Ex Parte Hoser

Board of Patent Appeals and Interferences

Sep 5, 2012

10546268 (B.P.A.I. Sep. 5, 2012)

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.
10/546,268 07/17/2006 Mark J. Hoser 0380-P03782US0/PJH 6450
110 7590 09/06/2012
DANN, DORFMAN, HERRELL & SKILLMAN
1601 MARKET STREET
SUITE 2400
PHILADELPHIA, PA 19103-2307
EXAMINER
CHUNDURU, SURYAPRABHA
ART UNIT PAPER NUMBER
1637
MAIL DATE DELIVERY MODE
09/06/2012 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte MARK J. HOSER
__________

Appeal 2011-005484
Application 10/546,268
Technology Center 1600
__________

Before FRANCISCO C. PRATS, MELANIE L. McCOLLUM, and
STEPHEN WALSH, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to analyzing
nucleic acid molecules. The Examiner entered a rejection for anticipation.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.
STATEMENT OF THE CASE
Claims 74-102 stand rejected and appealed (App. Br. 2). Claims 74,
89, and 97, the independent claims, illustrate the appealed subject matter and
read as follows (emphasis and paragraph formatting added):

Appeal 2011-005484
Application 10/546,268

2
74. A method for determining whether a template nucleic acid
molecule comprises a specific complementary base in its sequence,
the method comprising
contacting the template nucleic acid molecule with a conjugate
selected from the group consisting of (i) a deoxyribonucleotide
triphosphate (DNTP) and an intercalating dye and (ii) a nucleotide
analogue and an intercalating dye and
determining whether the DNTP or nucleotide analogue is
complementary to the specific complementary base in the template
nucleic acid molecule sequence,
said intercalating dye (a) being minimally fluorescent in the
presence of single stranded DNA or in the absence of DNA, and, on
binding to double stranded DNA, increases in fluorescence; or (b) on
binding to double-stranded DNA shows a spectral shift.

89. A method for labelling a nucleic acid molecule in a template-
primer complex using a nucleic acid processing enzyme, the method
comprising
contacting a conjugate selected from the group consisting of (i)
a deoxyribonucleotide triphosphate (DNTP) and an intercalating dye
and (ii) a nucleotide analogue and an intercalating dye in a template-
primer complex with a nucleic acid processing enzyme and
extending the nucleic acid molecule with the nucleic acid
processing enzyme to label the nucleic acid molecule with the
conjugate,
said intercalating dye (a) being minimally fluorescent in the
presence of single stranded DNA or in the absence of DNA, and, on
binding to double stranded DNA, increases in fluorescence; or (b) on
binding to double-stranded DNA shows a spectral shift.

97. A method for determining the sequence of at least one nucleic
acid base of a nucleic acid template molecule, wherein the at least one
base is downstream of a 3' terminus of a primer which is annealed to
the template forming a template-primer complex, the method
comprising:
(a) contacting the template-primer complex with (i) a nucleic
acid processing enzyme capable of binding to the complex and having
a binding site which is capable of binding a nucleotide triphosphate or
an analogue thereof that is complementary to the template nucleic acid
Appeal 2011-005484
Application 10/546,268

3
base that is being processed by the enzyme and (ii) one or more
inhibitors of the nucleic acid processing enzyme, wherein the
inhibitors are non-incorporable nucleotide analogues, so that a non-
incorporable nucleotide analogue which is complementary to the
downstream base of the template molecule binds to the nucleic acid
processing enzyme; and
(b) determining the identity of the non-incorporable
nucleotide analogue and hence the sequence of the complementary
base in the template nucleic acid molecule; wherein the non-
incorporable nucleotide analogue is selected from the group
consisting of a conjugate which comprises a deoxyribonucleotide
triphosphate (DNTP) and an intercalating dye and a conjugate which
comprises a nucleotide analogue and an intercalating dye, said
intercalating dye (a) being minimally fluorescent in the presence of
single stranded DNA or in the absence of DNA, and, on binding to
double stranded DNA, increases in fluorescence; or (b) on binding to
double-stranded DNA shows a spectral shift.

The sole rejection before us for review is the Examiner’s rejection of
claims 74-102 under 35 U.S.C. § 102(e) as anticipated by Stavrianopoulos
1

(Ans. 3-5).
DISCUSSION
Appellant contends that none of Stavrianopoulos’ allegedly
anticipatory embodiments uses a conjugate of an intercalating dye with
either a deoxyribonucleotide triphosphate (DNTP) or nucleotide analogue, as
required in each of the independent claims (see App. Br. 4-5). In particular,
Appellant argues that the cyanine dye used in Stavrianopoulos’ examples,
described as a Cy3 analogue, is not an intercalating dye, as evidenced by the
fact that the Amersham
2
reference lists Cy3 as a fluorescent label, but does

1
U.S. Patent No. 7,166,478 B2 (filed March 12, 2002).
2
AMERSHAM BIOSCIENCES TECHNICAL NOTE # 58 (Amersham Biosciences
August 1999).
Appeal 2011-005484
Application 10/546,268

4
not include it among the listed intercalating dyes (id. at 6 (citing Amersham
6)).
The Examiner responds that the claims do not require the intercalating
dye to be conjugated to either the DNTP or nucleotide analogue (see Ans. 6-
7). Moreover, the Examiner contends, the cyanine dye conjugated to
Stavrianopoulos’ DNTP is inherently an intercalating dye having the
functional properties recited in the independent claims, as evidenced by the
recitation of cyanine dyes as intercalating dyes in dependent claims 86 and
93 (see id.).
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.

Regarding anticipation rejections, an examiner cannot establish
inherency merely by demonstrating that the presence of an asserted
limitation in the prior art is probable or possible. In re Oelrich, 666 F.2d
578, 581 (CCPA 1981). Nonetheless, if “the disclosure is sufficient to show
that the natural result flowing from the operation as taught would result in
the performance of the questioned function, it seems to be well settled that
the disclosure should be regarded as sufficient.” Id. (quoting Hansgirg v.
Kemmer, 102 F.2d 212, 214 (CCPA 1939)).
In the instant case, we agree with Appellant that each of the
independent claims requires the intercalating dye to be conjugated to either a
DNTP or a nucleotide analogue. Specifically, claim 74 requires the template
Appeal 2011-005484
Application 10/546,268

5
nucleic acid to be contacted with one of two conjugates “(i)
deoxyribonucleotide triphosphate (DNTP) and an intercalating dye [or] (ii) a
nucleotide analogue and an intercalating dye” (App. Br., Claims Appendix
p. 1). Claim 86 contains a similar recitation, and claim 97 recites the use of
a “non-incorporable nucleotide analogue . . . selected from the group
consisting of a conjugate which comprises a deoxyribonucleotide
triphosphate (DNTP) and an intercalating dye and a conjugate which
comprises a nucleotide analogue and an intercalating dye” (id. at pp. 3, 5).
As Appellant points out, the Specification explains that the invention is
directed, at least in part, to an improvement of a prior art approach, the
“extension of this [prior art] approach is described here in which an
intercalating dye is covalently attached to a nucleotide triphosphate (DNTP)
or its non-incorporable analogue” (Spec. 4 (emphasis added)).
Thus, we acknowledge, as the Examiner points out, that
Stavrianopoulos discloses using a combination of an intercalating dye and a
labeled DNTP in its methods (see Stavrianopoulos, col. 39, l. 28, through
col. 40, l. 19; see id. at col. 61, l. 16, through col. 62, l. 21 (Examples 9-11)).
As Appellant urges, however, the intercalating dye, SYBR Green for
example, is not covalently conjugated to the deoxynucleotide triphosphate
(see id.). Rather, the dUTP is covalently conjugated to the Cy3 analogue
compound having the formula shown at column 60, lines 13-25. We are
therefore not persuaded that Stavrianopoulos’ use of an unconjugated
intercalating dye in combination with a labeled DNTP meets the
requirements of Appellant’s claims.
As to the Examiner’s alternative position, we note that the Cy3
analogue label conjugated to dUTP in Stavrianopoulos’ examples
Appeal 2011-005484
Application 10/546,268

6
(Stavrianopoulos, col. 60, ll. 7-31) is described as being a “Cyanine Dye”
(id. at col. 60, l. 6). We also note that Appellant’s dependent claims 86 and
93 recite that “the intercalating dye is a DNA binding monomeric or
multimeric asymmetric cyanine or acridine dye” (App. Br., Claims
Appendix, pp. 2, 4 (emphasis added); see also Spec. 9).
As noted above, however, Appellant has advanced evidence that the
cyanine dye Cy3, which is an analogue of the compound used in
Stavrianopoulos’ conjugate, is not listed among DNA-binding intercalating
dyes useful for staining DNA, whereas it is in fact listed among dyes useful
for covalent binding to nucleotides for fluorescent nucleic acid labeling (see
Amersham 6). Thus, it might be true, based on Appellant’s disclosure, that
certain cyanine dyes bind DNA in an intercalating fashion. Appellant has
nonetheless advanced evidence, in the form of the Amersham reference,
suggesting that cyanine dyes do not have the common property of being
DNA-binding intercalating dyes, and that an analogue of Stavrianopoulos’
cyanine dye is not a dye that has those properties.
In contrast, other than the dependency of claims 86 and 93 from
claims 74 and 89, the Examiner has not advanced any evidence specifically
suggesting that the Cy3 analogue used by Stavrianopoulos is a DNA-binding
intercalating cyanine dye, nor has the Examiner advanced any specific
evidence suggesting that cyanine dyes all have the common property of
being DNA-binding intercalating dyes. Thus, on the current record, we find
that the preponderance of the evidence supports Appellant’s position that
Stavrianopoulos’ labeled dUTP conjugate uses “a dye that does not have the
intercalating property called for in appellant’s claims” (App. Br. 6).
Appeal 2011-005484
Application 10/546,268

7
Accordingly, as we agree with Appellant that the preponderance of
the evidence does not support the Examiner’s finding that Stavrianopoulos
describes processes that use the conjugates required in independent claims
74, 89, and 97, we reverse the Examiner’s anticipation rejection of those
claims, and their dependents, over Stavrianopoulos.

REVERSED

cdc