Ex Parte Zheng et al

Board of Patent Appeals and Interferences

Jul 23, 2012

10667191 (B.P.A.I. Jul. 23, 2012)

UNITED STATES PATENT AND TRADEMARKOFFICE
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.
10/667,191 09/15/2003 Minxue Zheng 1300-0007 9085
28524 7590 07/23/2012
SIEMENS CORPORATION
INTELLECTUAL PROPERTY DEPARTMENT
170 WOOD AVENUE SOUTH
ISELIN, NJ 08830
EXAMINER
CHUNDURU, SURYAPRABHA
ART UNIT PAPER NUMBER
1637
MAIL DATE DELIVERY MODE
07/23/2012 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 MINXUE ZHENG, JOHN J. QUINN,
and BRIAN D. WARNER
____________

Appeal 2011-012759
Application 10/667,191
Technology Center 1600
____________

Before DONALD E. ADAMS, ERIC GRIMES and RICHARD M.
LEBOVITZ, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This appeal involves claims drawn to a dual-purpose primer for
amplifying a target nucleotide sequence in a target molecule. We have
jurisdiction under 35 U.S.C. § 134. We reverse the rejections.

Appeal 2011-012759
Application 10/667,191

2
STATEMENT OF THE CASE
Claims 1-18 and 26-35 are pending. The Examiner set forth following
rejections in the Answer:
1. Claims 1-5, 9-14, 26, and 32 under 35 U.S.C. § 102(b) as
anticipated by Honeyman;1
2. Claims 6-8, 15, and 16 under 35 U.S.C. § 103(a) as obvious in
view of Honeyman and Laibinis;2 and
3. Claims 10 and 11 under 35 U.S.C. § 103(a) as obvious in view of
Honeyman and Switzer.3
4. Claims 1 and 32 stand rejected under 35 U.S.C. § 103(a) as
obvious in view of Hogan.4
The Examiner stated that claims 1-18 and 26-35 were all rejected, but
did not set forth a rejection of claims 17, 18, 27-31, and 33-35. Answer 3, 4,
7, & 8. Claim 35 was apparently withdrawn from consideration. App. Br. 4.
However, claims 17, 18, 27-31, 33, and 34 depend from rejected claims
whose rejections we now reverse.
Claim 1 is representative and reads as follows:
1. A dual-purpose primer for amplifying a target nucleotide sequence in
a target molecule, wherein the target molecule has a secondary

1 Honeyman, K., et al., Development of a snapback method of Single-
Stranded Conformation Polymorphism Analysis for Genotyping Golden
Retrievers for the X-linked Muscular Dystrophy Allele. AJVR, Vol. 60, No.
6, pp. 734-37 (1999).
2 US Published Patent Application 2002/0028455 A1, published March 7,
2002).
3 Switzer, C.Y., et al., Enzymatic Recognition of the Base Pair Between
Isocytidine and Isoguanosine, Biochemistry, Vol. 32, pp. 10489-10496
(1993).
4 US Patent 5,030,557, issued July 9, 1991.
Appeal 2011-012759
Application 10/667,191

3
structure forming region and further wherein the target nucleotide
sequence contains a site of interest proximal to or contained within the
secondary structure forming region wherein the primer comprises: (a)
a primer sequence complementary to a segment of the target
nucleotide sequence other than the secondary structure forming
region; and (b) a blocking sequence substantially complementary to a
segment of the secondary structure forming region, wherein the
blocking sequence disrupts formation of the unwanted secondary
structure in an amplicon thereby enabling detection and amplification
of the site of interest.
App. Br. 30, Claims Appendix.

CLAIM 1
Claim 1 is directed to a “dual-purpose primer for amplifying a target
nucleotide sequence in a target molecule.”
The “target molecule has a secondary structure forming region.”
The primer comprises:
“(a) a primer sequence complementary to a segment of the target
nucleotide sequence other than the secondary structure forming region;” and
“(b) a blocking sequence substantially complementary to a segment of
the secondary structure forming region” of the target molecule.

1. ANTICIPATION BY HONEYMAN
Claims 1-5, 9-14, 26, and 32 stand rejected under 35 U.S.C. § 102(b)
as anticipated by Honeyman. Answer 4.
Rejection
On pages 6 and 7 of the Answer, the Examiner identified a primer
sequence in the Honeyman publication which the Examiner found met the
limitations of (a) and (b) of claim 1. The Examiner did not identify the
App
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Appeal 2011-012759
Application 10/667,191

6
structure in the target is said by the Examiner to be CTAGGCCTAG (see
paired region of “Target” reproduced above). The blocking sequence b) is
required by the claim to disrupt it. The Examiner did not establish that
either the region of secondary structure appeared in the target sequence of
Honeyman nor that the blocking sequence was part of Honeyman’s primer.
Moreover, the Examiner did not establish that Honeyman’s primer
hybridizes to a target sequence that includes any secondary structure.
During prosecution, Appellant had complained about the Examiner’s
failure to show the existence of the primer sequence’s complement in
Honeyman’s target. Appellant requested that the Examiner provide further
information:
If the Examiner's inherency reasoning comes from a source
other than Honeyman et al., then pursuant to MPEP §2144.03,
applicants request that the Examiner provide the source to
applicants. If the Examiner's inherency reasoning is based upon
judicial notice of facts not in the record or of information that
the Examiner considers to be common knowledge in the art,
then pursuant to MPEP § 2144.03, applicants request that the
Examiner provide documentary evidence to support the judicial
notice or the information that the Examiner considers to be
common knowledge in the art. If the Examiner's inherency
reasoning stems from personal knowledge, then pursuant to
MPEP § 2144.03 and 37 C.F.R. 1.104(d)(2), applicants request
that the Examiner submit an Affidavit or Declaration that
introduces the Examiner's personal knowledge into the record
for this case, along with a detailed description of how the
Examiner's personal knowledge would lead the Examiner to
interpret Honeyman et al. as set forth in the Office Action under
reply.
Amendment dated August 23, 2010, page 15.
In view of the deficiencies noted above, particularly the failure to
show a blocking sequence b) as claimed, Appellant’s request to the
Appeal 2011-012759
Application 10/667,191

7
Examiner was reasonable. Rather than embellish the rejection by showing
where each sequence element of the claim could be found in Honeyman, the
Examiner simply responded by asserting that the “facts” relied up in the
rejection “are expressly stated within the reference(s).” Final Rejection 10.
We have already explained why this position is deficient.

Summary
In view of the foregoing, we reverse the anticipation rejection over
Honeyman of independent claim 1 and dependent claims 2-5, 9-14, and 26.
Claim 32 has similar limitations to claim 1, and we reverse its rejection over
Honeyman, as well.

REJECTIONS 2 & 3 AS OBVIOUS IN VIEW OF HONEYMAN
AND SECONDARY REFERENCES
The Examiner relied on secondary references to meet limitations
recited in claims 6-8, 10, 11, 15, and 16. Answer 7-8. As none of the cited
references were said by the Examiner to disclose or suggest the claimed
primer and blocking sequences, we reverse the rejections for the same
reasons as for Rejection 1 over Honeyman.

4. OBVIOUSNESS IN VIEW OF HOGAN
Claims 1 and 32 stand rejected under 35 U.S.C. § 103(a) as obvious in
view of Hogan.
Rejection
The Examiner found that Hogan describes a combination of probe and
“helper” sequences, where “the ‘helper’ sequence acts functionally to block
Appeal 2011-012759
Application 10/667,191

8
intramolecular secondary hairpin target formation to facilitate PCR of the
target regions (see col. 4).” Answer 9. The probe corresponds to the
“primer sequence (a)” of claim 1; the “helper” corresponds to the “blocking
sequence (b)” of claim 1.
The Examiner acknowledged that Hogan’s probe and helper
sequences were not present in a single nucleic acid as required by claim 1,
but concluded it would have been obvious to have combined them as a
single contiguous sequence “because a single sequence results in a lower
cost assay which is less labor intensive and more practical.” Answer 10.
Appellant contends that one of ordinary skill in the art would not have
had reason to prepare a single sequence from Hogan’s probe and helper
sequences because Hogan teaches that the “helper sequences are in molar
excess,” and if combined, “the resulting probe would be so large that the
ordinary artisan would not have a reasonable expectation that the probe
would be successful at hybridizing to the target.” App. Br. 28.
The issues in this rejection are 1) whether a person of ordinary skill in
the art would have reason to have made a contiguous sequence with Hogan’s
probe and helper, and 2) whether the skilled worker would have had a
reasonable expectation that such contiguous sequence would perform as a
probe and helper as described by Hogan.

Findings of Fact (“Findings”)
1.
Usually the helper oligonucleotide is used in excess compared
to the probe. When the probe is used in excess to the target
nucleic acid, the helper oligonucleotide is typically used in a
molar concentration at least about 5 times that of the probe and
Appeal 2011-012759
Application 10/667,191

9
up to a molar concentration which is about 100 or more times
that of the probe. When target is in excess compared to probe,
the helper oligonucleotide typically is used in a molar
concentration at least about 10 times that of the target and up to
about 100 or more times that of the probe.
Hogan, col. 7, ll. 56-65.

2.
Typically the helper is added in substantial molar excess
compared to the amount of nucleic acid present in the sample in
order to more rapidly bind to the target nucleic acid and inhibit
intramolecular strands hybridizing, which impose the secondary
and tertiary structure which inhibits probe to target
hybridization.
Hogan, col. 14, ll. 36-41.
Discussion
To decide whether a composition is obvious in light of the prior art, it
must be determined whether, at the time of invention, a person having
ordinary skill in the art would have had “reason to attempt to make the
composition” and “a reasonable expectation of success in doing so.”
PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1360 (Fed.
Cir. 2007) (internal citations omitted).
The only reason the Examiner gave for combining the probe and
helper sequence in a single nucleic acid was that such configuration results
in a “lower cost assay which is less labor intensive and more practical.”
Answer 10. This reason is not supported by sufficient evidence.
The Examiner did not provide evidence that combining two smaller
oligonucleotide sequences into one larger oligonucleotide, rather than using
Appeal 2011-012759
Application 10/667,191

10
the two smaller oligonucleotides separately, would be cheaper and less work
to use.
In addition, as Hogan teaches that the helper sequence is used in
molar excess of the probe sequence (Findings 1 and 2), the most logical way
to adjust the concentrations would be to add the two sequences
independently, rather than as combined in a single sequence. The
Examiner’s proposed approach would eliminate the flexibility of varying the
molar concentrations as taught by Hogan, and would require a different
sequence each time the molar ratio was adjusted, making it more costly and
labor intensive – opposite to the conclusion drawn by the Examiner. Thus,
we are not persuaded that the Examiner’s reason to modify Hogan is
adequate to establish a prima facie case.
Hogan expressly teaches that the reason why the helper is utilized in
molar excess is to facilitate more rapid binding of the probe to the target and
to inhibit secondary and tertiary structure which would impede probe
binding. Finding 2. As argued by Appellant, if the probe and helper were
combined, the skilled worker would have had reason to use an excess of
probe sequences in the single nucleic acid, e.g., in a ratio of 5:1 or higher.
The Examiner did not provided sufficient evidence that a contiguous
sequence would allow the helper “to more rapidly bind to the target nucleic
acid and inhibit intramolecular strands hybridizing” as taught by Hogan.
Finding 2. Specifically, the Examiner did not establish that a single nucleic
acid with multiple helper sequences and one probe would have been
reasonably expected to achieve the result desired by Hogan.

Appeal 2011-012759
Application 10/667,191

11
Summary
We reverse the rejection of claims 1 and 32 as obvious in view of
Hogan.

REVERSED

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