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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 5th, 2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see pages 97 and 171). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Drawings
The colored drawings were received on August 8th, 2023 and April 28th, 2023. These drawings are accepted.
A petition for colored drawings were granted on December 7th, 2023.
Claim Objections
Claim 1 is objected to because of the following informalities: missing a period at the end of the claim. Appropriate correction is required.
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.
Claim 5 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 5 recites the limitation "a target nucleic acid sequence" in 20. There is insufficient antecedent basis for this limitation in the claim. There is no earlier introduction of “nucleic acid sequence”. Instead, “a target nucleic acid” is introduced.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Wimberger-Friedl et al. (US20150079585A1; published March 19th, 2015) in view of Ma et al. (Isothermal amplification method for next-generation sequencing, Proc. Natl. Acad. Sci. U.S.A. 110 (35) 14320-14323, https://doi.org/10.1073/pnas.1311334110 (2013)).
Regarding instant claim 1, Wimberger-Friedl teaches a method of sequencing a nucleic acid by synthesis using evanescent wave imaging. Wimberger-Friedl teaches a device comprising a substrate having a first surface on which at least one nucleic acid is immobilized [0014; 0075]. Wimberger-Friedl further teaches that an aqueous solution comprising a plurality of nucleotides and an enzyme is in contact with the first surface of the substrate [0030]. Wimberger-Friedl further teaches that the nucleotides comprise a 3’-unblocked reversible terminator as the blocking moiety (claim 3-4; [0033; 0036]. Wimberger-Friedl further teaches that the substrate is configured to confine excitation light and provide an evanescent wave of the excitation light at the first surface [0014], and the optical arrangement is configured to receive and detect fluorescent light emitted by the fluorescent label of a nucleotide incorporated into the molecule bound on the first surface [0014], thereby teaching contacting surface-immobilized nucleic acid molecules with an aqueous solution comprising sequencing reagents comprising a pool of 3’-unblocked protected nucleotides and teaching evanescent wave imaging of surface-immobilized nucleic acid molecules contacted with sequencing reagents comprising 3’-unblocked protected nucleotides.
Wimberger-Friedl does not teach isothermally amplifying a target nucleic acid present in the sample in a reservoir to produce one or more amplicons, wherein the one or more amplicons are immobilized to a bottom surface of the reservoir. This deficiency is made up in the teachings of Ma.
Ma teaches a solid-phase, in situ isothermal amplification method performed directly within the lanes of a sequencing flowchip and frames isothermal amplification method as a sample preparation method (p. 14320, left column, para 4), wherein the flowchip lane comprises a reservoir in which isothermal amplification takes place (p. 14323, left column, para 3). Ma further teaches that the amplicons produced by this isothermal amplification are immobilized to the bottom surface of the reservoir, with colonies confirmed on both the top and bottom surfaces of the flowchip (Fig. 2).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the isothermal surface amplification method of Ma with the evanescent wave sequencing of Wimberger-Friedl. Wimberger-Friedl teaches sequencing by synthesis using evanescent wave imaging and 3’-unblocked protected nucleotides that require surface-immobilized nucleic acid molecules as a starting molecule, but does not teach how those immobilized molecules are produced. Ma addresses this gap by providing a cost-effective, in situ isothermal monoclonal colony generation method that requires minimal hands-on time, taking less than 30 minutes (p. 14322, right column, para 4). A person of ordinary skill in the art would have had a reasonable expectation of success in combining both references as the immobilized monoclonal colonies produced by Ma are structurally and functionally equivalent to surface-immobilized nucleic acid molecules of Wimberger-Friedl (See MPEP 2141(III)).
Regarding instant claim 2, Wimberger-Friedl, in view of Ma, teaches the method of claim 1. Wimberger-Friedl further teaches coupling the reservoir with a component of an evanescent wave imaging apparatus, specifically that the substrate is coupled to an optical arrangement configured to direct excitation light and cleavage light to the substrate and to receive and detect fluorescent emissions from incorporated nucleotides [0014; 0043]. The substrate and the aqueous solution in contact with the first surface, as taught by Wimberger-Friedl correspond to the reservoir of the claimed method, and the optical arrangement constitutes a component of an evanescent wave imaging apparatus.
Regarding instant claim 3, Wimberger-Friedl, in view of Ma, teaches the method of claim 2. Wimberger-Friedl further teaches wherein coupling positions the reservoir above a detector, specifically that the optical arrangement comprises a fluorescence detector positioned to receive fluorescence photons emitted by the fluorescent labels of incorporated nucleotides directed downward through the optical elements of the apparatus [0083], wherein the substrate and solution defining the reservoir are positioned above the fluorescence detector, thereby teaching that coupling positions the reservoir above a detector.
Regarding instant claim 4, Wimberger-Friedl, in view of Ma, teaches the method of claim 3. Wimberger-Friedl further teaches wherein coupling aligns the one or more immobilized amplicons within view of the detector, specifically that the substrate comprises several adjacent binding positions at which molecules are immobilized to the first surface along a first direction, and that the optical arrangement is configured to perform an optical scan such that each binding position is sequentially irradiated with excitation light and imaged by the fluorescence detector [0049; 0083], thereby teaching that coupling aligns the immobilized molecules within view of the detector such that each binding position is sequentially brought into the field of view of the fluorescence detector.
Ma further supports this limitation by teaching that the immobilized amplicon colonies are present at a density exceeding 1 million per mm2 across the bottom surface of the flowchip lane (Fig. 2; p. 14321, left column, para 2), confirming that the immobilized amplicons would be within view of the detector across the full reaction surface.
Regarding instant claim 5, Wimberger-Friedl, in view of Ma, teaches the method of claim 1, wherein isothermally amplifying a target nucleic acid sequence comprises using WildFire to amplify the target nucleic acid sequence. Ma teaches WildFire amplification, as the template walking (TW) isothermal mechanism is the foundational WildFire technology (p. 14320, left column, para 1; right column, para 2). As evidenced by the ThermoFisher WildFire poster, Wildfire is defined as an isothermal amplification technology wherein sequencing libraries are in-situ isothermally amplified directly on the surface of a flowchip using the “template walking” protocol. Ma describes and demonstrates this same template walking mechanism (p. 14320, left column, para 4). The ThermoFisher poster identifies this template walking protocol as the WildFire method. Therefore, the template walking mechanism described and demonstrated by Ma constitutes WildFire amplification.
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nura Choudhury whose telephone number is (571)272-6148. The examiner can normally be reached M-F, 9-5 ET.
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/NURA M. CHOUDHURY/ Examiner, Art Unit 1683
/ANNE M. GUSSOW/ Supervisory Patent Examiner, Art Unit 1683
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