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 .
This action is in response to the papers filed on September 8, 2025.
Election/Restrictions
Applicant’s election without traverse of the single lectin Concanavalin A and the corresponding ligand mannose in the reply filed on October 28, 2024 is acknowledged.
Claims 9-10, 20-23, 26, and 28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 October 28, 2024.
Priority
This application claims the benefit of U.S. Provisional Patent Application No. 63/077,416, filed September 11, 2020.
Claim Status/Action Summary
Currently, claims 1, 5-7, 9-20, and 22-28 are pending.
Claims 9-10, 20, 22, 23, 26, and 28 are withdrawn as directed to a nonelected species.
Claims 2-4, 8, and 21 were canceled by applicant.
Claims 1, 5-7, 11-19, 24-25, and 27 are under examination.
Any objections and rejections not reiterated below are hereby withdrawn.
The 102(a)(1) rejections of record over Zhang et al., over Zhang et al. as evidenced by Moni et al., and over Chu et al. have been withdrawn in view of the amendments to claim 1.
Claim Objections
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
A series of singular dependent claims is permissible in which a dependent claim refers to a preceding claim which, in turn, refers to another preceding claim.
A claim which depends from a dependent claim should not be separated by any claim which does not also depend from said dependent claim. It should be kept in mind that a dependent claim may refer to any preceding independent claim. In general, applicant's sequence will not be changed. See MPEP § 608.01(n).
Claims 24 and 25 are objected to because claim 24 has been amended to depend from claim 25 rather than claim 1. As amended, claim 24 is a dependent claim that refers to claim 25 (i.e. claim 24 is not a dependent claim that refers to a preceding claim).
This is a new objection necessitated by the amendments to the claims.
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.
Claim 7 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 7 recites the limitation "the first and second elements" in line 1. There is insufficient antecedent basis for this limitation in the claims as amended.
This is a new grounds of rejection necessitated by the amendments to the claims.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 25 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Drmanac et al., US 2017/0240961 A1 (published August 24, 2017).
This rejection has been updated as necessitated by the amendments to the claims.
Regarding claim 25, Drmanac et al. teaches a method of sequencing (i.e. detecting an element or analyte) comprising: incorporating a nucleotide analogue comprising a non-fluorescent affinity tag (i.e. the element comprises a first nucleotide) into a primer immobilized to a substrate with a polymerase (i.e. coupling a first element-affinity tag complex to a first substrate comprises incorporating the first nucleotide into a first oligonucleotide coupled to the first substrate using a sequence of a second oligonucleotide; a template polynucleotide) and subsequently contacting the incorporated first nucleotide analogue with a detectably labeled affinity agent that specifically binds the first nucleotide analogue (i.e. after coupling the first element-affinity tag to the first substrate, coupling a labeled affinity agent to the first affinity tag), and finally, detecting the specifically labeled incorporated first nucleotide analogue. (i.e. after coupling the first affinity agent to the first affinity tag, detecting the first element (i.e. nucleotide analogue) using at least detection of the first affinity agent (Drmanac et al., paragraph 0009-0010). Drmanac et al. further teaches that the affinity agent and affinity tag are members of a specific binding pair and may be a lectin and carbohydrate (Drmanac et al., paragraphs 0028-0029). Therefore Drmanac et al. teaches all of the method steps in the order specifically recited by the amended claim 25. Furthermore, Drmanac et al. teaches that the first substrate comprises a bead (Drmanac et al., paragraph 0079).
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.
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, 5-7, 11-13, 18, 24-25, and 27 are rejected under U.S.C. 103 as being unpatentable over Drmanac et al., US 2017/0240961 A1 (published August 24, 2017) in view of Engelhardt et al., US 8,097,405 B1 (issued January 17, 2012).
This rejection has been updated as necessitated by the amendments to the claims.
Regarding claims 1 and 5, Drmanac et al. teaches a method of sequencing (i.e. detecting a nucleotide) comprising: incorporating a nucleotide analogue comprising a non-fluorescent affinity tag (i.e. the element comprises a first nucleotide) into a primer immobilized to a substrate with a polymerase (i.e. coupling a first element-affinity tag complex to a first substrate comprises incorporating the first nucleotide into a first oligonucleotide coupled to the first substrate using a sequence of a second oligonucleotide; a template polynucleotide) and subsequently contacting the incorporated first nucleotide analogue with a detectably labeled affinity agent that specifically binds the first nucleotide analogue (i.e. after coupling the first element-affinity tag to the first substrate, coupling a labeled affinity agent to the first affinity tag), and finally, detecting the specifically labeled incorporated first nucleotide analogue. (i.e. after coupling the first affinity agent to the first affinity tag, detecting the first element (i.e. nucleotide analogue) using at least detection of the first affinity agent (Drmanac et al., paragraph 0009-0010). Drmanac et al. further teaches that the affinity agent and affinity tag are members of a specific binding pair and may be a lectin and carbohydrate (Drmanac et al., paragraphs 0028-0029). Even more, Drmanac et al. teaches the method of sequencing comprises nucleotide analogues having different nucleobases where the nucleobases are linked to a detectable and distinguishable label or affinity tag (i.e. the different nucleobases, A,T,C,G have different affinity tags/carbohydrates) (Drmanac et al., paragraph 0077) and multiple detectably and distinguishably labeled affinity agents (i.e. lectins specific for the different tags), wherein the labels comprise fluorophores (Drmanac et al., paragraph 0077).
Drmanac et al. do not teach that the lectin affinity agent and carbohydrate affinity tag can be Concanavalin A and mannose, respectively.
However, Engelhardt et al. teaches a method of detecting a nucleic acid containing at least one nucleotide comprising a “Sig moiety”. Said “Sig moiety is a polysaccharide or oligosaccharide or monosaccharide (i.e. a nucleotide-sugar complex), which is capable of complexing with or being attached to a sugar or polysaccharide binding protein, such as a lectin, e.g. Concanavalin A.” (Engelhardt et al. column 25, line 3-7) and that said lectin can be labeled with fluorescein or an appropriate enzyme (i.e. a fluorophore or a polypeptide) (Engelhardt et al., column 19 line 52-62) Engelhardt et al. further teaches a method of preparing labeled oligonucleotide probes comprising incorporating glycosylated nucleotide analogs by nick translation. (Engelhardt et al., column 10, line 49-62) (i.e. the glycosylated nucleotide is a substrate for a DNA polymerase). Finally, Engelhardt et al. teaches nucleic acids can be labeled with multiple sugars including glucose, mannose, and maltotriose (Engelhardt, column 10 line 40-62) (i.e. the nucleotide sugar complex may further comprise a second sugar coupled to the nucleotide).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention for one of ordinary skill in the art to modify the method taught by Drmanac et al. by using the specific glycosylated nucleotides (i.e. comprising nucleotides labeled with mannose) taught by Engelhardt et al. and detecting the sugar-labeled nucleotides with a fluorescently-labeled lectin (i.e. comprising fluorescently-labeled Concanavalin A) as taught by Drmanac et al. and Engelhardt et al. The ordinary artisan would have been motivated to use the sugar-labeled nucleotides taught by Engelhardt in the method taught by Drmanac et al. because Engelhardt et al. teaches that “modified mono, oligo and polysaccharide moieties, when employed as the Sig moiety in the preparation of the special nucleotides of this invention, provide an added versatility with respect to the detection of the nucleotides.” (Engelhardt et al., column 30, line 45-59) Therefore, the ordinary artisan would have been reasonably confident that the sugar-labeled nucleotides taught by Engelhardt et al. would have been readily usable in the method taught by Drmanac et al. and that said sugar-labeled nucleotides would have succeeded in provided greater versatility in detection methodology than the generic carbohydrate-lectin binding pair(s) taught by Drmanac et al.
Regarding claims 6-7, Drmanac et al. teaches the template nucleic acid is immobilized on a solid surface such as a flow cell (Drmanac et al., paragraph 0079) and the incorporation reaction mixture comprises a mixture of nucleotide analogues having different nucleobases where the nucleobases are linked to a detectable and distinguishable label or affinity tag (i.e. the different nucleotides have different affinity tags/carbohydrates) (Drmanac et al., paragraph 0077). Finally, Drmanac et al. teaches that the incorporation mixture comprises multiple detectably and distinguishably labeled affinity agents (i.e. lectins), wherein the labels comprise fluorophores (Drmanac et al., paragraph 0077).
Regarding claim 11, Engelhardt et al. teaches nucleic acids can be labeled with multiple sugars including glucose, mannose, and maltotriose (Engelhardt, column 10 line 40-62) (i.e. the nucleotide sugar complex may further comprise a second sugar coupled to the nucleotide).
Regarding claim 12, Engelhardt et al. teaches Concanavalin binds to glucose and mannose (i.e. the first lectin couples to the first and/or second sugar) (Engelhardt, column 10, lines 49-62).
Regarding claim 13, Drmanac et al. teaches that the labeled affinity agent (i.e. the first lectin) is detectably labeled with a fluorophore (i.e. the fluorophore is coupled to the first lectin) (Drmanac et al., paragraph 0077).
Regarding claim 18, Drmanac et al. teaches that the affinity agents (i.e. lectins) are detectably labeled with a fluorophore prior to coupling the lectin to the affinity tag (i.e. carbohydrate labeled nucleotide) (Drmanac et al., paragraph 10).
Regarding claims 25 and 24, Drmanac et al. teaches that the first substrate comprises a bead (Drmanac et al., paragraph 0079).
Regarding claim 27, Engelhardt et al. teach the first sugar comprises mannose (i.e. a monosaccharide) (Engelhardt, column 10, lines 49-62).
Claims 1, 5-7, 11-13, and 27 are/remain rejected under 35 U.S.C. 103 as being unpatentable over US 6,013,431 A (Soderlund, issued December 2, 1993) in view of US-8,097,405 (Engelhardt, issued January 17, 2012).
This rejection has been revised as necessitated by the amendments to the claims.
Regarding claims 1 and 5-6, Soderlund teaches a method for detecting a single nucleotide variation (i.e. an element, an analyte, a first nucleotide) in a target sequence (i.e. a second oligonucleotide) comprising hybridizing a primer immobilized on a solid support (i.e. flowing a solution over a first oligonucleotide coupled to a substrate) immediately adjacent to the single nucleotide of interest and incorporating a single radioactively labeled ddNTP into the primer (Soderlund, figure 1, column 4, lines 7-15, and column 8, lines 19-38).
Soderlund does not teach that the first nucleotide may be labeled with a sugar and detected by a fluorescently labeled lectin.
However, Engelhardt teaches a method of detecting a nucleic acid (i.e. an element; an analyte) containing at least one nucleotide comprising a “Sig moiety”. Said “Sig moiety is a polysaccharide or oligosaccharide or monosaccharide (i.e. a nucleotide-sugar complex), which is capable of complexing with or being attached to a sugar or polysaccharide binding protein, such as a lectin, e.g. Concanavalin A.” (Engelhardt column 25, line 3-7) and that said lectin can be labeled with fluorescein or an appropriate enzyme (i.e. a fluorophore or a polypeptide) (Engelhardt, column 19 line 52-62) Engelhardt further teaches a method of preparing labeled oligonucleotide probes comprising incorporating glycosylated nucleotide analogs by nick translation. (Engelhardt, column 10, line 49-62) (i.e. the glycosylated nucleotide is a substrate for a DNA polymerase). Finally, Engelhardt et al. teaches nucleic acids can be labeled with multiple sugars including glucose, mannose, and maltotriose (Engelhardt, column 10 line 40-62) (i.e. the nucleotide sugar complex may further comprise a second sugar coupled to the nucleotide).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention for one of ordinary skill in the art to modify the method taught by Soderlund by replacing radioactively-labeled nucleotide analog taught by Soderlund with the sugar-labeled nucleotide analog taught by Engelhardt and detecting the sugar-labeled nucleotides with a fluorescently-labeled lectin as taught by Engelhardt. The ordinary artisan would have been motivated to use the sugar-labeled nucleotides taught by Engelhardt in the method taught by Soderlund because Engelhardt teaches that “modified mono, oligo and polysaccharide moieties, when employed as the Sig moiety in the preparation of the special nucleotides of this invention, provide an added versatility with respect to the detection of the nucleotides.” (Engelhardt, column 30, line 45-59) Therefore, the ordinary artisan would have been reasonably confident that the sugar-labeled nucleotides taught by Engelhardt would have been readily usable in the method taught by Soderlund and that said sugar-labeled nucleotides would have succeeded in provided greater versatility in detection methodology than the radioactively-labeled nucleotides taught by Soderlund.
Regarding claim 7, Engelhardt teaches purine and pyrimidine nucleotides may comprise the “sig moiety” (Engelhardt, column 22 line 39-50) and said “Sig moiety is a polysaccharide or oligosaccharide or monosaccharide (i.e. a sugar), which is capable of complexing with or being attached to a sugar or polysaccharide binding protein, such as a lectin, e.g. Concanavalin A.” (Engelhardt column 25, line 3-7) (i.e. different nucleotides are labeled with different sugars)
Regarding claim 11, Engelhardt teaches nucleic acids can be labeled with multiple sugars including glucose and maltotriose. (Engelhardt, column 10 line 49-62) (i.e. the element sugar complex may further comprise a second sugar coupled to the element)
Regarding claim 12, Engelhardt teaches a lectin (Concanavalin A) capable of binding to both glucose and maltotriose (i.e. the first lectin couples to the second sugar) (Engelhardt, column 10 line 40 and lines 49-62)
Regarding claim 13, Engelhardt teaches a method comprising detecting a glycosylated substrate or molecule with an appropriate lectin carrying a label, such as fluorescein (i.e. a fluorophore) (Engelhardt, column 19, line 51-62)
Regarding Claim 27, Engelhardt teaches that the first sugar comprises a monosaccharide (Engelhardt, column 25, line 3-7).
Claims 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Drmanac et al., US 2017/0240961 A1 (published August 24, 2017) in view of Engelhardt et al., US-8097405 (Engelhardt, issued January 17, 2012). as applied to claims 1, 5-7, 11-13, 18, and 27 above, and further in view of Babu et al., “Sugar-Quantum Dot Conjugates for a Selective and Sensitive Detection of Lectins”. Bioconjugate Chem. 18, 146-151 (2007).
This rejection has been updated as necessitated by the amendments to the claims.
Regarding claims 1, 5-7, 11-13, 18, and 27 as discussed in the 103 rejection above and briefly summarized here, Drmanac et al. in view of Engelhardt et al. teaches a method of massively parallel sequencing nucleic acids comprising incorporating sugar-labeled nucleotide analogues into substrate-immobilized primers using a sequence of a template molecule hybridized to the primer wherein the incorporated nucleotide analogues are indirectly detected using fluorescently labeled lectins that specifically bind to the sugar label on the incorporated nucleotide analogue.
Regarding claim 14, Drmanac et al. in view of Engelhardt et al. does not appear to explicitly teach that the lectins may be labeled with a plurality of fluorophores.
However, Babu teaches fluorescent quantum dots that are functionalized with maltotriose (MT) (a sugar bound by Concanavalin A) for the purpose of highly sensitive detection of as little as 100 nM lectin (Concanavalin A) by fluorescent agglutination. (Babu, Abstract)
Therefore, it would have been prima facie obvious prior to the effective filing date for one of ordinary skill in the art to modify the method of detecting incorporated sugar labeled nucleotide analogues using lectins that are directly labeled with a single fluorophore, taught by Drmanac et al. in view of Engelhardt et al. by replacing the direct fluorophore label pre-conjugated to the lectin with the Con A (i.e. a lectin) binding maltotriose-conjugated, fluorescent quantum dots taught by Babu. The ordinary artisan would have been motivated to replace the direct fluorescent labels taught by Drmanac et al. in view of Engelhardt et al. with unmodified Con A (i.e. lectin) and the MT-labeled quantum dots taught by Babu because Babu teaches quantum dots have several advantages over fluorophore labels including: single-wavelength excitation, size-dependent narrow emission, high luminescence, low photobleaching, and small size (1-100 nm) (Babu, page 1, column 2) Therefore, the ordinary artisan would have been reasonably confident that replacing the direct fluorophore lectin labels taught by Drmanac et al. in view of Engelhardt et al. with the MT-coupled quantum dots taught by Babu would have successfully increased the sensitivity of the assay taught by Drmanac et al. in view of Engelhardt et al. due to the advantageous properties of the quantum dot labels taught by Babu.
Regarding claim 14, Babu teaches multivalent binding of the MT-coupled quantum dots to Concanavalin A (i.e. a plurality of fluorophores are coupled to the lectin) (Babu, page 150, column 2, paragraph 2)
Regarding claim 15, Babu teaches coupling a polymer comprising the first fluorophore (the functionalized quantum dot) to the first lectin (Concanavalin A) through a sixth sugar (maltotriose) (Babu, page 149, column 2, paragraph 2)
Regarding claim 16, Babu teaches that the polymer comprises a nanoparticle (i.e. a quantum dot, a bead) (Babu, scheme 1 and figure 1)
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Drmanac et al., Engelhardt et al., and Babu et al. as applied to claims 14-16 above, and further in view of He et al., “One-Step Instant Synthesis of Protein-Conjugated Quantum Dots at Room Temperature.” Sci Rep 3, 2825 (2013).
This rejection has been updated as necessitated by the amendments to the claims.
Regarding claims 14-16, Drmanac et al., Engelhardt et al., and Babu et al. teach methods of massively parallel sequencing nucleic acids comprising incorporating sugar-labeled nucleotide analogues “affinity tags” comprising mannose into substrate-immobilized primers using a sequence of a template molecule hybridized to the primer wherein the incorporated nucleotide analogues are indirectly detected using lectin “affinity agents” comprising Concanavalin A that specifically bind to the sugar label on the incorporated nucleotide analogue. Drmanac et al. in view of Engelhardt et al. and Babu et al. further teach that the lectin “affinity agents” may be detected by direct or indirect labeling wherein the lectin comprises fluorophore(s) (i.e. direct detection) or is bound by maltotriose-coupled, fluorescent quantum dots (i.e. indirect detection).
Drmanac et al. in view of Engelhardt et al. and Babu et al. do not appear to teach that the polymer comprising the fluorophore and the second sugar comprises a polypeptide.
However, He et al. teaches a convenient method for one-step instant synthesis of protein-conjugated quantum dots at room temperature for a variety of proteins with a wide range of molecular weights and isoelectric points (He et al., Abstract), including small peptides (He et al., figure 6) and BSA (He et al., figure 1).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention for one of ordinary skill in the art to modify the method of detecting nucleotide-sugar complexes with a first lectin and sugar-conjugated quantum dots taught by Drmanac et al. in view of Engelhardt et al. and Babu et al. by generating quantum dots conjugated to mannose- or maltotriose-modified small peptides by the rapid quantum dot synthesis method taught by He et al. The ordinary artisan would have been motivated to generate quantum dots comprising sugars similar to those taught by Babu by the method of He et al. because He et al. teaches that the conjugation reaction is complete within 1 second. (He et al., Abstract) Therefore, the ordinary artisan would have reasonably expected second-sugar-peptide conjugated quantum dots generated by the “instant synthesis” method of He to successfully detect element-sugar complexes bound to a first lectin in the method taught by Drmanac et al. in view of Engelhardt et al. and Babu et al.
Claims 19 and 25-24 are rejected under 35 U.S.C. 103 as being unpatentable over Drmanac et al., Engelhardt et al., and Babu et al. as applied to claims 14-16 above, and further in view of Chu et al., US 2003/0104492 A1 (published June 5, 2003)
Regarding claims 19 and 25-24, Drmanac et al., Engelhardt et al., and Babu et al. teach methods of massively parallel sequencing nucleic acids comprising incorporating sugar-labeled nucleotide analogues “affinity tags” comprising mannose into substrate-immobilized primers using a sequence of a template molecule hybridized to the primer wherein the incorporated nucleotide analogues are indirectly detected using lectin “affinity agents” comprising Concanavalin A that specifically bind to the sugar label on the incorporated nucleotide analogue. Drmanac et al. in view of Engelhardt et al. and Babu et al. further teach that the lectin “affinity agents” may be detected by direct or indirect labeling wherein the lectin comprises fluorophore(s) (i.e. direct detection) or is bound by maltotriose-coupled, fluorescent quantum dots (i.e. indirect detection).
Drmanac et al. in view of Engelhardt et al. and Babu et al. do not appear to explicitly teach that the lectin “affinity agents” may be labeled after coupling the first lectin to the first lectin.
However, Chu et al. teaches a method of detecting Mannose-BSA (i.e. an element-sugar or analyte-sugar complex wherein the sugar comprises mannose) with colloidal-gold labelled Concanavalin A (i.e. the lectin comprises Concanavalin A) wherein the Mannose-BSA binds to labeled Concanavalin A on a membrane (i.e. a substrate) and the Mannose-BSA is detected by detection of the colloidal gold label on Concanavalin A. (Chu et al., paragraph 79-83). Chu et al. further teaches a method for rapid detection of at least a first carbohydrate in a carbohydrate-containing sample comprising steps of: (a) retaining the sample molecule on a region of one liquid permeable reaction membrane (i.e. coupling a first element-sugar complex to a first substrate), (b) flowing a solution of a first lectin capable of binding the first carbohydrate through the reaction membrane to bind the first lectin to the retained first carbohydrate, the lectin being directly conjugated to a label prior to binding the carbohydrate (i.e. after coupling the first element-sugar complex to the substrate, coupling a first lectin to the first sugar), and (c) thereafter, detecting the label bound on the one reaction membrane, indicating the presence of the first carbohydrate (i.e. after coupling the first lectin to the first sugar, detecting the first element using at least detection of the first lectin) (Chu, paragraph 0005-0008). Chu further teaches detecting Mannose-BSA (i.e. an element-sugar complex) by the method discussed above (Chu, paragraph 0069-0073). Chu does not teach that the lectin (Concanavalin A) is coupled to a fluorophore.
However, Babu teaches fluorescent quantum dots that are functionalized with maltotriose (MT) (a sugar bound by Concanavalin A) for the purpose of highly sensitive detection of as little as 100 nM lectin (Concanavalin A) by fluorescent agglutination. (Babu, Abstract)
Therefore, it would have been prima facie obvious prior to the effective filing date for one of ordinary skill in the art to modify the method taught by Drmanac et al. in view of Engelhardt et al. and Babu et al. of detecting a sugar-labeled “affinity tagged” nucleotide after incorporation of said nucleotide into an oligonucleotide immobilized to a solid support with a lectin “affinity agent” that has previously been labeled directly or indirectly (as with the fluorescent particles taught by Babu et al.) to couple the fluorescently-labeled particles to the lectin after binding of the lectin to the incorporated sugar-labeled nucleotide.
The ordinary artisan would have been motivated to perform this simple rearrangement of steps (indirect fluorescent detection after, rather than before the primary binding event) because this arrangement of steps is widely used in the biological arts to increase detection specificity by allowing for wash steps between the binding of the primary affinity agent (analogous to a primary antibody in (for example) a western blot or immunofluorescence assay) and the binding of the secondary (detectable) affinity agent to the first affinity agent (analogous to a secondary, fluorescently labeled antibody in (for example) a western blot or immunofluorescence assay).
Conclusion
No claim is 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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/Z.M.T./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682