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 .
Election/Restrictions
Applicant’s election without traverse of Group I, including claims 1-8, 10-19, 22, and 24-25 in the reply filed on 16 June 2026 is acknowledged.
Applicant’s election without traverse of [Pd(Allyl)Cl]2 as the species for Species Election 1, THP as the species for Species Election 2, cyclodextrins as the species for Species Election 3, and sulfonated β-cyclodextrin as the species for Species Election 4 in the reply filed on 16 June 2026 is acknowledged.
Claims 13-16 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 16 June 2026.
Information Disclosure Statement
The information disclosure statement (IDS) filed 22 July 2024 is considered, initialed, and attached hereto.
Claim Status
Claims 1-8, 10-19, 22, and 24-25 are pending.
Claims 9, 20-21, 23, and 26-64 are canceled.
Claims 13-16 are withdrawn, see Election/Restrictions section above.
Claims 1-8, 10-12, 17-19, 22, and 24-25 are under examination.
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.
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 1-8, 10-12, 17, 22, and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Francais et al. (US Patent Document Cite No 60 on the IDS filed 22 July 2024)(US 2021/0403500, published 30 December 2021, effectively filed 22 June 2020), herein Francais, in view of Fedorov et al. (US Patent Document Cite No 48 on the IDS filed 22 July 2024)(US 2014/0017674, published 16 January 2014, effectively filed 5 June 2012), herein Fedorov, and in view of Bricout et al. (“Chemically Modified Cyclodextrins: An Attractive Class of Supramolecular Hosts for the Development of Aqueous Biphasic Catalytic Processes” Sustainability 1(4), pages 924-945 (2009)), herein Bricout.
Regarding claim 1, Francais teaches a method of sequencing a plurality of different target polynucleotides ([0132-0133], [0152], [0204]), comprising:
(a) contacting a solid support with an incorporation mixture comprising DNA polymerase and one or more of four different types of nucleotides, wherein the solid support comprises a plurality of different target polynucleotides immobilized thereon, and sequencing primers that are complementary and hybridized to at least a portion of the target polynucleotides([0159] teaching the incorporation mixture; [0181] teaching the solid support; [0133], [0165], and [0188] teaching the sequencing primers);
(b) incorporating one type of nucleotides into the sequencing primers to produce extended copy polynucleotides, wherein each of the four types of nucleotides comprises a 3’ blocking group ([0153]);
(c) performing one or more fluorescent measurements of the extended copy polynucleotides ([0154] teaching detecting; [0150] teaching the detection being of a fluorescent label, similarly taught in [0017]; [0189] optical reading of the signal is equivalent to imaging; [0187] also teaching imaging for determination of the base incorporated);
(d) removing the 3’ blocking groups of the incorporated nucleotides in an aqueous solution comprising an active palladium catalyst ([0155], [0161]).
However, Francais does not teach the method wherein the aqueous cleavage solution comprises one or more additives that comprise one or more water soluble macrocycles. This deficiency is made up for in the teachings of Fedorov and Bricout.
Regarding claim 1, Fedorov teaches the use of various cyclodextrins, a type of water soluble macrocycle, as additives in biochemical assays involving fluorescent labels (such as the sequencing by synthesis reaction taught by Francais) for reducing/preventing non-specific association of reagents that interfere with the assay, thereby improving the assay with reduced background signal levels ([0003], [0005-0006], [0018], [0025-0027], [0055-0056], [0060-0062], [0088-0089]).
Regarding claim 1, Bricout teaches that cyclodextrins stabilize metallic catalysts including palladium catalysts (Section 2.3 pages 933-935).
Regarding claim 2, the combination of Francais, Federov, and Bricout teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 above), and Francais further teaches the method wherein the active palladium catalyst is Pd(0) ([0128]).
Regarding claim 3, the combination of Francais, Federov, and Bricout teach the method of claim 2 (see 35 U.S.C. 103 rejection of claim 2 above), and Francais further teaches the method wherein the Pd(0) is formed in situ from a Pd(II) complex and one or more water soluble phosphine ([0128]).
Regarding claims 4 and 5, the combination of Francais, Federov, and Bricout teach the method of claim 3 (see 35 U.S.C. 103 rejection of claim 3 above), and Francais further teaches the method wherein the Pd(II) complex comprises [Pd(Allyl)Cl]2, the elected species of Pd(II) complex ([0128]).
Regarding claims 6 and 7, the combination of Francais, Federov, and Bricout teach the method of claim 3 (see 35 U.S.C. 103 rejection of claim 3 above), and Francais further teaches the method wherein the one or more water soluble phosphines comprise THP, the elected species of water soluble phosphine ([0128]).
Regarding claims 8 and 10-12, the combination of Francais, Federov, and Bricout teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 above), and Federov and Bricout each further teach that the one or more water soluble macrocycles comprise water soluble cyclodextrins or optionally substituted analogs, salts, or hydrates thereof that comprise sulfonated beta-cyclodextrin, the elected species of water soluble macrocycle and water soluble cyclodextrin respectively (Bricout teaches on the last paragraph of page 928 through the second paragraph of page 929 that water-soluble phosphines can form inclusion complexes with beta-cyclodextrin that lead to a decrease in activity of the catalytic system, which would be possible in the combination with Francais because in [0128] Francais teaches using water-soluble phosphines in the method, and further teaches that this negative interaction could be avoided by modifications of the beta-cyclodextrin such as the introduction of sulfobutyl ether groups on the beta-cyclodextrin, thereby teaching the use of a sulfonated beta-cyclodextrin; Federov teaches in [0026] the additive being a cylodextrin and specifically beta-cyclodextrin when n is 7 and in [0057] that the additive may include a water solubilizing group such as a sulfonyl, thereby teaching that the additive may be a sulfonated beta-cyclodextrin).
Regarding claim 17, the combination of Francais, Federov, and Bricout teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 above), and Francais further teaches the method wherein the aqueous cleavage solution further comprises one or more oxygen scavengers and/or phosphine reducing agents ([0129] and [0163] teach including ascorbic acid or a salt thereof, which is identified in the instant specification at [0085] as a species of oxygen scavenger; Examiner further notes that Francais identifies ascorbic acid as a reducing agent).
Regarding claim 22, the combination of Francais, Federov, and Bricout teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 above), and Francais further teaches the method further comprising (e) washing the solid support with an aqueous wash solution, and wherein steps (a) to (e) are repeated at least 50, 100, 150, 200, 250 or 300 cycles to determine the target polynucleotide sequences ([0156-0157]).
Regarding claim 24, the combination of Francais, Federov, and Bricout teach the method of claim 22 (see 35 U.S.C. 103 rejection of claim 22 above), and Francais further teaches the method wherein the aqueous wash solution comprises at least one Pd(II) scavenger ([0173]).
Regarding claim 25, the combination of Francais, Federov, and Bricout teach the method of claim 22 (see 35 U.S.C. 103 rejection of claim 22 above), and Francais further teaches the method wherein the incorporation mixture and/or aqueous wash solution further comprises at least one Pd(0) scavenger ([0167-0168], [0173]).
In view of the advantages of cyclodextrins in reducing background fluorescent signal levels as taught by Federov and stabilizing palladium catalysts as taught by Bricout, one of ordinary skill in the art would be motivated to modify the sequencing-by-synthesis method taught by Francais with the inclusion of a cyclodextrin, a type of water soluble macrocycle, in the aqueous cleavage solution in order to improve the method with improved stability of the palladium catalyst and reduced background signal. One of ordinary skill in the art would have a reasonable expectation of success in this combination because Federov teaches the compatibility of cyclodextrins with fluorescence based assays, such as the sequencing-by-synthesis method of Francais. Therefore, the invention of as whole of claims 1-8, 10-12, 17, 22, and 24-25 would have been prima facie obvious to one of ordinary skill in the art prior to the effect filing date of the claimed invention.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Francais et al. (US Patent Document Cite No 60 on the IDS filed 22 July 2024)(US 2021/0403500, published 30 December 2021, effectively filed 22 June 2020), herein Francais, in view of Fedorov et al. (US Patent Document Cite No 48 on the IDS filed 22 July 2024)(US 2014/0017674, published 16 January 2014, effectively filed 5 June 2012), herein Fedorov, and in view of Bricout et al. (“Chemically Modified Cyclodextrins: An Attractive Class of Supramolecular Hosts for the Development of Aqueous Biphasic Catalytic Processes” Sustainability 1(4), pages 924-945 (2009)), herein Bricout, as applied to claims 1-8, 10-12, 17, 22, and 24-25 above, and further in view of Arslan et al. (US 11,220,707, issued 11 January 2022, effectively filed 17 June 2021), herein Arslan.
Regarding claim 18, the combination of Francais, Federov, and Bricout teach the method of claim 17 (see 35 U.S.C. 103 rejection of claim 17 above). However, neither Francais, Federov, nor Bricout teach the method wherein the one or more oxygen scavengers comprise sodium sulfite, sodium bisulfite, or sodium metabisulfite, or combinations thereof. This deficiency is made up for in the teachings of Arslan.
Regarding claim 18, Arslan teaches a method of sequencing-by-synthesis similar to that taught by Francais wherein the removal of the 3’ blocking group/chain terminating moiety can be conducted using a cleaving reagent, wherein the cleaving reagent can include oxygen scavengers (paragraph starting on col 217 line 41), wherein the cleaving reagent comprises at least one cleaving compound (col 246 lines 52-55), wherein the cleaving compound comprises a palladium catalyst (col 246 lines 60-61), and wherein the cleaving compound can include at least one oxygen scavenger such as sodium sulfite (col 248 lines 64-68).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to perform the simple substitution of the sodium sulfite oxygen scavenger taught by Arslan for the reducing agent exemplified by ascorbic acid, since ascorbic acid is a type of oxygen scavenger and oxygen scavengers are a type of reducing agent, in the method for determining the sequence of polynucleotides taught by the combination of Francais, Federov, and Bricout (MPEP §2143 I. B.). One of ordinary skill in the art could have performed this substitution and would have found the results of this substitution predictable because both ascorbic acid and sodium sulfite are oxygen scavengers and therefore perform the same function in the method and because both are methods of sequencing-by-synthesis. Therefore, the invention as a whole of claim 18 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Francais et al. (US Patent Document Cite No 60 on the IDS filed 22 July 2024)(US 2021/0403500, published 30 December 2021, effectively filed 22 June 2020), herein Francais, in view of Fedorov et al. (US Patent Document Cite No 48 on the IDS filed 22 July 2024)(US 2014/0017674, published 16 January 2014, effectively filed 5 June 2012), herein Fedorov, and in view of Bricout et al. (“Chemically Modified Cyclodextrins: An Attractive Class of Supramolecular Hosts for the Development of Aqueous Biphasic Catalytic Processes” Sustainability 1(4), pages 924-945 (2009)), herein Bricout, as applied to claims 1-8, 10-12, 17, 22, and 24-25 above, and further in view of Rzelewska-Piekut et al. (“Studies on the Formation of Catalytically Active PGM Nanoparticles from Model Solutions as a Basis for the Recycling of Spent Catalysts” Molecules 27(2), 390 (2022)), herein Rzelewska-Piekut.
Regarding claim 19, the combination of Francais, Federov, and Bricout teach the method of claim 17 (see 35 U.S.C. 103 rejection of claim 17 above). However, though Francais teaches a buffer including a borate salt in ([0163]), since a borate salt is not a reducing agent, Francais does not teach that the one or more phosphine reducing agents comprise borohydrides, boranes, silatrane, or a combination thereof. Neither Federov nor Bricout teach these phosphine reducing agents either. This deficiency is made up for in the teachings of Rzelewska-Piekut.
Regarding claim 19, Rzelewska-Piekut teaches that NaBH4 (sodium borohydride) is a more efficient reducer of palladium than AA (ascorbic acid) based on the precipitation of palladium with these reducing agents in the presence of PVP (polyvinylpyrrolidone) (Table 1; Figure 3, second column from the left in each cluster of columns is Pd; “AA is an inefficient reducer for palladium (PPd < 10%)” page 6 paragraph 2; “The most effective reducing agent for all metals is NaBH4” page 7 paragraph 1; Examiner notes that sodium borohydride is identified in the instant specification at [0085] as a species of phosphine reducing agent).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to perform the simple substitution of the sodium borohydride reducing agent taught by Rzelewska-Piekut for the reducing agent exemplified by ascorbic acid in the method for determining the sequence of polynucleotides taught by the combination of Francais, Federov, and Bricout (MPEP §2143 I. B.). The teaching of Rzelewska-Piekut that sodium borohydride is more efficient at reducing palladium than ascorbic acid would also motivate one of ordinary skill in the art to perform this substitution in order to improve the efficiency of the reduction of Pd(II) into the Pd(0) catalyst in the method (MPEP §2143 I. G.). One of ordinary skill in the art could have performed this substitution and would have found the results of this substitution predictable because both ascorbic acid and sodium borohydride perform the same function of reducing palladium. Therefore, the invention as a whole of claim 19 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Conclusion
Claims 1-8, 10-12, 17-19, 22, and 24-25 are rejected. Claims 9, 20-21, 23, and 26-64 are canceled. Claims 13-16 are withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jeffrey Lawrence Bellah whose telephone number is (571)272-1024. The examiner can normally be reached M-Th, 7:30-5 ET.
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/JEFFREY BELLAH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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