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 .
Priority
This application is a 371 of PCT/US2020/061755 11/23/2020, which claims benefit of 62/941,153 11/27/2019.
Information Disclosure Statement
The Information Disclosure Statements (IDS) filed on 03/31/2026 and 08/06/2026 have been considered by the Examiner inasmuch as foreign documents have been submitted into the file wrapper in English.
Claim Status
Applicant’s remarks filed May 28, 2026 have been entered.
Claims 3, 9 and 22-30 are canceled.
Thus, claims 1-2, 4-8 and 10-21 are examined on the merits herein.
Response to Arguments
The rejection of claims 1-2, 4-8 and 10-21 under 35 U.S.C. 103 is maintained.
Applicant argues:
(A) The combination of Wu and Gao, specifically the use of a β-cyanoethyl phosphate protection in combination with TIPS as the protecting group for the vicinal 3’-OH via base protection at temperatures ≥30-35°C for synthesizing oligonucleotides comprising 2’→5’ internucleoside linkages is contrary to the teachings of the prior art as a whole, see pg. 2 of 12, last paragraph of the page.
(B) Applicant refers to the prior art PCT publication WO 2012/024776 which Applicant argues discloses the very combination at issue which is the use of β-cyanoethyl phosphoramidite chemistry in the context of RNA synthesis employing TIPS as the protecting group for the vicinal 2’-OH in a block (dimer/trimer) 3’→5’ internucleoside linker strategy, see Applicant’s remarks, pg. 3 of 12, paragraph 2.
(C) The ‘776 publication explains that β-cyanoethyl protection on the phosphorous is base labile and gives rise to significant practical difficulties, including premature loss of the cyanoethyl (CNEt) phosphate protecting group and which is also encountered during purification of cyanoethyl (CNEt) protected dimers, see Applicant’s remarks, pg. 3 of 12, paragraph 3.
(D) The ‘776 publication discloses the cyanoethyl phosphate protecting group was base liable, as was the phosphitylation, which posed a problem for the synthesis of the dimer which must be kept in mind throughout the synthesis and purification; where Applicant argues such disclosure by ‘776 reflects the experimental deficiencies directly attributable to the use of β-cyanoethyl protection in the presence of a TIPS-protected vicinal hydroxyl group, see Applicant’s remarks, pg. 3 of 12, paragraph 3.
(E) The ‘776 publication therefore expressly abandons the β-cyanoethyl approach in favor of alternative protecting group strategies, and is a direct response to the identified instability and purification problems associated with β-cyanoethyl protection; and reflects an affirmative preference for methyl protection under precisely the conditions relevant to the present claims, see Applicant’s remarks, pg. 3 of 12, last paragraph – pg. 4 of 12, lines 1-2.
(F) The ‘776 publication would have discouraged a person of ordinary skill in the art from adopting the Office’s modification, even if the approach is not technically impossible. Therefore, the ‘776 publication as a whole teaches away from the Office’s proposed route under the relevant conditions and the Office’s rationale of “routine optimization” lacks the required articulated reasoning with rational underpinning, see Applicant’s remarks, pg. 4 of 12, first full paragraph.
(G) Gao’s disclosure does not supply a reasonable motivation to modify Wu in the manner proposed as Gao addresses a materially different synthetic context and does not grapple with the specific incompatibilities demonstrated in the art for this claimed approach, see Applicant’s remarks, pg.4 of 12, third full paragraph.
With respect to Applicant’s arguments (A)-(G), the Examiner notes the thrust of Applicant’s argument is the ‘776 publication (see IDS filed 10/17/2024) teaches away from the proposed modification of including a cyanoethyl phosphate protecting group within oligonucleotide synthesis due to the problem for synthesizing and purifying said oligonucleotides as the cyanoethyl phosphate is base labile and therefore can result in premature loss of said cyanoethyl protecting group during oligonucleotide synthesis.
The Examiner notes the instant claims are drawn to a method of synthesizing oligonucleotides, using a nucleoside phosphoramidite monomer of Formula I, see independent claim 1; and independent claim 21 recites the nucleoside phosphoramidite monomer of Formula I, wherein said monomer comprises a β-cyanoethyl phosphate at the 2’-OH position of the ribose sugar core of Formula (I).
Therefore, the Examiner notes the instant claims are not drawn to purification of oligonucleotides as argued by Applicant above.
Moreover, the Examiner notes that Applicant seems to concede in their argument the Office’s proposed route of synthesis “is not technically impossible”, see argument (F). This point is further supported as the ‘776 publication discloses the base lability of the cyanoethyl phosphate protecting group “must be kept in mind throughout the synthesis and purification”, see Applicant’s remarks, pg. 3 of 12, third paragraph.
Accordingly, the Examiner notes the considerations as argued by Applicant, specifically the teaching away, are known considerations in the art as disclosed by the ‘776 publication itself.
Furthermore, the Examiner notes the ‘776 publication provides an explicit resolution to the problem of base lability of the β-cyanoethyl as a phosphate protecting group in the same paragraph it proposed the problem, where the ‘776 publication teaches “to overcome these problems, very little excess of diisopropylethylamine was used during the synthesis, just enough to quench the HCl formed from the chlorophosphite. As well, the reaction mixtures were kept reasonably concentrated and reaction times were kept short. Even if there was a small amount of starting material left after 1.5 hours the reaction was worked up, see pg. 101, line 15 – pg. 102, line 5.
(H) Wu’s disclosed methods are incompatible with β-cyanoethyl phosphoramidite chemistry as its teachings counsel against their use in this context; as Wu’s workflow teaches the 2’-silyl group isomerizes in neutral protic solvents, whereas their isomerically pure when stable in dry aprotic solvents, see Applicant’s remarks, pg. 4, last paragraph.
(I) Substituting β-cyanoethyl for methyl would fundamentally disrupt Wu’s workflow, as the β-cyanoethyl removal requires base-mediated beta-elimination, thus moving a strong-base step into the phosphate deprotection slot, earlier in the sequence than any base exposure in Wu; and Gao’s own β-cyanoethyl deprotection conditions are protic/aqueous media at elevated temperatures, exactly the conditions Wu identifies as promoting 2’-silyl migration and isomerization, see Applicant’s remarks, pg. 5 of 12, paragraph 2.
With respect to Applicant’s arguments (H)-(I), the Examiner reiterates their arguments above; and further notes Wu discloses different solvents if it’s desired to have an isomerically pure form of the nucleoside monomers (3a-d) as discussed by Wu on pg. 4718, right column, paragraph 2; for use in oligonucleotide synthesis of oligonucleotides with 3’→5’ internucleoside linkages within Wu’s scheme II, see pg. 4719, scheme II.
Moreover, the Examiner notes the instant claims, particularly independent claims 1 and 21 do not require an isomerically pure form of either the nucleoside phosphoramidite monomer having the structure of Formula (I) recited instant claim 1 and instant claim 21; nor within the oligonucleotide synthesized in instant claim 1.
(J) A skilled artisan would have no motivation to replace Wu’s methyl with β-cyanoethyl, a protecting group whose removal demands the very conditions Wu warns against; and no reasonable expectation the 2’→5’ linkages or 2’-silyl protection would survive the resulting deprotection conditions, see Applicant’s remarks, pg. 5 of 12, paragraph 3.
(K) Second there is no teaching or suggestion in Gao to prepare an oligonucleotide comprising a 2’→5’ linkage, as a PHOSITA reading Gao would associate 2’→5’ phosphodiester bonds with fragility and deliberate cleavage, not with stable inter-nucleoside connectivity, see Applicant’s remarks, pg. 5 of 12, paragraph 4.
(L) Gao’s synthesis protocol is exclusively 3’→5’ internucleoside linkages, see pg. 6 of 12, paragraph 2.
With respect to Applicant’s arguments (J)-(L), the Examiner reiterates their arguments above, and further notes Wu’s scheme III prepares fully deprotected dinucleotides containing 2’→5’ phosphate linkages, see pg. 4720, scheme III, 14a-d.
Additionally, Gao teaches in the 103 rejection that those skilled in the art will recognize that cyanoethyl moieties are preferred phosphate protecting groups for their stability under oligonucleotide synthesis and their ease of removal with ammonia or methylamine; and further teaches removal of protective groups from the nucleobases and the phosphate backbone where the process usually takes about 24 hours at room temperature or about 6 hours at 55°C.
Moreover, the Examiner notes deprotection of the protected intermediate, recited in instant claim 1, line 10, requires treating with a base at a temperature of 30°C or higher; where the base is methylamine, required in instant claim 10; for at least 30 min, required in instant claim 13 or for at least 4 hours, required in instant claim 14.
(M) Applicant respectfully submits that the Examiner’s interpretation conflates two distinct disclosures and misapprehends what Table 3 and Table 5 each depict within Applicant’s specification, see Applicant’s remarks, pg. 7 of 12 – pg. 8 of 12, paragraph 2.
With respect to Applicant’s argument (M), the Examiner respectfully submits Applicant has conflated and misinterpreted the Examiner’s position, as Table 3 was only referenced in order to provide a visual depiction corresponding to the 2-OH or 3-OH protecting groups referenced in Table 5.
(N) The claimed invention is characterized by surprising and unexpected technical effects, i.e. stability against prolonged exposure to aqueous base at elevated temperatures at the point of cleaving and deprotecting the fully synthesized oligonucleotide, prior to removing the protecting group on the 3’-hydroxyl, i.e. the triisopropyl group, see Applicant’s remarks, pg. 6 of 12, paragraph 4.
(O) Table 5 discloses the percentage of fully protected oligonucleotide (%FLP-OX) with the proposed modification of the 2’-O or 3’-O protecting groups under reaction conditions where ammonium hydroxide is the base at a temperature of 35°C for 15 hours, where in sequence 6, the 3’-OH is modified with TIPS and shows a percentage of %FLP-OX, where X is the 3’-OTIPS of 96%, where only 3% was cleaved, see Applicant’s remarks, pg. 8 of 12, last paragraph.
(P) Wu treats silyl protecting groups as functionally equivalent, see Applicant’s remarks, pg. 9 of 12, paragraph 1.
With respect to Applicant’s arguments (N)-(P), the Examiner reiterates their arguments above, and notes the 2’-phosphoramidites of Wu differed form formula (I) of claim 1 in one way, the 2’-phosphoamidate comprised a β-cyanoethyl, which Gao teaches as discussed above, and where the Examiner reiterates said teachings of Gao include β-cyanoethyl as a preferred phosphate protecting groups for their stability under oligonucleotide synthesis.
The Examiner also notes in scheme I of Wu, the 2’-phosphoramidite known as 4c is explicitly depicted as having TIPS and the silyl ether protecting group for the 3’-OH of the ribose sugar.
The Examiner further respectfully notes, Applicant recites in claim 1, deprotection occurs with the protected intermediate with any base; at any temperature at 30°C or higher; for any time duration, see instant claim 1, lines 10-11.
(Q) The ‘776 publication actually combined RNA 3’-β cyanoethyl phosphoramidite employing TIPS as the protecting group on the vicinal 2’-OH group in RNA synthesis which resulted in an unfavorable outcome, see Applicant’s remarks, pg. 9 of 10, last paragraph.
With respect to Applicant’s argument (Q), the Examiner notes the ‘776 publication depicts TBDMS as the 2’-OH protecting group and not TIPS as argued by Applicant, see the ‘776 publication, pg. 99, lines 10-15 and pg. 101, lines 15-16.
Thus, Applicant’s arguments (A)-(Q) have been fully considered but are not found persuasive.
Claim Objections
Claim 15 is objected to because of the following informalities:
Claim 15, last line of the claim, the Examiner notes claim 15 does not end with a period denoting the end of the claim.
Thus, the Examiner suggests a period be added as discussed above.
Appropriate correction is required.
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.
(I) Claims 1-2, 4-8, 10-14 and 19-21 remain rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (Published 01 July 1990, The Journal of Organic Chemistry, Vol. 55, Issue 15, pp. 4717-4724, IDS filed 04/30/2024) in view of Gao et al. (Published 03 October 2013, US-20130261026-A1, IDS filed 05/25/2022).
Regarding claims 1-2, 4-8, 10-14 and 19-21, Wu teaches oligoribonucleotide synthesis, see pg. 4717, title.
Wu teaches isomeric dinucleotides with 2’-5’-interlinkages (ApU, CpU, GpU UpU) were prepared with 3’-silylated nucleoside 2’-phosphoramidites (e.g. synthesizing oligonucleotides having one nucleoside with a 3’-OH and a 2’-5’-internucleoside linkage, claim 21, lines 1-2), see abstract.
The Examiner respectfully notes dinucleotides are included within the term oligonucleotide as evidenced by Applicant’s specification which discloses oligonucleotides refers to a nucleic acid molecule (RNA or DNA) for examples of length less than 100, 200, 300, or 400 nucleotides, and as used herein an oligonucleotide also encompasses dinucleotides, see specification, pg. 14, paragraph [0077],
Wu exemplifies a scheme of preparing 2’-5’ dinucleotides depicted as follows,
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605
625
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, see pg. 4720, Scheme III.
Wu teaches in the synthesis of protected dinucleotides 6a-d collidine (250 µL) was added to the solution, followed by the dropwise addition of an aqueous iodine solution (0.1 M, 7/3 water/THF), see pg. 4723, right column, synthesis of protected dinucleotides (5a-d, 6a-d), paragraph 1.
The Examiner respectfully notes compounds 4a-d as discussed above are coupled with the free 5’-hydroxyl group on a silyl protected nucleoside, exemplified as a uridine within Scheme III above, when tetrazole is added as the first reagent and then collidine/I2 (e.g. the weak base and reaction conditions, required in claims 4-6) is added as the second reagent as shown above to produce compounds 6a-d as shown in Scheme III, see Scheme III of Wu above. The Examiner also respectfully notes this step corresponds to the coupling and oxidizing steps as required in claim 1, lines 4-9.
With respect to the limitations of “to form a phosphite triester intermediate”, required in claim 1, lines 6-7 and “to form a protected intermediate”, required in claim 1, lines 8-9; the Examiner reasonably interprets both of these limitations are physical limitations when synthesizing the oligonucleotide as recited in claim 1, line 1.
Since Wu teaches a protected phosphodiester bond within the structure of compounds 6a-d as shown in Scheme III of Wu above, the physical limitations as recited above are met by the teachings of Wu above.
Wu teaches in Scheme I both ribonucleoside 3’-phosphoramidites and 2’-phosphoramidites depicted as,
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494
498
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, see pg. 4717, right column, scheme I.
The Examiner respectfully notes within Scheme I above compound 4c contains a triisopropylsilyl group (TIPS) at the 3’-position of the ribose sugar moiety and a bis(diisopropylamino)methoxyphosphine at the 2’-position of said ribose as shown in Scheme I of Wu above.
The Examiner respectfully notes within Scheme 1 of Wu that compound 4c comprises a N2-phenoxyacetylguanine (e.g. B is a modified nucleobase, required in claim 1, line 15 and claim 21, line 4); R1 is monomethoxytrityl (MMT) (e.g. R1 is a hydroxyl protecting group, required in claim 1, line 16 and claim 21, line 5); R2 is triisopropylsilyl (TIPS), (e.g. R2 is -Si(R4)3, wherein each R4 is isopropyl, required in claim 1, line 17 and line 19 and claim 21, line 6 and line 8); R3 is a methyl diisopropylphosphoramidite (e.g. -P(NR5R6OR7, wherein R5=R6=alkyl, required in claim 1, line 18 and claim 21, line 7 and line 9).
Although, Wu does not teach (a) the nucleoside phosphoramidite monomer has a β-cyanoethyl as R7, required in claim 1, pg. 3 of 14, line 3 and claim 21, line 11; and (b) deprotecting the protected intermediate with a base, wherein said treating with the base is at a temperature of 30°C or higher, see claim 1, lines 10-11.
However, in the same field of endeavor of oligoribonucleotide synthesis, with respect to limitations (a)-(b), Gao teaches oligonucleotide synthesis and purification on solid supports, see title; wherein Figure 7 presents a schematic depiction of the synthesis of an exemplary oligonucleotide, see paragraph [0034] and Sheet 7, Fig. 7. Gao teaches the term “oligonucleotide” as used herein is defined as a molecule comprising two or more deoxyribonucleotides or ribonucleotides (e.g. the number of nucleotides, required in claims 19-20), see paragraph [0050].
Gao teaches phosphate groups are usually protected as 2-cyanoethyl phosphoramidites, see paragraph [0097]; and those skilled in the art will recognize that cyanoethyl moieties are preferred phosphate protecting groups for their stability under oligonucleotide synthesis and their ease of removal with ammonia or methylamine (e.g. methylamine, required in claim 1, line 9 and claim 10), see paragraph [0092].
Gao teaches nucleosides with the 3’-O protecting group of t-butyldimethylsilyl (TBDMS) or other protecting groups used for 3’-O protection of ribonucleotides, see paragraph [0010] and [0011].
Gao teaches protective groups are easily removed after completion of the oligonucleotide synthesis by treatment with a concentrated solution of ammonium hydroxide (e.g. deprotecting with ammonium hydroxide, required in claim 1, line 9 and claim 10), see paragraph [0096].
Gao teaches removal of protective groups from the nucleobases and the phosphate backbone where the process usually takes about 24 hours at room temperature or about 6 hours at 55°C (e.g. the temperature of the base, required in claim 11, line 2; and treating time with the base, required in claims 13-14), see paragraph [0097].
Gao exemplifies a deoxyribonucleotide is linked through thioate phosphate (PS) bonds, where PS bonds form in regular DNA or DNA chemical synthesis when the oxidation step employs 3H-1,2-benzodithiol-3-one 1,1-dioxide (BDTD) for sulfurizing phosphite triesters formed from coupling of phosphoramidites (e.g. the sulfurizing agent required in claim 1, claim 7 and claim 8), see paragraph [0017].
Gao teaches the oligonucleotide synthesis used an automated DNA synthesizer (e.g. the synthesizer, required in claim 2), see paragraph [0118].
With respect to the limitation of “treating with the base is at a temperature of 35°C”, required in claim 12; the Examiner reasonably interprets this limitation to be a physical limitation of the deprotection reaction using the base as recited in claim 1, from which claim 12 depends.
Therefore, since Gao teaches removal of the protecting groups from the nucleobases and phosphate backbone at room temperature for 24 hours or at 55°C for 6 hours it would have been well within the scope of the artisan through routine experimentation to optimize the amount of time required for deprotection by optimizing the temperature at which the deprotection takes place, because the Examiner respectfully notes Gao teaches the amount of time required for deprotection changes as the temperature of the deprotection reaction changes. Therefore, the teachings of Gao in view of the interpretation above make obvious instant claim 12.
Moreover, MPEP 2144.05(II)(A) states “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. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have incorporated the teachings of Gao particularly with respect to limitation (a) in substituting the methyl protected phosphoramidite taught by Wu above for the 2-cyanoethyl protected phosphoramidite taught by Gao above as within the scope of the artisan as a simple substitution of one known element for another in the method of oligonucleotide synthesis to yield predictable results.
One of ordinary skill in the art would have been particularly motivated to make the substitution as discussed above because Gao explicitly teaches phosphate groups are usually protected as 2-cyanoethyl phosphoramidites and that 2-cyanoethyl is a preferred phosphate protecting group because of its stability under oligonucleotide synthesis as discussed above. One of ordinary skill in the art would have had a reasonable expectation of success to have made the substitution as discussed above as both Wu and Gao are drawn to synthesis of oligonucleotides as discussed above.
With respect to limitation (b), it would have been prima facie obvious to one of ordinary skill in the art at the invention’s effective filing date to have incorporated limitation (b) within the method of Wu above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results.
One of ordinary skill in the art would have been motivated to deprotect the silyl protecting groups from the synthesized oligonucleotide of Wu, exemplified as a dinucleotide in Scheme III of Wu as discussed above. One of ordinary skill in the art would have had a reasonable expectation of success of incorporating limitation (b) as taught by Gao into the method of Wu discussed above, because both Wu and Gao use silyl protecting groups at the 3’-OH position of the sugar moiety of the nucleoside; both particularly teach TMBDS and other silyl protecting groups; and wherein Wu specifically teaches both TMBDS and TIPS protecting groups at the 3’-OH position of the ribose sugar moiety as discussed above.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included the teachings of Gao into the method of Wu as discussed above for the reasons discussed above. One of ordinary skill in the art would have been motivated to conduct oligoribonucleoside synthesis by synthesizing oligonucleotides as taught by both Wu and Gao above, for example the dinucleotides exemplified and taught by Wu above.
One of ordinary skill in the art would have had a reasonable expectation of success of incorporating the teachings of Gao into the method of Wu, because both Wu and Gao are drawn to using silyl protecting groups and protected phosphoramidites for oligonucleotide synthesis as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the teachings of the prior art.
(II) Claims 15-18 remain rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (Published 01 July 1990, The Journal of Organic Chemistry, Vol. 55, Issue 15, pp. 4717-4724, IDS filed 04/30/2024) and Gao et al. (Published 03 October 2013, US-20130261026-A1, IDS filed 05/25/2022) as applied to claims 1-2, 4-8, 10-14 and 19-21 above, and further in view of Beigelman et al. (Published 29 August 2002, US-20020120129-A1, IDS filed 05/25/2022).
Wu and Gao address claims 1-2, 4-8, 10-14 and 19-21 as written above. Although, Wu and Gao do not teach treating with a deprotecting reagent effective to convert the TIPS-protected hydroxyl group to a free hydroxyl group, required in claims 15-18.
However, in the same field of endeavor of protection/deprotection using triisopropylsilyl groups for synthesizing nucleosides, Beigelman teaches methods for the chemical synthesis of nucleosides and derivatives thereof, see abstract. Beigelman teaches silyl deprotection of the invention for example of the 3' hydroxyl of a nucleoside is performed with an acid, a fluoride source, or a combination thereof, for example HF/pyridine (e.g. the deprotecting reagent, required in claims 16-17), see paragraph [0375]; and defines “silylation” to include tert-butyldimethylsilyl (TBDMS) and triisopropylsilyl (TIPS), see paragraph [0067].
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have substituted the ammonium hydroxide deprotecting reagent as taught by Gao above for the HF/pyridine deprotecting reagent as taught by Beigelman above as within the scope of the artisan as a simple substitution of one known element for another according to known methods of deprotection of silyl groups to yield predictable results.
One of ordinary skill in the art would have been motivated to substitute the ammonium hydroxide deprotecting reagent as taught by Gao for the HF/pyridine deprotecting reagent as taught by Beigelman in order to deprotect the silyl protecting groups from the synthesized oligonucleotide of Wu above.
One of ordinary skill in the art would have had a reasonable expectation of success to have substituted the ammonium hydroxide deprotecting reagent taught by Gao for the HF/pyridine deprotecting reagent taught by Beigelman in the method of Wu above, as both Wu and Beigelman use both tert-butyldimethylsilyl (TBDMS) and triisopropylsilyl (TIPS) as protecting groups of the 3’-hydroxyl of nucleosides as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed in this action.
THIS ACTION IS MADE FINAL. 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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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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