Ex Parte 7449289 et al

Patent Trial and Appeal Board

Aug 27, 2014

95001599 (P.T.A.B. Aug. 27, 2014)

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.
95/001,599 04/08/2011 7449289 GENOM.051X(P-7330
RX)
7698
95896 7590 08/28/2014
David W. Highet, VP and Chief IP Counsel
Becton, Dickinson and Company
(Knobbe Martens)
1 Becton Drive, MC-110
Franklin Lakes, NJ 07417
EXAMINER
TURNER, SHARON L
ART UNIT PAPER NUMBER
3991
MAIL DATE DELIVERY MODE
08/28/2014 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
____________

BECKMAN COULTER, INC.
Requester and Respondent

v.

GENEOHM SCIENCES CANADA, INC.
Patent Owner and Appellant
____________

Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289
Technology Center 3900
____________

Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN, and
JEFFREY B. ROBERTSON, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on the appeal by the Patent Owner from the Patent
Examiner’s decision to reject claims 1, 2, and 5 in the above-identified inter partes
reexamination of US 7,449,289 B2. This is also a decision on the cross-appeal by
the Third Party Requester appealing the Examiner’s decision to adopt rejections of
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

2

claims 1-5. The Board’s jurisdiction for this appeal is under 35 U.S.C. §§ 6(b),
134, and 315.
We affirm-in-part.
I. BACKGROUND
The patent in dispute in this appeal is US 7,449,289 B2 (“the ’289 patent”)
which issued November 11, 2008. Ann Huletsky and Valery Rossbach are named
as the inventors of the patent.
A request for inter partes reexamination of the ’289 patent under 35 U.S.C.
§§ 311-318 and 37 C.F.R. §§ 1.902-1.997 was filed April 8, 2011 (“Request”).
The Requester is Beckman Coulter, Inc. (“Requester”). Request 1. The assignee
of the ’289 patent and the real party in interest is Geneohm Sciences Canada, Inc.
(“Patent Owner”). Patent Owner Appeal Brief (“PO Appeal Br.”) 5.
The claimed subject matter of the ’289 patent relates to a method to detect
the presence of a methicillin-resistant Staphylococcus aureus (MRSA) strain in a
specimen. S. aureus is a human opportunistic pathogen which is major cause of
morbidity and mortality. ’289 patent, col. 1, ll. 28-31. “Some of the most common
infections caused by S. aureus involve the skin.” Id. at col. 1, ll. 31-32. “Some of
the more serious infections produced by S. aureus are bacteremia, pneumonia,
osteomyelitis, acute endocarditis, myocarditis, pericarditis, cerebritis, [and]
meningitis.” Id. at col. 1, ll. 34-37.
“Methicillin-resistant S. aureus (MRSA) emerged in the 1980s as a major
clinical and epidemiologic problem in hospitals.” ’289 patent, col. 1, ll. 45-47.
MRSA are resistant to all β-lactams, including penicillins and cephalosporins,
which are some of the most commonly used antibiotics to treat S. aureus
infections. Id. at col. 1, ll. 47-50.
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

3

Methicillin-resistance is conferred by the acquisition of the mecA gene.
’289 patent, col. 1, l. 65 to col. 2, l. 5. It was discovered previously that the mecA
gene is carried by a genetic element, designated as the staphylococcal cassette
chromosome mec (SCCmec), which is inserted into the chromosomal DNA. Id. at
col. 2, ll. 8-11. It was also discovered that SCCmec is inserted into a specific site
of the methicillin-sensitive S. aureus (“MSSA”) chromosome identified as “orfX.”
Id. at col. 2, ll. 30-42.
The ’289 patent describes published methods of characterizing different
MRSA strains by using primers that “specifically hybridize to the right extremities
of the 3 types of SCCmec DNAs in combination with a primer specific to the S.
aureus chromosome, which corresponds to the nucleotide sequence on the right
side of the SCCmec integration site.” ’289 patent, col. 3, ll. 1-5. The ’289 patent
describes the work of Ito
1
and Hiramatsu 1996,
2
two of the publications which are
cited in the appealed rejections, which are said to teach MREP typing (mec right
extremity polymorphism), a method that “takes advantage of the polymorphism at
the right extremity of SCCmec DNAs adjacent to the integration site” by using
primers that amplify the polymorphic regions. Id. at col. 3, ll. 9-17. The ’289
patent discloses that Hiramatsu’s method does not detect all MRSA strains. Id. at
col. 3, ll. 31-40. Based on this finding, the ’289 patent concludes:
This finding demonstrates that some MRSA strains have sequences at
the right extremity of SCCmec-chromosome right extremity junction

1
Ito et al., Structual Comparison of Three Types of Staphylococcal Cassette
Chromosome mec Integrated in the Chromosome in Methicillin-Resistant
Staphylococcus aureus, 45 ANTIMICROBIAL AGENTS AND CHEMOTHERAPY p.
1323-1336 (2001).

2
Hiramatsu, Keiichi, Genetic Basis for Molecular Epidemiology of MRSA, J. Infect
Chemother 2:117-129 (1996)(hereinafter “Hiramatsu 1996”).
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

4

different from those identified by Hiramatsu et al. Consequently, the
system developed by Hiramatsu et al. does not allow the detection of
all MRSA. The present invention relates to the generation of
SCCmec-chromosome right extremity junction sequence data required
to detect more MRSA strains in order to improve the Hiramatsu et al.
assay. There is a need for developing more ubiquitous primers and
probes for the detection of most MRSA strains around the world.
Id. at col. 3, ll. 40-50.
II. CLAIMS
Claim 1 is the only independent claim on appeal. Claim 1 reads as follows:
1. A method to detect the presence of a methicillin-resistant
Staphylococcus aureus (MRSA) strain in a specimen, comprising:
obtaining a sample from said specimen to be analyzed for the
presence of a
MRSA strain that includes an SCCmec insert containing a mecA
gene, said SCCmec being inserted into chromosomal DNA, thereby
generating a polymorphic right extremity junction (MREJ) region
sequence that includes sequence from both the SCCmec insert right
extremity and chromosomal DNA adjoining that right extremity;
contacting the sample with at least two primers, wherein the at
least two primers amplify the MREJ region sequence of at least one of
SEQ ID NOs: 42, 43, 44, 45, 46, 51, 47, 48, 49, 50, 171, 165, 166, 167
and/or 168 under conditions of 50 mM KCl, 10 mM Tris-HCl (pH 9.0),
0.1% Triton X-100, 2.5 mM MgCl2 at 55°C, and wherein said
contacting takes place under annealing conditions wherein an amplicon
is produced if any of said SEQ ID NOs are present in said sample,
thereby generating an amplicon if a MRSA strain of at least one of
MREJ types iv-ix is present in the sample; and
detecting said amplicon as indicative of the presence of a MRSA
strain in said specimen.

III. CLAIM INTERPRETATION
Claim 1 is directed to a method to detect a MRSA strain in a specimen. The
method involves obtaining a sample from a specimen, contacting the sample with
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

5

at least two primers which are used to generate an amplicon comprising a
nucleotide sequence from a list of sequences, and then detecting the amplicons as
indicative of the presence of the MRSA strain in the specimen. The “obtaining”
step of the claim reads as follows:
obtaining a sample from said specimen to be analyzed for the
presence of a MRSA strain that includes an SCCmec insert containing
a mecA gene, said SCCmec being inserted into chromosomal DNA,
thereby generating a polymorphic right extremity junction (MREJ)
region sequence that includes sequence from both the SCCmec insert
right extremity and chromosomal DNA adjoining that right extremity.
The “sample” is from a MRSA strain having an SCCmec insert inserted into
the chromosomal DNA of the bacterial strain. The claim defines this region of
insertion as “a polymorphic right extremity junction (MREJ) region sequence that
includes sequence from both the SCCmec insert right extremity and chromosomal
DNA adjoining that right extremity.”
The meaning of the term “SCCmec insert right extremity” is in dispute.
Because this term requires a spatial understanding of the MRSA chromosome, a
figure from Ito is reproduced below, which represents a MRSA bacterial
chromosome into which SCCmec has inserted. For the purposes of discussion, the
figure has been annotated with the pertinent regions of the chromosome.

Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

6

The region between the mecA element and the “junction between SCCmec
insert and chromosome” is labeled the “right downstream region.” A thick grey
line shows this region spanning from mecA to the junction. To the right of the
junction, shown in the figure as a lightly hatched bar thicker than the SCCinsert, is
the chromosome of S. aureus. The Examiner characterizes the “right downstream
region” as the “SCC insert right extremity.” Patent Owner disputes this
interpretation, asserting that this region is not the extremity of the insert, but the
entire downstream region.
The term “right extremity” is not defined in the ’289 patent. There are
numerous examples, however, of sequences which are described to be present in
the right extremity region of the SCCmec insert. ’289 patent, col. 17, ll. 41-65.
These regions are shown in Figures 1 and 2 of the ’289 patent to be in close
proximity to the junction between the SCCmec insert and bacterial chromosome.
To support the Examiner’s interpretation, the Examiner referred to teachings
in the ’289 patent of long amplicons “extending 12 to 20 kb in size, column 15,
lines 59-62 and column 16, lines 4-14” which are “produced from flanking
mecA/orfX primer sets.” RAN 16. These amplicons, however, are not identified
as right extremity sequences. Figure 3, which is referenced at column 16, lines 2-
3, shows the entire right downstream region in contrast to Figures 1 and 2 which
show only the right extremity region. PO Rebuttal Br. 3.
The ’289 patent refers to both “the downstream region of mecA” (col. 16, l.
64; col. 32, Table 4, about ll. 5-10) and “right extremity” (col. 7, ll. 44-50),
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

7

indicating that the two phrases have a different meaning. See also PO Rebuttal Br.
4-5. The ’289 patent specifically references the ’507 patent
3
as having described:
a PCR assay specific for MRSA by using primers that can specifically
hybridize to the right extremities of the 3 types of SCCmec DNAs in
combination with a primer specific to the S. aureus chromosome,
which corresponds to the nucleotide sequence on the right side of the
SCCmec integration site. . . This PCR assay also supplied information
for MREP typing (standing for «mec right extremity polymorphism»)
of SCCmec DNA (Ito et a., 2001, Antimicrob. Agents Chemother.
45:1323-1336; Hiramatsu et al., 1996, J. Infect. Chemother. 2:117-
129). This typing method takes advantage of the polymorphism at the
right extremity of SCCmec DNAs adjacent to the integration site
among the three types of SCCmec.
’289 patent, col. 2, l. 66 to col. 3, l.17.
The term “right extremity region” is also used in the prior art in the same
way as in the ’289 patent. For example, Ito describes “MREP typing” as “a
method to amplify the right extremity region of SCCmec by using primer sets
bracketing the right SCCmec-chromosome junction point.” Ito at 1324 (legend to
Table 1). Figure 1 of Ito shows these primers (e.g., mR2, cR4, and mN16) as
downstream and not including mecA. Id. at Table 1 (legend) and Table 3 (“MREP
typing”).
The ordinary usage of the term “extremity” is consistent with how the
term is used in the ’289 patent and Ito. “Extremity” is defined as “the
farthest or most remote part, section, or point.”
4
The “right extremity,”
therefore would be understood to be the right remote section of the insert,
distinguishing it from the insert’s left extremity and the region between the

3
Hiramatsu et al., U.S. Patent 6,156,507, issued Dec. 5, 2000 (“’507 patent”).
4
http://www.merriam-webster.com/dictionary/extremity. Attached.
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

8

left and right extremities. The Examiner’s construction of “right extremity”
to include the entire downstream region ignores an express limitation of the
claim. We acknowledge there is no bright-line test or demarcation of when
a region is in the right extremity rather than upstream of it (to the left in the
context of the figure annotated above) in the right downstream region. It
appears that the right extremity region was defined by the Hiramatsu 1996,
Ito, and the ’507 patent by the existence of polymorphisms in the DNA close
to the integration site. (“This typing method takes advantage of the
polymorphism at the right extremity of SCCmec DNAs adjacent to the
integration site among the three types of SCCmec.”) Consequently, the
Examiner’s interpretation of “right extremity region” to include all
sequences in the right downstream region is not a reasonable interpretation
of the claim.
The second step of claim 1 recites, inter alia, “contacting the sample with at
least two primers, wherein the at least two primers amplify the MREJ
[polymorphic right extremity junction] region sequence of at least one of SEQ ID
NOs: 42, 43, 44, 45, 46, 51, 47, 48, 49, 50, 171, 165, 166, 167 and/or 168 . . .,
thereby generating an amplicon if a MRSA strain of at least one of MREJ types iv-
ix is present in the sample.
We interpret the contacting step to including amplifying a part of the listed
sequences, as long as that part would be indicative of at least one of MREJ types
iv-ix is present in the sample. The reason for this interpretation is that claim states
“amplify the MREJ region sequence of” one of listed SEQ ID NOS, indicating that
the MREJ portion of the recited sequences is amplified and not necessarily the
entire sequence represented by the sequence identifier.
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

9

The Examiner characterizes claim 1 as a “positive or negative assay.” RAN
4. “If an amplicon is detected, the method indicates the presence of a MRSA strain
in the sample. If an amplicon is not detected, no MRSA is present.” Id. The
Examiner’s interpretation of the claim is reasonable. The “contacting” step recites
“thereby generating an amplicon if a MRSA strain of at least one of MREJ types
iv-ix is present in the sample,” indicating that sample is contacted with the primers,
but only “if” one of the MREJ types is present will an amplicon be generated.

IV. APPEAL
Although a number of sequences are listed in the claims, the rejections are
based on the examination of only SEQ ID NO: 42. According to the ’289 patent,
SEQ ID NO: 42 “exhibited nearly 100% identity with IS431.” ’289 patent, col. 17,
ll. 45-46. The patent discloses that the inventors’ “sequence data revealed for the
first time the location of this IS431 sequence at the right extremity of SCCmec
adjacent to the integration site.” Id. at col. 17, ll. 47-49. IS431 encodes a
transposase and had been described previously “within the right segment of
SCCmec. Id. at col. 13, ll. 64-67.
Claims 1, 2, and 5 stand rejected by the Examiner as follows:
1. Claims 1, 2, and 5 under 35 U.S.C. §102(b) (pre-AIA) as anticipated by
the ’507 patent with evidence from Alignment 1,
5
sequence of AB037671,
6
and
Cheng.
7
RAN 6.

5
Basic Local Alignment Search Tool, http://blast.ncbi.nlm.nih.gov/Blast.cgi,
printed 04/01/2011.
6
Staphylococcus aureus DNA, type-III staphylococcal cassette chromosome mec
and SCCmercury: strain 85/2082,
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

10

2. Claims 1, 2, and 5 under 35 U.S.C. §102(b) as anticipated by Hiramatsu
with evidence from Alignment 1, sequence of AB037671, and Cheng. RAN 13.
3. Claims 1, 2, and 5 under 35 U.S.C. §102(b) as anticipated by Ito with
evidence from Alignment 1, sequence of AB037671, and Cheng. RAN 6.
4. Claims 1 and 2 under 35 U.S.C. §102(b) as anticipated by Oliveira 2000
8

with evidence from Alignment 3
9
and Cheng.
5. Claims 1, 2, and 5 under 35 U.S.C. §102(b) as anticipated by Oliveira
with evidence from Alignment 2, sequence of AF411934,
10
and Sambrook.
11

1. ANTICIPATION BY THE ‘507 PATENT
The ’507 patent describes a method of detecting MRSA strains “by making
combined use of a part of a mecDNA, which is an integrated adventitious DNA
existing on a chromosome of the MRSA . . . and carrying an mecA gene thereon,
and a part of a nucleotide sequence of a chromosomal DNA surrounding the

http://www.ncbi.nlm.nih.gov/nuccore/14020964?sat=OLD02&satkey=1956705,
printed on 04/01/2011.
7
Cheng et al., Effective amplification of long targets from cloned inserts and
human genomic DNA, Proc. Natl. Acad. Sci USA, Vol. 91, pp. 5695-5699 (1994).
8
Oliveira et al., Genetic Organization of the Downstream Region of the mecA
Element in Methicillin-Resistant Staphylococcus aureus Isolates Carrying
Different Polymorphisms of This Region, 44 ANTIMICROBIAL AGENTS AND
CHEMOTHERAPY, p. 1906-1910 (2000).
9
Sequence alignment 3 aligns the nucleotide sequence of Staphylococcal aureus
strains 85/2082, HDG2, and N315(D86934) at the nucleic acid location
downstream of mecA gene. Printed on March 31, 2011.
10
Staphylococcus aureus strain HDG2 genomic sequence downstream of mecA,
printed on 04/08/2011.
11
Sambrook et al., Components of the Polymerase Chain Reaction, In Vitro
Amplification of DNA by the Polymerase Chain Reaction (2001).
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

11

integrated DNA.” ’507 patent at Abstract. Figure 7 of the ’507 patent “is a
diagram illustrating an outline of an MRSA identification method.” Id. at col. 3, ll.
51-52. Figure 7A is reproduced below:

Figure 7A shows the primers (depicted as arrows) that flank the mec-intM
junction. The mec-side primers are shown to be downstream of mecA and are
located in the right extremity of the mec insert. IntM represents the chromosomal
region of the strain. ’507 patent at col. 4, l. 10. IntM is the integration site in the
chromosomal DNA for the mec region DNA. Id. at col. 5, ll. 54-57 and col. 6, ll.
7-12. It is also known as orfX. The primers, thus, amplify a region that comprises
the right extremity of the mec insert and the chromosomal DNA of the bacterial
strain.

Rejection
The Examiner found that the ’507 patent describes amplification of the
MREJ region, the same region said to be recited in the claims. RAN 6. The region
was amplified from strain 85/2082. Id. at 19. Strain 85/2082 is a MRSA bacterial
strain disclosed in the ’507 patent, e.g., at col. 9, l. 18; Table 2 at cols. 13-14.
The Examiner found that the amplification method described in the ’507
patent “utilizes primers which hybridize to the same right extremity region of
SCCmec (mecA) (mec-side or upstream primer) and the same staphylococcus
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

12

chromosomal DNA to the right of the mecA integration site (intM or orfX)
(MSSA-side or downstream primer).” RAN 6. The Examiner’s findings are
supported by a preponderance of the evidence as set forth above by the specific
references to the ’507 patent.
The Examiner also found: “Sequence alignment 1 verifies that the
Hiramatsu ’507 [patent] MRSA strain 85/2082 disclosed within Tables 1-5
correspond in sequence to AB037671 with 100% identity to the MREJ region
identified as SEQ ID NO:42 in the ’289 patent.” Id.
AB037671 is a GenBank nucleotide sequence listing for “Staphylococcus
aureus DNA, type-III staphylococcal cassette chromosome mec and SCCmercury:
strain 85/2082.” Strain 85/2082 is disclosed in the ’507 patent, but the sequence
listing for this strain is not disclosed in the ’507 patent. However, it is asserted to
have been available prior to the ’289 patents’ filing date of Jun. 4, 2002 (PCT
filed). PO Appeal Br. 23; RAN 3: 1-3.
The Examiner did not provide adequate evidence that the ’507 patent
sequence listed in alignment 1 is present in the right extremity of the MREJ region
as required by the claim. The Examiner stated:
In strain 85/2082, SEQ ID NO:42 is a 1045 bp sequence evidenced to
lie within the MREJ region, specifically downstream of mecA and the
first IS431 element, within the second IS431 element, and
approximately 30 kb from the integration site, see Exhibit B,
Attachment 1.
RAN 19.
Attachment 1 or Exhibit B is a sequence alignment. It has arrows which
indicate the position of IS431 and of SEQ ID NO: 42 (which is shown on the
attachment as only containing a part of IS431). Attachment 1 does not identify the
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

13

junction of the integration site of SCCmec into the S. aureus chromosome (which
corresponds to the right extremity) or the mecA gene. Thus, without further
guidance, the location of SEQ ID NO: 42 on the insert relative to the junction
cannot be determined.
According to Patent Owner, the strain of MRSA identified in their patent is
different from strain 85/2082 of the ’507 patent. Patent Owner acknowledged the
85/2082 does have a “region of homology” to the type IV strains described in their
patent, but this region is said to be 31 kb away from the junction. PO Appeal Br.
11. We take this “region of homology” as a reference to SEQ ID NO: 42, or
IS431, to which it is nearly identical. Patent Owner did not provide a map of
85/2082 to pinpoint the location of SEQ ID NO: 42, but it was not disputed that
such sequence was located 31 kb from the integration junction. This location is in
the downstream region, but not in the right extremity as required by the claim as
interpreted above.
The Examiner also did not establish by a preponderance of the evidence that
primers were described in the ’507 patent that would amplify SEQ ID NO: 42. For
example, the Examiner stated:
Hiramatsu ‘507 teaches the relevant MREJ region and the location of
primer pairs spanning the region. Hiramatsu ‘507 also specifically
teaches the full MREJ sequence from strain 85/2082 which includes
SEQ ID NO:42, and thus any number of flanking primer pairs are
immediately envisaged.
RAN 19.
Hiramatsu ‘507 discloses a number of primer and probe sequences
throughout this MREJ region which may be utilized for amplification
via any number of procedures such as the polymerase chain reaction
(PCR), ligase chain reaction (LCR) and nucleic acid sequence based
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

14

amplification (NASBA), see column 2, lines 43-61, columns 7-8 and
the sequence listing.
RAN 20.
The Examiner specifically mentioned primers Gmec1045 and J3 primers as
capable of amplifying SEQ ID NO: 42. RAN 20. But the Examiner did not point
to where this primer pair was utilized to produce an amplicon that contains SEQ ID
NO: 42 or provide adequate evidence that it could be used to do so.
Requester also identifies Gmec1045 and J3 as a specific set of primers that
would meet the claim limitation of a pair of primers, identifying the disclosure at
column 23, ll. 1-50, of the ’507 patent for support. Requester states:
Gmec 1045 is the forward primer, 10 nucleotides of which hybridize
at position 25399 to 25408, upstream of SEQ ID NO:42 in strain
85/2082 and J3 is the reverse primer in the orfX region. 67968 to
67988 of strain 85/2082 as evidenced by AB037671.
TPR Resp’t Br. 10 (fn. 32).
The sequence of primer J3 is shown at columns 19-20 of the ’507 patent.
The sequence of Gmec1045 is shown in Example 6 at column 18. Column 23,
lines 1-50, which Requester identified as support for the primers, has a Table that
lists Gmec1045 and an example with forward primers Gmec1045 and Nmec5 and
reverse primer jun3. J3, however, does not appear at column 23 and Requester did
not identify an example in which Gmec1045 and J3 had been used, or suggested, to
amplify a sequence from a bacterial strain in the ’507 patent.
Disclosure of a specific working example is not required to establish
anticipation. In re Petering, 301 F.2d 676, 681 (CCPA 1962); WM. Wrigley Jr.
Co. v. Cadbury Adams USA LLC, 683 F.3d 1356, 1361-62 (Fed. Cir. 2012). As
held in Petering:
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

15

[W]e think it is immaterial that Karrer did not expressly spell out the
limited class as we have done here. It is our opinion that one skilled
in this art would, on reading the Karrer patent, at once envisage each
member of this limited class, even though this skilled person might
not at once define in his mind the formal boundaries of the class as we
have done here.
A simple calculation will show that, excluding isomerism within
certain of the R groups, the limited class we find in Karrer contains
only 20 compounds. However, we wish to point out that it is not the
mere number of compounds in this limited class which is significant
here but, rather, the total circumstances involved, including such
factors as the limited number of variations for R, only two alternatives
for Y and Z, no alternatives for the other ring positions, and a large
unchanging parent structural nucleus. With these circumstances in
mind, it is our opinion that Karrer has described to those with ordinary
skill in this art each of the various permutations here involved as fully
as if he had drawn each structural formula or had written each name.
Petering, 683 F.2d at 681.
The question is whether one of ordinary skill in the art would have
envisaged – in the absence of an example – utilizing the primer pair of Gmec1045
and J3 to amplify a sequence comprising SEQ ID NO: 42 from one of the bacterial
strains in the ’507 patent. Unlike Petering, neither the Examiner nor the Requester
has referenced an identifiable class of primers in the ’507 patent from which the
skilled worker would have envisaged the specific primer pair of J3 and Gmec1045.
As indicated above, the primers are mentioned in disparate disclosures. The
Examiner did not provide a reason as to why the skilled worker would have
selected this primer pair to amplify a SCCmec sequence from a bacterial strain. In
Petering, the Karrer publication had disclosed a formula, which covered a genus of
species. The issue was whether one of ordinary skill in the art would have
envisaged from that formula the specific species which was claimed by Petering.
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

16

The court, in that case answered yes, because the genus was a limited class of
species, each of which could be identified as its structure had been drawn or its
name written.
The standard set forth in Petering has not been met here. It is not disputed
that the sequence 42 is contained in certain bacterial strains of the ’507 patent.
However, the inquiry does not end there. The claims all require “contacting the
sample with at least two primers, wherein the at least two primers amplify the
MREJ region sequence.” A preponderance of the evidence does not show that the
’507 patent teaches one of ordinary skill in the art to have utilized J3 and
Gmec1045 to amplify the MREJ region sequence. It is not enough to identify
those primers in the patent. It must be shown the one of ordinary skill in the art
would have envisaged using them to amplify a region of the bacterial strain which
would comprise IS431. Such evidence is simply not before us on this record.
Accordingly, the rejection of claims 1, 2, and 5 are reversed.

2. ANTICIPATION BY HIRAMATSU 1996
Two of the co-inventors of the ’507 patent (Hiramatsu and Ito) are also co-
authors of Hiramatsu 1996. Hiramatsu 1996 has overlapping disclosure with the
’507 patent. Hiramatsu 1996 describes a MRSA assay as follows:
We have developed a rapid diagnostic method for MRSA based on the
nucleotide sequence analysis of 3 types of mec DNAs. Previous
methods to identify MRSA, based on the detection of the mecA gene
or its gene product, PBP2', encountered difficulty in discriminating
MRSA from MRC-NS, because the mecA gene is distributed in both
S. aureus and C-NS species. We found that the mec DNAs are
integrated at a specific site of MSSA chromosome, and the right
extremities of mec DNAs adjacent to the integration site are
polymorphic. By preparing primers that can specifically hybridize to
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

17

the polymorphic right extremities of mec DNAs, and by using them in
combination with an MSSA chromosome primer corresponding to the
nucleotide sequence to the right of the mec integration site, we could
establish a diagnostic PCR of MRSA (MREP typing; standing for mec
right extremity polymorphism).
Hiramatsu 1996 at 122.

Rejection
The Examiner found that Hiramatsu 1996 “reviews molecular genotyping
methods for multiple MRSA strains including strain 85/2082, see p. 117, 119-120,
122, 124, Tables 1-4 and Figures 1-5.” RAN 13. The Examiner stated that the
methods of Hiramatsu “include analysis of the nucleic acid sequences within the
right extremity of mec via PCR amplification with primers flanking the right
extremity region of mec and the MSSA chromosome.” Id. While the Examiner
urged that the claims do not require any specific pair of primers (RAN 28), the
claims do require a primer pair and the Examiner failed to identify any primers in
Hiramatsu 1996 that would meet the claimed requirements.
Requester also contends that primers are described in Hiramatsu 1996:
[Both the’ 507 patent and Hiramatsu 1996] disclose mec-DNA
(forward) primers derived from the region of SCCmec that extends
from IS431 on the right side of mec to the right (downstream) mec-
intM junction.
31
Primers that amplify sequences between IS431 and
the right integration junction would amplify SEQ ID NO:42 in strain
85/2082.
TPR Resp’t Br. 10.
Footnote 31 references page 122, column 1, of Hiramatsu 1996. We have
reviewed that page and column number and cannot find specific primer pairs
mentioned there.
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

18

In sum, a preponderance of the evidence does not support the Examiner’s
finding that Hiramatsu 1996 anticipates claim 1, and dependent claims 2 and 5.
The anticipation rejection is reversed.

3. ANTICIPATION BY ITO
The Ito publication includes Ito and Hiramatsu as co-authors, both who are
also listed co-inventors of the ’507 patent.
Ito describes “a detailed structural comparison of the three types of
SCCmec” found in MRSA strains. Ito at 1323, col. 2. Ito describes amplification
of DNA fragments by PCR and determination of the entire nucleotide sequence of
the SCCmec of 85/2082. Id. at 1324, col. 2. Specific primer pairs are identified by
Ito for isolating different fragments of the region. Id. at 1325, col. 1. “By using
these DNA fragments amplified by long-range PCR, the nucleotide sequence of the
entire SCCmec of 85/2082 was determined.” Id.
Ito also describes the “PCR typing method designated mec right extremity
polymorphism (MREP) typing.” Ito at 1331. Ito explains “MREP typing is a
quick SCCmec typing method that takes advantage of the polymorphism among
the three types of SCCmec in the right extremity.” Id. Ito specifically describes
three primers used for MREP typing: cR4, mR2, and mN16. Ito at 1332. The
primers are depicted in Figure 1 of Ito.

Rejection
The Examiner found “Ito teaches sequence analysis of the chromosomal
DNA fragments to the left and right boundaries of SCCmec, see paragraph
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

19

spanning p. 1323-1324 and paragraph spanning 1324-1325.” RAN 7. The
Examiner found:
Ito utilized PCR (MRE/P) typing via amplification of the right
extremity polymorphism region with primers that bracket the same
MREJ region, at the right SCCmec chromosome junction point, see p.
1328, column 2, line 20-p. 1332, column 2, line 2. Such primers
generate PCR amplicons corresponding to the same region of 85/2082
MREJ DNA, see p. 1332.
Id.
The Examiner specifically cited “primers Cr4 and mN16.” Id. There is no
“Cr4” primer in Ito, but there is “cR4.” The Examiner concluded that sequence
alignment shows 100% identity between SEQ ID NO: 42 and sequence in strain
85/2082. Id.
Requester states that the “combination of tetK4 with the primers cR2 or cR4,
shown at the right junction in Figure 1 of Ito, would amplify a sequence that
includes SEQ ID NO: 42 of strain 85/2082 and the junction.” TPR Resp’t Br. 10-
11;
For clarity, Figure 1C of Ito is reproduced below containing the same
annotations described supra:

Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

20

Figure 1C shows strain 85/2082 (having sequence AB037671), which is the
focus of the discussion by the Examiner and Requester. See legend to Fig. 1 on Ito
at 1327 and Resp’t Br. 12 (fn. 39). cR2 and cR4 are shown in Figure 1C at the
junction (orfX) where SCCmec integrated into the bacterial chromosome. tetK4 is
not depicted in the figure.
The Examiner’s reliance on primers cR4 and mN16 that would amplify a
region comprising SEQ ID NO: 42 is not factually supported. As shown in Figure
1C, primers mN16 and cR4 flank the junction where the SCCmecA insert
integrated into the chromosome and do not include IS431 sequence which
corresponds in part to SEQ ID NO: 42. Figure 1C shows three labeled IS431
sequences, but these are all upstream of the region that would be amplified by cR4
and mN16.
With respect to the Examiner’s more generic assertion that primers could be
chosen that would amplify a right extremity comprising SEQ ID NO: 42, there is
no evidence put forth by the Examiner that such a pair had been used or that such a
pair would be envisaged by one of ordinary skill in the art upon reading the Ito
disclosure. The same Petering analysis set forth in the rejection over the ’507
patent applies here.
Requester did not establish that the pair of tetK4 and cR2 or cR4 had been
used by Ito, or that, even if not actually used for amplification, one of ordinary
skill in the art would have immediately envisaged their use for amplification of a
MRSA bacterial strain. The argument is therefore defective under Petering for the
same reasons as described for the anticipation rejection over the ’507 patent.
Ito also teaches a set of primers that includes “tetK4 and merA1 (the region
from pT181 to the mercury operon)” (Ito at 1325, col. 1), but not in combination
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

21

with cR2 and cR4. Figure 1C, depicting strain 85/2082 (AB037671), shows pT181
and mer (apparently the mercury operon) between which two IS431 elements lie.
Requester cited attachment 1 as showing “nucleotides 28981-41460 of strain
85/2082 (AB037671) and primers disclosed in Ito that amplify a region of
SCCmec downstream of mecA and IS431 in strain 85/2082 that includes the full
sequence of SEQ ID NO:42.” Resp’t Br. 11 (fn. 39). Requester did not cite these
primers as anticipatory, but nonetheless we shall consider them here.
Attachment 1 shows tetK4 on page 2 in the sequence of 85/2082 and merA1
on page 4. SEQ ID NO: 42 appears on page 3 and is labeled as the second IS431
sequence. IS431 is located between tetK4 and merA1, and thus is amplified by
them. See Figure 1C. This amplified region, however, does not appear to be
located at the extremity of the insert which extends to orfX all the way on the right
of the figure. Ito does not refer to this region as the right extremity, and as pointed
out above, describes only three primers for MREP typing, none of which would
amplify SEQ ID NO: 42. Ito at 1332 (“MREP typing”); see locations of primers in
Ito’s Figure 1. In contrast, primers tetK4 and merA1 are characterized by Ito as
primers for “Amplification of DNA fragments for nucleotides sequences.” Id.
There is insufficient evidence to find that the region between tetK4 and merA1,
which contains IS431 having identity with SEQ ID NO: 42, constitutes a
“polymorphic right extremity junction (MREJ) region sequence” as required by the
claims. In sum, it has not been established by a preponderance of the evidence that
Ito anticipates claims 1, 2, and 5. The rejection is reversed.

Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

22

4. ANTICIPATION BY OLIVEIRA 2000
Oliveira 2000 describes “the genetic organization of the mec element
downstream of the mecA gene in 34 different methicillin-resistant Staphylococcus
aureus (MRSA) clinical isolates carrying 13 of the most frequent polymorphisms
of mecA and representing the major epidemic clones of MRSA.” Oliveira 2000 at
1906 (Abstract).

Rejection
The Examiner found that Oliveira 2000 used primers that “flank the MREJ
region, see p. 1908, Table 3 and Figure 1. Alignment 3 is said to further show
location of Oliveira primers IS P1 and IS P4 (Table 3) within the downstream
region of mecA.” RAN 14.
Requester further argued “primers that anneal to IS431, such as ISP 1 or
ISP4 in combination with any of MDVR1, MDVR2 MDVR5, and MDVR6 that
bind to orfX or chromosomal DNA, would necessarily amplify SEQ ID NO:42 in
strain 85/2082.” TPR Resp’t Br. 16.
For clarity, a part of Oliveira 2000’s Figure 1 is reproduced below. This part
of the figure was selected since it displays the primers referred to by Requester

Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

23

The figure has been annotated by circling ISP4 on the top part of the figure.
The bottom part of figure (right) shows primers MDVR1, MDVR2 MDVR5, and
MDVR6 referenced by Requester.
Table 3, as found by the Examiner, contains a list of 18 primers. “IS P4” and
“MDVR1,” “MDVR2,” “MDVR5, and “MDVR6” are among the listed primers.
Requester contends that a primer pair consisting of IS P4 and one of the MDV
primers “would necessarily amplify SEQ ID NO: 42 in strain 85/2082.” TPR
Resp’t Br. 16. However, Requester has not identified strain 85/2082 in Oliveira
2000. Table 2 on page 1907 shows a list of 34 MRSA strains. Oliveira 2000 at
1908. None of these strains are identified as 85/2082.
The Examiner found that Oliveira 2000 describes primers that flank the
MREJ region. The Examiner did not specifically name a primer pair, but the
Examiner referred to Table 3 and Figure 1. RAN 14. MDV primers shown on the
bottom of Figure 1 combined with the circled IS P4 primer on the far top left
encompass a region that would include IS431 (there are two IS P4 primer sites
shown in Figure 1; we are referring to the first IS P4 from left to right). Primers
mecA P1, HVR P1, and IS P1 are also listed in Table 3 which flank IS431 as
shown in Figure 1. The Examiner concluded:
The artisan was well skilled in the art of amplification and would
understand that any of the flanking primers would be sufficient to
produce an amplicon. Only the relevant size of the amplicon would
vary depending upon the sample strain and primer pairs selected. As
above, claims 1-2 are directed to a positive or negative assay, while an
amplicon would be produced under art standard conditions, the
production of an amplicon is not required.
RAN 29.
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

24

Because of the number of primers disclosed in Oliveira is small – 18 in total
listed in Table 3 – one ordinary skill in the art could readily envisage forward and
reverse primers for amplifying different downstream regions of the various MRSA
strains disclosed in Oliveira 2000, the express purpose of the primers. Oliveira
2000 at 1908 (“TABLE 3. Primers used for screening the mecA downstream
vicinity”).
Specifically, as indicated above and shown in Figure 1, IS P4 in combination
with a reverse MDV primer would amplify a region comprising IS431 which
contains SEQ ID NO: 42. Oliveira 2000 describes performing long-range PCR.
Id. at 1907, col. 1. The IS431 is adjacent to the dcs region that adjoins orfX. See
Oliveira 2000, Figure 1 reproduced above. The IS431 element is reasonably
believed to be located in the right extremity of the polymorphic region since it
appears to be only separated from the junction by the 2-kb dcs sequence. Id. at
1909 (“A unique 2-kb sequence, the downstream constant segment (dcs) (Fig. 1),
was detected in each polymorph.”). In sum, there is sufficient evidence to
establish that Oliveira anticipates claim 1.
Claim 2 depends from claim 1 and is further drawn to at least two primers
that amplify additionally recited sequences. The Examiner did not provide
evidence that one of these sequences is described in Oliveira 2000. Consequently,
we reverse the anticipation rejection of claim 2.

5. ANTICIPATION BY OLIVEIRA 2001
Oliveira 2001 is cited as anticipatory under 35 U.S.C. § 102(a) (pre-AIA).
To rebut the rejection, Patent Owner provided a declaration under 37 C.F.R. §
1.131 to establish that the inventors reduced to practice as much of the
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

25

embodiment of claims 1, 2, and 5 said to be shown in Oliveira 2001. PO Appeal
Br. 24; Declaration of Ann Huletsky, dated July 30, 2011. A declaration under 37
C.F.R. § 1.131 can be used by an inventor to antedate a reference that qualifies as
prior art under 35 U.S.C. § 102(a) by showing that the inventor made that portion
of the claimed invention that is disclosed in the prior art reference.
12
In re Stempel,
241 F.2d 755 (CCPA 1957).
The claims require contacting a sample with at least two primers that
amplify the MREJ region of a list of SEQ ID NOs, “generating an amplicon if a
MRSA strain of at least one of MREJ types iv-ix is present in the sample,” and
detecting the amplicon as indicative of the presence of a MRSA strain in the
sample. The Examiner found that these steps were described in Oliveira 2001 for
an amplicon comprising SEQ ID NO: 42 when performed on the strain HDG2 with
a Genbank accession number of AF411934. The Examiner found “[a]lignment 2
and AF411934 establish sequence similarity between AF411934 of HDG2 DNA
and '289 SEQ ID NO's:42-46 and 51.” RAN 8. Requester also identified primer
pairs that they asserted “produce an amplicon from IS431 to orfX in HDG2 that
would include sequences having significant identity with sequences SEQ ID
NO.42.” TPR. Resp’t Br. 15.
Declarant Ann Huletsky is a co-inventor of the ’289 patent. The
experiments she identified to establish reduction to practice of an embodiment of
the claims are described in Canadian Patent Application No. CA 02348042 (“the

12
“The applicant need show priority with respect to only so much of the claimed
invention as the references disclose, In re Stempel, 241 F.2d 755, 760, 44 CCPA
820, 826,113 USPQ 77, 81 (1957), or only so much as to render the claimed
invention obvious. In re Spiller, 500 F.2d 1170, 1177, 182 USPQ 614, 619 (Cust.
& Pat.App.1974).” In re Scheiber, 587 F. 2d 59, 62, 199 USPQ 782, CCPA 1978).
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

26

’042 Application”) which was filed on June 4, 2001. The ’042 Application is
listed under the foreign application priority data of the ’289 patent and names the
same co-inventors as the patent.
Ms. Huletsky testified that 31 MRSA strains were tested as described in the
’507 patent, but 12 did not give a positive result. Huletsky Decl. ¶6. Ms. Huletsky
further testified that “[b]ased upon the sequences of the SCCmec/orfX
amplification products generated in the experiments described in Example 3 of the
’042 Application, new oligonucleotides were designed that bracket and amplify . . .
[the polymorphic right extremity] and the S. aureus chromosome adjacent to the
SCCmec cassette on the right side of the SCCmec cassette insertion point.” Id. at
¶8.
Ms. Huletsky further stated
The ’042 Application describes experiments in which the sample was
contacted with a primer pair, e.g., SEQ ID: NO:64 and 79 of the '042
Application, that amplified the SCCmec/orfX junction region
sequences, including the polymorphic right extremity sequences from
SCCmec and orfX chromosomal sequences. In the experiments
described in the ’042 Application, the MREJ region of at least one of
SEQ ID NOs: 42, 43, 44, 45, 46, and 51 was amplified to produce an
amplicon. The amplicon was detected, which indicated the presence
of an MRSA strain in the sample.
Huletsky Decl. at p. 3.
As indicated by Ms. Huletsky, the ’042 Application discloses the sequences
of primers 79 and 64 (at p. 64), shows their position in type IV SCCmec (Figure
2b), lists SEQ ID NO:42 as indicative of type IV SCCmec (at p. 41), and describes
SEQ ID NO:42 as sharing nearly 100% identity to IS431 (at p. 20: 18-19).
The Examiner found the evidence unsatisfactory because the “declaration
does not specify other primer pairs or state that all of the sequences were produced
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

27

and thus the declaration does not make clear that the inventor was in possession of
more than a single species, whereas the prior art discloses numerous
embodiments.” RAN 18.
In Stempel, the court held that to antedate a prior art publication “under the
law all the applicant can be required to show is priority with respect to so much of
the claimed invention as the references happens to show.” Stempel, 241 F.2d at
759. Oliveira 2001 is said by the Examiner to teach using two primers to amplify
an amplicon in a MRSA strain comprising SEQ ID NO: 42. RAN 8. This teaching
corresponds to one of embodiment of the claimed invention of contacting a sample
with at least two primers to amplify an amplicon comprising SEQ ID NO: 42.
Under Stempel, all that is necessary is that the inventor show as much of the
claimed invention as the reference discloses. In this case, Oliveira 2001 is said to
disclose the claimed embodiment in which primers are used to detect the presence
of SEQ ID NO: 42. The Huletsky declaration established that this embodiment
was reduced to practice in the Canadian patent application with a filing date of
June 4, 2001, which was not challenged to be before the publication date of
Oliveira 2001.
The Examiner improperly required the inventors to show amplification with
more than one primer set because, allegedly, Oliveira 2001 showed amplification
with more than one primer set. Claim 1 does not require a specific primer pair.
Rather, the claim requires a primer pair to amplify a MREJ region sequence of
SEQ ID NO: 42. The claimed invention is not the primer pair, per se, but the
discovery of SEQ ID NO: 42 in a polymorphic right extremity of SCCmec. ’289
patent, col. 17, ll. 41-49. Since identification of the MREJ region in SEQ ID NO:
42 was said to have been accomplished by Oliveira 2001 using primers, it is only
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

28

necessary that the inventors have amplified this region prior to Oliveira’s
publication date and showed that it is indicative of the presence of SEQ ID NO: 42.
Based on the ’042 Application and the Declaration of Ann Huletsky, we conclude
that the latter was completed by the inventors prior to the publication date of
Oliveira 2000, removing it as prior art to the’289 patent with respect to SEQ ID
NO:42 in claim 1. The rejection of claim 1, and dependent claim 2, as anticipated
by Oliveira 2001 is reversed.

V. CROSS-APPEAL
Requester appeals the Examiner’s decision not to adopt the following
proposed rejections (pre-AIA):
8. (Ground A) Claim 4 as anticipated under 35 U.S.C. § 102(b) by the ’507
patent with evidence from Alignment 1, sequence in AB037671, and Cheng.
9. (Ground B) Claim 4 as anticipated under 35 U.S.C. § 102(b) by Ito with
evidence from Alignment 1, sequence in AB037671 and Cheng.
10. (Ground C) Claims 4 and 5 are anticipated under 35 U.S.C. § 102(a) by
Oliveira 2001, Alignment 2, sequence in AF41193415, and Sambrook
11. (Ground D) Claims 1-5 as obvious under 35 U.S.C. § 103(a) in view of
the ‘507 patent, Hiramatsu 1996, Cheng, Alignments 1 and 3, and AB037671.
12. (Ground E) Claims 1-5 as obvious under 35 U.S.C. § 103(a) in view of
Ito, Hiramatsu 1996, Cheng, sequence in AB037671, and Alignments 1 and 3.
13. (Ground F) Claims 1-4 as obvious under 35 U.S.C. § 103(a) in view of
Oliveira 2001, Hiramatsu 1996, Alignment 2, sequence in AF411934, and
Sambrook.
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

29

14. (Ground G) Claims 1-4 as obvious under 35 U.S.C. § 103(a) in view of
Oliveira 2001, Alignment 2, sequence in AF411934, Sambrook, and the ’507
patent or Ito.
15. (Ground H) Claims 1-5 as obvious under 35 U.S.C. § 103(a) in view of
Oliveira 2000, Alignments 1 and 3, Cheng, and the ’507 patent or Hiramatsu 1996.
16. (Ground I) Claims 1-5 as obvious under 35 U.S.C. § 103(a) over
Oliveira 2000, Oliveira 2001, Hiramatsu 1996, Alignments 2 and 3, sequence in
AF411934, and Sambrook.

REJECTIONS 8 and 9
Requester contends that the Examiner erred in not adopting the proposed
rejection of claim 4 as anticipated by the ’507 patent and Ito. Claim 4 is directed
to the method of claim 1, “further comprising detecting the presence of SEQ ID
NO: 172 as indicative of the presence of MREJ type x.” Requester contends that
the Examiner erred in requiring the claims to “explicitly” disclose the detection of
SEQ ID NO:172. TPR Appeal Br. 7. “This was in error as an explicit disclosure
that SEQ ID NO: 172 is detected is not required for anticipation to be present.” Id.
According to Requester, the ’507 patent and Ito provide a detailed enabling
methodology for amplifying a region that would comprise SEQ ID NO:172. Id. at
8. Requester concludes that “Claim 4 is anticipated because detection of SEQ ID
NO: 172 is the natural result of the explicit methods taught by each of the '507
patent, Ito, and Oliveira 2001. Claim 4, like claim 1, does not limit MREJ region
to a particular size or location downstream of mecA. (emphasis added)[.] All that
is required is the detection of SEQ ID NO: 172.” Id. at 9.
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

30

Despite Requester’s assertion that the’ 507 patent and Ito enable primers that
would amplify a MREJ region comprising sequence 172, Requester has not
identified such primers or provided evidence that primers would be envisaged upon
reading either of the publications. See Petering supra. Consequently, we conclude
that a preponderance of the evidence does not support Requester’s contention that
the Examiner erred in rejecting claim 4 as anticipated by the ’507 patent or Ito.

REJECTIONS 10, 13, 14, AND 16
Rejections 10, 13, 14, and 16 rely on Oliveira 2001, which has been
determined not to be prior art to the ‘289 patent claims. The Examiner’s decision
not to adopt the rejections is therefore affirmed.

REJECTIONS 11 and 12
Requester contends that the Examiner erred in not adopting the rejection of
claim 1-5 as obvious in view of the ’507 patent and Hiramatsu 1996 (Rejection 11)
or Ito and Hiramatsu 1996 (Rejection 12). Cheng, sequence alignments 1 and 3,
and the sequence of AB037671 are also cited as evidence of the obviousness of the
claimed subject matter. Requester grouped these rejections together.
Requester provides evidence that the ’507 patent describes a primer design
strategy for amplifying regions downstream of mecA, “including a primer that
amplifies a region downstream of mecA and a primer that amplifies upstream of
the chromosomal integration region.” TPR Appeal Br. 11. Figure 7 of the ’507
patent, reproduced below, is said to show this strategy.
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

31

Figure 7 shows mec-side primers (downstream from mecA) and MSSA-side
primers (includes chromosomal DNA from the bacteria strain into which the
SCCmec inserted) to produce an amplicon. “Arrow marks indicate primers for
PCR.” ’507 patent, col. 3, ll. 51-53.
Requester argues:
The fact that the same strategy of the ‘507 patent was applied to
strains of bacteria having different SCCmec right extremity sequences
in the ‘289 patent does not render the claims patentable, especially in
view of the fact that the ‘289 patent admits that it used sequences
available in publicly available databases. All the ‘289 patent did was
use the strategy of the ‘507 patent and apply it to different strains of
bacteria, at least some of which were known prior to the effective date
of the ‘289 patent.
TPR Appeal Br. 13 (footnotes omitted).
Even if the same strategy of the ’507 patent was utilized by the inventors of
the ’289 patent to find sequences in the polymorphic right extremity junction
(MREJ) region, claim 1 further requires “contacting the sample with at least two
primers” which amplify this region, where the region contains “at least one of SEQ
ID NOs: 42, 43, 44, 45, 46, 51, 47, 48, 49, 50, 171, 165, 166, 167 and/or 168.”
Claim 1. As discussed earlier, to construe the amplification region to be anywhere
in the right downstream of the bacterial chromosome is inconsistent with the
recitation of “extremity” in the claim. While claim 1, itself, does not expressly
require that an amplicon be detected, the claim does require that the primers be
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

32

capable of producing an amplicon with one of the listed sequences located in the
polymorphic right extremity junction (MREJ) region. To anticipate or render
obvious claim 1, a bacterial strain having one of the listed sequences in the
polymorphic right extremity junction (MREJ) region must be identified because
the claim requires that the amplicon be indicative of the MREJ type and thus must
have been identifiable at the time of the invention. The strains specifically
mentioned by Requester as having this characteristic include 85/2082, HDG2,
N315, R35, and HDE288. TPR Appeal Br. 14 and 16.
The only source of HDG2 identified by Requester is in Oliveira 2001, which
is not prior art. TPR Appeal Br. 16, 18, 19, and 22. R35 is mentioned several
times in Requester’s Appeal Brief (14, 25, and 27) without clearly identifying a
source from which it could be obtained prior to the filing date of the application
which led to the ’289 patent. HDE288 is also mentioned in the brief but with no
indication of its source. In sum, the availability HDG2, R35, and HDE288 prior to
the filing date of the ’289 patent has not been established. Consequently, the only
two strains we will address are 85/2082 and N315. Both strains are disclosed in
the ’507 patent.
Requester contends it would have been obvious to have used the strategy
depicted in Figure 7 to produce an amplicon containing SEQ ID NO: 42 in strain
85/2082. TPR Appeal Br. 13.
Strain 82/2082 has the sequence of AB037671. SEQ ID NO: 42 is present in
strain AB037671, but was found by the Examiner to be about 30 kb from the
integration cite of SCCmec. RAN 19. Requester did not dispute this fact. While
there is no bright-line test for how far away a sequence can be from the integration
site and still be characterized as residing in the polymorphic right extremity
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

33

junction (MREJ), 30 kb is outside the region that Ito used to identify
polymorphisms in the right extremity and is not reasonably interpreted as part of
the right extremity. As shown below, IS431, which contains SEQ ID NO:42, also
appears relatively significantly distanced from the right extremity junction. A
helpful of map of strain 82/2082 is depicted in Figure 1C of Ito. Figure 1C is
reproduced below.

Fig. 1C shows IS431 upstream to primers mN16, cR2, and cR4, the primers
which are used in the MREP typing of Ito. Ito, 1332 (Table 3). Requester did not
provide an adequate explanation as why IS431 would be considered to be present
in the polymorphic right extremity junction (MREJ) as required by the claims,
when it is located about 30 kb away.
Requester also referenced strain N315 (D86934). However, Requester did
not identify primers for this strain that would identify SEQ ID NO: 42 as required
by claim 1.

Claim 3
Claim 3 depends from claim 1 and lists primer pairs for detecting MREJ
types of MRSA strains, including “SEQ ID NO: 64 and at least one of the
following primers: SEQ ID NO: 79 for the detection of MREJ type iv.” SEQ ID
NO: 64 is shown in Figure 2B of the ’289 patent to be present to the right of the
SCC integration site in the orfX region of the S. aureus chromosome. SEQ ID
NO:79 is depicted to the left of the integration site in the right extremity of the
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

34

SCCmec insert. Table 7 of the ‘289 Patent discloses that primer pair 64/79
produces an amplicon of 215 bases in length when used to detect MREP type iv
MRSA. ’289 patent, col. 34, ll. 12. The amplicon spans the junction where the
SCCmec insert integrated into the S. aureus chromosome.
Requester contends that strain 82/2082 contains “a primer pair of claim 3
(SEQ ID NO: 64 and SEQ ID NO:79) that would amplify a portion of SEQ ID NO:
42 in strain 85/2082.
46
” TPR Appeal Br. 13. According to footnote 46:
Alignment 1 and AB037671. SEQ ID NO:79 is found at nucleotides
35953 to 35981 and SEQ ID NO:64 is found at nucleotides 67932 to
67914 of AB037671. SEQ ID NO:42 is found at nucleotide positions
34954-35998, which includes SEQ ID NO:79. At least a portion of
SEQ ID NO:42 in stain 85/2082 would be amplified by this primer.
Requester does not identify a specific primer pair in the ’507 patent or Ito
that would have made it obvious to have selected SEQ ID NOs 64 and 79 to have
amplified a right extremity region. As indicated above, primer 79 (35953 to
35981) is about 31,000 bases, or 31 kb, away from chromosomal primer 64 (67932
to 67914). Requester did not articulate a reason for choosing such primers to have
amplified a 31 kb region.
Requester also contends that, as shown in Alignment 3, “some of the primers
of the ’289 patent (including SEQ ID NO:79 of claim 3) are found in the same
region as the Nmec primers of the ’507 patent,” making it obvious to have selected
primers from this region to produce an amplicon according to the claim. TPR
Appeal Br. 11-12, 13.
Requester’s explanation is inadequate. Alignment 3 contains aligned
sequences 85/2082, HDG, and D86934. The Nmec sequences depicted in
Alignment 3 are from D86934. D86934 is strain N315. We therefore understand
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

35

Requester to be arguing that the Nmec primers in strain N315 are in the same
region of the type IV strain of the ’289 patent from which SEQ ID NOs 64 and 79
were selected. Significantly, Requester did not identify which sequence in
Alignment 3 corresponds to a type iv strain of the ’289 patent. However, HDG
shown in Alignment 3 is apparently a type iv strain. Request 85.
Requester also did not explain Alignment 3. Consequently, we copied
portions of the sequence where the primers are identified to reside. It is evident
from these copied portions, as shown below, that there are numerous differences
between HDG and D86934:
On page 6 of Alignment 3:
[1]

[2]

On page 7:
[3]

[4]
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

36

On page 8:
[5]

On page 9:
[6]

[7]

Despite these numerous differences in sequence between HDG and D86934,
Requester argued “some of the primers of the ‘289 patent (including SEQ ID
NO:79 of claim 3) are found in the same region as the Nmec primers of the ‘507
patent.” TPR Appeal Br. 11-12 (emphasis added). When there are significant
differences in sequence between HDG and D86934 in the region where the Nmec
primers are found, it is not clear how these regions can be characterized as “the
same region.” Requester has not offered a reasonable explanation. Consequently,
Requester’s logic that it would have obvious have chosen SEQ ID NO:79 from this
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

37

“same region” is not credible because the regions have not been shown by a
preponderance of the evidence to be the same.
Furthermore, as indicated above, primer 79 is about 31 kb, away from
chromosomal primer 64 in strain 85/2082. This region includes the MREJ
junction, but it has not been established that the amplicon produced using these
primers to amplify DNA from 85/2082 comprises a MREJ region sequence
indicative of MREJ type iv as recited in claim 3.

Claim 4
Claim 4 is drawn to the method of claim 1, “further comprising detecting the
presence of SEQ ID NO: 172 as indicative of the presence of MREJ type x.” SEQ
IDS NO: 172 is downstream and to the right of the integration site of the SCCmec
insert, i.e., in the chromosomal DNA at the MREJ. ’289 patent, col. 18. ll. 48-56.
Requester argues it is not necessary that any of the cited publications disclose
detection of SEQ ID NO. 172. TPR Appeal Br. 9. “One of the skill in the art
using the same strategy and methods as explicitly disclosed in any of the cited
references would detect a sequence of SEQ ID NO: 172 if it was present in a strain
using primers in accord with the disclosure of the ’507 patent, Ito, and Oliveira
2001.” Id. Requester has not specifically identified primers in the ’507 patent and
Ito that would amplify an MREJ region comprising sequence 172 or a reason for
choosing such primers.
With respect to strain N315, Requester contends that “using a primer
downstream of mecA and a primer on the MSSA chromosomal side as taught by
the ’507 patent or Ito could produce an amplicon containing a sequence with 96%
sequence identity with SEQ ID NO:172, because N315 contains such a sequence
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

38

near to and downstream of orfX.” TPR Appeal Br. 13. Requester did not explain
how a sequence with 96% identity to SEQ ID NO: 172 satisfies the limitation of
claim 4 of “further comprising detecting the presence of SEQ ID NO: 172 as
indicative of the presence of MREJ type x.” The claim requires detecting SEQ ID
NO: 172, not a sequence with 96% identity to it.
In sum, we affirm the Examiner’s determination not to adopt Rejections 11
and 12.
REJECTION 15
Requester contends that the Examiner erred in not rejecting claims 1-5 as
obvious in view of Oliveira 2000, the ’507 patent, or Hiramatsu. We assume “or”
is used to indicate that either the ’507 patent or Hiramatsu 1996 can be relied upon
for the same teachings.

Claim 1
We have already found claim 1 to be anticipated by Oliveira 2000 since
there is a limited number of primers disclosed in it, and one of ordinary skill in the
art would have envisaged using the primer set which amplifies the second
occurrence of IS431 which is 2kb away from the insertion point of the SCCmec
and thus, absent evidence to the contrary, resides in the MREJ region.
Accordingly, we need not reach the Examiner’s decision not to adopt the rejection
of claim 1.

Claim 2
Claim 2 is directed to the method of claim 1, further comprising at least two
primers which amplify the MREJ region sequence of any one of recited list of
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

39

sequences. Requester has not provided any arguments as to why the subject matter
of claim 2 would have been obvious in view of Oliveira 2000, the ’507 patent, or
Hiramatsu. Since Requester did not identify an error in the Examiner’s factual
findings or reasoning, we affirm the Examiner’s decision not reject claim 2 as
obvious.

Claim 3
Requester contends that it would have been obvious to have chosen primers
having SEQ ID NOS. 64 and 79 from strain 85/2082 which is said to be disclosed
in the ’507 patent. TPR Appeal Br. 13. This argument has already been
considered and found to be unpersuasive. Since Requester did not identify an error
in the Examiner’s factual findings or reasoning, we affirm the Examiner’s decision
not reject claim 3 as obvious.

Claim 4
Claim 4 involves primers for detecting SEQ ID NO:172. Requester states
that it would have been obvious to one of ordinary skill in the art to detect a
sequence with 96% identity to sequence 172. TPR Appeal Br. 15. This argument
is not persuasive since the claim requires primers for sequence 172, not sequences
with 96% identity to it. Since Requester did not identify an error in the Examiner’s
factual findings or reasoning, we affirm the Examiner’s decision not reject claim 4
as obvious.

Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

40

Claim 5
Claim 5 appears to be of the same scope of claim 1, but further comprising
“determining” which of the recited sequences is present in the sample. Oliveira
2000 describes determining the sequence of different regions within the MRSA
bacterial strains. Consequently, we agree that the Examiner erred in not rejecting
claim 5 as obvious in view of Oliveira 2000.

SUMMARY
Appeal
Rejections 1-3 of claims 1, 2, and 5 are reversed.
Rejection 4 of claim 1 is affirmed; Rejection 4 of claim 2 is reversed
Rejection 5 of claims 1, 2, and 5 is reversed.
Claim 1 stands rejected. Claims 2 and 5 are not rejected.

Cross-Appeal
The Examiner’s decision not to adopt Rejections 8-14 and 16 involving
claims 1-5 is affirmed.
The Examiner’s decision not to adopt Rejection 15 of claim 5 is reversed.
The Examiner’s decision not to adopt Rejection 15 of claims 2-4 is affirmed.
Claims 2, 3, and 4 are not rejected.
Claim 5 is rejected under a new ground of rejection.

TIME PERIOD FOR RESPONSE; NEW GROUND OF REJECTION
37 C.F.R. § 41.77(a) states that “[t]he reversal of the examiner’s
determination not to make a rejection proposed by the third party requester
constitutes a decision adverse to the patentability of the claims which are subject to
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

41

that proposed rejection which will be set forth in the decision of the Board of
Patent Appeals and Interferences as a new ground of rejection.” Accordingly, for
the reasons given above, we enter the following new grounds of rejection: Claims
1 and 5 as obvious in view of Oliveira 2000, the ’507 patent, and Hiramatsu 1996,
with the evidence of Alignments 2 and 3, and Sambrook.
This decision contains new grounds of rejection pursuant to 37 C.F.R.
§ 41.77(b) which provides that “[a]ny decision which includes a new ground of
rejection pursuant to this paragraph shall not be considered final for judicial
review.” Accordingly, no portion of the decision is final for purposes of judicial
review. A requester may also request rehearing under 37 C.F.R. § 41.79, if
appropriate, however, the Board may elect to defer issuing any decision on such
request for rehearing until such time that a final decision on appeal has been issued
by the Board.
For further guidance on new grounds of rejection, see 37 C.F.R. § 41.77(b)-
(g). The decision may become final after it has returned to the Board. 37 C.F.R.
§ 41.77(f).
37 C.F.R. § 41.77(b) also provides that the Patent Owner, WITHIN ONE
MONTH FROM THE DATE OF THE DECISION, must exercise one of the
following two options with respect to the new grounds of rejection to avoid
termination of the appeal as to the rejected claims:
(1) Reopen prosecution. The owner may file a response requesting
reopening of prosecution before the examiner. Such a response must be either an
amendment of the claims so rejected or new evidence relating to the claims so
rejected, or both.
(2) Request rehearing. The owner may request that the proceeding be
reheard under § 41.79 by the Board upon the same record. …
Any request to reopen prosecution before the examiner under 37 C.F.R.
§ 41.77(b)(1) shall be limited in scope to the “claims so rejected.” Accordingly, a
request to reopen prosecution is limited to issues raised by the new ground(s) of
rejection entered by the Board. A request to reopen prosecution that includes
issues other than those raised by the new ground(s) is unlikely to be granted.
Furthermore, should the patent owner seek to substitute claims, there is a
presumption that only one substitute claim would be needed to replace a cancelled
claim.
A requester may file comments in reply to a patent owner response.
37 C.F.R. § 41.77(c). Requester comments under 37 C.F.R. § 41.77(c) shall be
limited in scope to the issues raised by the Board's opinion reflecting its decision
Appeal 2014-002900
Reexamination Control 95/001,599
Patent 7,449,289 B2

42

to reject the claims and the patent owner's response under paragraph 37 C.F.R.
§ 41.77(b)(1). A newly proposed rejection is not permitted as a matter of right. A
newly proposed rejection may be appropriate if it is presented to address an
amendment and/or new evidence properly submitted by the patent owner, and is
presented with a brief explanation as to why the newly proposed rejection is now
necessary and why it could not have been presented earlier.
Compliance with the page limits pursuant to 37 C.F.R. § 1.943(b), for all
patent owner responses and requester comments, is required.
The examiner, after the Board’s entry of a patent owner response and
requester comments, will issue a determination under 37 C.F.R. § 41.77(d) as to
whether the Board’s rejection is maintained or has been overcome. The
proceeding will then be returned to the Board together with any comments and
reply submitted by the owner and/or requester under 37 C.F.R. § 41.77(e) for
reconsideration and issuance of a new decision by the Board as provided by
37 C.F.R. § 41.77(f).

AFFIRMED IN PART; 41.77(B)

alw

Patent Owner:

Ned A. Israelsen
KNOBBE, MARTENS, OLSON & BEAR LLP
12790 El Camino Real
San Diego, CA 92130

Third Party Requester:

Katherine M. Kowalchyk
MERCHANT & GOULD, P.C.
Representative for Beckman Coulter, Inc.
P.O. Box 2903
Minneapolis, MN 55402-0903