DETAILED ACTION
Claim Status
Claim 25 has been amended.
Claims 27-34, 38, and 42-48 have been canceled.
Claims 49-51 have been added.
Claims 25, 26, 35-37, 39-41 and 49-51 are pending and under examination.
Objections Withdrawn
The objection to claim 25 as containing periods within the claim is withdrawn in view of applicant’s amendment to the claim.
Rejections Withdrawn
The rejection of claims 25-34 and 37-43 under 35 USC 102(a)(1) as being anticipated by Leamon, et al. is withdrawn in view of applicant’s amendment to the claims. For clarity of the record it is noted that the previous office action contained a typographical error rejecting claims 25-24.
Rejections Maintained/New Grounds of Rejection
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 50 and 51 recite the limitation "sensor" in line 1. There is insufficient antecedent basis for this limitation in the claim. Neither claims 25 or 26 from which the claims depend contain a “sensor” limitation.
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.
Claims 25, 26, 35-37, and 39-41 remain, and new claims 49-51 are, rejected under 35 U.S.C. 103 as being unpatentable over Leamon et al. (US 20060040297) in view of Xu et al. (2016).
Leamon teaches solid-phase PCR carried out with a single copy of a single-stranded DNA fragment (nucleic acid sample). (Paragraph 747.) Specifically, Leamon teaches (a) taking a system having a first liquid in contact with a solid support wherein the first liquid volume contains a single-stranded DNA fragment (nucleic acid sample), a forward and a reverse non-immobilized amplification primer (F and R), and PCR reaction mix (reagents for nucleic acid amplification), and the solid support has immobilized R primers. (Figure 22, stage 1; paragraph 748.) Leamon then teaches (b) performing thermal cycling using the non-immobilized amplification primers to produce a non-immobilized amplification product. (Figure 22, stages 2-4; paragraphs 749-751.) Leamon then teaches (c) amplifying the resulting amplification product using the immobilized primers to make an immobilized second amplification product. (Figure 22, stages 5-6; paragraphs 752-753.) Leamon then teaches (d)(ii) removing the first liquid and replacing it with an alkali-denaturation agent that removes non-immobilized single strands. (Figure 22, stage 7; paragraph 754.) Leamon teaches providing an extension primer that hybridizes to the immobilized single-stranded DNA near a target position, then subjecting the primer to a polymerase reaction. (Paragraph 38.) Leamon teaches that (e) the fluorescently labeled probes provide fluorescent signals. (Figure 22, stage 8; paragraphs 755-756.) Leamon teaches that the reaction event (e.g., photons generated by luciferase) may be detected by CMOS, among other apparatuses. (Paragraph 325.)
Leamon does not teach that the method is performed on the surface of a CMOS chip. Regarding claims 35 and 36, Leamon does not specifically teach detecting protons or ISFET. Regarding claim 49, Leamon does not teach an array of silicon-based sensors. Regarding claim 50 (which is interpreted for this rejection as depending from claim 49 since that is the only claim that recites a plurality of sensors), Leamon does not specifically teach that the sensors integrate a spatial and/or temporal signal. Regarding claim 51 (which is interpreted for this rejection as depending from claim 36 rather than claim 26), Leamon does not teach detecting protons. These teachings are made up for in the teachings of Xu.
Xu teaches a CMOS-ISFET biosensor for the detection of real-time DNA hybridization. (Abstract, Figs. 1 and 2.) Specifically, regarding claims 35, 36, and 51, Xu teaches a ISFET detects protons as the technology was initially developed to measure pH sensitivity (p 3249 2nd col).
It would have been obvious to perform Leamon’s solid-phase PCR on the CMOS-ISFET biosensor of Xu because Xu teaches that CMOS-ISFET is useful for detecting DNA hybridization data. In particular, Xu demonstrates probe DNA immobilized on the surface of a CMOS-ISFET chip (Fig. 2) and subsequent detection of DNA hybridization by that chip (Fig. 4). It would have been obvious to use the detection sensors of Xu in the methods of Leamon because Xu teaches that ISFET of different sizes were detected from two different chips with different hybridization signals and that their results are generally applicable to detecting other types of biomolecules. Furthermore, Leamon teaches that CMOS is suitable for gathering data on hybridization events.
Regarding claim 26, Leamon’s non-immobilized amplification primers are in solution above the solid phase, so they are separate from it. (Figure 22, stage 1.) In addition, Xu depicts target DNA (primers) being in solution above the probe DNA immobilized on the surface of the CMOS-ISFET chip. (Fig. 2.)
Regarding claim 37, Leamon teaches detecting the amplified products with fluorescent reporter probes and fluorescence measurement. (Paragraphs 755-756.)
Regarding claims 49 and 50, Xu’s CMOS-ISFET biosensor is an array of silicon-based sensors, wherein each sensor integrates a signal sensed over time. (Fig. 1, Fig. 4a; p 3250.)
Response to Arguments
Regarding the anticipation rejection of record, applicant contends that Leamon does not address the structural requirements of the claims and “lacks a CMOS chip entirely.” (Reply at 8.) Applicant’s concerns about the new requirement in claim 26 that the method be performed on a CMOS chip are fully addressed by Xu, which teaches detecting hybridization events at the surface of a CMOS chip. Furthermore, Leamon is not fully silent on CMOS technology; the reference expressly contemplates CMOS as a detection apparatus useful in its method.
Regarding the obviousness rejection of record, applicant alleges that the “fully integrated CMOS chip” newly required by the claimed invention is not taught by Leamon. (Reply at 9.) This concern is addressed by Xu.
Applicant alleges that the skilled artisan would not have been motivated to modify Leamon with Xu because Leamon only suggests using a “detector at a distance.” (Reply at 10.) Xu, however, expressly teaches immobilizing probe DNA to the surface of a CMOS-ISFET chip in the same field of endeavor (i.e., detection of hybridization events).
Applicant alleges that Leamon’s bead-based immobilization is “entirely incompatible with fully integrating the reaction and analysis onto a CMOS chip surface.” (Reply at 10-11.) Applicant alleges that Leamon teaches away from on-chip integration. (Reply at 11.) Xu, however, illustrates and exemplifies a method in which the probe DNA is immobilized directly onto the surface of the CMOS-ISFET chip responsible for detecting its hybridization with the target DNA. (Fig. 2.) Both references rely on the principle of probe immobilization, and Xu demonstrates that hybridization events can be detected between a surface-immobilized probe DNA and a target in the solution surrounding it.
Conclusion
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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/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
Prosecution Insights