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 [Pd(Allyl)Cl]2 as the species of palladium complex in election 1 (encompassed by claims 7 and 8),
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as the species of N,N-bidentate ligand in election 2 (encompassed by claim 14), and
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as the species of Pd(0) scavenger in election 3 (encompassed by claims 20-22) in the reply filed on 22 April 2026 is acknowledged.
Claim 21 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 22 April 2026.
Information Disclosure Statement
The information disclosure statements (IDS) filed 22 March 2024, 25 June 2024, and 23 April 2026 are considered, initialed, and attached hereto.
Claim Status
Claims 1-25 and 29 are pending.
Claim 21 is withdrawn as being drawn to a nonelected species.
Claims 26-28 and 30-51 are canceled.
Claims 1-20, 22-25, and 29 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 1-10, 12, and 16-18 are rejected under 35 U.S.C. 103 as being obvious over Francais et al. (U.S. Patent Documents Cite No 55 in IDS filed 22 March 2024)(US 2020/0216891, published 9 July 2020, effectively filed 26 December 2018), herein Francais 1, 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.
The applied reference of Francais 1 appears to have a common assignee and common joint inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claim 1, Francais 1 teaches a method for determining sequences of a plurality of target polynucleotides (“a method for determining the sequence of a target single-stranded polynucleotide” [0176]), comprising: (a) contacting a solid support with sequencing primers under hybridization conditions, wherein the solid support comprises a plurality of target polynucleotides immobilized thereon; and the sequencing primers are complementary to at least a portion of the target polynucleotides (“In any embodiments of the method described herein, the target polynucleotide strand is attached to a solid support” [0186]; “a primer bearing the free 3′—OH group may be added as a separate component (e.g., a short oligonucleotide) that hybridizes to a single-stranded region of the template to be sequenced” [0195]); (b) contacting the solid support with a first aqueous solution comprising DNA polymerase and one or more of four different types of nucleotides under conditions suitable for DNA polymerase-mediated primer extension, wherein each of the nucleotides comprises a 3’ blocking group comprising an unsubstituted or substituted allyl group (“a synthetic step is carried out and may optionally comprise incubating a template polynucleotide strand with a reaction mixture comprising labeled 3′ blocked nucleotides of the disclosure. A polymerase can also be provided under conditions which permit formation of a phosphodiester linkage between a free 3′—OH group on a polynucleotide strand annealed to the template polynucleotide strand and a 5′ phosphate group on the nucleotide” [0188]; “Non-limiting embodiments of the blocking groups described herein including those having the structure selected from the group consisting of: (AOM)” [0105],
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in [0105] clearly comprises an allyl group on the right side); (c) incorporating one type of nucleotides into the sequencing primers to produce extended copy polynucleotides (“(a) incorporating a nucleotide comprising a 3′-OH blocking group and a detectable label as described herein into a copy polynucleotide strand complementary to at least a portion of the target polynucleotide strand” [0177]); (d) performing one or more fluorescent measurements of the extended copy polynucleotides (“(b) detecting the identity of the nucleotide incorporated into the copy polynucleotide strand” [0178]; “detecting the labeled nucleotide(s) incorporated into the polynucleotide by detecting the fluorescent signal from the new fluorescent dye attached to said nucleotide(s)” [0175]); (e) removing the 3’ blocking group of the incorporated nucleotides in a second aqueous solution comprising a transition metal catalyst and one or more reducing agents, the transition metal catalyst is generated from a palladium or nickel complex with a water-soluble non-reducing phosphine or a N,N-bidentate non-phosphine ligand (“(c) chemically removing the label and the 3′-OH blocking group from the nucleotide incorporated into the copy polynucleotide strand” [0179]; “removing the 3′ blocking group from the nucleotide incorporated into the copy polynucleotide strand comprises contacting the copy strand including the incorporated nucleotide with a second cleavage solution. In some such embodiments, the second cleavage solution contains a palladium (Pd) catalyst. In some further embodiments, the Pd catalyst is a Pd(0) catalyst […] one or more reducing agents may be added, such as ascorbic acid” [0182]; “the Pd(0) complex may be generated in situ from reduction of a Pd(II) […] the Pd(0) complex is generated in an aqueous solution by mixing a Pd(II) complex with a phosphine. Suitable phosphines include water soluble phosphines, such as […] TCEP” [0124], TCEP is a water-soluble non-reducing phosphine); and (f) washing the solid support with a third aqueous solution after the removal of the 3’ blocking group of the incorporated nucleotides (“(d) washing the chemically removed label and the 3′ blocking group away from the copy polynucleotide strand” [0180]).
However, though Francais 1 teaches a buffer including a borate salt in ([0182]), since a borate salt is not a reducing agent, Francais 1 does not teach that the one or more reducing agents comprise a boron-containing reducing agent. This deficiency is made up for in the teachings of Rzelewska-Piekut.
Regarding claim 1, 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).
Regarding claim 2, the combination of Francais 1 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 1 and Rzelewska-Piekut above), and Francais 1 further teaches repeating claimed steps (B) through (f) until sequences of at least a portion of the target polynucleotides are determined (“In some embodiments, steps (a) to (d) is repeated until a sequence of the portion of the template polynucleotide strand is determined” [0181], see steps (a) to (d) of Francais 1 in [0177-0180] and the rejection of claim 1).
Regarding claim 3, the combination of Francais 1 and Rzelewska-Piekut teach the method of claim 2 (see 35 U.S.C. 103 rejection of claim 2 over Francais 1 and Rzelewska-Piekut above), and Francais 1 further teaches that the claimed steps (b) through (f) are repeated at least 50 times, at least 100 times, at least 150 times, at least 200 times, at least 250 times, or at least 300 times (“In some such embodiments, steps (a) to (d) is repeated at least 50 times, at least 75 times, at least 100 times, at least 150 times, at least 200 times, at least 250 times, or at least 300 times” [0181], see steps (a) to (d) of Francais 1 in [0177-0180] and the rejection of claim 1).
Regarding claim 4, the combination of Francais 1 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 1 and Rzelewska-Piekut above), and Francais 1 further teaches that the transition metal catalyst is a Pd(0) catalyst and the Pd(0) catalyst is generated from the palladium complex with the water-soluble non-reducing phosphine (“the Pd(0) complex is generated in an aqueous solution by mixing a Pd(II) complex with a phosphine. Suitable phosphines include water soluble phosphines, such as […] TCEP” [0124]).
Regarding claims 5-10, the combination of Francais 1 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 1 and Rzelewska-Piekut above), and Francais 1 further teaches the method wherein the water-soluble non-reducing phosphine comprises tris(substituted C1-C6 alkyl)phosphine or tris(substituted C6-C10 aryl)phosphine, the transition metal catalyst is a Pd(0) catalyst generated in situ from the palladium complex and the water-soluble non-reducing tris(substituted C1-C6 alkyl)phosphine, the tris(substituted C1-C6 alkyl)phosphine is TCEP, which is a species of tris(carboxy substituted C1-C6 alkyl)phosphine, and the palladium complex comprises the elected species (species election 1) of [Pd(Allyl)Cl]2 (“the Pd(0) complex may be generated in situ from reduction of a Pd(II) complex […] the palladium source is allyl palladium(II) chloride dimer [(PdCl(C3H5))2] […] the Pd(0) complex is generated in an aqueous solution by mixing a Pd(II) complex with a phosphine. Suitable phosphines include water soluble phosphines, such as […] TCEP” [0124]).
Regarding claim 12, the combination of Francais 1 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 1 and Rzelewska-Piekut above), and Francais 1 further teaches the method wherein the molar ratio of the palladium complex and the water-soluble non-reducing phosphine is about 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, or 1:10 (“Suitable phosphines include water soluble phosphines, such as […] THP […] TCEP” [0124], teaching THP and TCEP as alternatives; “The molar ratio of the Pd(II) complex and the THP may be about 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, or 1:10” [0182], since THP and TCEP are taught as alternatives it would be obvious to apply these ratios to the method with TCEP, the claimed ratios of about 1:1 and about 1:1.5 are therefore anticipated by the taught ratio of about 1:2 in view of the recitation ‘about’, the other claimed ratios of about a number ending in .5 are anticipated by the taught ratios nearest to the claimed ratio in view of the recitation ‘about’; furthermore, the difference in ratio from about 1:1 and about 1:1.5 as claimed to the taught ratio of about 1:2 are obvious, as they would be arrived at in the routine course of optimization of the ratio because these are ratios near to the taught ratio and therefore unlikely to prevent the reaction from occurring, see MPEP §2144.05 II. A.: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical”).
Regarding claim 16, the combination of Francais 1 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 1 and Rzelewska-Piekut above), and Francais 1 further teaches the method wherein the pH of the second aqueous solution is from about 7.0 to about 10, or from about 7.5 to about 9.5 (“the second cleavage solution contains a palladium (Pd) catalyst and one or more buffer reagents described herein (e.g., a tertiary amine such as DEEA) and have pH of about 9.0 to about 10.0” [0182]).
Regarding claims 17-18, the combination of Francais 1 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 1 and Rzelewska-Piekut above), and Francais 1 further teaches the method wherein the 3’ blocking group has the structure
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attached to the 3’ oxygen of the nucleotide (“In some further embodiments, the 3′ blocked nucleotide contains a AOM group” [0182]; “Non-limiting embodiments of the blocking groups described herein including those having the structure selected from the group consisting of: (AOM) […] covalently attached to the 3’ carbon of the ribose or deoxyribose” [0105],
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in [0105], note that the first O on the left would be the 3’ oxygen of the nucleotide as it is connected to the 3’ carbon of the sugar backbone).
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 a polynucleotide taught by Francais 1 (MPEP §2143 I. B.). The teaching of Rzelewska-Piekut that sodium borohydride 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 taught by Francais 1 (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 claims 1-10, 12, and 16-18 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claims 1-10, 12, 17-20, and 22-25 are rejected under 35 U.S.C. 103 as being obvious over Mariana et al. (US 2022/0396832, published 15 December 2022, effectively filed 20 May 2021), herein Mariana, 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.
The applied reference of Mariana appears to have a common assignee and common joint inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claim 1, Mariana teaches a method for determining the sequences of a plurality of target polynucleotides ([0118]), comprising: (a) contacting a solid support with sequencing primers under hybridization conditions, wherein the solid support comprises a plurality of target polynucleotides immobilized thereon; and the sequencing primers are complementary to at least a portion of the target polynucleotides ([0119]); (b) contacting the solid support with a first aqueous solution comprising DNA polymerase and one or more of four different types of nucleotides under conditions suitable for DNA polymerase-mediated primer extension, wherein each of the nucleotides comprises a 3’ blocking group comprising an unsubstituted or substituted allyl group ([0120]); (c) incorporating one type of nucleotides into the sequencing primers to produce extended copy polynucleotides ([0121]); (d) performing one or more fluorescent measurements of the extended copy polynucleotides ([0122]); (e) removing the 3’ blocking group of the incorporated nucleotides in a second aqueous solution comprising a transition metal catalyst ([0123]) and one or more reducing agents, the transition metal catalyst is generated from a palladium or nickel complex with a water-soluble non-reducing phosphine or a N,N-bidentate non-phosphine ligand (“In some such embodiments, the Pd catalyst is the active Pd(0) form. In some instances, the Pd(0) catalyst may be generated in situ from reduction of a Pd complex or Pd precatalyst (e.g., a Pd(II) complex) by reagents” [0168], said reagents for the reduction of a Pd complex or precatalyst are the one or more reducing agents; “In some embodiments, the Pd(0) catalyst is generated in an aqueous solution by mixing a Pd(II) complex with a water soluble phosphine. Suitable phosphines include water soluble phosphines, such as […] TCEP” [0168], TCEP is a water-soluble non-reducing phosphine); and (f) washing the solid support with a third aqueous solution after the removal of the 3’ blocking group of the incorporated nucleotides (“the method further comprises step (f): washing the solid support with a second aqueous solution after the removal of the 3′ blocking group of the incorporated nucleotides” [0128]).
However, though Mariana teaches a buffer including a borate salt in ([0170]), since a borate salt is not a reducing agent, Mariana does not teach that the one or more reducing agents comprise a boron-containing reducing agent. This deficiency is made up for in the teachings of Rzelewska-Piekut.
Regarding claim 1, 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).
Regarding claims 2-3, the combination of Mariana and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Mariana and Rzelewska-Piekut above), and Mariana teaches the method further comprising: repeating claimed steps (b) through (f) until sequences of at least a portion of the target polynucleotides are determined, wherein steps (b) through (f) are repeated at least 50 times, at least 100 times, at least 150 times, at least 200 times, at least 250 times, or at least 300 times ([0128]).
Regarding claims 4-6 and 9-10, the combination of Mariana and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Mariana and Rzelewska-Piekut above), and Mariana teaches the method wherein the transition metal catalyst is a Pd(0) catalyst and the Pd(0) catalyst is generated from the palladium complex with the water-soluble non-reducing phosphine, wherein the water-soluble non-reducing phosphine comprises tris(substituted C1-C6 alkyl)phosphine or tris(substituted C6-C10 aryl)phosphine, wherein the Pd(0) catalyst is generated in situ from the palladium complex and the water-soluble non-reducing tris(substituted C1-C6 alkyl)phosphine, wherein the tris(substituted C1-C6 alky)phosphine is a tris(carboxy substituted C1-C6 alkyl)phosphine, and wherein the tris(substituted C1-C6 alkyl)phosphine is TCEP (“the Pd catalyst is the active Pd(0) form. In some instances, the Pd(0) catalyst may be generated in situ from reduction of a Pd complex or Pd precatalyst (e.g., a Pd(II) complex) […] the Pd(0) catalyst is generated in an aqueous solution by mixing a Pd(II) complex with a water soluble phosphine. Suitable phosphines include water soluble phosphines, such as […] TCEP” [0168]).
Regarding claims 7-8, the combination of Mariana and Rzelewska-Piekut teach the method of claim 6 (see 35 U.S.C. 103 rejection of claim 6 over Mariana and Rzelewska-Piekut above), and Mariana teaches the method wherein the palladium complex comprises [Pd(Allyl)Cl]2 (“Suitable palladium sources include […] [Pd(Allyl)Cl]2” [0168]).
Regarding claim 12, the combination of Mariana and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Mariana and Rzelewska-Piekut above), and Mariana teaches the method wherein the molar ratio of the palladium complex and the water-soluble non-reducing phosphine is about 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, or 1:10 (“Suitable phosphines include water soluble phosphines, such as […] THP […] TCEP” [0168], teaching THP and TCEP as alternatives; “The molar ratio of [(Allyl)PdCl]2 and the THP may be about 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, or 1:10” [0169], since THP and TCEP are taught as alternatives it would be obvious to apply these ratios to the method with TCEP, the claimed ratios of about 1:1 and about 1:1.5 are therefore anticipated by the taught ratio of about 1:2 in view of the recitation ‘about’, the other claimed ratios of about a number ending in .5 are anticipated by the taught ratios nearest to the claimed ratio in view of the recitation ‘about’; furthermore, the difference in ratio from about 1:1 and about 1:1.5 as claimed to the taught ratio of about 1:2 are obvious, as they would be arrived at in the routine course of optimization of the ratio because these are ratios near to the taught ratio and therefore unlikely to prevent the reaction from occurring, see MPEP §2144.05 II. A.: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical”).
Regarding claims 17-18, the combination of Mariana and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Mariana and Rzelewska-Piekut above), and Mariana teaches the method wherein the 3’ blocking group of the nucleotide has the structure
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attached to the 3’ oxygen of the nucleotide (“In one embodiment, the 3’ blocking group is
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” [0183]).
Regarding claims 19-20 and 22-23, the combination of Mariana and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Mariana and Rzelewska-Piekut above), and Mariana teaches the method wherein the first aqueous solution or the third aqueous solution comprises a least one Pd(0) scavenger (“wherein at least a portion of remaining palladium catalyst is inactivated by one or more palladium scavengers after step (e)” [0124]), wherein the Pd(0) scavenger comprises one or more allele moieties in the group presented in instant claim 20 ([0124], [0126], [0127]), wherein the Pd(0) scavenger comprising one or more –NR-allyl or –N+RR’-allyl moieties is the elected species (election 3)
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Cl- (“Non-limiting examples of the palladium scavenger comprising one or more –NR-allyl or –N+RR’-allyl moieties include the following: […]
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Z-, wherein Z- is an anion (e.g., […] Cl-)” [0165]), and wherein the Pd(0) scavenger comprising one or more allyl moieties is in the first aqueous solution (“In some embodiments of any of the methods described herein, the palladium scavenger comprises one or more allyl moieties is in the first aqueous solution” [0137]).
Regarding claims 24-25, the combination of Mariana and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Mariana and Rzelewska-Piekut above), and Mariana teaches the method wherein the third aqueous solution further comprises at least one Pd(II) scavenger wherein the Pd(II) scavenger comprises L-cysteine or sodium thiosulfate (“the method may further use additional palladium scavenger(s), such as Pd(II) scavenger(s) […] the Pd(II) scavenger (e.g., L-cysteine or sodium thiosulfate) is in the post cleavage wash solution (i.e., the second aqueous solution)” [0174]).
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 generally recited reagent for reduction of Pd complex or precatalyst into a Pd(0) catalyst in the method for determining the sequence of polynucleotides taught by Mariana (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 sodium borohydride is a species of the generally recited reagent for reduction and both perform the same function of reducing palladium. Therefore, the invention as a whole of claims 1-10, 12, 17-20, and 22-25 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claims 1-10, 12, 16-20, and 23-25 are rejected under 35 U.S.C. 103 as being obvious over Francais et al. (U.S. Patent Documents Cite No 59 in IDS filed 22 March 2024)(US 2021/0403500, published 30 December 2021, effectively filed 22 June 2020), herein Francais 2, 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.
The applied reference of Francais 2 appears to have a common assignee and common joint inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding claim 1, Francais 2 teaches a method for determining the sequences of a plurality of target polynucleotides, comprising: (a) contacting a solid support with sequencing primers under hybridization conditions, wherein the solid support comprises a plurality of target polynucleotides immobilized thereon; and the sequencing primers are complementary to at least a portion of the target polynucleotides ([0152], [0181], [0188]); (b) contacting the solid support with a first aqueous solution comprising DNA polymerase and one or more of four different types of nucleotides under conditions suitable for DNA polymerase-mediated primer extension, wherein each of the nucleotides comprises a 3’ blocking group comprising an unsubstituted or substituted allyl group ([0153], [0183]); (c) incorporating one type of nucleotides into the sequencing primers to produce extended copy polynucleotides ([0153]); (d) performing one or more fluorescent measurements of the extended copy polynucleotides ([0154]); (e) removing the 3’ blocking group of the incorporated nucleotides in a second aqueous solution comprising a transition metal catalyst ([0155], [0161]) and one or more reducing agents (“In some further embodiments, one or more reducing agents may be added, such as ascorbic acid” [0163]), the transition metal catalyst is generated from a palladium or nickel complex with a water-soluble non-reducing phosphine or a N,N-bidentate non-phosphine ligand (“In some such embodiments, the Pd(0) is prepared by mixing a Pd(II) reagent with one or phosphine ligands in situ” [0162]; “In some such embodiments, the second cleavage solution contains one or more phosphines, such as a trialkylphosphine. None-limiting examples of trialkylphosphines include […] TCEP” [0164], TCEP is a water-soluble non-reducing phosphine); and (f) washing the solid support with a third aqueous solution after the removal of the 3’ blocking group of the incorporated nucleotides (“the sequencing method further comprises (d) washing the chemically removed label and the 3′-OH blocking group away from the copy polynucleotide strand by using a post-cleavable washing solution” [0156]).
However, though Francais 2 teaches a buffer including a borate salt in ([0163]), since a borate salt is not a reducing agent, Francais 2 does not teach that the one or more reducing agents comprise a boron-containing reducing agent. This deficiency is made up for in the teachings of Rzelewska-Piekut.
Regarding claim 1, 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).
Regarding claims 2-3, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 2 and Rzelewska-Piekut above), and Francais 2 teaches the method further comprising: repeating claimed steps (b) through (f) until sequences of at least a portion of the target polynucleotides are determined, wherein steps (b) through (f) are repeated at least 50 times, at least 100 times, at least 150 times, at least 200 times, at least 250 times, or at least 300 times ([0157]).
Regarding claims 4-6 and 9-10, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 2 and Rzelewska-Piekut above), and Francais 2 teaches the method wherein the transition metal catalyst is a Pd(0) catalyst and the Pd(0) catalyst is generated from the palladium complex with the water-soluble non-reducing phosphine, wherein the water-soluble non-reducing phosphine comprises tris(substituted C1-C6 alkyl)phosphine or tris(substituted C6-C10 aryl)phosphine, wherein the Pd(0) catalyst is generated in situ from the palladium complex and the water-soluble non-reducing tris(substituted C1-C6 alkyl)phosphine, wherein the tris(substituted C1-C6 alky)phosphine is a tris(carboxy substituted C1-C6 alkyl)phosphine, and wherein the tris(substituted C1-C6 alkyl)phosphine is TCEP (“the Pd(0) complex may be generated in situ from reduction of a Pd(II) complex […] the Pd(0) catalyst is generated in an aqueous solution by mixing a Pd(II) complex with a water soluble phosphine. Suitable phosphines include water soluble phosphines, such as […] TCEP” [0128]).
Regarding claims 7-8, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 6 (see 35 U.S.C. 103 rejection of claim 6 over Francais 2 and Rzelewska-Piekut above), and Francais 2 teaches the method wherein the palladium complex comprises [Pd(Allyl)Cl]2 (“Suitable palladium sources include […] [PdCl(Allyl)]2” [0128]).
Regarding claim 12, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 2 and Rzelewska-Piekut above), and Francais 2 teaches the method wherein the molar ratio of the palladium complex and the water-soluble non-reducing phosphine is about 1:1, 1:1.5, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:4.5, 1:5, 1:5.5, 1:6, 1:6.5, 1:7, 1:7.5, 1:8, 1:8.5, 1:9, 1:9.5, or 1:10 (“Suitable phosphines include water soluble phosphines, such as […] THP […] TCEP” [0128], teaching THP and TCEP as alternatives; “The molar ratio of [(Allyl)PdCl]2 and the THP may be about 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, or 1:10” [0129], since THP and TCEP are taught as alternatives it would be obvious to apply these ratios to the method with TCEP, the claimed ratios of about 1:1 and about 1:1.5 are therefore anticipated by the taught ratio of about 1:2 in view of the recitation ‘about’, the other claimed ratios of about a number ending in .5 are anticipated by the taught ratios nearest to the claimed ratio in view of the recitation ‘about’; furthermore, the difference in ratio from about 1:1 and about 1:1.5 as claimed to the taught ratio of about 1:2 are obvious, as they would be arrived at in the routine course of optimization of the ratio because these are ratios near to the taught ratio and therefore unlikely to prevent the reaction from occurring, see MPEP §2144.05 II. A.: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical”).
Regarding claim 16, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 above over Francais 2 and Rzelewska-Piekut), and Francais 2 further teaches the method wherein the pH of the second aqueous solution is from about 7.0 to about 10, or from about 7.5 to about 9.5 (“the cleavage solution contains a palladium (Pd) catalyst […] and one or more buffer reagents described herein (e.g., a tertiary amine such as DEEA) and have pH of about 9.0 to about 10.0” [0163]).
Regarding claims 17-18, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 2 and Rzelewska-Piekut above), and Francais 2 teaches the method wherein the 3’ blocking group of the nucleotide has the structure
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attached to the 3’ oxygen of the nucleotide (“In some embodiments, the nucleoside or nucleotide described herein comprises or has the structure of Formula (I):
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” [0100]; “In some embodiments of the nucleoside or nucleotide described herein, the ribose or deoxyribose moiety comprises a 3′-OH blocking group (i.e., R5 in Formula (I) is a 3’-OH blocking group) […] non-limiting embodiments of R5 include
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” [0109]).
Regarding claims 19-20 and 23, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 2 and Rzelewska-Piekut above), and Francais 2 teaches the method wherein the first aqueous solution or the third aqueous solution comprises a least one Pd(0) scavenger, wherein the Pd(0) scavenger comprises one or more allele moieties in the group presented in instant claim 20, and wherein the Pd(0) scavenger comprising one or more allyl moieties is in the first aqueous solution ([0168]).
Regarding claims 24-25, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 2 and Rzelewska-Piekut above), and Francais 2 teaches the method wherein the third aqueous solution further comprises at least one Pd(II) scavenger wherein the Pd(II) scavenger comprises L-cysteine or sodium thiosulfate ([0173]).
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 a polynucleotide taught by Francais 2 (MPEP §2143 I. B.). The teaching of Rzelewska-Piekut that sodium borohydride 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 taught by Francais 2 (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 claims 1-10, 12, 16-20, and 23-25 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 11 is rejected under 35 U.S.C. 103 as being unpatentable over Francais et al. (U.S. Patent Documents Cite No 55 in IDS filed 22 March 2024)(US 2020/0216891, published 9 July 2020, effectively filed 26 December 2018), herein Francais 1, 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, as applied to claims 1-10, 12, and 16-18 above, and further in view of Schaub et al. (US 2023/0374254, effectively filed 13 October 2020), herein Schaub.
Regarding claim 11, the combination of Francais 1 and Rzelewska-Piekut teach the method of claim 5 (see 35 U.S.C. 103 rejection of claim 5 over Francais 1 and Rzelewska-Piekut above). However, neither Francais 1 nor Rzelewska-Piekut teach the method wherein the tris(substituted C1-C6 alkyl)phosphine is DIPA or diBuPpropSO3. This deficiency is made up for in the teachings of Schaub.
Regarding claim 11, Schaub teaches using DIPA as water-soluble non-reducing phosphine ligand that forms a transition metal catalyst with a palladium complex such as allylpalladium chloride dimer (“the homogeneous transition metal catalyst complex comprises at least one ligand in order to solubilize the transition metal in the reaction solution and to maintain the transition metal in an active form for hydrogenation. Preferred ligands are polydentate ligands having at least one nitrogen atom and at least one phosphorous atom which are capable of coordinating to the transition metal” [0036]; “the at least one polydentate ligand is selected from compounds A to G, wherein […] iPr is isopropyl” [0069],
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, compound G is DIPA; “Suitable palladium pre-catalysts are selected from […] allylpalladium chloride dimer” [0082]).
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 DIPA as a ligand for the generation of a palladium catalyst from a palladium pre-catalyst taught by Schaub for phosphine used to generate a Pd(0) catalyst from a Pd(II) complex in the method taught by the combination of Francais 1 and Rzelewska-Piekut (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 DIPA taught by Schaub and the phosphines taught by Francais 1 have the same function of generating a palladium catalyst from a palladium pre-catalyst complex. Therefore, the invention as a whole of claim 11 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 11 is rejected under 35 U.S.C. 103 as being unpatentable over Mariana et al. (US 2022/0396832, published 15 December 2022, effectively filed 20 May 2021), herein Mariana, 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, as applied to claims 1-10, 12, 17-20, and 22-25 above, and further in view of Schaub et al. (US 2023/0374254, effectively filed 13 October 2020), herein Schaub.
Regarding claim 11, the combination of Mariana and Rzelewska-Piekut teach the method of claim 5 (see 35 U.S.C. 103 rejection of claim 5 over Mariana and Rzelewska-Piekut above). However, neither Mariana nor Rzelewska-Piekut teach the method wherein the tris(substituted C1-C6 alkyl)phosphine is DIPA or diBuPpropSO3. This deficiency is made up for in the teachings of Schaub.
Regarding claim 11, Schaub teaches using DIPA as water-soluble non-reducing phosphine ligand that forms a transition metal catalyst with a palladium complex such as allylpalladium chloride dimer (see 35 U.S.C. 103 rejection of claim 11 over Francais 1 in view of Rzelewska-Piekut and further in view of Schaub above).
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 DIPA as a ligand for the generation of a palladium catalyst from a palladium pre-catalyst taught by Schaub for phosphine used to generate a Pd(0) catalyst from a Pd(II) complex in the method taught by the combination of Mariana and Rzelewska-Piekut (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 DIPA taught by Schaub and the phosphines taught by Mariana have the same function of generating a palladium catalyst from a palladium pre-catalyst complex. Therefore, the invention as a whole of claim 11 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 11 is rejected under 35 U.S.C. 103 as being unpatentable over Francais et al. (U.S. Patent Documents Cite No 59 in IDS filed 22 March 2024)(US 2021/0403500, published 30 December 2021, effectively filed 22 June 2020), herein Francais 2, 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, as applied to claims 1-10, 12, 16-20, and 23-25 above, and further in view of Schaub et al. (US 2023/0374254, effectively filed 13 October 2020), herein Schaub.
Regarding claim 11, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 5 (see 35 U.S.C. 103 rejection of claim 5 over Francais 2 and Rzelewska-Piekut above). However, neither Francais 2 nor Rzelewska-Piekut teach the method wherein the tris(substituted C1-C6 alkyl)phosphine is DIPA or diBuPpropSO3. This deficiency is made up for in the teachings of Schaub.
Regarding claim 11, Schaub teaches using DIPA as water-soluble non-reducing phosphine ligand that forms a transition metal catalyst with a palladium complex such as allylpalladium chloride dimer (see 35 U.S.C. 103 rejection of claim 11 over Francais 1 in view of Rzelewska-Piekut and further in view of Schaub above).
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 DIPA as a ligand for the generation of a palladium catalyst from a palladium pre-catalyst taught by Schaub for phosphine used to generate a Pd(0) catalyst from a Pd(II) complex in the method taught by the combination of Francais 2 and Rzelewska-Piekut (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 DIPA taught by Schaub and the phosphines taught by Mariana have the same function of generating a palladium catalyst from a palladium pre-catalyst complex. Therefore, the invention as a whole of claim 11 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Francais et al. (U.S. Patent Documents Cite No 55 in IDS filed 22 March 2024)(US 2020/0216891, published 9 July 2020, effectively filed 26 December 2018), herein Francais 1, 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, as applied to claims 1-10, 12, and 16-18 above, and further in view of Didgikar et al. (“Oxidative carbonylation of amine using water-soluble palladium catalysts in biphasic media” Journal of Molecular Catalysis A: Chemical, 334(1-2), pages 20-28 (2011)), herein Didgikar.
Regarding claims 13-14, the combination of Francais 1 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 1 and Rzelewska-Piekut above) and Francais 1 further teaches that the transition metal catalyst is a Pd(0) catalyst (“the Pd catalyst is a Pd(0) catalyst” [0182]). However, neither Francais 1 and Rzelewska-Piekut teach the method wherein the Pd(0) catalyst is generated from the palladium complex with the N,N-bidentate non-phosphine ligand. This deficiency is made up for in the teachings of Didgikar.
Regarding claims 13-14, Didgikar teaches using
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, the elected species (election 2) of N,N-bidentate ligand as a ligand for preparing a palladium catalyst from a palladium precursor and that this ligand has the advantage of being resistant to oxidation in the presence of oxygen, (“water soluble sulfonated phosphine ligands such as TPPTS are prone to oxidation, but their N-analogues are resistant to oxidation in the presence of oxygen or air. Therefore, N-containing heterocyclic ligands along with TPPTS were chosen for the screening purpose in the present study. Commercially available as well as laboratory synthesized ligands from published literature were used for preparing water-soluble palladium catalysts (from Pd(OAc)2 precursor). These were evaluated for oxidative carbonylation of aniline, using a toluene–water biphasic medium and sodium iodide as a halide promoter. The N-containing ligands screened were: […] bathophenanthroline disulfonic acid disodium salt (BathP-DS) […] as bidentate ligands […] Catalysts prepared from bidentate N-containing ligands were more active […] compared to those with monodentate N-containing ligand” page 22 left column section 3.2; Table 2).
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 N,N-bidentate ligand BathP-DS as a ligand for preparing a palladium catalyst from a palladium precursor taught by Didgikar for the phosphine used to generate a Pd(0) catalyst from a Pd(II) complex in the method taught by the combination of Francais 1 and Rzelewska-Piekut (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 BathP-DS taught by Didgikar and the phosphines taught by Francais 1 have the same function of generating a palladium catalyst from a palladium pre-catalyst precursor. Therefore, the invention as a whole of claims 13-14 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Mariana et al. (US 2022/0396832, published 15 December 2022, effectively filed 20 May 2021), herein Mariana, 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, as applied to claims 1-10, 12, 17-20, and 22-25 above, and further in view of Didgikar et al. (“Oxidative carbonylation of amine using water-soluble palladium catalysts in biphasic media” Journal of Molecular Catalysis A: Chemical, 334(1-2), pages 20-28 (2011)), herein Didgikar.
Regarding claims 13-14, the combination of Mariana and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Mariana and Rzelewska-Piekut above) and Mariana further teaches that the transition metal catalyst is a Pd(0) catalyst (“In some such embodiments, the Pd catalyst is the active Pd(0) form” [0168]). However, neither Mariana and Rzelewska-Piekut teach the method wherein the Pd(0) catalyst is generated from the palladium complex with the N,N-bidentate non-phosphine ligand. This deficiency is made up for in the teachings of Didgikar.
Regarding claims 13-14, Didgikar teaches using
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, the elected species (election 2) of N,N-bidentate ligand as a ligand for preparing a palladium catalyst from a palladium precursor and that this ligand has the advantage of being resistant to oxidation in the presence of oxygen, (see 35 U.S.C. 103 rejection of claims 13-14 over Francais 1 in view of Rzelewska-Piekut in further view of Didgikar above).
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 N,N-bidentate ligand BathP-DS as a ligand for preparing a palladium catalyst from a palladium precursor taught by Didgikar for the phosphine used to generate a Pd(0) catalyst from a Pd(II) complex in the method taught by the combination of Mariana and Rzelewska-Piekut (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 BathP-DS taught by Didgikar and the phosphines taught by Mariana have the same function of generating a palladium catalyst from a palladium pre-catalyst precursor. Therefore, the invention as a whole of claims 13-14 would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention.
Claims 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over Francais et al. (U.S. Patent Documents Cite No 59 in IDS filed 22 March 2024)(US 2021/0403500, published 30 December 2021, effectively filed 22 June 2020), herein Francais 2, 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, as applied to claims 1-10, 12, 16-20, and 23-25 above, and further in view of Didgikar et al. (“Oxidative carbonylation of amine using water-soluble palladium catalysts in biphasic media” Journal of Molecular Catalysis A: Chemical, 334(1-2), pages 20-28 (2011)), herein Didgikar.
Regarding claims 13-14, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 2 and Rzelewska-Piekut above) and Francais 2 further teaches that the transition metal catalyst is a Pd(0) catalyst (“In some further embodiments, the Pd catalyst is a Pd(0) catalyst” [0162]). However, neither Francais 2 and Rzelewska-Piekut teach the method wherein the Pd(0) catalyst is generated from the palladium complex with the N,N-bidentate non-phosphine ligand. This deficiency is made up for in the teachings of Didgikar.
Regarding claims 13-14, Didgikar teaches using
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, the elected species (election 2) of N,N-bidentate ligand as a ligand for preparing a palladium catalyst from a palladium precursor and that this ligand has the advantage of being resistant to oxidation in the presence of oxygen, (see 35 U.S.C. 103 rejection of claims 13-14 over Francais 1 in view of Rzelewska-Piekut in further view of Didgikar above).
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 N,N-bidentate ligand BathP-DS as a ligand for preparing a palladium catalyst from a palladium precursor taught by Didgikar for the phosphine used to generate a Pd(0) catalyst from a Pd(II) complex in the method taught by the combination of Francais 2 and Rzelewska-Piekut (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 BathP-DS taught by Didgikar and the phosphines taught by Francais 2 have the same function of generating a palladium catalyst from a palladium pre-catalyst precursor. Therefore, the invention as a whole of claims 13-14 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 15 is rejected under 35 U.S.C. 103 as being unpatentable over Francais et al. (U.S. Patent Documents Cite No 55 in IDS filed 22 March 2024)(US 2020/0216891, published 9 July 2020, effectively filed 26 December 2018), herein Francais 1, 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, as applied to claims 1-10, 12, and 16-18 above, and further in view of Molander et al. (“Scope of the Palladium-Catalyzed Aryl Borylation Utilizing Bis-Boronic Acid” J Am Chem Soc 134(28), pages 11667-11673 (2012)), herein Molander.
Regarding claim 15, the combination of Francais 1 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 1 and Rzelewska-Piekut above). However, neither Francais 1 and Rzelewska-Piekut teach the method wherein the boron-containing reducing is NH3BH3 or B2(OH)4. This deficiency is made up for in the teachings of Molander.
Regarding claim 15, Molander teaches that B2(OH)4 generates Pd(0) catalyst from Pd(II) complex (Scheme 2, page 11668 right column).
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 B2(OH)4 taught by Molander for NaBH4 taught by Rzelewska-Piekut in the method of the combination of Francais 1 and Rzelewska-Piekut (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 B2(OH)4 and NaBH4 are taught as being used in the reduction of Pd(II) to Pd(0). Therefore, the invention as a whole of claim 15 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 15 is rejected under 35 U.S.C. 103 as being unpatentable over Mariana et al. (US 2022/0396832, published 15 December 2022, effectively filed 20 May 2021), herein Mariana, 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, as applied to claims 1-10, 12, 17-20, and 22-25 above, and further in view of Molander et al. (“Scope of the Palladium-Catalyzed Aryl Borylation Utilizing Bis-Boronic Acid” J Am Chem Soc 134(28), pages 11667-11673 (2012)), herein Molander.
Regarding claim 15, the combination of Mariana and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Mariana and Rzelewska-Piekut above). However, neither Mariana and Rzelewska-Piekut teach the method wherein the boron-containing reducing is NH3BH3 or B2(OH)4. This deficiency is made up for in the teachings of Molander.
Regarding claim 15, Molander teaches that B2(OH)4 generates Pd(0) catalyst from Pd(II) complex (Scheme 2, page 11668 right column).
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 B2(OH)4 taught by Molander for NaBH4 taught by Rzelewska-Piekut in the method of the combination of Mariana and Rzelewska-Piekut (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 B2(OH)4 and NaBH4 are taught as being used in the reduction of Pd(II) to Pd(0). Therefore, the invention as a whole of claim 15 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 15 is rejected under 35 U.S.C. 103 as being unpatentable over Francais et al. (U.S. Patent Documents Cite No 59 in IDS filed 22 March 2024)(US 2021/0403500, published 30 December 2021, effectively filed 22 June 2020), herein Francais 2, 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, as applied to claims 1-10, 12, 16-20, and 23-25 above, and further in view of Molander et al. (“Scope of the Palladium-Catalyzed Aryl Borylation Utilizing Bis-Boronic Acid” J Am Chem Soc 134(28), pages 11667-11673 (2012)), herein Molander.
Regarding claim 15, the combination of Francais 2 and Rzelewska-Piekut teach the method of claim 1 (see 35 U.S.C. 103 rejection of claim 1 over Francais 2 and Rzelewska-Piekut above). However, neither Francais 2 and Rzelewska-Piekut teach the method wherein the boron-containing reducing is NH3BH3 or B2(OH)4. This deficiency is made up for in the teachings of Molander.
Regarding claim 15, Molander teaches that B2(OH)4 generates Pd(0) catalyst from Pd(II) complex (Scheme 2, page 11668 right column).
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 B2(OH)4 taught by Molander for NaBH4 taught by Rzelewska-Piekut in the method of the combination of Francais 2 and Rzelewska-Piekut (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 B2(OH)4 and NaBH4 are taught as being used in the reduction of Pd(II) to Pd(0). Therefore, the invention as a whole of claim 15 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 29 is rejected under 35 U.S.C. 103 as being unpatentable over Francais et al. (U.S. Patent Documents Cite No 55 in IDS filed 22 March 2024)(US 2020/0216891, published 9 July 2020, effectively filed 26 December 2018), herein Francais 1, 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, as applied to claims 1-10, 12, and 16-18 above, and further in view of Ahern (“Biochemical, Reagent Kits Offer Scientists Good Return On Investment” The Scientist (1995)).
Regarding claim 29, Francais 1 teaches an aqueous cleavage mixture for sequencing comprising a transition metal catalyst and one or more reducing agents, wherein the transition metal catalyst is generated from a palladium or nickel complex with a water-soluble non-reducing phosphine or a N,N-bidentate non-phosphine ligand (“removing the 3′ blocking group from the nucleotide incorporated into the copy polynucleotide strand comprises contacting the copy strand including the incorporated nucleotide with a second cleavage solution. In some such embodiments, the second cleavage solution contains a palladium (Pd) catalyst. In some further embodiments, the Pd catalyst is a Pd(0) catalyst […] one or more reducing agents may be added, such as ascorbic acid” [0182]; “the Pd(0) complex may be generated in situ from reduction of a Pd(II) […] the Pd(0) complex is generated in an aqueous solution by mixing a Pd(II) complex with a phosphine. Suitable phosphines include water soluble phosphines, such as […] TCEP” [0124], TCEP is a water-soluble non-reducing phosphine). However, Francais 1 does not teach the mixture as part of a kit or that the one or more reducing agents comprise a boron-containing reducing agent. These deficiencies are made up for in the teachings of Rzelewska-Piekut and the teachings of Ahern.
Regarding claim 29, 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). However, neither Francais 1 nor Rzelewska-Piekut teach the mixture as part of a kit. This deficiency is made up for in the teachings of Ahern.
Regarding claim 29, Ahern teaches that it is advantageous to package reagents for biochemical processes into a kit to provide convenience and to save time (“More researchers are buying premade reagents and kits because they are convenient and they save time” page 1, section titled ‘The Kit Concept’).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to combine the teachings of Francais 1 and Rzelewska-Piekut as laid out in the 35 U.S.C. 103 rejection of claims 1-10, 12, and 16-18 over Francais 1 and Rzelewska-Piekut above. One of ordinary skill in the art would be motivated to combine the teachings of Francais 1 and Rzelewska-Piekut with the teaching of Ahern to package reagents into a kit in order to improve the invention with the advantage of increased convenience and time saving as taught by Ahern. On of ordinary skill in the art would have a reasonable expectation of success in this combination because both teachings are in the biochemical arts and packaging a reagent would not be expected to impact the ability for the reagent to function in methods that use it. Therefore, the invention as a whole of claim 29 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 1-20, 22-25, and 29 are rejected. Claim 21 is withdrawn. Claims 26-28 and 30-51 are canceled.
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/JEFFREY BELLAH/Examiner, Art Unit 1683 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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