Ex Parte Exner

Patent Trial and Appeal Board

May 13, 2013

11314202 (P.T.A.B. May. 13, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/314,202 12/20/2005 Maurice Exner 054769-1501 4453
22428 7590 05/13/2013
FOLEY AND LARDNER LLP
SUITE 500
3000 K STREET NW
WASHINGTON, DC 20007
EXAMINER
SALMON, KATHERINE D
ART UNIT PAPER NUMBER
1634
MAIL DATE DELIVERY MODE
05/13/2013 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte MAURICE EXNER
__________

Appeal 2011-003706
Application 11/314,202
Technology Center 1600
__________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and
LORA M. GREEN, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
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1. A method for detecting and differentiating between
HSV-1 and HSV-2 in a sample, said method comprising, detecting a
first target sequence specific for HSV-1 when HSV-1 nucleic acids are
present in said sample, and detecting a second target sequence specific for
HSV-2 when HSV-2 nucleic acids are present in said sample, wherein said
first target sequence and said second target sequence are from different
genes, and wherein detection of said first target sequence is indicative of an
HSV -1 infection and detection of said second target sequence is indicative of
an HSV-2 infection,
wherein said first target sequence is from the HSV-1 glycoprotein B
gene.

3. A method for detecting and differentiating between HSV-1 and
HSV-2 in a sample, said method comprising, detecting a first target sequence
specific for HSV-1 when HSV-1 nucleic acids are present in said sample, and
detecting a second target sequence specific for HSV-2 when HSV-2 nucleic
acids are present in said sample, wherein said first target sequence and said
second target sequence are from different genes, and wherein detection of
said first target sequence is indicative of an HSV-1 infection and detection of
said second target sequence is indicative of an HSV-2 infection,
wherein said second target sequence is from the HSV-2 UL-8 gene.

4. A method for detecting and differentiating between HSV-1 and
HSV-2 in a sample, said method comprising, detecting a first target sequence
specific for HSV-1 when HSV-1 nucleic acids are present in said sample, and
detecting a second target sequence specific for HSV-2 when HSV-2 nucleic
acids are present in said sample, wherein said first target sequence and said
second target sequence are from different genes, and wherein detection of
said first target sequence is indicative of an HSV-1 infection and detection of
said second target sequence is indicative ofan HSV-2 infection,
wherein said first target sequence is from the HSV-1 glycoprotein B
gene and said second target sequence is from the HSV-2 UL-8 gene.

7. A method according to claim 1, wherein said detecting of said first
and second target sequences occurs in the same reaction vessel.

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40. A method according to claim 4, wherein said detecting comprises,
amplifying a region of the HSV-l glycoprotein B (gB) gene with a first
pair of type-specific primers when HSV-l nucleic acids are present in said
sample, amplifying a region of the HSV-2 UL-8 gene with a second pair of
type-specific primers when HSV-2 nucleic acids are present in said sample,
and
detecting said amplified regions with a first gene-specific probe and a
second genespecific probe.

43. A method according to claim 40, wherein at least one of said type-
specific primers comprises a sequence selected from the group consisting of
SEQ ID NOs: 3, 4, 6, 7 and complements thereof.

44. A method according to claim 40, wherein at least one of said gene-
specific probes comprises a sequence selected from the group consisting of
SEQ ID NOs: 5, 8 and complements thereof.

Cited References

Hogan et al. US 5,541,308 Jul. 30, 1996
Draper et al. US 6,310,044 B1 Oct. 30, 2001

Dolan et al., The Genome Sequence of Herpes Simplex Virus Type 2, 72 J.
Virol. 2010-2021 (1998).

Egli et al., Quantitative TaqMan® RT-PCR for the detection and
differentiation of European and North American strains of porcine
reproductive and respiratory syndrome virus, 98 J. VIROL. METH. 63-75
(2001).

Weidmann et al., Rapid Detection of Herpes Simplex Virus and Varicella-
Zoster Virus Infections by Real-Time PCR, 41 J. CLIN. MICROBIO. 1565-
1568 (2003).

Adelson et al., Simultaneous detection of herpes simples virus types 1 and 2
by real-time PCR and Pyrosequencing, 33 J. CLIN. VIROL. 25-34 (2005).

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Grounds of Rejection

1. Claims 1, 5, 45, and 46 are rejected under 35 U.S.C. § 103(a) as
being unpatentable over Weidmann in view of Adelson.
2. Claims 7 and 47 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Weidmann and Adelson in view of Egli.
3. Claims 3, 35, 48, and 49 are rejected under 35 U.S.C. § 103(a)
as being unpatentable over Weidmann in view of Draper and
Dolan.
4. Claims 36 and 47 are rejected under 35 U.S.C. § 103(a) as
being unpatentable over Weidmann in view of Draper, Dolan
and Egli.
Claims 4, 37, 39, 40, 51, 52, 54, and55 are rejected under
35U.S.C. § 103(a) as being unpatentable over Weidmann in
view of Adelson, Draper, and Dolan.
5. Claims 38, 41-42, 53, 56, and 57 are rejected under 35 U.S.C. §
103(a) as being unpatentable over Weidmann in view of
Adelson, Draper, Dolan, and Egli.
6. Claims 43-44, 58, and 59 are rejected under 35 U.S.C. § 103(a)
as being unpatentable over Weidmann in view of Adelson,
Draper, Dolan, and Hogan.

FINDINGS OF FACT
The Examiner’s findings of fact (Ans. 4-6) are set forth below.
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1. Weidmann et al. teaches a method of detecting and differentiating HSV-1
and HSV-2 by detection of two target sequences wherein the target
sequences are from different genes (Abstract and Table 1).
2. Weidmann teaches two distinct primer sets, one for detecting HSV-1 and
one for detecting HSV-2. (Table 1.)
3. Weidmann et al. teaches that the detection of HSV-1 and HSV-2 can
diagnose infections (Abstract).
4. Weidmann et al. teaches a method of amplifying the first and second
target sequence using a PCR (p. 1566 1st column 3rd full paragraph-5th
paragraph).
5. Weidmann et al. does not teach a method of detecting HSV-1
glycoprotein B gene.
6. Adelson et al. teaches detecting HSV-1 in a PCR by using primers from
the glycoprotein B gene (gB2) (Abstract).
7. Adelson et al. teaches primers and probes specific to the HSV-1 which
can be used in a reaction that also contains HSV-2 (Abstract).
8. Adelson et al. teaches a method wherein the combination of primers and
probe designed from the gB2 gene was designed such that only 12 of the
31 nucleotides were complementary to the HSV-2 genome and results in
a primer/probe combination which detected only HSV-1 and not the
HSV-2. Therefore Adelson et al. teaches a primer/probe combination
which is specific for HSV-1. (Page 30, col. 1.)
9. Adelson et al. teaches that the design of the primer and probe was done
by aligning known sequences of the HSV-1 and HSV-2 gB2 in BLAST
to determine variations between the two in order to find regions which
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are not complementary between HSV-1 and HSV-2 (page 28 Specificity
and Sensitivity). (Ans. 4-5.)

Discussion
1. Claims 1, 5, 45, and 46 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Weidmann in view of Adelson.
2. Claims 7 and 47 are rejected under 35 U.S.C. § 103(a) as being
unpatentable over Weidman, Adelson, and Egli.

ISSUE
The Examiner concludes that
it would have been prima facie obvious to one of
ordinary skill in the art at the time the invention was made to
modify the method of Weidmann et al. to detect HSV-1 using
primers designed from the gB2 gene as taught by Adelson et al.
The ordinary artisan would be motivated to modify the method
of Weidmann et al. to detect HSV-1 using primers designed
from the gB2 gene as taught by Adelson et al because Adelson
et al. teaches primers and probes which will distinctly amplify
HSV-1 by designing primers and probes specifically to regions
of the gB2 gene that varies between the HSV-1 and HSV-2 (p.
28 Specificity and Sensitivity). The ordinary artisan would be
motivated to amplify the gB2 region to detect HSV-1 because
Adelson et al. teaches that the detection is specific and sensitive
(p. 31 2nd column 1st paragraph).

(Ans. 5.)

Appellant argues that Weidmann fails to motivate Adelson and
Adelson teaches away from the claimed invention. In particular, Appellant
argues that
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Adelson emphasizes the hazards of “untoward cross-
reactivities, which could be inherent to the incorporation of four
oligonucleotide primers and two dual-labeled probes into a
single reaction.” Id. Therefore, Adelson et al. specifically
advise the skilled artisan to avoid designing HSV-1- and HSV-
2- specific primers to different (heterogeneous) genes because
of a fear that the assay would be unable to differentiate between
HSV-1 and HSV-2. Adelson makes this statement even though
the Weidmann reference was available.

(App. Br. 9.) Similarly, Appellant argues that
the Examiner impermissibly uses half of the primer probe
combinations that Adelson discloses, ignores the other
combination directed to HSV-2, and ignores Adelson's direct
caution that:

A distinct set of primers toward heterogeneous genes of HSV
was avoided to minimize untoward cross-reactivities, which
could be inherent to the incorporation of four oligonucleotide
primers and two dual-labeled probes in a single reaction.

(Reply Br. 4.)

The issue is: Does the cited prior art render the invention as claimed
obvious?

PRINCIPLES OF LAW
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed.
Cir. 1993) (citations omitted).
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In order to determine whether a prima facie case of obviousness has
been established, we consider the factors set forth in Graham v. John Deere
Co., 383 U.S. 1, 17 (1966): (1) the scope and content of the prior art; (2) the
differences between the prior art and the claims at issue; (3) the level of
ordinary skill in the relevant art; and (4) objective evidence of
nonobviousness, if present.
It is proper to “take account of the inferences and creative steps that a
person of ordinary skill in the art would employ.” KSR Int’l Co. v. Teleflex
Inc, 550 U.S. 398, 418 (2007). See also id. at 421 (“A person of ordinary
skill is also a person of ordinary creativity, not an automaton.”).
“In determining whether obviousness is established by combining the
teachings of the prior art, the test is what the combined teachings of the
references would have suggested to those of ordinary skill in the art.” In re
GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal quotations
omitted). Thus, “[t]he combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield predictable
results.” KSR, 550 U.S. at 416.
A reference may be said to teach away when a person of
ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference, or
would be led in a direction divergent from the path that was
taken by the applicant. The degree of teaching away will of
course depend on the particular facts; in general, a reference
will teach away if it suggests that the line of development
flowing from the reference’s disclosure is unlikely to be
productive of the result sought by the applicant.

In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
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“The fact that the motivating benefit comes at the expense of another
benefit … should not nullify its use as a basis to modify the disclosure of
one reference with the teachings of another. Instead, the benefits, both lost
and gained, should be weighed against one another.” Medichem S.A. v.
Rolabo S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006).
Obviousness is determined in view of the sum of all of the relevant
teachings in the art, not isolated teachings in the art. See In re Kuderna, 426
F.2d 385, 389 (CCPA 1970); see also In re Shuman, 361 F.2d 1008, 1012
(CCPA 1966). In assessing the teachings of the prior art references, the
examiner should also consider those disclosures that may teach away from
the invention. See In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997).

ANALYSIS
We agree with the Examiner’s fact finding, statement of the rejection
and responses to Appellant’s arguments as set forth in the Answer. We find
that the Examiner has provided evidence to support a prima facie case of
obviousness.
Appellant argues that Adelson’s disclosure that a distinct set of
primers toward heterogeneous genes of HSV was avoided to minimize
untoward cross-reactivities, teaches away from the combination of the cited
references. (App. Br. 8-9.)
We are not persuaded by Appellant’s argument. Weidman teaches
that it is known in the art to detect and differentiate between HSV-1 and
HSV-2 by detection of two target sequences wherein the target sequences
are from different genes (FF1). Weidmann further teaches that it is known
in the art to use two distinct primer sets, one specific for HSV-1 and one
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specific for HSV-2 in such an assay (FF2), and that when such distinct
primers are used a successful assay is obtained.
Adelson teaches that those of ordinary skill in the art are aware of
methodology to design specific primer probes for HSV-1 and HSV-2 by
aligning known sequences of the HSV-1 and HSV-2 gB2 in BLAST to
determine variations between the two in order to find regions which are not
complementary between HSV-1 and HSV-2. (FF9.) Adelson teaches a
method wherein the combination of primers and probe designed from the
gB2 gene was designed such that only 12 of the 31 nucleotides were
complementary to the HSV-2 genome and results in a primer/probe
combination which detected only HSV-1 and not the HSV-2. Therefore
Adelson teaches a primer/probe combination which is specific for HSV-1.
(FF8.) One of ordinary skill in the art further knows from Weidmann that it
is conventional in such assays to use positive and negative controls for each
type of virus to assure accurate results. (Weidmann, p.1568, col. 1.)
Therefore, while Adelson may have cautioned one of ordinary skill in
the art that heterogeneous primers sometimes leads to cross-reactivities,
Weidmann is evidence that when distinct primers for HSV-1 and HSV-2 are
used, cross-reactivity is not an issue and a successful assay is obtained.
Accurate results are further substantiated with the use of positive and
negative controls taught by Weidmann. Thus, when one of ordinary skill in
the art looks to the combined teachings of the cited art, one would
understand that while cross-reactivities are possible when heterogeneous
primers are used in an assay, they can be addressed by selection of distinct
primers for each virus type, as evidenced by Adelson, and by the use of
positive and negative controls. In other words, one of ordinary skill in the
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art is not an automaton and understands from the combined teachings in the
art how to address the cross-reactivity issue discussed in Adelson.
Appellant argues that Egli does not overcome the deficiencies of the
combination of Weidmann and Adelson. (App. Br. 9-10.) Having found no
deficiencies in the combination of Weidman and Adelson, the obviousness
rejections 1 and 2 are affirmed.

Discussion
3. Claims 3, 35, 48, and 49 are rejected under 35 U.S.C. § 103(a)
as being unpatentable over Weidmann in view of Draper and Dolan.
4. Claims 36 and 47 are rejected under 35 U.S.C. § 103(a) as
being unpatentable over Weidmann in view of Draper, Dolan, and Egli.
5. Claims 4, 37, 39, 40, 51, 52, 54-55 are rejected under 35 U.S.C.
§ 103(a) as being unpatentable over Weidmann in view of Adelson, Draper,
and Dolan.
6. Claims 38, 41-42, 53, and 56-57 are rejected under 35 U.S.C.
§ 103(a) as being unpatentable over Weidmann in view of Adelson, Draper,
Dolan, and Egli.

Additional Examiner’s Findings of Fact (Ans. 7-8)
10. Weidmann et al. does not teach a method of detecting HSV-2 UL8
gene.
11. Draper et al. teaches the UL8 gene of HSV-1and HSV-2 (abstract).
Draper et al. teaches oligonucleotides which specifically hybridize to the
UL8 gene (column 3, lines 1-5). Draper et al. teaches that the
oligonucleotides are designed so those specifically hybridize to either
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HSV-1 or HSV-2 (column 3, lines 10-15). Draper et al. teaches that the
sequence of both HSV-1 and HSV-2 UL8 gene are known (column 3,
lines 1-5).
12. Dolan et al. teaches the genome sequence of HSV-2 (abstract)
including UL8 (Table 3). Thereby providing the necessary sequence to
create an alignment and determine critical regions as taught by Draper et
al.
ISSUE
The Examiner contends that
it would have been prima facie obvious to one of
ordinary skill in the art at the time the invention was made to
modify the method of Weidmann et al. to detect HSV-2 using
primers designed from the UL8 gene as taught by Draper et al.
The ordinary artisan would be motivated to modify the method
of Weidmann et al. to detect HSV-2 using primers designed
from the UL8 gene as taught by Draper et al because Draper et
al. teaches that oligonucleotides can be designed that
specifically hybridize to either HSV-1 or HSV-2. Therefore
Draper et al. teaches a methodology to specifically detect HSV-
2 by designing oligonucleotides in regions of the UL8 gene
which are specific to HSV-2 (Column 3 lines 1-15). Further the
addition of Dolan et al., teaches the genome sequence including
the UL8 gene. Therefore it would be prima facie obvious to
design oligonucleotides in regions of the UL8 gene which are
specific to HSV-2, because Draper et al. teaches design of
primers and probes and the methodology of alignment of
critical regions between HSV-1 and HSV-2.
Weidmann et al. describes a RT-PCR method which is
specific and lack false positive results due to nonspecific
amplification products (p. 1565 2nd column 1st full paragraph).
The ordinary artisan would use different primers from different
genes in order to reduce the occurrence of nonspecific
amplification. The ordinary artisan would be motivated to use
the UL8 gene to detect HSV-2 as taught by Draper et al. and
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Dolan et al. because Draper et al. teaches oligonucleotides can
be designed to specifically hybridized to HSV-2 (column 3
lines 10-15). Dolan et al. teaches the genome sequence of HSV-
2 (abstract) including UL8 (Table 3). Thereby providing the
necessary sequence to create an alignment and determine
critical regions as taught by Draper et al. Draper et al. teaches
the UL8 is critical for viral DNA replication (column 7 lines 5-
15) and therefore is a critical region in HSV-2.

(Ans. 8-9.)
Appellant argues that
Draper does not teach any method detecting and
differentiating HSV-1 from HSV-2. So, the Examiner's
reliance on Draper for the proposition that it discloses
oligonucleotides that can be designed that specifically hybridize
to either the HSV-l or HSV-2 UL-8 gene is unfounded. Draper
merely discloses that the UL-8 gene exists in both organisms.
This would not lead the skilled artisan to modify the method of
Weidmann without guidance from the instant specification
either to select another gene or to specifically select the UL-8
gene.

(App. Br. 10.)

Appellant further argues that

Draper provides antisense oligonucleotides for viral
inhibition. Specifically Draper is focused on the UL-8 gene of
HSV-1; the only UL-8 gene for which Draper knew the
nucleotide sequence. Because of this, Draper assumes the
genes’ homology and therefore presumes that the HSV-2 would
share enough in common that an antisense oligonucleotide
would hybridize to the UL-8 gene of both viral variants.
Appellant submits therefore that when Draper states that an
oligonucleotide will “specifically hybridize to either HSV-1 or
HSV-2,” Draper means that the oligonucleotide can hybridize
to both viruses not distinguish the two.
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(Reply Br. 6.)

The Issue is: Does the cited prior art support the Examiner’s
conclusion that the claimed subject matter is obvious to one of ordinary skill
in the art?

ANALYSIS
We agree with the Examiner’s fact finding, statement of the rejection
and responses to Appellant’s arguments as set forth in the Answer. We find
that the Examiner has provided evidence to support a prima facie case of
obviousness.
Appellant essentially argues that Draper does not teach any method
of detecting and differentiating HSV-1 from HSV-2, and that when Draper
states that an oligonucleotide will specifically hybridize to either HSV-1 or
HSV-2, Draper means that the oligonucleotide can hybridize to both viruses
not distinguish the two. Thus Appellant concludes that “[i]t is therefore
clear that Draper advises the skilled artisan to compare similarities of gene
sequences, not differences. Thus, this assumption of homology between the
UL-8 gene in HSV-l and HSV-2 would not motivate the artisan to consider
this gene as a useful target for differentiation.” (Reply Br. 8.)
We are not persuaded by Appellant’s argument. Weidman teaches
that it is known in the art to detect and differentiate between HSV-1 and
HSV-2 by detection of two target sequences wherein the target sequences
are from different genes (FF1). Weidmann further teaches that it is known
in the art to use two distinct primer sets, one specific for HSV-1 and one
specific for HSV-2, in such an assay, one for detecting HSV-1 and one for
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detecting HSV-2 (FF2) and that when such distinct primers are used a
successful assay is obtained. In addition, those of ordinary skill in the art are
aware of methodology to design specific primer probes for HSV-1 and HSV-
2 by aligning known sequences of gene to determine variations between the
two in order to find regions which are not complementary between HSV-1
and HSV-2. Thus, we agree with the Examiner that it would have been
prima facie obvious to one of ordinary skill in the art at the time the
invention was made to modify the method of Weidmann to detect HSV-2
using primers designed from the UL8 gene as taught by Draper et al. The
ordinary artisan would be motivated to modify the method of Weidmann to
detect HSV-2 using primers designed from the UL8 gene as taught by
Draper because Weidmann teaches that oligonucleotides can be designed
that specifically hybridize to either HSV-1 or HSV-2 target genes, which
would include the UL8 gene.
Appellant argues that assumption of homology between the UL-8
gene in HSV-l and HSV-2 in Draper would not motivate the artisan to
consider this gene a useful target for differentiation. With respect to this
argument, Weidmann teaches that it is desirable for one of ordinary skill in
the art to select two different genes for an assay which distinguishes between
HSV-1 and HSV-2 and select distinct primers for each of the specific viral
genes. Thus one of ordinary skill in the art would not select the UL-8 gene
for both the HSV-1 and HSV-2 assay genes, in view of Weidmann.
Therefore homology between HSV-1 and HSV-2 UL-8 is not an issue as
long as separate and distinct primers and target genes for each virus are
selected for the assay. UL-8 gene is known to be found in HSV-2 and thus
may be selected as a target gene for HSV-2 as long as a distinct primer for
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HSV-2 is used. It is within the skill of one of ordinary skill in the art to
determine a distinct primer for HSV-2, and as long as adequate positive and
negative controls are also included in the assay, as suggested by Weidman,
an accurate result would have been expected.
Rejections 4, 5, and 6 above are traversed for the same reasons put
forth for Rejection 3. (App. Br. 12-14.) For the reasons herein we are not
persuaded, and Rejections 4, 5 and 6 are affirmed for the reasons of record.

Discussion
7. Claims 43-44, 58, and 59 are rejected under 35 U.S.C. § 103(a)
as being unpatentable over Weidmann et al. in view of Adelson, Draper, and
Dolan as applied to Claims 4,37, 39-40, 51-52,54, and 55 in further view of
Hogan.

Additional Examiner’s Findings of Fact (Ans. 15-17)
13. Hogan et al. provides guidance for the selection of probes.
"Once the variable regions are identified, the sequences
are aligned to reveal areas of maximum homology or 'match'.
At this point, the sequences are examined to identify potential
probe regions. Two important objectives in designing a probe
are to maximize homology to the target sequence(s) (greater
than 90% homology is recommended) and to minimize
homology to non-target sequence(s) (less than 90% homology
to non-targets is recommended). We have identified the
following useful guidelines for designing probes with the
desired characteristics.
Fi[r]st, probes should be positioned so as to minimize the
stability of the probe: nontarget nucleic acid hybrid. This may
be accomplished by minimizing the length of perfect
complementarily to non-target organisms, avoiding G and C
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rich regions of homology to non-target sequences, and by
positioning the probe to span as many destabilizing mismatches
as possible (for example, dG:rU base pairs are less destabilizing
than some others). Second, the stability of the probe: target
nucleic acid hybrid should be maximized. This may be
accomplished by avoiding long A and T rich sequences, by
terminating the hybrids with G: C base pairs and by designing
the probe with an appropriate Tm. The beginning and end
points of the probe should be chosen so that the length and %G
and %C result in a Tm about 2-10 °C higher than the
temperature at which the final assay will be performed. The
importance and effect of various assay conditions will be
explained further herein. Third, regions of the rRNA which are
known to form strong structure inhibitory to hybridization are
less preferred. Finally probes with extensive self[-]
complementarity should be avoided." (See Column 6 lines 66-
67 and Column 7 lines 1-29).

(Ans. 16.)

14. Hogan et al. teaches that, “[w]hile oligonucleotide probes of different
lengths and base composition may be used, oligonucleotide probes
preferred in this invention are between about 15 and about 50 bases in
length” (see Column 10, lines 28-32).

ISSUE
The Examiner argues that
Weidmann et al. teaches a method of detecting and
differentiating HSV-1 and HSV-2 by detection of two target
sequences wherein the target sequences are from different genes
(abstract and Table 1). Weidmann et al. teaches that the
detection of HSV-1 and HSV-2 can diagnose infections
(abstract). Adelson et al. teaches the detection of HSV-1 GB2.
Draper et al. teaches the detection of HSV-2 UL8. Dolan et al.
teaches the sequence of UL8 in HSV-2. However, the
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combination of Weidmann et al., Adelson et al., Draper et al.,
and Dolan et al. does not teach detection using the specific SEQ
10 No. of 3-8 as primers and probes to detect the HSV-1 GB2
gene of Adelson et al. and the HSV-2 UL8 of Draper et al. and
Dolan et al.
Hogan teaches guidance for the selection of primers and
probes. …
. . .
Therefore Hogan et al. teaches taking a sequence and
fragmenting the sequence into smaller oligonucleotides to be
used as probes. Hogan et al. teaches that these probes are
preferable to be between about 15 and about 50 bases in length.
Though, Hogan et al. does not specifically teach the SEQ
10 Nos 3-8 but he does provide guidance as to the making of
primers and probes from larger fragments.

Appellant argues that, “Hogan does not teach any oligonucleotides
having the sequence of SEQ ID NOs: 3-8. Hogan merely discloses general
strategies for oligonucleotide design. Therefore, Hogan fails to teach or
suggest specific guidance for the selection of primers and probes for the
HSV genes of the instant invention.” (App. Br. 14.)
The Issue is: Does the cited prior art render the specific primers
claimed obvious?

ANALYSIS
We agree with the Examiner that although Hogan et al. does not
specifically teach guidance for nucleic acid probes for HSV genes
specifically, Hogan et al. provides guidance for the selection of probes and
primers to detect a target gene to maximize homology to the target
sequences and to minimize homology to non-target sequences. (FF 13.)
This teaching of Hogan of how to make and select specific probes combined
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with the teaching of Weidmann et al, Adelson et al, Draper et al and Dolan
et al., suggest making probes and primers to known genes of HSV to detect
specifically HSV-1 and HSV-2. The Examiner finds that the design of
primers and probes to any gene has similar known requirements as provided
by Hogan et al. Further, the ordinary artisan would know that these primers
and probes would be designed in regions which are heterogeneous between
the two subtypes in order to design primers and probes specific to the
individual subtypes. (FF 8.)
The law presumes skill on the part of the artisan rather than the
converse. See In re Sovish, 769 F.2d 738, 742-43 (Fed. Cir. 1985). We
agree with the Examiner that one of ordinary skill in the art reading Hogan
in the context of Weidmann, Adelson, Draper and Dolan would have been
readily able to design any number of primers or probes, including the
claimed primers and probes. Appellant has provided no evidence that one of
ordinary skill in the art following the combined teachings of Hogan,
Weidman or Adelson, in particular, would not have been able to design or
arrive at the claimed primers or probes given the specific target genes.
Rejection 7 is affirmed for the reasons of record.

CONCLUSION OF LAW
The cited references support the Examiner’s obviousness rejections
which are affirmed for the reasons of record.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED
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