Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group II, first oligonucleotide probe SEQ ID NO: 16 and second oligonucleotide probe SEQ ID NO: 21, in the reply filed on 10/10/25 is acknowledged.
Claims 1-12 and 76-79 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/10/25.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 63-75 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 63 is indefinite when it refers to “the base sequence” because it is not clear if this is referring to the “base” as a foundation or basis, or if it is attempting to require that only the nucleobases recited in the SEQ ID NO: are present in the claim. As a consequence, it is unclear if the claim is employing open or closed language relative to the structure of the probes in the collection of probes. Dependent claims are also rejected over this same issue.
Claim 70 additionally recites “a base sequence” and is similarly indefinite. Furthermore, the claim recites an oligonucleotide…”with” a base sequence and it is not clear what it means for an oligonucleotide to be “with” a sequence- whether this language is meant to be open or closed language defining the structure of the probe.
All dependent claims incorporate these issues and are indefinite for the same reasons.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 63-75 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Kri Kirstiansen (J Clin Microbiol 54:1593–1597. doi:10.1128/JCM.00012-16, 5 pages) and Talarico (WO2016061398).
The specification does not define a “probe reagent” directly. In the table entitled “Oligonucleotide Reagents” the specification lists oligonucleotide molecules identified by SEQ ID NO, function, and sequence, see Table 1, Table 3, Table 5.
With regard to claim 63, since the “probe reagent” comprises “a collection…of probes” this is being interpreted as a single composition containing at least two probes.
With regard to claim 70, since the “probe reagent” comprises “an oligonucleotide” this is being interpreted as a single probe comprising the oligonucleotide 16 nucleotides in length. Here, since there is only one element to the reagent, the “comprising” transitional language controls, and the claim is interpreted to recite a probe “comprising” an oligonucleotide 16 bases in length, and the encompassed probe includes oligonucleotides that are longer than 16 bases in length. This interpretation of “probe reagent” as being an oligonucleotide is consistent with the specification at table 3 which is titled “Oligonucleotide probe reagents” and it is implied that a single probe is a “probe reagent.”
Kristiansen teaches that macrolide resistance in M. genitalium is caused by mutation at positions 2058 and 2059, including A2058G and A2058C (Abstract). Kristiansen teaches oligonucleotide probes that are fully complementary to the wild type, the A2058G and A2058C mutations. See Figure 1. Kristiansen shows sequence of the M. genitalium 23S gene containing the resistance related mutations in Figure 1. Instant SEQ ID NO: 16 is a fragment of the wild type, except that there is a C at position 2058 (corresponding to the known A2058C mutation), and instant SEQ ID NO: 21 has a G at position 2058. The probe taught by Kirstiansen as A2058G Comprises instant SEQ ID NO: 21.
Kirstiansen does not teach a probe comprising SEQ ID NO: 16, or a probe comprising SEQ ID NO: 16 in a composition with at least one other probe.
Talarico teaches compositions comprising differently labeled oligonucleotide probes for detecting macrolide resistance in H. pylori. Like Kirstiansen, the target for detection is mutations in the 23S gene (para 7, 45). The compositions are for use in sample partition digital polymerase chain reaction (para 23). Talarico teaches that probes can be from 15-20 nucleotides (para 29), and that the central part of the probe is essential for its hybridization characteristics, and that variations are possible in the length of the probes and that the central part of the prove is essential for its hybridization conditions (para 28).
Talarico exemplifies a set of probes for detecting the 23S mutations after amplification (p. 35, see also Example 3, p. 48). SEQ ID NO: 19 taught by the reference comprises nucleotides 1-15 of instant SEQ ID NO: 16. SEQ ID NO: 25 taught by the reference comprises all of instant SEQ ID NO: 21. Talarico teaches a different probe specific for each mutation of the 23S disclosed. Talarico teaches a fluorophore moiety attached to the 5’ end and a quencher attached to the 3’ end, Talarico teaches FAM, a fluorescein moiety attached to the probes, and in a set, all of the probes have the same quencher moiety. See p. 35. The reference teaches that the probes are labeled with FAM which inherently absorbs light at about 495 and emits light at about 520nm.
It would have been prima facie obvious, following the teachings of Kirstiansen in view of Talarico to have produced a set of oligonucleotide probe reagents between 15 and 20 nucleotides, using the sequence set forth in Kristiansen et al. as a basis to select the probes. One would have been motivated by the teachings of Talarico to provide probes for the detection of any 23S mutation present in the sample, and by the exemplification of Talarico of a method which employs compositions of allele specific probes for the multiplex detection of 23S resistance related mutations. An ordinary artisan would have been motivated to do so with a reasonable expectation of success, since: (i) Talarico and Kristiansen expressly demonstrated alleles specific probes for the detection of 23S macrolide resistance related mutations and (ii) the sequence of the 23S gene surrounding the mutations was known in the art at the time of the invention. The combined teachings of the cited references would have suggested a finite number of possible oligonucleotide probes, with Talarico specifically suggesting the selection of probes 15-20 nucleotides in length, and, based on the teachings of Talarico and Kristiansen, the ordinary artisan would have expected predictable results in selecting these oligonucleotides to provide reagents for detecting macrolide resistance. It is inherent that these oligonucleotides would hybridize to their complement templates, namely SEQ ID NO: 13 and 18, and be hydrolyzed, but not when hybridized to SEQ ID NO: 11; this would be optimizable based on the reaction conditions. Thus, the claimed invention is prima facie obvious in view of the prior art.
Conclusion
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682