Ex Parte Nazarenko

Patent Trial and Appeal Board

Aug 29, 2016

13016004 (P.T.A.B. Aug. 29, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/016,004 01/28/2011
84538 7590
MMWVIP,LLC
10 N JEFFERSON ST
SUITE 100
FREDERICK, MD 21707
08/31/2016
FIRST NAMED INVENTOR
Irina Nazarenko
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. CONFIRMATION NO.
2912943-069001 3681
EXAMINER
CHUNDURU, SURYAPRABHA
ART UNIT PAPER NUMBER
1637
NOTIFICATION DATE DELIVERY MODE
08/31/2016 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):
docketing@mmwvlaw.com
cgmoore@mmwvlaw.com
dwoodward@mmwvlaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte IRINA NAZARENK0 1
Appeal2014-008020
Application 13/016,004
Technology Center 1600
Before FRANCISCO C. PRATS, JACQUELINE T. HARLOW,
and TIMOTHY G. MAJORS, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of genotyping nucleic acids, and especially for genotyping target nucleic
acids for human papillomavirus ("HPV"). The claims have been rejected as
anticipated. We have jurisdiction under 35 U.S.C. § 6(b ).
We reverse.
STATEMENT OF THE CASE
"The present disclosure relates to methods ... for determining and
confirming the presence of target nucleic acid in a sample and genotyping
1 Appellant identifies the Real Party in Interest as Qiagen Gaithersburg, Inc.
(App. Br. 3.)
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Application 13/016,004
the target nucleic acid." (Spec. i-f 2.) "Where abnormal cytological
examinations of samples are observed, it is often beneficial to determine
whether the tissue is infected with human papillomavirus (HPV) associated
with cervical cancer." (Id. at i-f 4.) According to the Specification, "it would
be beneficial to develop materials and methods for performing [HPV
genotyping] ... with reduced [sample] volume." (Id. i-f 5.)
Claims 1-14 are on appeal. Claim 1 is the only independent claim:
1. A method for genotyping a target nucleic acid in a sample
is provided comprising:
(a) generating a first detection mixture by a method
comprising contacting a portion of the sample with a first probe
set, wherein the first probe set comprises a nucleic acid probe
specific for a first genotype of the target nucleic acid and a
nucleic acid probe specific for a second genotype of the target
nucleic acid, but does not comprise a nucleic acid probe specific
for a third genotype of the target nucleic acid;
(b) generating a second detection mixture by a method
comprising contacting a portion of the sample \~1ith a second
probe set, wherein the second probe set comprises a nucleic acid
probe specific for the second genotype of the target nucleic acid
and a nucleic acid probe specific for the third genotype of the
target nucleic acid, but does not comprise a nucleic acid probe
specific for the first genotype of the target nucleic acid; and
( c) treating the first and second detection mixtures under
conditions wherein the nucleic acid probes hybridize specifically
to the first, second, and/ or third genotype of the target nucleic
acid; and
( d) detecting hybridization of the nucleic acid probe to the
target nucleic acid, wherein:
(i) hybridization in the first detection mixture, but
not the second detection mixture indicates that the sample
comprises the first genotype of the target nucleic acid;
(ii) hybridization in the second detection mixture,
but not the first detection mixture, indicates that the
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Application 13/016,004
sample comprises the third genotype of the target nucleic
acid; and
(iii) hybridization in the first detection mixture and
the second detection mixture indicates that the sample
comprises the second genotype of the target nucleic acid.
(App. Br. 13 (Claims App'x).)
The claims stand rejected as follows:
Claims 1--4, 6, 7, and 11-13 as anticipated under 35 U.S.C. § 102(b)
by Anthony. 2
Claims 1--4 and 6-14 as anticipated under 35 U.S.C. § 102(b) by
N azarenko I. 3
Claims 1-14 as anticipated under 35 U.S.C. §§ 102(a) and (e) by
N azarenko II. 4
DISCUSSION
The issues for each of the three anticipation rejections is similar: Has
the Examiner established by a preponderance of the evidence that Anthony,
Nazarenko I, or Nazarenko II anticipate the claimed methods? For the
reasons discussed below, we conclude the answer is no and thus reverse.
Anticipation of Claims 1-4. 6. 7. and 11-13 by Anthony
In order to compare the claims to the prior art, we begin with claim
construction. During prosecution, we give claim terms the broadest
2 Anthony et al., US 7,439,016 Bl, issued Oct. 21, 2008 ("Anthony").
3 Nazarenko et al., US 2006/0051809 Al, published Mar. 9, 2006
("Nazarenko I").
4 Nazarenko, US 2009/0298187 Al, published Dec. 3, 2009 ("Nazarenko
II").
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Application 13/016,004
reasonable interpretation as understood by a person of ordinary skill in the
art in light of the specification - this interpretation is informed by
"whatever enlightenment by way of definitions or otherwise may be
afforded by the written description contained in the applicant's
specification." In re Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997).
Claim 1 recites a method for genotyping a target nucleic acid in a
sample. Claim 1 requires, inter alia, "generating" first and second detection
mixtures from the sample. In other words, and consistent with the
Specification, the sample is separated into first and second detection
mixtures. (See, e.g., Spec. i-f 47 ("After the sample comprising the nucleic
acid is prepared for hybridization, it is separated into two aliquots, each of
which is contacted with a probe set ... ".)
In addition, each detection mixture of claim 1 is contacted with a
unique probe set. In the first detection mixture, the probe set includes
probes specific for a first and second genotype of the target nucleic acid, but
no probe for the third genotype. In the second detection mixture, the probe
set includes probes specific for the second and third genotype of the target
nucleic acid, but no probe for the first genotype. Claim 1 thus requires
overlapping (i.e., probes for the second genotype), but non-identical probe
sets in the first and second detection mixtures.
With these interpretations in mind, we tum to whether Anthony
anticipates claim 1 by disclosing each of the limitations in the same manner
as claimed. Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed.
Cir. 2008) ("[U]nless a prior art reference discloses within the four comers
of the document not only all of the limitations claimed but also all of the
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Application 13/016,004
limitations arranged or combined in the same way as recited in the claim, it
cannot be said to prove prior invention of the thing claimed and, thus, cannot
anticipate under 35 U.S.C. § 102.")
The Examiner, citing Example 13 and Tables 23 and 24 of Anthony,
finds that Anthony teaches the method of claim 1. (Ans. 2.) More
particularly, the Examiner finds "example 13 of Anthony et al. discloses use
of four specific probe sets for genotyping HPV 16, HPVl 8, HPV31 and
HPV 45, wherein each probe set comprises a CSP [capture sequence probe]
and an SSP [signal sequence probe]." (Id. at 6.) Moreover, according to the
Examiner, Anthony discloses "table 23 and 24, wherein HPVl 8/HPV 45
mixture of probe sets were used, which can be interpreted as a first detection
mixture comprising first probe set for HPVl 8 and a second probe set for
HPV45." (Id. at 6-7) The Examiner further finds "example 13 requires a
third probe set HPVl 6 and a fourth probe set HPV 31, thus the example 13
encompasses a second detection mixture which includes a combination of
second probe set HPV 45 and a third probe set HPVl 6; and a third detection
mixture which includes second probe set HPV 45 and a fourth probe set
HPV31 and any additional detection mixtures .... " (Id. at 7 .)
Appellant counters that Anthony does not disclose generating the
detection mixtures as recited in claim 1. (App. Br. 6-7; Reply Br. 5---6.)
Appellant contends that "Example 13 of Anthony demonstrates that 'capture
sequence probes' designed to be specific for HPV18 do not cross-react with
HPV45, and vice versa." (App. Br. 6.) Moreover, according to Appellant,
in Anthony"[ e Jach reaction mixture contains a single 'capture sequence
probe' and a single 'signal sequence probe' specific for the same target
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Application 13/016,004
nucleic acid." (Id. at 7.) Appellant further argues the Examiner's
interpretation of Tables 23 and 24 as teaching a "first detection mixture"
having probe sets for both HPVl 8 and HPV 45 is incorrect. That is not
possible, according to Appellant, because the concentrations ofHPV18 and
HPV 45 are different in the experiment of Table 23 versus the experiment
illustrated in Table 24. (Id. at 6) ("the Examiner's assertion ... is refuted by
the impossibility of a mixture simultaneously containing 10 pg/ml and 4
ng/ml ofHPV18 DNA-or, alternatively, HPV DNA.".)
Appellant has the better position. We are not persuaded that Anthony
teaches separating a nucleic acid sample into two (or more) detection
mixtures in the same way as claimed. Anthony discloses "[i]n this study [of
Example 13], the ability of the two methods to detect HPV18 and HPV45
was assessed using HPV18 and HPV45 plasmid DNA." (Anthony col. 25,
11. 24--26.) As Appellant correctly points out, each reaction mixture of
Anthony includes probes specific for one HPV genotype. (App. Br. 6; Reply
Br. 5.) For example, the experiment illustrated in Table 23 uses CSP and
SSP probes specific for HPVl 8 - confirming that these probes are highly
specific and sensitive to HPV18 with low cross-reactivity with HPV45.
(Anthony col. 47---67 .) Also, although Table 24 teaches use of SSP and CSP
probes specific for HPV 45, Anthony does not teach a single detection
mixture that includes probes for both HPVl 8 and HPV 45 - the mixtures in
Table 23 and 24 are different as illustrated by the different concentrations of
HPVl 8 and HPV45. Insofar as the Examiner finds the mixtures and probes
in Table 23 are somehow combined with the mixtures and probes in Table
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24 to satisfy the "first detection mixture" of claim 1, that finding is not
consistent with the teachings of Anthony.
The Examiner's finding that Anthony teaches a "second detection
mixture" that includes probes for both HPV 45 and HPVl 6 also lacks
support. (Ans. 7.) Anthony states that "[c]apture sequence probes (CSPs)
for each of the four [HPV] types: HPV16, HPV18, HPV31, and HPV45,
were designed" (Anthony, col. 25, 11. 27-29), but Anthony does not provide
any specific details of testing ofHPV types other than HPV18 and HPV45.
Even if one assumed that mixtures such as described in Tables 23 and 24
were designed to test sensitivity and cross-reactivity ofHPV16 (as opposed
to HPVl 8) and HPV 45, there would remain inadequate evidence to show a
single mixture including probes for both HPV16 and HPV45. Quite the
opposite, these would be different mixtures, each containing probes specific
for either HPVl 6 or HPV 45 respectively, just as discussed above.
In sum, claim 1 requires generating first and second detection
mixtures from a nucleic acid sample, where the detection mixtures have
overlapping but non-identical probe sets. Anthony does not teach these
steps and thus does not anticipate claim 1. Because Anthony does not teach
all the limitations of claim 1, it also cannot anticipate claims 2--4, 6, 7, and
11-13, which all depend (directly or indirectly) from claim 1.
Anticipation of Claims 1-4. 6-14 by Nazarenko I
The Examiner finds that Examples 6 and 12 ofNazarenko I teach all
the limitations of claim 1. (Ans. 2-3.) The Examiner further finds that
table 1 [of Nazarenko I] indicates use of different mixtures of
probe sets and . . . each Luminex bead comprises a set of two
probes (CSP and SSP) for same target and utilizes different
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Application 13/016,004
mixtures of probe sets for 13 HPV types which includes any
combination of probe sets, such as HPV 45/HPV 18;
HPV 45/HPVl 6; or HPV 45/HPV 31.
(Id. at 7-8.)
Appellant argues the portions ofNazarenko cited by the Examiner
relate to two assay methods - one involving Luminex beads, and the other
involving a 96-well NucleoLink plate-neither of which is the same as
claim 1. (App. Br. 8-9 (describing Example 6 and 12 ofNazarenko I).)
Critically, according to Appellant, neither method ofNazarenko I teaches
that a "sample should first be separated into two different portions ... or
suggest contacting the different portions of the same purified and amplified
sample with overlapping, but not identical, probe cocktails." (Id. at 9.) To
the contrary, Appellant contends the first method uses "a cocktail of probes
specific for 13 HPV types ... Luminex[] beads specific for each of the 13
HPV types [are] added to the amplified sample and allov,red to hybridize to
the targets." (Id. at 8.) And, in the second method, Appellant contends
"[ e Jach well of the 96-well plate is coated with two oligonucleotides
complementary to the late and early regions of a single HPV type" and
"[s]amples are added to the wells to permit hybridization." (Id. at 9)
Here again, Appellant has the better position. Table 1 ofNazarenko I,
which the Examiner cites, identifies capture sequence probes for different
HPV types, but does not clearly disclose "use of different mixtures of probe
sets" in the assays that the Examiner otherwise relies upon to show
anticipation-Example 6 and Example 12. Nor does the Examiner clearly
identify in either Example 6 or 12 the claimed first and second detection
mixtures prepared from a sample, where each mixture includes partially
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overlapping probe sets. Appellant, on the other hand, has persuasively
argued that the cited examples in Nazarenko I use probes specific to
individual (non-overlapping) HPV types. (App. Br. 7-9; Reply Br. 6-7.) In
short, we are not persuaded that Nazarenko I teaches the claimed steps of
generating first and second detection mixtures from one sample, where each
detection mixture has different, yet partially overlapping probe sets as
required in claim 1.
For these reasons, we conclude the Examiner did not establish by a
preponderance of the evidence that claims 1--4 and 6-14 are anticipated by
N azarenko I.
Anticipation of Claims 1-14 by Nazarenko 115
The Examiner finds that Nazarenko II teaches all the limitations of
claim 1. (Ans. 4 (citing Nazarenko II at i-fi-159-61, 146-166).) According to
the Examiner,
the cited portion teach combination of probe sets, such as HPV
45/HPV 18, HPV 45/HPVl 6, or HPV 45/HPV 31. The TSHC
analysis detects specific type of HPV depending on the type of
HPV target present in the sample. Second, as discussed in the
rejection detection mixture comprises a combination of probe
sets, wherein each probe set specific for each HPV type
comprises capture and signal probes as opposed to the
Applicants' arguments drawn to capture and signal probes as a
combination of HPV probe sets.
(Id. at 8.)
5 The Examiner rejected these claims under both §102(a) and §102(e). We
address the rejections together on appeal.
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We are not persuaded. Instead, we agree with Appellant that the
portions of N azarenko II cited by the Examiner appear to relate to general
hybridization of nucleic acids (N azarenko II i-fi-1 59---61) and testing for cross-
reaction (id. at i-fi-f 144--165). We further find persuasive Appellant's
argument that "[n]othing [in the cited portions ofNazarenko II] indicates
that the sample should first be separated into two different portions, nor is
there a suggestion to contact different portions of the same sample with
overlapping, but not identical, probe cocktails." (App. Br. 10.) The
Examiner has not satisfied the burden to demonstrate by a preponderance of
the evidence that N azarenko II teaches each limitation of claim 1. We thus
reverse the rejection of claim 1-14 by Nazarenko II.
SUMMARY
We reverse the rejection of: (i) claims 1--4, 6, 7, and 11-13 as
anticipated under 35 U.S.C. § 102(b) by Anthony; (ii) claims 1--4 and 6-14
as anticipated under 35 U.S.C. § 102(b) by Nazarenko I; and (iii) claims 1-
14 as anticipated under 35 U.S.C. § 102(a) and§ 102(e) byNazarenko II.
REVERSED
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