Ex Parte Fort

Patent Trial and Appeal Board

May 18, 2018

14568855 (P.T.A.B. May. 18, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/568,855 12/12/2014 Thomas L. Fort
147462 7590 05/22/2018
Botos Churchill IP Law LLP
430 Mountain A venue
Suite 401
New Providence, NJ 07974
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
ATTORNEY DOCKET NO.
BECTON 3.3-077 CON
CON(E
CONFIRMATION NO.
3545
EXAMINER
HORLICK, KENNETH R
ART UNIT PAPER NUMBER
1637
NOTIFICATION DATE DELIVERY MODE
05/22/2018 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
rbotos@bciplaw.com
ip.docket@bd.com
pto@bciplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Exparte THOMAS L. FORT
Appeal2017-005239
Application 14/568,855
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
JOHN G. NEW, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to kits for
an amplification or detection reaction and a method fbr detecting the
presence or absence of Cytomegalovin1s (ClVlV) in a sample. The Examiner
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
Statement of the Case
Background
Cytomegalovirus (CMV) is a member of the herpes virus
family, which includes among others herpes simplex virus types
1 and 2, varicella-zoster virus and Epstein-Barr virus. Between
1 Appellant identifies the Real Party in Interest as Becton, Dickinson and
Company (see App. Br. 1 ).
Appeal2017-005239
Application 14/568,855
50% and 85% of adults in the United States are infected by this
virus by 40 years of age .... Once infected, the virus remains
alive, but dormant within the infected individual's body for life.
. . . CMV remains the most important cause of congenital viral
infection in the United States and is an important cause of
morbidity and mortality in certain high-risk groups, such as
neonates and immunocompromised and immunosuppressed
patients.
(Spec. ,r 4). The Specification teaches a "need, therefore, exists for a rapid
and sensitive means of detecting CMV in clinical samples" (Spec. ,r 6). The
Specification teaches "a kit" and a "method for detecting the presence or
absence of Cytomegalovirus (CMV) in a sample" (Spec. ,r,r 8-9).
The Claims
Claims 1-12 are on appeal. Claims 1 and 5 are representative and
read as follows:
1. A kit for an amplification or detection reaction comprising:
a first amplification primer comprising a target binding sequence
selected from the group consisting of the target binding sequences of
SEQ ID NOs. 1 and 2; and a second amplification primer comprising
a target binding sequence selected from the group consisting of the
target binding sequences of SEQ ID NOs. 3, 4 and 5; and a detector
probe, wherein the detector probe comprises a sequence that is
capable of hybridizing to an amplified target sequence provided by the
first amplification primer and the second amplification primer tagged
with a moiety that is detectable.
5. A method for detecting the presence or absence of
Cytomegalovirus (CMV) in a sample, the method comprising
performing polymerase chain reaction (PCR) on sample nucleic acids
wherein the PCR comprises: (a) hybridizing (i) a first amplification
primer having a sequence selected from the group consisting of the
target binding sequences of SEQ ID NOs: 1 and 2 and (ii) a second
amplification primer having a sequence selected from the group
consisting of the target binding sequences of SEQ ID NOs: 3, 4 and 5,
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Application 14/568,855
to a target sequence; (b) amplifying the target sequence; and ( c)
detecting the amplified target sequence.
The Issue
The Examiner rejected claims 1-12 under 35 U.S.C. § 103(a) as
obvious over Aquino, 2 Paoletti, 3 and Rychlik4 (Ans. 2-3).
The Examiner finds that Aquino teaches "oligonucleotide primers and
their use in PCR amplification for detection of CMV, said primers targeting
the glycoprotein H gene (gH)" (Ans. 2).
The Examiner finds that Paoletti teaches "a CMV glycoprotein H gene
nucleotide sequence which contains within it the target binding sequences of
instant SEQ ID NO: 1-5. See Paoletti et al. SEQ ID NO: 188, within
nucleotides 1381-1450" (Ans. 3). The Examiner finds that Paoletti suggests
"the disclosed CMV nucleotide sequence is useful for generating probes or
primers for detecting and amplifying CMV nucleic acid in a sample (see
column 21, lines 45-49)" (Ans. 3).
The Examiner finds that Rychlik teaches that "at the time of the
instant invention, the skilled artisan was well aware of the various criteria to
use in selecting useful oligonucleotide probes and primers based on known
nucleotide sequences (see entire reference on pages 8543-8551 )" (Ans. 3).
2 V.H. Aquino and L.T.M. Figueiredo, Cytomegalovirus infection in renal
transplant recipients diagnosed by nested-PCR, 34(1) Brazilian J. Medical
Biol. Res. 93-101 (2001) (hereinafter "Aquino").
3 Paoletti et al., US 5,997,878, issued Dec. 7, 1999 (hereinafter "Paoletti").
4 Wojciech Rychlik and Robert E. Rhoads, A computer program for
choosing optimal oligonucleotides for filter hybridization, sequencing and in
vitro amplification of DNA, 17 (21) Nucleic Acids Res. 8543-8551 (1989)
(hereinafter "R ychlik").
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Application 14/568,855
The Examiner finds it obvious "to make and use oligonucleotides
having the CMV target binding sequences required in the claims" (Ans. 3).
The Examiner finds that "the skilled artisan was aware of the CMV
glycoprotein H gene sequence by which any number of primers and probes
suitable for various amplification procedures like PCR would have been
routinely and predictably designed, and used with reasonable expectation of
success" (Ans. 3).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that the combination of Aquino,
Paoletti, and Rychlik render the claims obvious?
Findings of Fact
1. Aquino teaches "nested-PCRs were carried out using 2 primer
sets that recognize part of the glycoprotein B (gB) and H (gH) genes"
(Aquino 95, col. 1 ).
2. Aquino teaches "[b ]oth nested-PCRs used for CMV detection
were highly sensitive as compared to the observation of cytopathic effects in
tissue culture" (Aquino 96, col. 1 ).
3. Paoletti teaches that the DNA from recombinant poxvirus can
be used to generate PCR probes and primers, specifically teaching the
"recombinant poxvirus DNA is useful for probes for CMV or HCMV or for
preparing PCR primers for detecting the presence or absence of CMV or
HCMV or antigens thereof' (Paoletti 2:1--4; cf abstract, 10:40--45; 21:45-
50).
4. Paoletti teaches the "sequence of HCMV gH lacking its
transmembrane region and cytoplasmic tail is presented in FIG. 67 (SEQ ID
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Application 14/568,855
NO: 188)" (Paoletti 94:40-50; cf Sequence listing present from cols. 295-
298).
5. The Examiner identifies nucleotides 13 81-1450 of SEQ ID
NO: 188 as the sequences that SEQ ID NO: 1-5 will bind (see Ans. 3).
6. Rychlik teaches:
A method is presented for choosing optimal
oligodeoxyribonucleotides as probes for filter hybridization,
primers for sequencing, or primers for DNA amplification.
Three main factors that determine the quality of a probe are
considered: stability of the duplex formed between the probe
and target nucleic acid, specificity of the probe for the intended
target sequence, and self-complementarity.
(Rychlik 8543, abstract).
7. Rychlik evidences that at the time of the invention the skilled
artisan was well aware of the various criteria to use in selecting useful
oligonucleotide probes and primers based on known nucleotide sequences
and teaches that a computer program selects primers (see Rychlik 8543; cf
8549).
Principles of Law
An "obviousness finding was appropriate where the prior art
'contained detailed enabling methodology for practicing the claimed
invention, a suggestion to modify the prior art to practice the claimed
invention, and evidence suggesting that it would be successful. "' In re
Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re O'Farrell, 853
F.2d 894, 902 (Fed. Cir. 1988). The court commented that "[r]esponding to
concerns about uncertainty in the prior art influencing the purported success
of the claimed combination, this court [ in O 'Farrell] stated: ' [ o ]bviousness
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does not require absolute predictability of success ... all that is required is a
reasonable expectation of success."' Kubin, 561 F.3d at 1360 (citing In re
O'Farrell, 853 F.2d at 903-904).
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 2-3; FF 1-7) and agree with the
conclusion that the claims are obvious over Aquino, Paoletti, and Rychlik.
Aquino teaches nested PCR amplification and sequencing of the gH
gene of CMV (FF 1-2). Paoletti teaches that DNA from recombinant
poxvirus can be used to generate PCR probes and primers, teaches that one
of these recombinant poxviruses is SEQ ID NO: 188, and teaches the
sequence of SEQ ID NO: 188. (FF 3-5). Rychlik teaches the routine nature
of primer selection for PCR (FF 6-7).
We agree with the Examiner's finding that "the skilled artisan was
aware of the CMV glycoprotein H gene sequence by which any number of
primers and probes suitable for various amplification procedures like PCR
would have been routinely and predictably designed, and used with
reasonable expectation of success" (Ans. 3).
In comparing the obviousness of the instant primers and probes to the
NAIL nucleic acid at issue in Kubin, we note that the instant obviousness
case is better than that in Kubin. Unlike in Kubin where the NAIL sequence
was unknown, the complete region of gH sequence from which the instant
primers and probes were selected was disclosed in Paoletti and was
suggested as a target for primer and probe selection by Paoletti and Aquino
(FF 1-5). The method of using the primers and probes in PCR reactions was
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well known in the art (FF 6-7). Thus, we conclude that it is more than
reasonable to find that selection of particular PCR primer and probe
sequences from a known sequence "would have had a resoundingly
'reasonable expectation of success' in deriving the claimed invention in light
of the teachings of the prior art." Kubin, 561 F.3d at 1360.
Appellant does not identify any teaching in the Specification
suggesting any criticality to the particular primers exemplified, nor does
Appellant identify any comparative data or other evidence to show any
unexpected results for the particular primers of SEQ ID NO: 1-5 relative to
other primers selected from the CMV gH gene.
Appellant contends that Paoletti does not disclose "a useful target site
for CMV detection" and "cannot be fairly characterized to one skilled in the
art as providing any guidance whatsoever on the selection of primers for the
amplification and detection of CMV using the portion of the gH gene
targeted by the assay" (App. Br. 5; see also Reply Br. 4).
We are not persuaded. Paoletti discloses the gene sequence and states
that primers and probes can be made from poxviruses such as SEQ ID NO:
188 (FF 3--4). Although Paoletti discloses a long sequence, it is expected
that one would be able to select primers and probes from a disclosed
sequence given the guidance in Rychlik (FF 6-7). In Merck, the court found
that prior art disclosing 1200 "effective combinations does not render any
particular formulation less obvious. This is especially true because the
claimed composition is used for the identical purpose taught by the prior
art." Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir.
1989). Here, the obvious primers would have been used for PCR of CMV
(FF 1).
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Appellant contends that Aquino requires two targets: gH and gB, and
Appellant discovered that only gH is needed for reliable detection,
specifically contending "Aquino et al. requires two target regions.
Therefore, Applicant has discovered a target region of the glycoprotein H
gene that, alone, provides for the reliable detection of CMV. This is
contrary to what is taught in Aquino et al. (i.e., that reliable detection
requires two genes targets)" (App. Br. 4--5; Reply Br. 3).
We are not persuaded. Aquino provides motivation for developing
primers for gH and teaches creating primers which bind to gH in order to
detect CMV. While Aquino also teaches creating primers for gB, the claims
are not limited to only detecting gH. Moreover, we agree with the Examiner
(see Ans. 4) that the use of the open "comprising" language in claims 1 and
5 does not exclude the presence of other primers including gB primers. See
Georgia-Pacific Corp. v. US. Gypsum Co., 195 F.3d 1322, 1327 (Fed. Cir.
1999) (The transitional term "comprising" is "inclusive or open-ended and
does not exclude additional, unrecited elements or method steps.")
Even assuming arguendo that Applicant argues that detecting gH is
not the preferred embodiment of Aquino, a reference may be relied upon for
all that it would have reasonably suggested to one having ordinary skill in
the art, including non-preferred embodiments. In re Susi, 440 F.2d 442, 446
n.3 (CCPA 1971). See Merck & Co., 874 F.2d at 807 ("That the [prior art]
discloses a multitude of effective combinations does not render any
particular formulation less obvious.") Here, Aquino also teaches detecting
gH using nested PCR and therefore can be relied upon to teach detecting gH
with PCR.
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Appellant contends that
Paoletti 's suggestion that the pox viruses described in Paoletti
et al. are useful for generating DNA for probes and primers to
detect HCMV ... does not bring the skilled person any closer
to the claimed invention, because Paoletti et al. predates
Aquino et al. and the specific observation in Aquino et al. of the
need for two gene targets (gB and gH) are required for CMV
detection.
(App. Br. 5---6).
We are not persuaded. The length of time and the age of the
references are not persuasive of non-obviousness. See In re Wright, 569
F.2d 1124, 1127 (CCP A 1977). In addition, "where a rejection is predicated
on two references each containing pertinent disclosure ... we deem it to be
of no significance, but merely a matter of exposition, that the rejection is
stated to be on A in view of B instead of on B in view of A, or to term one
reference primary and the other secondary." In re Bush, 296 F.2d 491, 496
(CCPA 1961). Moreover, as explained above, Aquino teaches that gH can
be used for detecting CMV.
Appellant contends that Xie5 "reflects the uncertainties with regard to
primer/probe design at that time" (App. Br. 7).
We find this unpersuasive because Xie at 1 teaches "[ w ]ith help of
commercial bio-software such as Oligo or on-line primer design tools such
as primer3, experienced researchers can pick out optimized primer pairs
under certain parameters to guarantee the efficiency and specificity of
the amplification," thereby indicating that one could use software to pick
primers with a reasonable expectation of success. While Xie states the
5 Xie et al., Primer-Chaperon: An Accessory to PCR primer design, undated
(hereinafter "Xie").
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Application 14/568,855
amplification process is still unpredictable, this refers to the amplification of
an extra, undesired product by the primers, not the failure of the primers to
amplify the desired target. Specifically, Xie states "[ n ]evertheless, the
whole process of primer-template amplification is still unpredictable. The
designed pair could, sometimes, amplify some undesired products,
yielding multiple products and smears observed in gel-electrophoresis" (Xie
at 1, cited on App. Br. 6.). Xie teaches improvements to software to
eliminate amplification of undesired products (see id.). We do not agree
with Appellant's interpretation that Xie teaches choosing primers based on a
known sequence is unpredictable. Moreover, Appellant has not presented
evidence that primers for gH will amplify some undesired products or any
secondary consideration regarding the claimed primers whatsoever.
Appellant contends "Rychlik et al. does not guide the skilled person
on the selection of the assay template. Rychlik et al. 's guidance assumes a
known target, where the OLIGO tool is used to design primers against that
target" (App. Br. 7; cf Reply Br. 4).
We find this argument unpersuasive because Aquino suggests the
CMV gH gene as a target for PCR (FF 1) and Paoletti discloses the known
sequence of the CMV gH gene as well as teaching generating PCR primers
and probes to these targets (FF 3--4 ). We agree with the Examiner that
selecting primers based on the known and desired target sequence of Aquino
and Paoletti based on the parameters and software taught by Rychlik would
have been obvious (FF 6-7; cf Ans. 3).
Appellant contends "the Examiner's conclusion that Aquino et al.
instructs the skilled person to focus an assay on a gH target is only based on
impermissible hindsight, not from the reference itself' (Reply Br. 2).
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We are not persuaded. While we are fully aware that hindsight bias
may plague determinations of obviousness, Graham v. John Deere Co., 383
U.S. 1, 36 (1966), we are also mindful that the Supreme Court has clearly
stated that the "combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield predictable
results." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,416 (2007).
Here, the Examiner has provided specific reasons based on evidence
disclosed in the prior art for obtaining the obvious combination, specifically
relying on Aquino to suggest a reason to make primers to the gH gene,
Paoletti to demonstrate that the gH gene sequence was known, and Rychlik
to teach that primer selection parameters were known, thereby rendering the
primers of claim 1 and method of claim 5 obvious (FF 1-7).
Appellant also contends "Aquino [] teaches that the gB target is better
suited to CM[V] detection than the gH target" (Reply Br. 3).
We are not persuaded. Aquino does not teach away from creating
primers for gH. A teaching away requires a reference to actually criticize,
discredit, or otherwise discourage the claimed solution. See In re Fulton,
391 F.3d 1195, 1201 (Fed. Cir. 2004) ("The prior art's mere disclosure of
more than one alternative does not constitute a teaching away from any of
these alternatives because such disclosure does not criticize, discredit, or
otherwise discourage the solution claimed"). Appellant does not identify,
and we do not find, any teaching in any of the cited prior art that criticizes,
discredits, or discourages the use of detecting gH using primers.
Finally, Appellant contends there are unexpected results (Reply Br. 4--
5). We are not persuaded. Appellant has not shown nor identified evidence
of the unexpected results. "'It is well settled that unexpected results must be
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established by factual evidence. Mere argument or conclusory statements
... [do] not suffice."' In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995).
Conclusion of Law
The evidence of record supports the Examiner's conclusion that the
combination of Aquino, Paoletti, and Rychlik render the claims obvious.
SUMMARY
In summary, we affirm the rejection of claims 1 and 5 under
35 U.S.C. § 103(a) as obvious over Aquino, Paoletti, and Rychlik. Pursuant
to 37 C.F.R. § 4I.37(c)(l), we also affirm the rejection of claims 2--4 and 6-
12 as these claims were not argued separately.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
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