Ex Parte Tabb et al

Patent Trial and Appeal Board

Mar 25, 2016

12116364 (P.T.A.B. Mar. 25, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/116,364 05/07/2008 Michelle M. Tabb
22428 7590 03/29/2016
Foley & Lardner LLP
3000 K STREET N.W.
SUITE 600
WASHINGTON, DC 20007-5109
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.
054769-9931 6936
EXAMINER
BERTAGNA, ANGELA MARIE
ART UNIT PAPER NUMBER
1637
NOTIFICATION DATE DELIVERY MODE
03/29/2016 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):
ipdocketing@foley.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MICHELLE M. TABB,
MING-CHOU LEE, LILLY I. KONG, NING LU,
MICHAEL A YE, FAN CHEN,
and JULES CHEN
Appeal2013-004103 1
Application 12/116,364
Technology Center 1600
Before FRANCISCO C. PRATS, MELANIE L. McCOLLUM, and
JACQUELINE T. HARLOW, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to processes of
identifying the presence or absence of Bordetella pertussis and/or Bordetella
parapertussis in a biological sample. The Examiner finally rejected the
claims for obviousness, and entered a new ground of rejection for
indefiniteness.
We have jurisdiction under 35 U.S.C. § 6(b ). We affirm the
Examiner's obviousness rejections, but reverse the rejection for
indefiniteness.
1 The Real Party in Interest is Quest Diagnostics Investment, Inc. App. Br.
1.
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Application 12/116,364
STATEMENT OF THE CASE
The majority of whooping cough cases are caused by "the small gram-
negative bacteria Bordetella pertussis; however, a significant minority of
cases (2-20%) are caused by Bordetella parapertussis." Spec. i-f 4.
Appellants' invention is directed to determining the presence or absence of
those bacteria in biological samples by detecting target nucleotide sequences
characteristic of those organisms. Id. i-f 61. "In certain embodiments, target
nucleic acids may include the IS481 insertion sequence (and fragments
thereof) from B. pertussis, and the IS 1001 insertion sequence (and fragments
thereof) from B. parapertussis." Id.
The following rejections are before us for review (Ans. 4--13):
(1) Claims 1, 7-10, 13-15, 24, 25, 27, 30-33, 58, 59, 61, and 62,
under 35 U.S.C. § 112, second paragraph (Ans. 4 (new ground of
rejection))2 ;
(2) Claim 25, under 35 U.S.C. § 103(a) for obviousness over Kosters, 3
van der Zee,4 and Lowe5 (Final Action 8-10);
2 This application was filed on May 7, 2008. Accordingly, the versions of
§§ 112 and 103 in effect before the Leahy-Smith America Invents Act
("AIA") apply to the claims on appeal. See AIA, Public Law 112-29, § 4(e),
125 Stat. 297; id. § 3, 125 Stat. 288.
3 Katrin Kosters et al., Real-Time LightCycler PCRfor Detection and
Discrimination of Bordetella pertussis and Bordetella parapertussis, 40 J.
Clin. Microbiol. 1719-1722 (2002) (hereinafter "Kosters").
4 Anneke van der Zee et al., Characterization of !SJ 001. an Insertion
Sequence Element of Bordetella parapertussis, 175 J. Bacteriol. 141-147
(1993) (hereinafter "van der Zee").
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Application 12/116,364
(3) Claims 1, 7, 9, 10, 12, 14, 15, 24, 27, 29, 31-33, 58, 59, and 61-
67, under 35 U.S.C. § 103(a) for obviousness over Kosters, Sloan, 6
GenBank Accession Number M28220 for Bordetella pertussis IS481, 7 van
der Zee, and Lowe (Final Action 10-14); and
(4) Claims 8, 13, 30, 68, and 69, under 35 U.S.C. § 103(a) for
obviousness over Kosters, Sloan, GenBank Accession Number M28220 for
Bordetella pertussis IS481, van der Zee, Lowe, and Whitcombe8 (Final
Action 14--16).
Claims 1, 25, and 27 are representative and read as follows (App. Br.
22-24):
1. A method for identifying the presence or absence
of Bordetella pertussis and/or Bordetella parapertussis in a
biological sample, comprising:
(a) providing a first primer pair suitable for amplifying an
IS481 target nucleic acid comprising the nucleotide
sequence of SEQ ID NO: 3 or a full complement
thereof, and amplifying said IS481 target sequence if
present in the sample,
5 Todd Lowe et al., A computer program for selection of oligonucleotide
primers for polymerase chain reactions, 18 Nucl. Acids Res. 1757-1761
(1990) (hereinafter "Lowe").
6 Lynne M. Sloan et al., Multiplex LightCycler PCR Assay for Detection and
Differentiation of Bordetella pertussis and Bordetella parapertussis in
Nasopharyngeal Specimens, 40 J. Clin. Microbiol. 96-100 (2002)
(hereinafter "Sloan").
7 (4-August-1993 [online], [retrieved on 2010-11-07], retrieved from the
Internet: . (hereinafter "GenBank
Accession Number M28220 for Bordetella pertussis IS481 ").
8 David Whitcombe et al., Detection of PCR products using self-probing
amplicons andfluorescence, 17 Nature Biotech. 804--807 (1999) (hereinafter
"Whitcombe").
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(b) providing a second primer pair suitable for
amplifying an IS 1001 target nucleic acid comprising the
nucleotide sequence of SEQ ID NO: 9, amplifying said IS 1001
target sequence if present in the sample, and detecting the
IS 1001 target sequence by hybridizing with an oligonucleotide
consisting essentially of the nucleotide sequence of SEQ ID
NO: 11 or a full complement thereof,
wherein the presence of said IS481 target nucleic acid
identifies the presence of B. pertussis, and the presence of the
nucleotide sequence of SEQ ID NO: 11 within said IS 1001
target nucleic acid identifies the presence of B. parapertussis
and wherein at least one primer of the primer pair for
amplifying an IS 1001 target nucleic acid does not hybridize to
nucleic acid from Salinibacter ruber.
25. A method for detecting the presence or absence of
Bordetella parapertussis in a biological sample comprising
detecting the presence or absence of an IS 1001 target nucleic
acid comprising the nucleotide sequence of SEQ ID NO: 9,
wherein the length of said target nucleic acid is between 73 and
180 nucleotides and wherein said detecting of an IS 1001 target
nucleic acid does not detect nucleic acid from Salinibacter
ruber.
27. The method of claim 25, wherein said method
comprises:
(a) providing a primer pair suitable for amplifying said
IS 1001 target nucleic acid comprising the nucleotide sequence
of SEQ ID NO: 9;
(b) performing a primer extension reaction comprising
the primer pair of step (a) under conditions suitable to produce
a reaction product when said IS 1001 target nucleic acid is
present in said sample; and
( c) determining the presence of Bordetella parapertussis
by detecting the IS 1001 target nucleic acid by hybridizing with
an oligonucleotide consisting essentially of the nucleotide
sequence of SEQ ID NO: 11 or a full complement thereof.
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fNDEFINITENESS
The Examiner's Rejection
In rejecting claims 1, 7-10, 13-15, 24, 25, 27, 30-33, 58, 59, 61, and
62 under 35 U.S.C. § 112, second paragraph, the Examiner concludes that
claims 1 and 27 are indefinite "because the relationship between the
detecting step and the rest of the method is not clear." Ans. 4. Specifically,
the Examiner contends, it is not clear whether the claimed detecting step
"conducted using the oligonucleotide consisting essentially of SEQ ID NO:
11 or a full complement thereof occurs during the amplification reaction,
e.g., if the oligonucleotide is used as a labeled amplification primer, or if the
detection step occurs in a reaction completely separate from the
amplification step." Id.
Analysis
Appellants contend that the claims need not recite specifically
whether the detecting step using the oligonucleotide consisting essentially of
SEQ ID NO: 11 occurs in the amplification reaction or in a reaction separate
from the amplification because the Specification "clearly indicates that an
oligonucleotide that detects by hybridizing to a target nucleic acid can be a
primer as well as a probe." Reply Br. 4 (citing Spec. i-fi-140-41).
We conclude that Appellants have the better position. We note
initially that, as Appellants argue, claim 25 does not recite a detecting step
involving hybridization with an oligonucleotide consisting essentially of
SEQ ID NO: 11, unlike claims 1 and 27. See Reply Br. 3; App. Br. 23-24
(claim 25). Accordingly, because the allegedly indefinite language is not
present in claim 25, we reverse the Examiner's indefiniteness rejection as to
that claim.
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As to claims 1 and 27, and their dependent claims subject to this
rejection, we acknowledge that the language at issue in claims 1 and 27 is
sufficiently broad to encompass situations in which the step of hybridizing
with an oligonucleotide consisting essentially of SEQ ID NO: 11 is part of
an amplification reaction, as well as a simple hybridization reaction
conducted separately from the claimed amplification step. It is well settled,
however, that "breadth is not to be equated with indefiniteness." In re
Miller, 441F.2d689, 693 (CCPA 1971).
Thus, that the claims broadly encompass the use of the
oligonucleotide of SEQ ID NO: 11 in more than one fashion does not
persuade us that the scope of claims 1 and 27 is unclear. See Amgen Inc. v.
Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1342 (Fed. Cir. 2003) ("A
claim is indefinite if, when read in light of the specification, it does not
reasonably apprise those skilled in the art of the scope of the invention.").
We, therefore, reverse the Examiner's indefiniteness rejection of claims 1
and 27, as well as their dependent claims subject to this rejection.
OBVIOUSNESS-CLAIM 25
The Examiner's Rejection
In rejecting claim 25 for obviousness over Kosters, van der Zee, and
Lowe, the Examiner initially notes that the oligonucleotide sequence of SEQ
ID NO: 9, recited in claim 25, consists of nucleotides 730-802 of the IS1001
element of Bordetella parapertussis. Final Action 8. The Examiner cites
Kosters as describing a method of detecting Bordetella parapertussis in a
biological sample by amplifying an IS 1001 target nucleic acid by real-time
polymerase chain reaction ("PCR") "using a primer pair that produces an
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amplicon that is 464 nucleotides in length and comprises nucleotides 733-
1196 of the instant SEQ ID NO: 9." Id. at 9.
The Examiner cites van der Zee to show that the full sequence of the
IS 1001 element was known in the art. Id. The Examiner cites Lowe as
teaching "a computer program for designing all possible oligonucleotide
primers from a known nucleic acid sequence based on a set of user-specified
conditions (see abstract and pages 1757-1758). Lowe teaches that the
disclosed program simplifies and automates oligonucleotide primer design
(see pages 1757-1758 and pages 1760-1761)." Id.
Based on the references' teachings, the Examiner reasons that an
ordinary artisan would have considered it obvious to perform Kosters's
method "using oligonucleotide primers capable of producing an IS 1001
amplicon 73-180 nucleotides in length and comprising SEQ ID NO: 9" as
required by claim 25. Id. In particular, the Examiner reasons:
Id.
An ordinary artisan would have been motivated to do so
with a reasonable expectation of success, since: (i) K[ 6 ]sters
expressly taught designing oligonucleotide primers from the
known IS1001 sequence, (ii) the complete IS1001 sequence
was known in the art at the time of the invention, and (iii) Lowe
taught rules for designing amplification primers and disclosed a
publicly available program that uses the disclosed rules to
design primers from any known target nucleic acid sequence.
The Examiner reasons further that an ordinary artisan would have
considered it obvious to select a portion of the IS 1001 sequence that would
not detect nucleic acid from Salinibacter ruber, as claim 25 requires, given
that "it was conventional in the art at the time of the invention to minimize
the production of non-target nucleic acids when designing amplification
primers (see, for example, page 1757 of Lowe)." Id. at 10.
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Analysis
As stated in Jn re Oetiker, 977F.2d1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability ....
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
Appellants' arguments do not persuade us that a preponderance of the
evidence fails to support the Examiner's prima facie case of obviousness.
As the Examiner contends, Kosters is directed to a method that, like
claim 25, detects B. parapertussis in biological samples by detecting the
presence of the B. parapertussis IS 1001 element in those samples. See
Kosters 1719--20. Kosters notes that, using its PCR-based techniques, "[a]ll
primer-probe combinations were able to amplify and detect B. parapertussis
DNA specifically." Id. at 1720.
As Appellants contend, Kosters differs from claim 25 in that Kosters's
target sequence of the IS 1001 element is larger than the maximum length of
180 nucleotides recited in claim 25. App. Br. 8; Kosters 1720 (Table 1 ). As
Appellants contend, Kosters also differs from claim 25 in that Kosters
targets nucleotides 733-1196 of the IS1001 sequence (see Kosters 1720
(Table 1 )), whereas the target sequence of claim 25, SEQ ID NO: 9, consists
of nucleotides 730-802 of the IS1001 sequence (see Spec. i-f 96 (as amended
Nov. 20, 2008)). App. Br. 8. We acknowledge also the differences between
claim 25, and van der Zee and Lowe. App. Br. 8-9.
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As the Supreme Court has pointed out, however, "the mere existence
of differences between the prior art and an invention does not establish the
invention's nonobviousness." Dann v. Johnston, 425 U.S. 219, 230 (1976).
As the Supreme Court has noted also, "the [obviousness] analysis
need not seek out precise teachings directed to the specific subject matter of
the challenged claim, for a court can take account of the inferences and
creative steps that a person of ordinary skill in the art would employ." KSR
Int'! v. Teleflex Inc., 550 U.S. 398, 418 (2007); see also id. at 421 ("A
person of ordinary skill is ... a person of ordinary creativity, not an
automaton.").
In the instant case, we agree with the Examiner that an ordinary
artisan would have reasonably inferred, based on Kosters' s teaching that
subsequences of the IS 1001 element were useful for detecting B.
parapertussis, that other known subsequences of the IS 1001 element,
different from those used by Kosters, also would be useful for detecting B.
parapertussis, using Kosters' s methods. We find this inference particularly
reasonable with respect to claim 25, given the significant overlap between
the claimed target, SEQ ID NO: 9, and Kosters's amplified sequence.
Although we acknowledge the length difference between Kosters' s
amplified sequence and the target sequence of claim 25, as the Examiner
points out, the full sequence of the IS 1001 element was known in the art.
See van der Zee 145. Thus, to the extent claim 25 requires detection of an
IS 1001 subsequence not taught expressly in Kosters, an ordinary artisan
knew the nucleotide sequence of IS 1001 subsequences useful for detecting
B. parapertussis.
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Moreover, that claim 25 recites a target sequence shorter than that
used by Kosters does not negate the fact that claim 25 recites detection of a
target nucleic acid that would reasonably have been expected to be useful for
detecting B. parapertussis, particularly given the significant overlap between
the claimed target sequence and Kosters' s amplified sequence, noted above.
Indeed, Appellants concede that IS 1001 subsequences other than those
expressly used by Kosters would have been known to be useful for detecting
B. parapertussis. See App. Br. 9 ("There are numerous possibilities of target
sequences within the IS 1001 sequences ... [;] the wide array of presumably
equivalent options available to the artisan .... ") (emphasis added).
We acknowledge that claim 25 recites that the "detecting of an IS 1001
target nucleic acid does not detect nucleic acid from Salinibacter ruber."
App. Br. 24. We acknowledge that none of the cited references states
expressly that, when applying Kosters' s methods, one should avoid
sequences that detect S. ruber. See App. Br. 9-11.
As the Examiner points out, however (Final Action 10), Lowe teaches
that, when amplifying a target nucleic acid, practitioners should avoid
preparing "nonspecific product." Lowe 1757. We acknowledge, as
Appellants argue (App. Br. 10; Reply Br. 6), that Lowe's statement
regarding avoiding nonspecific product is not an express statement that one
should avoid amplifying and detecting known sequences of microorganisms,
such as S. ruber, which are not the objective of the detection methods.
Nonetheless, as noted above, a "person of ordinary skill is ... a
person of ordinary creativity, not an automaton." KSR, 550 U.S. at 421.
Given Lowe's teaching of avoiding amplification of nonspecific nucleic
acid, we agree with the Examiner that an ordinary artisan would have
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reasonably inferred that, to ensure the accuracy of the analysis, it would be
desirable to avoid amplifying known sequences of microorganisms not
specific to the test, such as S. ruber, when detecting B. parapertussis IS 1001
sequences by Kosters's methods. In that regard, we note the Specification's
disclosure that S. ruber sequences were known in the prior art and accessible
via BLAST search. See Spec. i-f 97. That Appellants discovered that certain
IS 1001 subsequences suitable for detecting B. parapertussis according to
Kosters inherently do not hybridize with S. ruber sequences does not
demonstrate that the Examiner erred in concluding that it would have been
obvious to use those IS 1001 subsequences, recited in claim 25, to detect B.
parapertussis. See In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed.
Cir. 1991) ("Mere recognition of latent properties in the prior art does not
render nonobvious an otherwise known invention."); see also In re
Woodruff, 919 F.2d 1575, 1577-78 (Fed. Cir. 1990) (obviousness rejection
affirmed where using claimed elements in the manner suggested by the prior
art necessarily resulted in claim-recited effect).
In sum, for the reasons discussed, Appellants do not persuade us that a
preponderance of the evidence fails to support the Examiner's prima facie
case of obviousness as to claim 25. As Appellants do not advance secondary
evidence of nonobviousness to rebut the Examiner's prima facie case, we
affirm the Examiner's rejection of claim 25 for obviousness over Kosters,
van der Zee, and Lowe.
OBVIOUSNESS-
CLAIMS 1, 7, 9, 10, 12, 14, 15, 24, 27, 29,
31-33, 58, 59, AND 61---67
In rejecting claims 1, 7, 9, 10, 12, 14, 15, 24, 27, 29, 31-33, 58, 59,
and 61-67, for obviousness over Kosters, Sloan, GenBank Accession
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Number M28220 for Bordetella pertussis IS481, van der Zee, and Lowe, the
Examiner notes initially that the first-recited sequence detected in claim 1,
SEQ ID NO: 3, consists of nucleotides 580-665 of the B. pertussis IS481
sequence. Final Action 11. The Examiner notes also that the second-recited
sequence detected in claim 1, SEQ ID NO: 9, consists of nucleotides 730-
802 of the B. parapertussis IS 1001 sequence. Id.
The Examiner cites Kosters as teaching a process of detecting B.
pertussis and B. parapertussis in biological samples, using PCR to amplify
and detect portions of the IS481 and IS1001 from those organisms. Id. at
11-12. The Examiner notes that Kosters uses a primer pair that "produces
an amplicon that is 464 nucleotides in length and comprises nucleotides 733-
1196 of [the instant] SEQ ID NO: 9." Id. at 11. The Examiner concedes,
nonetheless, that Kosters's PCR primers and probes "are different from the
claimed primers and probes and do not produce an amplification product
comprising SEQ ID NO: 3 and SEQ ID NO: 9, respectively." Id. at 12.
The Examiner cites Sloan as also teaching a process of detecting B.
pertussis and B. parapertussis in biological samples, using PCR to amplify
and detect portions of the IS481 and IS1001 from those organisms. Id. at 12.
The Examiner notes that Sloan amplifies a region that is 262 nucleotides
long and includes a portion of SEQ ID NO: 3 recited in claim 1. Id.
The Examiner cites GenBank Accession Number M28220 to show
that the full sequence of the B. pertussis IS481 element was known in the
art. Id. at 12-13. The Examiner cites van der Zee to show that the full
sequence of the B. parapertussis IS 1001 element was known in the art. Id.
at 13. The Examiner cites Lowe as teaching "a computer program for
designing all possible oligonucleotide primers from a known nucleic acid
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sequence based on a set of user-specified conditions (see abstract and pages
1757-1758). Lowe teaches that the disclosed program simplifies and
automates oligonucleotide primer design (see pages 1757-1758 and pages
1 7 60-1761)." Id.
Based on the references' teachings, the Examiner reasons that an
ordinary artisan would have considered it obvious to perform Kosters's
method "using primers and probes designed from the known IS481 and
IS 1001 sequences, such as the claimed primers and probes." Id.
Specifically, the Examiner reasons:
Since, as evidenced by K[o]sters and Sloan, the regions of the
IS481 and IS 1001 sequences targeted by the claimed primers
were known in the art to be suitable for primer design, the
ordinary artisan would have been motivated to utilize the
conventional primer design rules and software disclosed by
Lowe to design additional primers and probes from the known
IS481 and IS 1001 sequences, such as the claimed primers and
probes, with a reasonable expectation of success.
Id. The Examiner contends that the references' combined teachings would
have suggested "a finite number of possible primer pairs and oligonucleotide
probes that could be designed from the known IS 1001 and IS481 sequences
to the ordinary artisan, and, based on the teachings of Lowe, the ordinary
artisan would have expected predictable results in obtaining and using these
oligonucleotides" in Kosters's methods. Id. at 13-14.
Analysis
We select claim 1 as representative of the rejected claims. See
37 C.F.R. § 41.37(c)(iv). For the reasons discussed, Appellants' arguments
do not persuade us that a preponderance of the evidence fails to support the
Examiner's prima facie case of obviousness as to claim 1.
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Claim 1 recites a method for identifying the presence or absence of
Bordetella pertussis and/or Bordetella parapertussis in a biological sample.
App. Br. 22. To detect B. pertussis, claim 1 requires its practitioner to
provide a first primer pair suitable for amplifying, if present in the sample,
the target nucleotide sequence of SEQ ID NO: 3, a subsequence of the B.
pertussis IS481 element. Id. The presence of the target IS481 sequence
identifies the presence of B. pertussis in the sample. Id.
As the Examiner finds, Sloan, like claim 1, describes the use of
nucleic acid amplification for identifying the presence or absence of
Bordetella pertussis and/or Bordetella parapertussis in a biological sample.
Sloan 96. Like claim 1, for detecting B. pertussis, Sloan amplifies as its
target a subsequence of the B. pertussis IS481 element. Id. at 97 ("A 262-bp
target sequence from IS481 of B. pertussis was amplified .... ").
We agree with the Examiner, based on Sloan's teaching that
subsequences of the IS481 element were useful for detecting B. pertussis,
that an ordinary artisan would have reasonably inferred that other known
subsequences of the IS481 element, different from those used by Sloan, also
would be useful for detecting B. pertussis. We find this inference
particularly reasonable with respect to claim 1, given the Examiner's
undisputed finding (Final Action 12) that the target of claim 1, SEQ ID NO:
3, overlaps and is adjacent to Sloan's amplified sequence.
We acknowledge, as Appellants argue (App. Br. 13-14; Reply Br. 9)
that Sloan does not use precisely the same primer pair in its amplification as
that recited in claim 1. As the Examiner points out, however, the full
sequence of the IS481 element was known in the art. See GenBank
Accession Number M28220. Thus, to the extent claim 1 requires detection
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of an IS481 subsequence not taught expressly in Sloan, an ordinary artisan
knew the nucleotide sequence of IS48 l subsequences useful for detecting B.
pertussis.
To detect B. parapertussis, claim 1 requires its practitioner to provide
a second primer pair suitable for amplifying, if present in the sample, an
IS 1001 target nucleic acid including the nucleotide sequence of SEQ ID NO:
9, a subsequence of the B. parapertussis ISlOOl target sequence. App. Br.
22. The IS 1001 target sequence is detected by hybridizing with an
oligonucleotide consisting essentially of the nucleotide sequence of SEQ ID
NO: 11, or a full complement thereof. Id. The presence of the nucleotide
sequence of SEQ ID NO: 11 within the IS 1001 target nucleic acid identifies
the presence of B. parapertussis. Id. We note that SEQ ID NO: 11 is a
subsequence of SEQ ID NO: 9. See Spec. i-f 96 (as amended Nov. 20, 2008)
(SEQ ID NO: 9 consists of nucleotides 730-802 of the ISlOOl sequence;
SEQ ID NO: 11 consists of nucleotides 777-802 of the IS 1001 sequence).
As discussed above, Kosters is directed to a method that, like claim 1,
detects B. parapertussis in biological samples by detecting the presence of
the B. parapertussis IS 1001 element in those samples. See Kosters 1719-
20. Kosters notes that, using its PCR-based techniques, "[a]ll primer-probe
combinations were able to amplify and detect B. parapertussis DNA
specifically." Id. at 1720. As to target sequence, Kosters amplifies
nucleotides 733-1196 of the IS 1001 sequence (see Kosters 1720 (Table 1) ),
in contrast to claim l's SEQ ID NO: 9 (nucleotides 730-802 of the ISlOOl
sequence). Claim l's SEQ ID NO: 11 (nucleotides 777-802 of the ISlOOl
sequence) is contained entirely within Kosters's amplified sequence.
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We agree with the Examiner that an ordinary artisan would have
reasonably inferred, based on Kosters's teaching that subsequences of the
IS 1001 element were useful for detecting B. parapertussis, that other known
subsequences of the IS 1001 element, slightly different from those used by
Kosters, also would be useful for detecting B. parapertussis, using Kosters' s
methods. We find this inference particularly reasonable with respect to
claim 1, given the significant overlap between the claimed target sequences,
SEQ ID NO: 9 and SEQ ID NO: 11, and Kosters's amplified sequence.
Although we acknowledge the differences between Kosters' s
amplified sequence and the target sequences of claim 1, as the Examiner
points out, the full sequence of the IS 1001 element was known in the art.
See van der Zee 145. Thus, to the extent claim 1 requires detection of an
IS 1001 subsequence not taught expressly in Kosters, an ordinary artisan
knew the nucleotide sequence of IS 1001 subsequences useful for detecting
B. parapertussis.
We acknowledge that claim 1 recites that "at least one primer of the
primer pair for amplifying an IS 1001 target nucleic acid does not hybridize
to nucleic acid from Salinibacter ruber." App. Br. 22. We acknowledge
that none of the cited references states expressly that, when applying
Kosters' s methods, one should avoid sequences that detect S. ruber. See id.
at 12-13, 15-19. We acknowledge further Appellants' assertion that SEQ
ID NO: 11 has no homology with S. ruber sequences, whereas certain of
Kosters's primers would hybridize to S. ruber sequences. Id. at 13.
SEQ ID NO: 11, nonetheless, was an undisputedly known
subsequence of the same target sequence of the B. pertussis IS 1001 element
used by Kosters to detect B. pertussis. As noted above, Kosters amplifies as
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its target nucleotides 733-1196 of the IS1001 sequence (see Kosters 1720
(Table 1)), and claim 1 's SEQ ID NO: 11 consists of nucleotides 777-802 of
the ISIOOI sequence (Spec. i-f 96 (as amended Nov. 20, 2008)). Given that
SEQ ID NO: 11 is totally contained within Kosters's target sequence, we
agree with the Examiner that an ordinary artisan would have reasonably
inferred that SEQ ID NO: 11 would have been suitable as a target sequence
for detecting B. parapertussis. That SEQ ID NO: 11 possesses the inherent
property of not hybridizing to S. ruber sequences does not persuade us that,
given Kosters' s teachings, an ordinary artisan lacked a reason to use SEQ ID
NO: 11 as a target for detecting B. parapertussis.
Moreover, that Appellants discovered that SEQ ID NO: 11 inherently
does not hybridize with S. ruber sequences does not demonstrate that the
Examiner erred in concluding that it would have been obvious to use SEQ
ID NO: 11 to detect B. parapertussis. See Baxter Travenol Labs., 952 F.2d
at 392 ("Mere recognition of latent properties in the prior art does not render
nonobvious an otherwise known invention."); see also Woodruff, 919 F.2d at
1577-78 (obviousness rejection affirmed where using claimed elements in
the manner suggested by the prior art necessarily resulted in claim-recited
effect).
Given that claim 1 recites the use of known subsequences of the IS481
and IS 1001 elements to detect B. pertussis and B. parapertussis,
respectfully, Appellants do not persuade us that an ordinary artisan lacked
motivation to use the claimed sequences for detecting those microorganisms
in biological samples. In particular, as noted above, the target sequences
recited in claim 1 significantly overlap the target sequences taught in Kosters
and Sloan. Indeed, Appellants concede that IS481 and IS 1001 subsequences
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other than those expressly taught by Sloan and Kosters would have been
known to be useful for detecting B. pertussis and B. parapertussis. See App.
Br. 15 ("There are virtually endless possibilities of target sequences within
the IS481 and IS 1001 sequences ... [;] the wide array of presumably
equivalent options available to the artisan .... ") (emphasis added).
Appellants contend that claim 1 's SEQ ID NO: 11, at 26 nucleotides
in length, is longer than the 18-22 nucleotide primer length range specified
in Lowe and, therefore, "a skilled artisan will never arrive at the claimed
primers or probes for amplifying and detecting B. parapertussis IS 1001
target sequence." App. Br. 17. As noted above, however, given that SEQ
ID NO: 11 is totally contained within Kosters's target sequence, we agree
with the Examiner that an ordinary artisan would have reasonably inferred
that SEQ ID NO: 11 would have been suitable as a target sequence for
detecting B. parapertussis. As noted above, moreover, in traversing the
Examiner's indefiniteness rejection, Appellants concede that claim 1
encompasses the use of SEQ ID NO: 11 as a straightforward hybridization
probe, as well as an amplification primer. See Reply Br. 4. Thus, as probe,
SEQ ID NO: 11 need not comply with Lowe's rules for amplification
primers.
We are also not persuaded that Lowe teaches away from using the
target sequences recited in claim 1 as primers to detect B. pertussis and B.
parapertussis. A reference does not teach away "if it merely expresses a
general preference for an alternative invention but does not 'criticize,
discredit, or otherwise discourage' investigation into the invention claimed."
DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc., 567 F.3d 1314, 1327
(Fed. Cir. 2009) (citing In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004)).
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In the instant case, while we acknowledge Lowe's disclosure that
amplification primers "should be" 18-22 nucleotides in length (Lowe 1757),
Appellants do not direct us to disclosures in Lowe that clearly or specifically
criticize or discredit the use of longer primers. Indeed, as the Examiner
points out, Lowe expressly contemplates flexibility in, and deviation from,
its rules. Id. ("The program also allows the stringency of certain criteria to
be varied to better suit the needs of particular experiments. . . . To maintain
the flexibility of the program, but prevent inappropriate values from being
entered, very loose limits on some of the variables have been included.").
By using primers 25 nucleotides in length (Sloan 97), Sloan supports the
Examiner's position that an ordinary artisan would have understood that
Lowe's rules for amplification primers were not absolute, and that Lowe did
not teach away from using longer primers. In that vein, given Lowe's
disclosure that GC content may vary from 10-90% (Lowe 1758), we are not
persuaded that claim 1 's SEQ ID NO: 11 target sequence, with a GC content
of 42%, is outside Lowe's suggested range.
In sum, for the reasons discussed, Appellants' arguments do not
persuade us that a preponderance of the evidence fails to support the
Examiner's prima facie case of obviousness as to claim 1. As Appellants do
not advance secondary evidence of nonobviousness to rebut the Examiner's
prima facie case, we affirm the Examiner's rejection of claim 1 for
obviousness over Kosters, Sloan, GenBank Accession Number M28220, van
der Zee, and Lowe. Because they were not argued separately, claims 9, 10,
12, 14, 15, 24, 27, 29, 31-33, 58, 59, and 61---67 fall with claim 1. 37 C.F.R.
§ 41.37(c)(iv).
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Appellants argue also that, because the forward primer of SEQ ID
NO: 4 recited in claim 7 has a GA at its 3' end, use of the primer in claim 7
violates Lowe's recommendation that primers have a GC pair at that
location. App. Br. 17.
In addition to SEQ ID NO: 4, however, claim 7 additionally recites
the use of SEQ ID NO: 5 as a member of the primer pair. App. Br. 22.
Appellants do not explain adequately why SEQ ID NO: 5 fails to meet
Lowe's recommendation for a GC pair at the primer's 3' end. See Lowe,
1758 ("All primers should contain a GC-type sequence pair (i.e., either a
CC, GG, GC, or CG) at their 3' end."); see also Spec. i-fi-189-90 (showing
SEQ ID NO: 4 with GA at 3' end; SEQ ID NO: 5 with CC at 3' end).
Accordingly, that SEQ ID NO: 4 might not fall within Lowe's
recommendations for primers does not demonstrate that claim 7 fails to
encompass primers with structures suggested by Lowe. Moreover, as to the
fact that the GC content of the primer of SEQ ID NO: 4 of claim 7 is 61 %
(App. Br. 17), as noted above, Lowe states expressly that GC content may
vary from 10-90%. Lowe 1758.
Accordingly, Appellants' arguments do not persuade us that a
preponderance of the evidence fails to support the Examiner's prima facie
case as to claim 7. We, therefore, affirm the Examiner's rejection of that
claim as well.
OBVIOUSNESS-
CLAIMS 8, 13, 30, 68, AND 69
Claims 8, 13, 30, 68, and 69 all depend directly or ultimately from
claims 1 or 65, discussed above. See App. Br. 22-24, 26-27. In rejecting
claims 8, 13, 30, 68, and 69 for obviousness, the Examiner relies on the
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teachings of Kosters, Sloan, GenBank Accession Number M28220, van der
Zee, and Lowe for the teachings discussed above as to claims 1 and 65, but
concedes that those references do not teach or suggest PCR primers having
the sequences or stem-loop structures of the Scorpion-type primers recited in
claims 8, 13, 30, 68, and 69. Final Action 14--15.
To address that deficiency, the Examiner cites Whitcombe as teaching
that Scorpion-type primers provide certain advantages in PCR reactions,
including allowing real-time monitoring of reactions, as well as producing a
more efficient assay with faster reaction kinetics. Id. at 15. Although the
Examiner concedes that Whitcombe does not describe primers for detecting
B. pertussis or B. parapertussis, the Examiner concludes that preparing
primers of the type described in Whitcombe for use in the methods taught in
Kosters and Sloan would have been obvious, given that IS481 and IS 1001
sequences were taught in those references to be useful in amplification
reactions for detecting those organisms. Id. at 15-16. Accordingly, the
Examiner concludes the use of the primers recited in claims 8, 13, 30, 68,
and 69 would have been prima facie obvious to an ordinary artisan. Id. at
16.
As to this ground of rejection, Appellants contend only that
Whitcombe fails to remedy the deficiencies, argued above, as to the
combination of Kosters, Sloan, GenBank Accession Number M28220, van
der Zee, and Lowe, vis-a-vis claims 1 and 65, from which claims 8, 13, 30,
68, and 69 depend. App. Br. 21; Reply Br. 13. As discussed above,
however, Appellants' arguments do not persuade us that a preponderance of
the evidence fails to support the Examiner's conclusion that the combined
teachings in those references render obvious the processes recited in claims
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1 and 65. Accordingly, because Appellants do not identify, nor do we
discern, error in the Examiner's prima facie case as to claims 8, 13, 30, 68,
and 69, we affirm the Examiner's obviousness rejection of those claims.
SUMMARY
We reverse the Examiner's rejection of claims 1, 7-10, 13-15, 24, 25,
27, 30-33, 58, 59, 61, and 62, under 35 U.S.C. § 112, second paragraph.
We affirm the Examiner's rejection of claim 25 for obviousness over
Kosters, van der Zee, and Lowe.
We affirm the Examiner's rejection of claims 1, 7, 9, 10, 12, 14, 15,
24, 27, 29, 31-33, 58, 59, and 61---67 for obviousness over Kosters, Sloan,
GenBank Accession Number M28220 for Bordetella pertussis IS481, van
der Zee, and Lowe.
We affirm the Examiner's rejection of claims 8, 13, 30, 68, and 69 for
obviousness over Kosters, Sloan, GenBank Accession Number M28220 for
Bordetella pertussis IS481, van der Zee, Lowe, and Whitcombe.
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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