Ex Parte Brookes

Board of Patent Appeals and Interferences

Sep 22, 2006

09755747 (B.P.A.I. Sep. 22, 2006)

The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte ANTHONY J. BROOKES
__________

Appeal No. 2006-0258
Application No. 09/755,747
__________

ON BRIEF
__________

Before ADAMS, MILLS, and GREEN, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on the appeal under 35 U.S.C. § 134 from the
examiner’s final rejection of claims 1-5, 7-18, 20-31, 33-44, 46-52, and 67-76,
which are all the claims pending in the application.
Claim 1 is illustrative of the subject matter on appeal and is reproduced
below:
1. A method of detecting DNA variation by monitoring the formation or
dissociation of a complex consisting of:
(a) a single DNA strand of a double stranded DNA of at least
40 base pairs containing the locus of a variation, wherein
said single DNA strand is within a monolayer of single
DNA strands which are bound to a solid surface,
(b) an oligonucleotide or DNA analogue probe specific for
one allele of the variation and capable of hybridizing to
the single strand (a) to form a DNA duplex,

Appeal No. 2006-0258 Page 2
Application No. 09/755,747
(c) an intercalating dye specific for the DNA duplex structure
of (a) plus (b) which forms a complex with the duplex and
reacts uniquely when interacting within the DNA duplex,
which method comprises:
(1) steadily and progressively adjusting temperature at a
rate of between 0.01 to 1°C per second,
(2) continually measuring an output signal indicative of
interaction of the dye with duplex formed from the
strand (a) and probe (b), and
(3) recording the temperature at which a change in reaction
output signal occurs which is attributable to formation or
dissociation of the complex and is thereby correlated
with the strength with which the probe (b) has
hybridized to the single strand (a).

The references relied upon by the examiner are:
Konrad 5,789,167 Aug. 4, 1998
Heller, et al. (Heller) 6,048,690 Apr. 11, 2000
Wittwer, et al. (Wittwer) 6,174,670 Jan. 16, 2001

Stimpson et al. (Stimpson), “Real-time detection of DNA hybridization and
melting on oligonucleotide arrays by using optical wave guides,” Proc. Natl. Acad.
Sci., Vol. 92, pp. 6379-6383 (1995)

Jordan et al. (Jordan), “Surface Plasmon Resonance Imaging Measurements of
DNA Hybridization Adsorption and StreptavidinlDNA Multilayer Formation at
chemically Modified Gold Surfaces,” Anal. Chem., Vol. 69, pp. 4939-4947 (1997)

GROUNDS OF REJECTION
Claims 1-5, 7-18, 20-31, 33-44, 46-52, and 67-76 stand rejected under
35 U.S.C. § 112, first paragraph, as failing to comply with the written description
requirement.
Claims 1-5, 8, 10-18, 21, 23-31, 34, 36-44, 47, 49-52, 67-71, 73, 74, and
76 stand rejected under 35 U.S.C. § 103(a) as being unpatentable over the
combination of Stimpson and Wittwer.

Appeal No. 2006-0258 Page 3
Application No. 09/755,747
Claims 1-5, 7, 8, 10-18, 20, 21, 23-31, 33, 34, 36-44, 46, 47, 49-52, and
67-76 stand rejected under 35 U.S.C. § 103(a) as being unpatentable over the
combination of Stimpson, Wittwer, and Heller.
Claims 1-6, 8-19, 21-32, 34-45, 47-52, 67-71, 73, 74, and 76 stand
rejected under 35 U.S.C. § 103(a) as being unpatentable over the combination of
Stimpson, Wittwer and Konrad.
We reverse.

DISCUSSION
New Matter:
Claims 1-5, 7-18, 20-31, 33-44, 46-52, and 67-76 stand rejected under
35 U.S.C. § 112, first paragraph, as failing to comply with the written description
requirement. More specifically, the examiner finds appellant’s September 3,
2003 amendment of the claims to include the term “monolayer” introduces new
matter into the specification. According to the examiner (Answer, page 4,
emphasis added),
[t]he amendment to include the term “monolayer” is new matter.
The specification of the instant application was word[ ]searched,
both by an optical character recognition of the specification in the
computer version of the application as well as by a word search of
the published application. The word “monolayer” as well as the
broader term “layer” were both searched (including plurals) and no
basis was found for these terms. The response confines itself to
the bare statement that “no new matter has been added by the
amendments or new claims (see page 14 of response)” but no
specific support for the term “monolayer” is identified in the
response. Therefore, in the absence of any identified support for
the term, the claims are rejected as containing new matter.

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Application No. 09/755,747
From the foregoing, it is clear that the basis for the examiner’s rejection is
that the term “monolayer” does not appear in appellant’s specification. We note,
however, that it is not necessary for the specification to describe the claimed
invention ipsissimis verbis; all that is required is that it reasonably convey to
those skilled in the art that, as of the filing date sought, the inventor was in
possession of the claimed invention. Union Oil of California v. Atlantic Richfield
Co., 208 F.3d 989, 997, 54 USPQ2d 1227, 1232 (Fed. Cir. 2000); Vas-Cath Inc.
v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991);
In re Gosteli, 872 F.2d 1008,1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989);
In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978).
So the question before us is not whether appellant’s specification contains
the word “monolayer,” rather the question is whether a person of ordinary skill in
the art1 would have recognized from appellant’s specification that appellant was
in possession of a “monolayer of single DNA strands which are bound to a solid
surface,” as required by appellant’s claimed invention. The specification need
not always spell out every detail; only enough “to convince a person of skill in the
art that the inventor possessed the invention and to enable such a person to
make and use the invention without undue experimentation.” LizardTech Inc., v.
Earth Resource Mapping, Inc., 424 F.3d 1336, 1344-45,
76 USPQ2d 1724, 1732 (Fed. Cir. 2005).

1 We remind the examiner that written description is determined from the perspective of what the
specification conveys to one skilled in the art. In re GPAC Inc., 57 F.3d 1573, 1579, 35 USPQ2d
1116, 1121 (Fed. Cir. 1995); Vas-Cath Inc. v. Mahurkar, 935 F.2d at 1563-64. 19 USPQ2d at
1117.

Appeal No. 2006-0258 Page 5
Application No. 09/755,747
For his part, appellant directs attention (Brief, page 9), to page 11, lines 9
and 10 of his specification, which discloses “[t]he current binding surface format
used is a 96 well microtitre plate that has been coated with streptavidin (available
from various manufacturers).” According to appellant (Brief, page 10, emphasis
removed), “these types of plates are a generic staple of commerce,” which “can
be obtained from a slew of commercial suppliers.” The examiner finds (Answer,
page 12), however, that claim 1 “has no limitation to the specific plate used but
[instead, it] is broadly drawn to any solid surface.” According to the examiner
(Answer, page 13), “[t]he current claims encompass beads, nitrocellulose paper,
nylon, slides, silicon chips and any other support used in the art.”
While we agree with the examiner’s interpretation of the scope of claim 1,
the question before us on appeal is not an issue of claim scope, e.g., the number
of different solid surfaces that fall within the scope of appellant’s claim. To the
contrary, the question before us on this appeal is whether appellant’s
specification provides written descriptive support for a solid surface to which a
monolayer of single DNA strands are bound.2 Stated differently, is a 96 well
microtitre plate that has been coated with streptavidin, or more specifically,
whether the Boehringer-Mannheim streptavidin-coated plate3 set forth in

2 See e.g., (Answer, page 12), “[t]he question that now arises is whether this statement [at page
11, lines 9-10 of appellants’ specification] is sufficient to disclose a device with an inherent
property of having a ‘monolayer’.”

3 Appellants assert (Brief, page 9), “[t]he specification, at page 24, line 12, explicitly states that a
streptavidin-coated plate purchased from Boehringer-Mannheim was used.”

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Application No. 09/755,747
appellant’s specification at page 24, line 12; necessarily or inherently result in a
bound monolayer of single DNA stands.4
According to appellant (Brief, page 9), “product literature for six (6)
different commercially available strepavidin-coated surfaces,” demonstrates that
a monolayer is formed according to the requirements of appellant’s claimed
invention. In this regard, appellant directs attention to (Exhibit 1), which
according to appellant (Brief, page 10), describes a streptavidin-coated product
produced by Dynal Biotech. Appellant asserts (id.), “[t]he excerpt explicitly states
‘[a]nalysis and close calculations show that the bead-coating consists of a
mon[o]layer of covalently coupled streptavidin.’” From this appellant asserts (id.,
emphasis removed), “the Dynal product is unquestionably a surface modified to
contain a monolayer of streptavidin.”
While we acknowledge appellant’s assertions, as we understand it, Exhibit
1 is directed to beads coated with “a monolayer of covalently coupled
streptavidin. . . .” The issue before us is not whether streptavidin is a monolayer
on streptavidin coated beads, but whether the disclosure in appellant’s
specification of microtiter plates in appellant’s specification provides support for
the term “monolayer” as it is used in the claimed invention. Exhibit 1 does not
address this issue, accordingly, we do not find Exhibit 1 persuasive.

4 Kennecott Corp. v. Kyocera Int'l, Inc., 835 F.2d 1419, 1422, 5 USPQ2d 1194, 1197 (Fed. Cir.
1987) (“By disclosing in a patent application a device that inherently performs a function,
operates according to a theory, or has an advantage, a patent applicant necessarily discloses
that function, theory, or advantage even though he says nothing concerning it.”)

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Appellant then directs attention (id.), to Exhibit 2, asserting that Promega
Corporation “markets a 96-well microtitre plate of the type referenced at page 11
of the present specification. In this regard, appellants asserts (id.), “Exhibit 2 is
the product insert literature for Promega’s SAM2-brand biotin capture membrane.
Of particular note is that the very name of the product, SAM, is a well-known
acronym for ‘self-assembled monolayer.’” Appellant refers to Exhibit 35 to
support the assertion that “SAM” is an art recognized acronym for “self-
assembled monolayer.”
Exhibit 2 also does not relate to microtiter plates, but instead refers to a
SAM2® Biotin Capture Membrane. There is no evidence on this record that this
membrane is the same as a microtiter plate. Therefore, Exhibit 2 does not
address the issue before us. Accordingly, we do not find Exhibit 2 persuasive.
According to appellant (id.), “[a] slew of other companies make equivalent
streptavidin-coated surfaces wherein the streptavidin is in the form of a
monolayer on the surface. Examples include Perkin Elmer (see Exhibit 4), Nunc
(Exhibit 5), Upstate (Exhibit 6), and Roche Applied Science (Exhibit 7). . . . They
are all surfaces modified to contain an immobilized streptavidin monolayer.”
While Exhibits 4-6 are directed to microtiter plates, upon review of these
Exhibits we find no disclosure of whether the plates contain a streptavidin
monolayer. Accordingly, we do not find Exhibits 4-6 persuasive with regard to
the issue before us. See also Answer, page 16, where the examiner finds that
these Exhibits “do not directly inform this analysis.”

5 According to appellant (Brief, page 11), “Exhibit 3 is an excerpt from the
www.acronymfinder.com website,” which defines the acronym “SAM” as, inter alia, “Self-

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Application No. 09/755,747
This leaves Exhibits 7 and 8. As appellant explains (Brief, bridging
paragraph, pages 9-10 and 11), as a result of from “a corporate merger/
restructuring, Boehringer-Mannheim was renamed Roche Molecular
Biochemicals on March 5, 1998 (see Exhibit 8 . . .), which company was then
subsequently re-named Roche Applied Science. The product formerly marketed
under the Boehringer-Mannheim name is now sold by Roche Applied Science
under the trademark StreptaWell (see Exhibit 7).”
Upon review of Exhibits 7 and 8, we find that like Exhibits 4-6, Exhibits 7
and 8 do not disclose whether the plates contain a streptavidin monolayer.
Accordingly, we do not find Exhibits 7 and 8 persuasive with regard to the issue
before us. See also Answer, page 16, where the examiner finds that these
Exhibits “do not directly inform this analysis.”
Having found that Exhibits 1-8 do not resolve the issue before us, we
move to the remaining two pieces of evidence that appellant relies upon to
support his position - the Strohner Declaration, and the Jordan reference.
According to Strohner (Strohner Declaration, paragraph 2), “[r]egardless of
coating procedure details, immobilization of streptavidin onto solid-surfaces (such
as plastic microtiter plates and membranes) will result in a reactive streptavidin
monolayer. DNA molecules which are bound to this reactive streptavidin
monolayer will inevitably form a superimposed DNA monolayer.” While the
examiner asserts (Answer, page 17), that weight was given to the Strohner
Declaration, the opinion expressed therein is rebutted by the Jordan reference.

Assembled Monolayer.”

Appeal No. 2006-0258 Page 9
Application No. 09/755,747
According to appellant (Brief, page 13, emphasis removed), “the probe
DNA is explicitly stated in Jordan et al. as forming a “probe DNA monolayer.”
(See Jordan et al., page 4940, right-hand column, middle of first full paragraph.)”
In response, the examiner finds (Answer, page 17), “[a]ppellant ignores the plain
statement of Jordan that “[t]he SPR signal resulted from hybridization onto
immobilized probes is further amplified by the formation of streptavidin/DNA
multilayers which grow by a combination of DNA hybridization and biotin-
streptavidin binding (see abstract of Jordan).” Upon review of Jordan, we find
that these statements by the examiner and appellant are both correct and are not
in conflict. Further, while Jordan refers to immobilization on a gold surface and
not a microtiter plate, we believe that some explanation is necessary to dispel the
conflict created on this record. With reference to figure 1 of Jordan, we note that
a “probe monolayer” is formed by adsorbing probe DNA onto the gold surface.
Notwithstanding any other step, this first step of adsorbing probe DNA onto the
gold surface results in the formation of a “probe monolayer.” Accordingly,
appellant is correct. Now, in a subsequent step, biotinylated complements (e.g.
biotinylated DNA) is hybridized to the probe DNA monolayer. Jordon, page
1440, second column, first full paragraph. The result is a probe DNA –
biotinylated complements multilayer. Accordingly, the examiner is correct.
For illustrative purposes, let’s consider this analysis in the context of a
streptavidin coated microtiter plate. Assume that a monolayer of streptavidin is
coated onto a microtiter plate. Then single DNA strands are attached to the
microtiter plate using streptavidin as a linker. For clarity, this means that each

Appeal No. 2006-0258 Page 10
Application No. 09/755,747
single DNA strand will be attached to a single streptavidin molecule that is
attached to the microtiter plate. Looking only at the DNA layer, one will see a
monolayer of single DNA strands. However, looking at a cross-section of the
wells of the microtiter plate, one will see a multi-layer, wherein the well forms the
base, streptavidin molecule is attached to the well, and single DNA strands are
attached to the streptavidin.
Now, considering page 24, lines 10-13 of appellant’s specification, “PCR
reaction products were mixed with an equal volume of Buffer . . . and transferred
to individual wells of a streptavidin coated thin wall microtiter plate. . . .” As we
understand it, the streptavidin is acting as a linker – linking the PCR reaction
products to the plate. So from the examiner’s point of view a multi-layer will
result, if one looks at a cross-section of the microtiter plate. However, looking at
each layer, Strohner (Strohner Declaration, paragraph 2), informs us that
regardless of how the streptavidin plate was coated, the result will be a
monolayer of streptavidin on the plate. Therefore, the “linkers” are in the form of
a monolayer. When the PCR products are added to this monolayer, the result
will be a monolayer of PCR products attached to the microtiter plate through a
monolayer of streptavidin linkers. See Strohner Declaration, paragraph 2, “DNA
molecules which are bound to this reactive streptavidin monolayer will inevitably
form a superimposed DNA monolayer.” Therefore, we see no conflict between
the Strohner Declaration and the teachings of Jordon. The interpretations of the
examiner and appellant differ only with regard to the manner in which you look at
the resulting plate.

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Application No. 09/755,747
In the context of appellant’s claimed invention, we find that part (a) of
claim 1 to read “a complex consisting of a single DNA strand of a double
stranded DNA of at least 40 base pairs containing the locus of a variation,
wherein said single DNA strand is within a monolayer of single DNA strands
which are bound to a solid surface. . . .” There is no requirement that the single
DNA strand be attached directly to the solid surface. Part (a) of claim 1 simply
requires that the single DNA strand be “bound” to a solid surface. With the
benefit of the Strohner Declaration we find that single DNA strands of a double
stranded DNA bound to a streptavidin coated microtiter plate, such as the one
described at page 24, lines 10-13, will inherently result in a monolayer of single
DNA strands as set forth in appellant’s first claim. As set forth in Kennecott
Corp., 835 F.2d at 1422, 5 USPQ2d at 1197, “[b]y disclosing in a patent
application a device that inherently performs a function, operates according to a
theory, or has an advantage, a patent applicant necessarily discloses that
function, theory, or advantage even though he says nothing concerning it.”
Accordingly, it is our opinion that by disclosing that PCR products can be
attached to streptavidin coated microtiter plates appellant has provided sufficient
descriptive support to include the term “monolayer” as done so in the claims
before us on appeal. Therefore, we reverse the rejection of claims 1-5, 7-18, 20-
31, 33-44, 46-52, and 67-76 stand rejected under 35 U.S.C. § 112, first
paragraph.

Obviousness:

Appeal No. 2006-0258 Page 12
Application No. 09/755,747
The combination of Stimpson and Wittwer:
Claims 1-5, 8, 10-18, 21, 23-31, 34, 36-44, 47, 49-52, 67-71, 73, 74, and
76 stand rejected under 35 U.S.C. § 103(a) as being unpatentable over the
combination of Stimpson and Wittwer.
The examiner finds (Answer, page 5), “Stimpson teaches a method of
detecting DNA variation by monitoring the formation or dissociation of a complex.
. . .” In this regard, the examiner finds (id.), the complex taught by Stimpson
consists of:
(a) a single strand of a DNA sequence . . . oligonucleotide
are attached to a glass solid support which is a monolayer of the
nucleic acids . . .,
(b) an oligonucleotide specific for the single stranded DNA
sequence specific for one allele of the variation and capable of
hybridizing to the single strand (a) to form a duplex . . .
(c) a marker detection of the duplex structure of (a) plus (b)
which forms a complex with the said duplex (here the selenium
label . . .).

According to the examiner (Answer, page 6), Stimpson’s method comprises
(1) steadily and progressively adjusting the temperature by
1°C increments . . .
(2) continually measuring an output signal indicative of the
duplex formed from the strand (a) and probe (b). . . and
(3) recording the conditions at which a change in reaction
output signal occurs which is attributable to formation or
dissociation of the complex and is thereby correlated with the
strength with which the probe (b) has hybridized to the single strand
(a). . . .
The examiner recognizes (id.), however, that “Stimpson does not teach
the use of a marker which is duplex specific in the analysis.” To make up for this
deficiency, the examiner relies on Wittwer, which according to the examiner
(Answer, page 6), “teaches a method of detecting DNA variation by monitoring

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Application No. 09/755,747
the formation or dissociation of a complex (abstract). . . .” In this regard, the
examiner finds (Answer, pages 6-7), the complex taught by Wittwer consists of:
(a) a single strand of a DNA sequence . . .,
(b) an oligonucleotide specific for the single stranded DNA
sequence. . .,
(c) a marker specific for the duplex structure of (a) plus (b)
which forms a complex with the said duplex and reacts uniquely
when interacting within the duplex.

In this regard, the examiner focuses attention on the fluorescent dye
SYBR green. Id.
According to the examiner (Answer, page 7), Wittwer’s method comprises:
(1) “monitoring fluorescence while changing temperature at a
rate of 0.1 degree C/second.” . . .
(2) continually measuring an output signal indicative of
interaction of the marker with duplex formed from the strand (a) and
probe (b) . . . and
(3) recording the conditions at which a change in reaction
output signal occurs which is attributable to formation or
dissociation of the complex and is thereby correlated with the
strength with which the probe (b) has hybridized to the single strand
(a) . . . .

Based on this evidence the examiner finds (Answer, bridging paragraph, pages
8-9),
It would have been prima facie obvious to one of ordinary skill in
the art at the time the invention was made to utilize the markers of
Wittwer in the mutation detection method of Stimpson since Wither
states “SYBRTM Green I is a preferred double strand specific dye
for fluorescence monitoring of PCR, primarily because of superior
sensitivity, arising from greater discrimination between double
stranded and single stranded nucleic acid. SYBRTM Green I can be
used in any amplification and is inexpensive. In addition, product
specificity can be obtained by analysis of melting curves . . . .”
Thus, an ordinary practitioner would have been motivated to use
SYBRTM Green I in the melting curve analytical method of Stimpson
since Wittwer teaches that this intercalator is superior in sensitivity,
is useful in the particular assay employed by Stimpson since the
waveguides would detect the fluorescent label and is inexpensive.

Appeal No. 2006-0258 Page 14
Application No. 09/755,747

In response appellant asserts (Brief, page 16), Stimpson “emphasize that
fluorescent-based systems are insensitive and therefore provides an alternative
optical wave guide system which improves sensitivity.” According to appellant
(17), the optical wave guide system taught by Stimpson is completely different
than using a fluorescent-based system and therefore a person of ordinary skill in
the art would not have been motivated to modify Stimpson for use with a
fluorescent dye like that taught by Wittwer. In addition, appellant asserts (id.),
Wittwer does not suggest or employ the SYBR Green dye in a “solid-phase
hybridization, which is the subject of the present claims.” In support of this
assertion appellant relies on the Baldeschwieler Declaration and the Kwok
Declaration.
Initially, we note that Baldeschwieler declares that he was the senior
investigator and coauthor of Stimpson. Baldeschwieler Declaration, paragraph 1.
In this regard, Baldeschwieler declares (Baldeschwieler Declaration, paragraph
2),
Both before and after the publication of Stimpson . . ., one skilled in
the art would not expect the DNA binding capacity of any of the
stable and common 2-D surfaces and chemistries to yield
sufficiently strong fluorescent signals sufficiently ‘instantly’
(sub0second0 in f fluorescence based assay method to allow for
dynamic tracking of signal changes in real-time, when applying
practically useful rates of heating. One skilled in the art would,
therefore, most rationally turn to 3-D (gel-type) arrays to solve this
widely recognized problem, since the considerable 3rd dimension
provides far greater capacity and scope for DNA binding and
manipulation.

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Application No. 09/755,747
According to Baldeschwieler (Baldeschwieler Declaration, paragraph 3), these
“known limitations of solid surface fluorescence assays . . . are repeated[ly]
emphasized in the Introduction, Results, and Discussion sections of
Stimpson. . . .” Similarly, Kwok explains that “[t]he methods [of Wittwer] involve
the liquid phase hybridization of amplified DNA strands either with each other or
with oligonucleotide probes. None of these methods would lead a worker in the
field to the expectation that allelic discrimination could be achieved . . . on a solid
surface . . . .”
Upon consideration of record, we find Stimpson teaches (page 6379,
column 2), “[b]ecause the amount of fluorescent label on the surface of a chip is
quite low, the time required to scan the array is on the order of 1 min.” As we
understand this statement, if a fluorescent dye is used (as is required by
appellant’s claimed invention) for every incremental increase in temperature 1
min. would be required to scan the array for fluorescence. In our opinion this is
contrary to the requirement in appellant’s claim that the method comprises a
steady and progress adjustment of temperature at a rate of between 0.01 to 1ºC
per second; and continually measuring an output signal indicative of interaction
of the dye with duplex formed . . . .” To the contrary, as we understand
Stimpson, the temperature would be adjusted and then it would take 1 min. for
the chip to be scanned. In our opinion, this is contrary to the requirements of
appellant’s claimed invention. See e.g., Stimpson (id.), “[m]elting curves could
provide an additional dimension to the system and allow differentiation of closely
related sequences. . . . However, if 1 min is required to read/wash a DNA chip,

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Application No. 09/755,747
then a high resolution melting curve from 30 to 70ºC would require 40 min; i.e.,
measurement is rate limiting.”
In addition, Stimpson teach (id.), “[r]emoval of background signal would
require some sort of washing system to eliminate the label as it dissociates from
the capture site.” The examiner has does not appear to have appreciated this
teaching in Stimpson which further leads away from appellant’s requirement for a
steady and progressive adjustment of temperature while continually measuring
output signal. As we understand it, it would be hard to meet the requirements of
appellant’s claimed invention if the one has to stop and wash the array after each
incremental increase in temperature.
Therefore, despite the accolades that the examiner gives to the SYBR dye
taught by Wittwer, it is a fluorescent dye. As such it would appear to suffer from
the same problems that Stimpson teaches as applying to fluorescent dyes.
There is no evidence on this record that the use of fluorescent dyes including
SYBR would not suffer the same problems that Stimpson teach as applying to
fluorescent dyes in a solid state environment. Accordingly, it is our opinion that
the examiner has not provided the evidence necessary to establish a prima facie
case of obviousness.
As set forth in In re Kotzab, 217 F.3d 1365, 1369-70, 55 USPQ2d 1313,
1316 (Fed. Cir. 2000):
A critical step in analyzing the patentability of claims pursuant to
section 103(a) is casting the mind back to the time of invention, to
consider the thinking of one of ordinary skill in the art, guided only
by the prior art references and the then-accepted wisdom in the
field. . . . Close adherence to this methodology is especially
important in cases where the very ease with which the invention

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Application No. 09/755,747
can be understood may prompt one “to fall victim to the insidious
effect of a hindsight syndrome wherein that which only the invention
taught is used against its teacher.”
. . .
Most if not all inventions arise from a combination of old elements.
. . . Thus, every element of a claimed invention may often be found
in the prior art. . . . However, identification in the prior art of each
individual part claimed is insufficient to defeat patentability of the
whole claimed invention. . . . Rather, to establish obviousness
based on a combination of the elements disclosed in the prior art,
there must be some motivation, suggestion or teaching of the
desirability of making the specific combination that was made by
the applicant. [Citations omitted].

In other words, “there still must be evidence that ‘a skilled artisan, . . . with
no knowledge of the claimed invention, would select the elements from the cited
prior art references for combination in the manner claimed.’” Ecolochem Inc. v.
Southern California Edison, 227 F.3d 1361, 1375, 56 USPQ2d 1065, 1075-76
(Fed. Cir. 2000). At best, the statement of the rejection establishes that
individual parts of the claimed invention were known in the prior art. The
examiner, however, has not established that a person of ordinary skill in the art
would recognize a fluorescent dye could be used in the method taught by
Stimpson, while steadily and progressively adjusting the temperature at a rate of
between -.-1 to 1 C per second and continually measuring an output signal
indicative of interaction of the dye with duplex formed. . .” as is required by
appellant’s claimed invention.
On reflection, we find that the examiner has not met his burden of
establishing a prima facie case of obviousness. Accordingly, we reverse the
rejection of claims 1-5, 8, 10-18, 21, 23-31, 34, 36-44, 47, 49-52, 67-71, 73, 74,

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Application No. 09/755,747
and 76 under 35 U.S.C. § 103(a) as being unpatentable over the combination of
Stimpson and Wittwer.

The combination of Stimpson, Wittwer and Heller:
Claims 1-5, 7, 8, 10-18, 20, 21, 23-31, 33, 34, 36-44, 46, 47, 49-52, and
67-76 stand rejected under 35 U.S.C. § 103(a) as being unpatentable over the
combination of Stimpson, Wittwer and Heller.
The examiner relies on the combination of Stimpson and Wittwer as set
forth above. According to the examiner (Answer, page 9), the combination of
Stimpson and Wittwer “do not teach immobilization of the oligonucleotide using
biotin-streptavidin.” To make up for this deficiency the examiner relies on Heller.
According to the examiner (id.), “Heller teaches immobilization of
oligonucleotides to arrays using biotin-streptavidin for nucleic acid detection
assays.” Heller, however, does not make up for the deficiencies in the
combination of Stimpson in view of Wittwer.
Accordingly, we reverse the rejection of claims 1-5, 7, 8, 10-18, 20, 21, 23-
31, 33, 34, 36-44, 46, 47, 49-52, and 67-76 under 35 U.S.C. § 103(a) as being
unpatentable over the combination of Stimpson, Wittwer and Heller.

The combination of Stimpson, Wittwer and Konrad:
Claims 1-6, 8-19, 21-32, 34-45, 47-52, 67-71, 73, 74, and 76 stand
rejected under 35 U.S.C. § 103(a) as being unpatentable over the combination of
Stimpson, Wittwer and Konrad.

Appeal No. 2006-0258 Page 19
Application No. 09/755,747
The examiner relies on the combination of Stimpson and Wittwer as set
forth above. According to the examiner (Answer, page 10), the combination of
Stimpson and Wittwer “do not teach the use of Hepes buffer in hybridization.” To
make up for this deficiency the examiner relies on Konrad. According to the
examiner (id.), Konrad teaches that the “conditions for hybridization of
oligonucleotide sequences are well known”, and may include a hepes buffering
system. Konrad, however, fails to make up for the deficiencies in the
combination of Stimpson in view of Wittwer.

Accordingly, we reverse the rejection of claims 1-6, 8-19, 21-32, 34-45,
47-52, 67-71, 73, 74, and 76 under 35 U.S.C. § 103(a) as being unpatentable
over the combination of Stimpson, Wittwer, and Konrad.

Appeal No. 2006-0258 Page 20
Application No. 09/755,747
REVERSED

Donald E. Adams )
Administrative Patent Judge )
)
) BOARD OF PATENT
)
Demetra J. Mills ) APPEALS AND
Administrative Patent Judge )
) INTERFERENCES
)
)
Lora M. Green )
Administrative Patent Judge )

DA/dym

Appeal No. 2006-0258 Page 21
Application No. 09/755,747
DEWITT ROSS & STEVENS S.C.
8000 EXCELSIOR DR
SUITE 401
MADISON WI 53717-1914