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 .
Claims 1-20 are pending. Claim 1 is amended. Claims 1-20 are under examination.
Response to Amendment
The Amendment filed 5/31/26 has been entered. Applicant has filed a terminal disclaimer that overcomes the nonstatutory double patenting rejections over U.S. Patent No. 11,891,643 previously set forth in the Non-Final Office Action mailed 3/3/26. Accordingly, the nonstatutory double patenting rejections are withdrawn.
Response to Arguments
Applicant’s arguments, see pages 1-3, filed 5/31/26, with respect to the rejections of claims 1-20 under 35 USC 103 have been fully considered and are found persuasive. Therefore, the rejections documented in the Non-Final mailed 3/3/26 have been withdrawn. However, upon further consideration, new grounds of rejections necessitated by claim amendments are made in this Final Office Action.
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 1-6, 8, 10, 12-14, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Lundquist et al. (2012; US 2012/0077190 A1; US Patent Document citation B in PTO-892 filed 2/10/25) in view of Madsen et al. (2019; NPL citation U in PTO-892 filed 6/16/25; “Chemistries for DNA Nanotechnology”; Chem. Rev. 2019, 119, 6384-6458; DOI http://dx.doi.org/10.1021/acs.chemrev.8b00570), Addgene (2017; NPL citation V in PTO-892 filed 2/10/25), Fuller et al. (2009; NPL citation U in PTO-892 filed 2/10/25), Korlach et al. (2010; WO 2010/129019 A2; FOR citation N in PTO-892), and Balley et al. (2012; WO 2012/061778 A2).
This new 103 rejection is necessitated by claim amendments filed 5/31/26 and addresses the amended claim 1 limitation “detecting a first distinct optical signature of a first distinct capping agent of the first single nucleotide using a ring resonator optically coupled to the waveguide.”
(i) Relevant to claims 1, 4-6, 8, 10, 12-14, and 16-17 limitations, Lundquist et al. teaches sequencing by synthesis (pages 6-7, paragraphs 0052-0061) and molecular arrays and other surface associated assays (page 7, paragraphs 0062-0067) that utilize “evanescent fields emanating from the waveguides [that illuminate] materials disposed upon or proximal to the surface of the substrate” (Abstract).
Relevant to claim 1, Lundquist et al. teaches “immobilization or deposition of the polymerase/template/primer complex upon or proximal to the surface of the waveguide core” (page 6, paragraph 0056). This teaching reads on immobilizing, using a surface of a waveguide, a nucleotide fragment, where the “template” of Lundquist et al. is understood to be the nucleotide fragment that undergoes immobilizing upon a surface of a waveguide and serves as the nucleic acid strand complementary to the incorporating nucleic acids within the sequencing by synthesis (page 6, paragraph 0054). The Lundquist et al. complex containing polymerase, template, and primer reads on a nucleotide binding locus adjacent to a first nucleotide sequence, as the incorporated first single nucleotide would be incorporated through base-pair homology as mediated by the polymerase, template, and primer cooperation (Figure 7).
Additionally relevant to claim 1, Lundquist et al. teaches that the nucleotide fragment can be exposed to “nucleotides or nucleotide analogs” with “optically detectable label[s]” (page 6, paragraph 0055. This teaching reads on exposing the nucleotide fragment to a first plurality of capped nucleotides, wherein: the first plurality of capped nucleotides include a first plurality of nucleotide types;… each nucleotide type has a distinct capping agent; and each distinct capping agent has a distinct optical signature. The “nucleotides or nucleotide analogs” with “optically detectable label[s]” of Lundquist et al. read on the instant capped nucleotides with distinct capping agent and distinct optical signature.
Relevant to claims 1 and 4-6, Lundquist et al. teaches that “fluorescent detection systems” can be used “to identify which base was incorporated” with the waveguide “illumination, and more notably in the case of fluorescence based assays, excitation” (page 6, paragraphs 0055 - 0056).
This teaching reads on claim 1 detecting a first distinct optical signature of a first distinct capping agent of the first single nucleotide using the waveguide; claim 4 wherein the first distinct optical signature is a fluorescent signature; claim 6 wherein detecting the first distinct optical signature further comprises: exciting the first distinct capping agent using a waveguide light source; and claims 5-6 detecting the fluorescent signature as a function of the exciting.
Further relevant to claim 5, Lundquist et al. teaches that the waveguide light source can be “provided in a substantially different configuration” such as at “a different spatial plane” (page 3, paragraph 0029), reading upon claim 5 wherein detecting the first distinct optical signature further comprises: exciting the first distinct capping agent using an out of plane light source.
Relevant to claim 8, Lundquist et al. further teaches that “by controlling the light from individual sources, e.g., where such sources have differing spectra, one can consequently control the wavelength of the light reaching a given waveguide and its associated reaction regions” (page 4, paragraph 0039). The “differing spectra” and controllable range of light wavelengths read upon claim 8 passing a broadband light through the waveguide. Lundquist et al. teaches “an optical detection system” with the ability to “receive and detect optical signals” when “light is passed through the waveguide” (page 1, paragraph 0009). This teaching reads on claim 8 detecting the first distinct optical signal further comprising determining an attenuation frequency of the broadband light.
Relevant to claim 10, Lundquist et al. teaches that the broadband light can be generated by a “laser 904 and optional additional laser 906” paired with an “optical train [that] includes a wedge prism for separating spectrally different signal components, and a focusing lens” (Figure 9, described in page 8, paragraph 0077). This teaching of a laser with tunable properties reads upon claim 10 wherein passing the broadband light through the waveguide further comprises generating the broadband light using a tunable laser.
Relevant to claims 12-14, Lundquist et al. teaches that their invention’s “evanescent light field emanating from the waveguides at the substrate surface” (page 3, paragraph 0028) can be used as the “photochemistry” that removes the “detectable label” within their sequence by synthesis “fluorescent detection system” and fluorescently detectable nucleotide incorporation (page 6, paragraph 0055).
Together, this reads upon claim 12 wherein detecting the first distinct optical signature further comprises propagating, using the waveguide, an evanescent wave from the surface, and detecting the first distinct optical signature as a function of the evanescent wave. The Lundquist et al. removal of the “detectable label” reads upon claim 13 removing the first distinct capping agent from the first single nucleotide. The “photochemistry” that Lundquist et al. teaches removing the detectable label can be understood to read upon claim 14 wherein removing the first distinct capping agent further comprises irradiating the first distinct capping agent using the waveguide.
Relevant to claim 16, Lundquist et al. teaches that their invention can perform iterative incorporation and detection steps within page 6, paragraph 0055, “the process is repeated to identify the next base in the sequence,” reading upon claim 16 performing at least a detection iteration.
Relevant to claims 1 and 16, Lundquist et al. discloses that the immobilized template (nucleotide fragment) is “interrogated with a base or mixture of bases” with “detectable label[s] (capped nucleotides),” reading upon exposing the nucleotide fragment to a second plurality of capped nucleotides (page 6, paragraph 0055). Lundquist et al. additionally teaches that the “complex is interrogated with a base or mixture of bases” (page 6, paragraph 0056), thus reading on both the first and second capped nucleotides. The immobilized template (nucleotide fragment) remains “provided upon the surface” of the waveguide as the process occurs (page 6, paragraph 0055), reading upon claims 1 and 16 limitation of the nucleotide fragment remains attached.
Lundquist et al. teaches that their “sequencing by synthesis exploits the template directed synthesis of nascent DNA strands, e.g., using polymerase mediated strand extension, and monitors the addition of individual bases to that nascent strand” (page 6, paragraph 0054), which reads upon claim 16 a second single nucleotide, of the second plurality of capped nucleotides, remains chained to the first single nucleotide, as the polymerase mediated strand extension catalyzes linkages, or chains, between the incorporated nucleotides.
Lundquist et al. teaches that waveguide’s “illumination of the [nucleic acid] probe then excites the fluorescent label 820 allowing observation of hybridization” (page 7, paragraph 0065, and Figure 8). This teaching reads on claim 16 detecting a second distinct optical signature of a second distinct capping agent of the second single nucleotide using the waveguide.
Relevant to claim 17, Lundquist et al. teaches that “Following additional processing to remove … the detectable label, the process is repeated to identify the next base in the sequence” (page 6, paragraph 0055). This reads upon claim 17 each detection iteration is performed after removal of a capping agent from a previous detection iteration.
(ii) Lundquist et al. is silent to nucleobases paired to peptides relevant to claim 1. However, these limitations were known in the prior art and taught by Madsen et al.
Relevant to claim 1, Madsen et al. teaches that “PNA [peptide nucleic acid] is a polymer based on an N-(2-aminoethyl)-glycine backbone with nucleobases attached to each repeating unit” (page 6400, first sentence of section “3.1. Peptide Nucleic Acid (PNA)”). Madsen et al. further teaches that “The importance of PNA in DNA nanotechnology is exemplified by the straightforward method it provides for incorporating peptides in DNA nanostructures. PNA is prepared using Fmoc-based solid-phase peptide synthesis using benzhydryloxycarbonyl (Bhoc) protecting groups for the exocyclic amines of the nucleobase (Figure 15A). Therefore, PNA-peptide conjugates can easily be prepared and incorporated into DNA nanostructures” (page 6400, column 1, paragraph 3 continued to column 1, paragraph 1).
Further relevant to claim 1, Madsen et al. additionally teaches Section “6.1 Covalently Linked Protein-DNA Conjugates”, with most pertinent subsections “6.1.3. Peptide Tags for Formation of Protein-DNA Conjugates” and “6.1.4. Self-Labeling Polypeptides for Formation of Protein-DNA Conjugates”, which include teachings relevant to facilitation of immobilization with surfaces.
These teachings read on claim 1 wherein each capped nucleotide of the first plurality of capped nucleotides comprises a nucleobase covalently linked to a peptide using an enzymatically catalyzed conjugation, wherein the peptide is conjugated to a peptide backbone, wherein the peptide backbone comprises a functional group configured to facilitate immobilization with the surface of the waveguide.
(iii) Lundquist et al. and Madsen et al. are silent to severing base pair connections between the nucleotide fragment and capped nucleotides, dividing and selecting of fragments, and amplifying the nucleotide fragment relevant to claims 1-3, 16, and 18. However, these limitations were known in the prior art and taught by Addgene and Fuller et al.
Relevant to claims 2-3, Fuller et al. teaches that sequencing by synthesis sample preparation “generally involves… fragmentation of the DNA” prior to “solid-phase attachment” (page 1014, “Sample preparation,” paragraph 1), which reads on claim 2 the nucleotide fragment is a fragment of a nucleotide sample and claim 3 immobilizing the first fragment further comprises: dividing the nucleotide sample into a plurality of fragments; and selecting the first fragment from the plurality of fragments.
Relevant to claims 1, 16, and 18, Fuller et al. teaches that “Several novel amplification techniques have been introduced,” specifying variations of PCR (page 1014, “Sample preparation,” paragraph 2). As seen in Fuller et al. Figure 2 and described within the page 1016 figure caption, “Sample preparation includes arraying individual fragments of DNA on beads or other solid surface. For ensemble methods the fragments are amplified, providing a collection of identical copies for sequencing.”
This reads on claim 18 locally amplifying the nucleotide fragment; and generating a cluster of identical nucleotide fragments immobilized on the surface of the waveguide as a function of the local amplification.
Relevant to claims 1 and 16, PCR amplification typically contains a denaturation step wherein double-stranded nucleic acids are separated (Addgene page 1, “Basic PCR Program,” Step 1). This teaching reads on claims 1 and 16 severing base pair connections between the at least a nucleotide fragment and the first / second plurality of capped nucleotides.
(iv) Lundquist et al. in view of Madsen et al., Addgene and Fuller et al. is silent to nucleotide types including all deoxyribonucleic and ribonucleic acid types relevant to claims 1 and 19-20. However, these limitations were known in the prior art and taught by Korlach et al.
Relevant to claims 1 and 19-20, Korlach et al teaches: “While certain embodiments are described as having an RNA template, it will be understood that the compositions, methods, and systems are not limited to the use of RNA templates, and other types of templates may also be used, e.g., DNA, PNA, LNA, etc., and analogs, mimetics, and combinations thereof” (page 9, paragraph 0030). Additionally relevant to claims 19-20, Korlach et al. teaches: “In certain embodiments, the nucleotide monomers incorporated comprise a detectable label that identifies the type of monomer being incorporated, e.g., what nucleobase it comprises (e.g., A, T, C, G, U, and other (e.g., modified or non-natural) nucleobases, e.g., inosine (I), thiouridine, pseudouridine, dihydrouridine, queosine, wyosine, methylated bases, artificial nucleobases used for metal base pairing” (page 9, paragraph 0031).
Collectively, these teachings read on claims 1 and 19-20 nucleotide types including all deoxyribonucleic and ribonucleic acid types.
(v) Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., and Korlach et al. is silent to a ring resonator optically coupled to the waveguide relevant to claim 1. However, these limitations were known in the prior art and taught by Balley et al. Balley et al. teaches “A system for detecting a nucleic acid molecule of interest in a sample…” (claim 1).
Relevant to claim 1, Balley et al. teaches “As shown, the chip 1202 includes a plurality of optical sensors 104 each comprising linear waveguides 202 and ring resonators 208. Accordingly, light may be injected into the linear waveguides 202 via an input coupler 922 and propagated to the ring resonator 208. A binding event that brings a bead or other object in close proximity to the sensor 104 (e.g., the ring resonator 208 and/or the waveguide 202 optically coupled thereto) may disrupt the confinement of the light propagating in the ring resonator 208 and/or the waveguide 202 optically coupled thereto and cause the light to scatter out of the waveguide into free space along a path such as 1206 (indicated by dashed arrows) shown in Figure 29A. This light could thus be detected by monitoring radiation exiting the optical sensor 104 using collection optics and a detector 1234. As discussed above, the scattering is greater for light having a wavelength corresponding to the resonance wavelength of the resonator” (paragraph 0329).
(vi) Taken together, Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al. teach a method of tagged-base DNA sequencing readout on waveguide surfaces. It would have been prima facie obvious to a skilled artisan to have modified the sequencing by synthesis on waveguide surfaces of Lundquist et al. to include the nucleobase-paired-peptide of Madsen et al.; Addgene PCR basics; the Fuller et al. fragmentation and local amplification processes; the expanded investigatory panels of nucleic acids of Korlach et al.; and the ring resonator of Balley et al. It is noted that Lundquist et al., Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al. are analogous disclosures to the instant invention.
A skilled artisan would have been motivated to modify the sequencing by synthesis method of Lundquist et al. to include the amplifications of Fuller et al. because Fuller et al. teaches that “many diverse polymerases are available commercially” (page 1018, column 2, paragraph 3). Although Lundquist et al. is silent in regards to explicit amplification steps, Lundquist et al. teaches that their invention “exploits the template directed synthesis of nascent DNA strands, e.g., using polymerase mediated strand extension” (page 6, paragraph 0054), which can be understood as the extension step within PCR amplification (Addgene, page 1, “Basic PCR Program,” Step 4). As such, by combining this widely available processivity component of Fuller et al. with the method of Lundquist et al., the sequencing by synthesis approach is able to investigate a greater variety of sequences and templates enabled by the wide range of polymerase chemistries.
The skilled artisan would have been motivated to include the fragmentations of Fuller et al. because Korlach et al. teaches that fragmentation overcomes template secondary/tertiary obstructions during polymerase processing (page 27, paragraph 0064), ultimately improving the sequencing by synthesis of Lundquist et al. The skilled artisan would have further been motivated to include the Fuller et al. local amplifications because the Lundquist et al. waveguide sequencing by synthesis methodology could take advantage of the widely commercially-available polymerase chemistries. Similarly, the Lundquist et al. methodology would further benefit from combining the expanded panel of nucleic acids of Korlach et al. in order to expand the investigatory sequencing ability because a skilled artisan would be motivated to further develop “technologies that enable rapid, cost-effective access to DNA sequence information for a myriad of research and personalized medical uses,” as taught by Fuller et al. on page 1022, column 1, last sentence of paragraph 1.
The skilled artisan would be motivated to include the Madsen et al. nucleobase-paired-peptide within the Lundquist et al. methodology because Madsen et al. teaches that “The development of systems for DNA-templated polymerization of PNA further highlights its potential… The importance of PNA is partly due to its very strong binding to both DNA and RNA… The high stability of PNA-DNA complexes was shown to significantly improve incorporation of PNA compared to DNA into the center of rectangular DNA origami… Besides improving incorporation and adding stability to structures, the stronger binding of PNA to DNA also allows for invasion of DNA-DNA duplexes without the need for toeholds” (page 6400, column 1, paragraph 2). Thus, the skilled artisan would be motivated to use nucleobase-paired-peptides in order to achieve strong and stable incorporations.
The skilled artisan would further have been motivated to include the Balley et al. ring resonator within the Lundquist et al. methodology because Balley et al. teaches that “the scattering is greater for light having a wavelength corresponding to the resonance wavelength of the resonator” (paragraph 0329), indicating a detection improvement.
The skilled artisan would have a reasonable expectation of success given the teachings of Lundquist et al. in view of Madsen et al. Addgene, Fuller et al., Korlach et al., and Balley et al.
Claims 7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Lundquist et al. (2012; US 2012/0077190 A1; US Patent Document citation B in PTO-892 filed 2/10/25) in view of Madsen et al. (2019; NPL citation U in PTO-892 filed 6/16/25; “Chemistries for DNA Nanotechnology”; Chem. Rev. 2019, 119, 6384-6458; DOI http://dx.doi.org/10.1021/acs.chemrev.8b00570), Addgene (2017; NPL citation V in PTO-892 filed 2/10/25), Fuller et al. (2009; NPL citation U in PTO-892 filed 2/10/25), Korlach et al. (2010; WO 2010/129019 A2; FOR citation N in PTO-892), and Balley et al. (2012; WO 2012/061778 A2), as applied to claims 1-6, 8, 10, 12-14, and 16-20 above, and further in view of Rothberg et al. (2016; WO 2016/187580 A1; FOR citation O in PTO-892 filed 2/10/25).
The teachings of Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al. are applied to instantly rejected claims 7 and 9 as they were previously applied to claims 1-6, 8, 10, 12-14, and 16-20. Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al. renders obvious a method of tagged-base DNA sequencing readout on waveguide surfaces.
Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al. is silent to an absorption signature or a waveguide with specific material having a broad transmission window. However, these limitations were known in the prior art and taught by Rothberg et al. Rothberg et al. teaches a method of sequencing by synthesis with waveguides and labeled nucleic acids.
Relevant to claim 7, Rothberg et al. teaches that the labels can be “identified or distinguished based on a property” including the “absorption spectra” (page 2, lines 23 and 25). This reads on claim 7 the first distinct optical signature is an absorption signature.
Relevant to claim 9, Rothberg et al. page 113 lines 1-16 teaches various waveguide materials that “may be selected for particular indices of refraction”. As such, the waveguide material of Rothberg et al. can be selected to have a broad transmission window through its configurable waveguide composition.
It would have been prima facie obvious to the skilled artisan to have included the absorption signature and broad transmission window of waveguide material of Rothberg et al. in the methodology rendered obvious by Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al. Lundquist et al., Madsen et al., Addgene, Fuller et al., Korlach et al., Balley et al., and Rothberg et al. are all analogous disclosures to the instant invention.
Rothberg et al. teaches that their methods of label detections (which include absorption signatures) allows for multiple molecules and labels in “different steps of a complex reaction to be monitored,” identification of “different components of a complex reaction product,” and determination of “the order in which the different types of molecules react or interact” (page 3, lines 17-21). Combined with the ability to configure the waveguide material to be of a broad transmission window, as taught by Rothberg et al., a skilled artisan would have been motivated by the ability to expand the investigative range and signal transmission sensitivity to modify the method of Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al., and further in view of Rothberg et al. The skilled artisan would have a reasonable expectation of success based on the disclosures of Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al., and further in view of Rothberg et al.
Claims 11 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Lundquist et al. (2012; US 2012/0077190 A1; US Patent Document citation B in PTO-892 filed 2/10/25) in view of Madsen et al. (2019; NPL citation U in PTO-892 filed 6/16/25; “Chemistries for DNA Nanotechnology”; Chem. Rev. 2019, 119, 6384-6458; DOI http://dx.doi.org/10.1021/acs.chemrev.8b00570), Addgene (2017; NPL citation V in PTO-892 filed 2/10/25), Fuller et al. (2009; NPL citation U in PTO-892 filed 2/10/25), Korlach et al. (2010; WO 2010/129019 A2; FOR citation N in PTO-892), Balley et al. (2012; WO 2012/061778 A2), and Rothberg et al. (2016; WO 2016/187580 A1; FOR citation O in PTO-892 filed 2/10/25), as applied to claims 1-10, 12-14, and 16-20 above, and further in view of Maxham et al. (2010; US 2010/0075309 A1; US Patent Document citation C in PTO-892 filed 2/10/25).
The teachings of Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al., and further in view of Rothberg et al. are applied to instantly rejected claims 11 and 15 as they were previously applied to claims 1-10, 12-14, and 16-20. Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al., and further in view of Rothberg et al. renders obvious a method of tagged-base DNA sequencing readout on waveguide surfaces.
Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al., and further in view of Rothberg et al. is silent to detection using at least a spectrometer or removing the first distinct capping agent using a chemical agent relevant to claims 11 and 15. However, these limitations were known in the prior art and taught by Maxham et al. Maxham et al. invention of a sequencing by synthesis uses waveguides for solid support and fluorescently labeled nucleotides.
Maxham et al. teaches that their “invention is generally applicable to any of a variety of optical assays that require substantial illumination and/or photoactivated conversion or excitation of chemical groups, e.g., fluorophores… and may be used with…. spectrophotometry” (page 15, paragraph 0085). This teaching reads upon the instant claim 11 limitation of detecting the first optical signature using at least a spectrometer, as the spectrometer is encompassed within the scope of “optical assays that require substantial illumination and/or photoactivated conversion” and spectrophotometry includes instrumentations that include spectrometers.
Maxham et al. additionally teaches an embodiment of their sequencing by synthesis invention includes “the label is naturally released upon incorporation of the labeled nucleotides by the polymerase, and so need not be released by alternative means, e.g., a photocleavage event” (page 24, paragraph 0140). This reads upon instant claim 15 removing the first distinct capping agent (“label”) using a chemical agent (“polymerase”).
It would have been prima facie obvious to the skilled artisan to include the Maxham et al. spectrometer and chemical agent within the sequencing by synthesis method rendered obvious by Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., and Balley et al., and further in view of Rothberg et al. Lundquist et al., Madsen et al., Addgene, Fuller et al., Korlach et al., Balley et al., Rothberg et al., and Maxham et al. are all analogous disclosures to the instant invention.
Rothberg et al. teaches that “output signals from the one or more sensors may then be used to distinguish a marker from among a plurality of markers” (page 99, lines 4-5). This teaching provides the motivation of including an additional means of detecting a first optical signature (“sensor”) in order to better resolve the optical signatures of the unique nucleotide capping agents (“distinguish a marker”) during the sequencing by synthesis process. A skilled artisan would be motivated to include a chemical agent because Maxham et al. teaches that using the polymerase chemical agent instead of photocleavage to remove the first distinct capping agent enables “the processive incorporation of multiple labeled nucleotides [that] can be monitored in real time… without stalling on the template nucleic acid” (page 24, paragraph 0140).
The skilled artisan would have a reasonable expectation of success based on the disclosures of Lundquist et al. in view of Madsen et al., Addgene, Fuller et al., Korlach et al., Balley et al., and Rothberg et al., and further in view of Maxham et al.
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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/SARAH JANE KENNEDY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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