and target binding region.”
(Whitcombe, col. 1, l. 66-col. 2, l. 1.)
FF7 According to Whitcombe, the primer is used as an amplification
primer in an amplification system, such as PCR, and the tail region is not
copied, remaining single stranded (id. at col. 2, ll. 52-58).
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FF8 The linker of the tailed nucleic acid primer thus may conveniently
comprise a blocking moiety, such as a hexethylene glycol (HEG) monomer,
which prevents polymerase mediated chain extension (id. at col. 2, ll.
61-64). Whitcombe also teaches the use of other blockers of polymerase
mediated chain extension (col. 2, l. 64-col. 3, l. 5).
FF9 Whitcombe teaches that the sole requirement of the primer tail “is that
the target binding region in the tail is available after primer extension to
hybridise with a complementary sequence (if present) in the primer
extension product.” (Id. at col. 7, ll. 1-5.)
FF10 Whitcombe provides an Example wherein “a PCR was performed
using primers which flank a polymorphism gene.” (Id. at col. 13, ll. 16-19.)
In the materials section, the Scorpion primers used contain a replication
blocking hexethylene glycol monomer that is placed between the hairpin
forming portion of the Scorpion primer (the tail region) and the portion used
as the PCR primer (id. at col. 12, l. 51-col. 13, l. 3).

PRINCIPLES OF LAW
“It is well settled that a claim is anticipated if each and every
limitation is found either expressly or inherently in a single prior art
reference.” Celeritas Techs. Ltd. v. Rockwell Int’l Corp., 150 F.3d 1354,
1361 (Fed. Cir. 1998).

ANALYSIS
Appellants contend that Whitcombe cannot anticipate the claims on
appeal as “the probes described [by Whitcombe] do not include a 5´ portion
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that is incorporated into an amplification product.” (App. Br. 5.) According
to Appellants, Whitcombe teaches that it is the 5´ end of the Scorpion probe
that forms the stem-loop structure, and Whitcombe teaches that the 5´ end of
the Scorpion probe is not amplified (id. at 7). Appellants therefore assert
“the Scorpion probes do not contain a 5´ region that is incorporated into the
amplification product and forms a stem-loop structure (when a certain target
sequence is present), as required by the present claims.” (Id.)
The Examiner responds that “Appellants’ arguments are based solely
on the detection probes of [Whitcombe] and are silent with regard to the
Scorpion primers, which are involved in the amplification process.” (Ans.
8.) As noted by Whitcombe, however, the primary purpose of the tail
region, which is not amplified and thus remains single stranded, is that the
target binding region of the tail is available after primer extension to
hybridize with a complementary sequence (if present) in the primer
extension product. Thus, the stem-loop structure of Whitcombe is formed
by the tail region of the Scorpion primer of Whitcombe, which is specifically
blocked from being incorporated into the amplification product, whereas the
independent claims on appeal (claims 10 and 16) require that one of the two
primers includes a 5´ portion which, when incorporated into an
amplification product, will upon further amplification yield products that
form a stable stem-loop structure.

CONCLUSION(S) OF LAW
We therefore find that Appellants have demonstrated that the
Examiner erred in finding that Whitcombe teaches the use of a primer
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including a 5´ portion which, when incorporated into an amplification
product, will upon further amplification yield products that form a stable
stem-loop structure, the stem of which is perfectly matched and includes the
polymorphic site only when the second nucleotide is present at the
polymorphic site, but not when the first nucleotide is present at the
polymorphic site.
The rejection of claims 10-16 under 35 U.S.C. § 102(e) as being
anticipated by Whitcombe is thus reversed.

REVERSED
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