DETAILED ACTION
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 .
Status of Claims
Currently, claims 1-2, and 4-20 are pending in the instant application. Claims 7-20 are withdrawn from consideration as being drawn to a non elected invention. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant Application. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 103
Claims 1-2 and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Wei 2018 (Wei et al; The Journal of Molecular Diagnostics, vol 20, 2018, pages 738-742; cited in the IDS filed 9/3/3035) in view of Wei 2017 (Wei et al; US 2017/0191118), and further in view of Poulson and Lahdenpera (Lahdenpera et al; Anal. Methods, vol 6, pp 5360-5368, 2014).
With regard to claim 1, Wei 2018 teaches a system for detecting nucleic acid molecules comprising a microtiter plate of 96 gold electrodes, a probe set comprising paired capture and detection probes, where the capture probe is copolymerized with a conduction gel and pyrrole onto the gold electrodes, and the detector probe is labeled with biotin at the 3’ terminal nucleotide (see eLB assay, page 739, col 2) and a plate washer (“after washing, detector probes were mixed…; col 2 page 739).
With regard to claims 2, and 4-5, Wei 2018 teaches detecting EGFR mutations associated with lung cancer including exon 19 deletion and L858R (page 739, col 2).
Wei 2018 does not describe the gold electrodes, or the electrochemical reader, however Wei 2017 teaches a system for detecting nucleic acid molecule targets, including the EGFR exon19 and L858R mutations associated with lung cancer, comprising a microtiter plate of sensors where each sensor comprising a working electrode, a counter electrode, and a reference electrode (para 0009), a probe set comprising paired capture and detection probes (para 0014), where the capture probe is copolymerized onto the gold electrodes, a plate washer (“after washing, detector probes were mixed…; col 2 page 739), and an amperometric current reader which controls an electric field (para 0027) and reports the current (figure 3). With regard to claim 6, the capture probe for the L858R mutation taught by Wei 2017 (SEQ ID NO: 1) comprises instantly claimed SEQ ID NO 13, and the detector probe taught by Wei (SEQ ID NO: 2) is found within instantly claimed SEQ ID NO; 6. Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, to have used the system taught by Wei 2017 in the method of Wei 2018 because Wei 2018 teaches that the system taught by Wei 2017 was used in the assay (see page 739, col 2 “The basic eLB assay has been previously described”). The longer detector probe of SEQ ID NO: 6 is considered routine optimization.
Wei 2018 and Wei 2017 do not teach a system where the capture probe comprises a polyA region. However Poulson teaches that constraints induced by tethering a capture probe onto a solid support occur and that steric hindrance can negatively affect hybridization with immobilized capture probes (see page 1, col 2). Poulson teaches that adding polyA spacers to the probes makes the capture portion (hybridization) more accessible (page 2, col 1). Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have included polyA spacers on the capture probe so as to make the hybridization portion of the capture probe more accessible to the target, as taught by Poulson, in the method of Wei 2018 and Wei 2017 with a reasonable expectation of success.
Wei 2018, Wei 2017, and Poulson do not teach a capture probe which comprises a poly sequence comprising at least 65 nucleotides, however Lahdenspera also teaches optimization of spacer length for capture probes in hybridization assays. Lahdenspera teaches that capture probes with the longest homopolymer spacer (67 dTs; see table 1) provided the most signal increase while reducing the background signal (see page 5365, col 2, “3.4 Spacer length”). Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have modified the length of the poly A spacer taught by Wei 2018, Wei2017, and Poulson, to have included a spacer comprising at least 65 adenine nucleotides for the obvious benefit of increasing signal. While Lahdenspera teaches that polyT25 and polyT67 were comparable and the polyT25 spacer was sufficient, the teachings of Lahdenspera illustrate the routine optimization in the field of capture probe spacer length and composition as well as illustrating the substitution of a 25 nucleotide spacer with a 67 nucleotide spacer produced comparable and predictable results. In modifying the length of the poly A capture probes taught by Wei 2018, Wei2 2017, and Poulson, to include at least 65 nucleotide spacer, the ordinary artisan would have necessarily arrived at a capture probe sequence wherein at least 80% of the nucleotides are adenine and wherein the polyA sequence is interrupted by non-adenine nucleotides as illustrated below (adenines are bold and underlined):
capture probe for exon 19del taught by Wei 2017 with additional polyA sequences for spacer as suggested by Lahdenspera: TGTTGCTTCCTTGATAGCGACGAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682