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 .
Claim Status
The claim set, Applicant’s remarks and the MIYAGAWA declaration filed November 14, 2025 have been entered. Claims 10, 15-17 and 21-22 are canceled. Thus, claims 1-9, 11-14, 18-20, and 23-28 as amended are examined on the merits herein.
Claim Interpretation
Claim 2, pg. 4, lines 15-17 recite “a non-nucleotide linker may be incorporated into the nucleic acid compound of the formula (4) instead of at least one nucleotide between nucleotides at 5’ terminus and 3’ terminus of the nucleic acid compound”.
Claim 2, pg. 5, lines 2-3, recite “a non-nucleotide linker may be incorporated instead of a nucleotide” when referring to formula (5) of claim 2.
Therefore, the Examiner reasonably interprets the recitation of “may be incorporated” when referring to the non-nucleotide linker is as an optional limitation of the claim and thus is not required by claim 2.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action on August 14, 2025:
(I) The objections to claims 2-3, 5 and 26 are all withdrawn in view of Applicant’s amendments to claims 2-3, 5 and 26.
(II) The rejection of claim 3 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicant’s amendment to claim 3.
(III) The rejection of claims 10-14 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph is withdrawn in view of the cancellation of claim 10 as discussed in the Claim Status section above; and in view of the amendments to claims 11-14.
(IV) The rejection of claims 10, 15-17 and 21-22 under 35 U.S.C. 103 is withdrawn in view of the cancellation of claims 10, 15-17 and 21-22 as discussed in the Claim Status section above.
Response to Arguments
The rejection of claims 1-9, 11-14, 18-20 and 23-28 under 35 U.S.C. 103 are maintained:
Applicant argues:
(A) The recitation of “such that a molar ratio of iodic acid to iodine (mole of iodic acid / mole of iodine) is 15 x 10-3 or less” is a feature not disclosed or suggested by the cited references which is considered in every possible combination, see Applicant’s remarks, pg. 13, paragraph 1.
(B) Applicant submits the MIYAGAWA declaration which describes the experiments carried out by Mr. MIYAGAWA or under his direct supervision and control, see Applicant’s remarks, pg. 13, paragraph 2.
(C) The MIYAGAWA declaration discloses experimental data was prepared by analyzing the molar ratio of iodic acid to iodine in an oxidizing solution purchased from Fujifilm Wako Pure Chemical Corporation. The oxidizing solution was the solution of Example 6 of the present specification (pg. 60, Table 4), the example references said oxidizing solution where eight (8) months had been passed after purchasing it (under conditions where the storage temperature was 25°C), as it was the same condition as those of Example 6, see Applicant’s remarks, pg. 13, paragraph 3.
(D) Applicant implies the solution used herein is the oxidizing solution that has been stored beyond the storage period disclosed by Thermo, which is “up to 6 months at 4°C or up to 6 weeks on a synthesizer”, where Applicant notes the storage conditions of Thermo on the synthesizer would have been around room temperature, which is around 20°C, see Applicant’s remarks, pg. 13, paragraph 3.
Therefore, MIYAGAWA’S oxidizing solution stored for 8 months at 25°C used to generate the data reported in the MIYAGAWA declaration was stored under harder conditions than those that would result from following Thermo Fischer’s instructions. See Applicant’s remarks, pg. 13, paragraph 3.
(E) The MIYAGAWA declaration discloses two points regarding how a person of skill would have understood the Thermo Fischer Scientific reference, (i) the oxidizing solution is stable (or does not deteriorate significantly) for up to 6 months at 4°C or up to 6 weeks on a synthesizer; and (ii) if the oxidizing solution is stored for a longer period, the quality of the oxidizing solution may deteriorate, and the quality of the nucleic acids synthesized may also deteriorate, see Applicant’s remarks, pg. 14, paragraph 1.
(F) Example 6 of the specification which is an oxidizing solution stored at 25°C for 8 months after purchase was used and nucleic acids were obtained with a purity of 57%; while on the other hand Examples 7-9 and Reference Example 1, which used oxidizing solutions stored at 25°C for 2 weeks – 24 hours, respectively, which is considered to be within the storage period recommended by Thermo, the purity of the nucleic acids obtained was 49-35% respectively, which can be confirmed to be lower than that of Example 6 which used oxidizing solutions stored for a longer period, see Applicant’s remarks, pg. 14, paragraph 2.
(G) Applicant discloses the data presented in Table 4 on pp. 60-61 of the specification demonstrates that nucleic acids of equivalent purity were obtained in Example 5 and Example 6, and that the purity was significantly reduced in Example 7; and Applicant argues when considering all of these data it is clear that it is important that the molar ratio of iodic acid to iodine be specified at “15 x 10-3 or less” as recited in amended claim 1, see Applicant’s remarks, pg. 14, last paragraph of the page.
(H) None of the cited references provides a reason to make or use an oxidizing solution in which the molar ratio of iodic acid to iodine is specified as “15 x 10-3 or less”, see Applicant’s remarks, pg. 15, paragraph 1.
(I) The molar ratio of iodic acid to iodine feature of the claimed process is more important than the age of the oxidizing solution and would not have been predicted based on the cited art and it is only from the benefit of hindsight provided by Applicant’s disclosure that the importance of this feature is revealed, see Applicant’s remarks, pg. 15, paragraph 2.
The Examiner respectfully notes that Applicant’s arguments (A)-(I) as discussed above correspond to paragraphs (#) 6-17 on pp. 1-4 of the MIYAGAWA declaration.
With regard to Applicant’s arguments (A)-(I), as well as the MIYAGAWA declaration above, the Examiner respectfully notes the new 103 rejections discussed in greater detail below are a combination including the Aoki and Pitsch references, wherein said combination teaches an oxidation solution comprising iodine, water, pyridine and tetrahydrofuran; and that Aoki also teaches acetonitrile can be included in said oxidizing solution.
Pitsch further teaches reagents within an oxidation solution used for oligonucleotide synthesis wherein said oxidation solution comprises iodine, tetrahydrofuran (THF), pyridine, and water; and wherein said solution is stored in a well-sealed bottle in the dark and cool (25°C) environment for up to 2 months.
The Examiner respectfully notes with particular respect to the limitation “such that a molar ratio of iodic acid to iodine (mole of iodic acid / mole of iodine) is 15 x 10-3 or less” discussed within Applicant’ arguments and the MIYAGAWA declaration above; the Examiner reasonably interprets this limitation to be a physical consequence of letting at least 6 week pass from the preparation of the oxidation solution to when it’s used; wherein the oxidation solution includes iodine, pyridine, water and acetonitrile as taught by Aoki and Pitsch above, as evidenced by Applicant’s specification which discloses Example 5, in Table 4, on pg. 60.
The Examiner respectfully notes Example 5 of Table 4 is an oxidation solution including iodine, pyridine, water and acetonitrile; stored for 6 weeks (e.g. 1.5 months) at a storage temperature of 25°C , wherein the resulting I2/HIO3 molar ratio is 10.1 x 10-3 (see specification, pg. 60, Table 4, Ex.5).
Therefore, since the combination of Aoki and Pitsch both teach an oxidation solution comprising iodine, water, pyridine and tetrahydrofuran as discussed above, and wherein Pitsch further teaches both a storage duration of up to 2 months and a storage temperature of 25°C, all structural and physical limitations of the oxidation solution required in claim 1 are met.
Thus, the Examiner respectfully notes the physical consequence of the oxidation solution having a molar ratio of iodic acid to iodine as argued by Applicant, declared by MIYGAWA, and recited within amended claim 1 will be met by the combine teachings of Aoki and Pitsch as discussed in greater detail within the 103 rejections below.
Additionally, with particular respect to Applicant’s argument (I) that the molar ratio of iodic acid to iodine feature of the claimed process is more important than the age of the oxidizing solution; the Examiner respectfully notes this argument is not particularly persuasive in view of Examples 1-9 and Reference Example 1 of Table 4 of the specification on pg. 60.
The Examiner respectively notes Example 1 and Reference Example 1 are both oxidation solutions comprising iodine, pyridine, water and acetonitrile, but vary in the concentration of iodine and the storage duration of the solution, as the Examiner respectfully notes that Table 4 discloses Example 1 which had been stored for 2 years has a I2/HIO3 molar ratio of 2.6 x10-3, while Reference Example 1 which had been stored for 24 hours has a I2/HIO3 molar ratio of 35.7 x10-3.
The Examiner also respectfully notes the oxidation solutions of Examples 1-5 and 7-8 each comprise iodine, pyridine, water and acetonitrile. The Examiner also respectfully notes both the storage duration as well as the concentration of iodine (I2) varies within each oxidization solution tested.
The Examiner further respectfully notes the varied iodine (I2) concentration within each of these oxidation solutions range between 10.11-11.78 nM as disclosed within Table 4 of the specification as discussed above.
The Examiner respectively notes Examples 6 and 9, which are oxidation solutions comprising iodine, pyridine and water, but do not comprise acetonitrile have a concentration of iodine (I2) of 50.73 and 50.08 nM respectively.
As a result, the Examiner respectfully notes the oxidation solutions tested without the inclusion of acetonitrile, e.g. Examples 6 and 9 discussed above, have an iodine (I2) concentration that is 4-5 times higher than Examples 1-5 and 7-8 which include acetonitrile within the oxidation solution.
Therefore, the Examiner respectfully notes in view of the foregoing reasons above and based on the data presented in Examples 1-9 and Reference Example 1 of Table 4 of Applicant’s specification; the Examiner considers whether the varied concentration of iodine within each oxidation solution of Examples 1-9 is a critical factor to be considered when observing the resulting I2/HIO3 molar ratio during the varied storage durations of Examples 1-9 of Table 4 as discussed above.
Additionally, the Examiner respectfully questions when preparing the oxidation solution, what role, if any, does the starting iodine concentration have on the resulting I2/HIO3 molar ratio?
What role, if any, does the inclusion or exclusion of acetonitrile within the oxidation solution have on the resulting I2/HIO3 molar ratio?
Moreover, what role, if any, does the storage duration of the oxidization solution have on the resulting I2/HIO3 molar ratio?
Furthermore, how does the Examiner consider these questions separately and in combination with each other and with other potential storage conditions, for example the storage temperature, light exposure, etc.?
Finally, the Examiner respectfully notes Applicant’s data within Table 4 as discussed above and in view of the specification as whole does not provide a clear direction as to how the Examiner should consider and answer these questions.
As a result, the Examiner respectfully reminds the Applicant of the burden of explaining why the data are evidence of non-obviousness. In addition to being unexpected and non-obvious, the difference(s) must be of both statistical and practical significance. Therefore, this submission does not meet this burden.
Thus, Applicant’s arguments (A)-(I) and the MIYGAWA declaration have been fully considered but are not found persuasive.
New Claim Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on November 14, 2025, where the limitations in pending claims 1-9, 11-14, 18-20, and 23-28 as amended now have been changed. Therefore, rejections from the previous Office Action, dated August 14, 2025, have been modified and are listed below.
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 1-3, 6-9, 11-14, 18-20 and 23-28 are rejected under 35 U.S.C. 103 as being unpatentable over Aoki et al. (Published 24 July, 2014, US-20140206856-A1, IDS filed 10/27/2022) in view of Pitsch et al. (Published Year 2001, "Chemical synthesis of RNA sequences with 2′-O-[(triisopropylsilyl)oxy]methyl-protected ribonucleoside phosphoramidites" in: Beaucage S.L. et al., Current Protocols in Nucleic Acid Chemistry (New York, John Wiley & Sons, Inc, 2001), pp. 3.8.1-3.8.15, PTO-892).
With respect to claims 1-3, 6-9, 11-14, 18-20 and 23-28, Aoki teaches a process of step A4 converting a phosphorous acid group in a glycoside compound (206),
PNG
media_image1.png
395
632
media_image1.png
Greyscale
, by reacting the glycoside compound [206] with an oxidant, see paragraph [0263]; resulting in a phosphate group in a glycoside compound (208),
PNG
media_image2.png
286
437
media_image2.png
Greyscale
, see pg. 22 and paragraph [0264]. Aoki teaches the oxidant may be used in the form of a solution, exemplified as obtained by dissolving iodine in a mixed solvent of water, pyridine and tetrahydrofuran (e.g. the oxidation solution, required in claim 11 and the process required in claim 27), see paragraph [0266].
The Examiner notes that compound (206) of Aoki corresponds to Formula (II) of the instant application and compound (208) corresponds to Formula (I) of the instant application wherein the substituents are as taught by Aoki below:
Aoki teaches R1 is a protecting group (e.g. wherein G1 is a protecting group for hydroxy group, required in claim 1, formulas (I) and (II)), see paragraph [0107];
Aoki teaches R2c is a hydrogen (e.g. wherein G4 is a hydrogen atom, required in claim 3, formula (6)), an electron-withdrawing group, or any substituent (e.g. wherein G2 is a protecting group for hydroxy group, required in claim 1, formulas (I) and (II)), see pg. [0110];
Aoki teaches R200 is a hydrogen (e.g. R is a hydrogen atom, required in claim 1, R) or a substituent represented by chemical formula (203) or chemical formula (204), see paragraph [0236]; and
Aoki teaches B is an atomic group having a nucleic acid base skeleton and optionally having a protecting group (e.g. Ba represents a nucleic acid base which may be optionally protected with a protecting group, required in claim 1, Ba), see paragraph [0009].
The Examiner notes that compound (206) of Aoki corresponds to formula (4), required in claim 2 and compound (208) of Aoki corresponds to formula (5) required in instant claim 2, wherein the substituents are as taught by Aoki below:
The Examiner notes that in compound (206) of Aoki depicted above shows an oxygen atom at the identical position of Y as depicted in formula (4) in claim 2;
Aoki teaches m is a positive integer (e.g. n is any integer of 1 to 200, required in claim 2, pg. 4, line 12);
Aoki teaches E is a substituent represented by chemical formula (204) depicted as
PNG
media_image3.png
82
119
media_image3.png
Greyscale
, wherein Q is a single bond, see paragraph [0244], L3 is a linker, and [S] is a solid phase carrier, see paragraph [0243]. The Examiner notes that chemical formula (204) would correspond to when W represents OZ, and wherein Z represents a group having a structure comprising a solid support and a connecting group, required in claim 2, pg. 4, lines 16-17;
Aoki teaches T is a hydrogen atom (e.g. X represents R, required in claim 2, pg. 4, line 15), see paragraph [0237].
Aoki teaches the reaction solvent in step A2, which the Examiner respectfully notes produces the glycoside compound (206) discussed above, can include acetonitrile, pyridine and tetrahydrofuran (e.g. the acetonitrile, required in claims 12 and 13), see paragraph [0257].
With respect to claim 3, Aoki teaches after step A4 and before performing the next step A5, the operation may return to step A1, repeating steps A1-A4 an appropriate number of times in this way, the chain length of the object nucleic acid (glycoside compound (208)) can become a desired (given) chain length (e.g. elongating a chain length of the nucleic acid compound of formula (5), required in claim 3, lines 2-4), see paragraph [0267].
The Examiner notes that compound (208) of Aoki corresponds to formula (5’) of instant claim 3 wherein the substituents are as taught by Aoki below:
Aoki teaches R1 is a protecting group (e.g. wherein G5 is a protecting group for hydroxy group, required in claim 3, formula (5’)), see paragraph [0107];
Aoki teaches m is a positive integer (e.g. m is an integer satisfying m ≥ n, required in claim 3, pg. 6, line 2); and
The Examiner notes that in compound (208) of Aoki depicted above shows an oxygen atom at the identical position of Y as depicted in formula (5’) in claim 3.
Aoki teaches step A5 is a step of cleaving (e.g. cutting out, required in claim 3, pg. 6, line 5) the glycoside compound (208) produced in the aforementioned step A4 from the aforementioned solid phase carrier, and deprotecting (e.g. required in claim 3, pg. 7, line 1) each nucleic acid base region and the hydroxyl group at each 2’-position, see paragraph [0268].
Aoki teaches compound (209) as the resulting compound of the deprotecting step, see paragraph [0268].
The Examiner notes after the cleaving step and the deprotection step is performed on compound (208) of Aoki would correspond to formula (6) and formula (7) wherein the substituents are as taught by Aoki below:
Aoki teaches R2c is a hydrogen (e.g. wherein G4 is a hydrogen atom, required in claim 3, formula (6));
The Examiner notes that in compound (208) of Aoki depicted above shows an oxygen atom at the identical position of Y as depicted in formula (6) in claim 3;
Aoki teaches R200 is a hydrogen (e.g. R’ is a hydrogen atom, required in claim 3, formula (7)), see paragraph [0236];
Aoki teaches Z is a hydrogen atom (e.g. W1 represents a hydroxyl group, required in claim 3, formula (6) and W10 represents a hydroxyl group, required in claim 3, formula (7)), see paragraph [0229].
Aoki teaches R100 is a hydrogen atom (e.g. X1 represents R, required in claim 3, formula (6) and X10 represents an R’ group, required in claim 3, formula (7)) or a hydroxyl group, see paragraph [0059].
The Examiner notes that R can a hydrogen atom as recited in claim 2, pg. 4, line 4 with respect to formula (6); and R’ can be a hydrogen atom as recited in claim 3, pg. 7 with respect to formula (7).
With respect to claims 6-9, Aoki teaches the concentration of the oxidant of step A4 is for example 0.05-2M, see paragraph [0266].
With respect to claim 23, the Examiner notes that when Z is H, it creates a hydroxyl group at the 3’ position of the nucleotide, and that when R100 is a hydroxyl group at the 2’ position of the nucleotide would correspond to wherein the nucleic acid is a ribonucleotide as recited in claim 23, line 2.
With respect to claims 24-25, Aoki teaches T is a substituent represented by chemical formula (203) as depicted as
PNG
media_image4.png
72
231
media_image4.png
Greyscale
, see paragraph [0237]; wherein n is a positive integer, see paragraph [0016], L1 is an ethylene group (-CH2CH2-), see paragraph [0015], and [D1] is an electron-withdrawing group, see paragraph [0017]. Aoki exemplifies the electron-withdrawing group as a cyano (-CN), see paragraph [0119], chemical formula (3).
The Examiner notes that T as taught by Aoki above corresponds to formula (12) of claims 24-25, when Ra and Rb are both hydrogen atoms and Ew is a cyano group as required in claim 25.
With respect to claim 28, Aoki teaches examples of protecting groups at the 2’-position of the aforementioned phosphoramidite include a TBDMS (tert-butyldimethylsilyl) group, a TOM (triisopropylsilyloxymethyl) group and a ACE (bis(2-acetoxyethoxy)methyl) group (e.g. the protecting group, required in claim 28), see paragraph [0002].
Although, Aoki does not teach (a) the oxidation solution has a molar ratio of iodic acid to iodine as recited, required in claims 1 and 18-20; and (b) the volume ratio, required in claims 13-14.
However, in the same field of endeavor of DNA/RNA synthesis, with respect to limitations (a)-(b), Pitsch teaches chemical synthesis of RNA sequences with 2′-O TOM protected Ribonucleoside Phosphoramidites, see pg. 2.8.1, title.
Pitsch teaches reagents used within the synthesis includes an oxidation solution, wherein the oxidation solution includes iodine, tetrahydrofuran (THF), pyridine, and water, where the iodine is dissolved in THF, then pyridine is added followed by water, The solution is stored in a well-sealed bottle in the dark and cool (25°C) environment for up to 2 months, see pg. 3.8.11, reagents and solutions, oxidation solution, lines 1-6.
With particular respect to the limitation “such that a molar ratio of iodic acid to iodine (mole of iodic acid / mole of iodine) is 15 x 10-3 or less, required in claim 1, pg. 3, lines 4-5; the Examiner reasonably interprets this limitation to be a physical consequence of letting at least 6 week pass from the preparation of the oxidation solution to when it’s used wherein the oxidation solution includes iodine, pyridine, water and acetonitrile as taught by Aoki above, as evidenced within Applicant’s specification disclosed by Example 5, in Table 4, on pg. 60; where the Examiner respectfully notes Example 5 of Table 4 is an oxidation solution including iodine, pyridine, water and acetonitrile, having a storage duration of 6 weeks (e.g. 1.5 months) and a storage temperature of 25°C , wherein the I2/HIO3 molar ratio is 10.1 x 10-3 (see specification, pg. 60, Table 4, Ex.5).
Therefore, since the combination of Aoki and Pitsch both teach an oxidation solution comprising iodine, water, pyridine and tetrahydrofuran as discussed above, all structural limitations of the oxidation solution required in claim 1 are met. Thus, the physical consequence of the oxidation solution having a molar ratio of iodic acid to iodine as recited in claim 1, pg. 3, lines 4-5, will be met by the combine teachings of Aoki and Pitsch as discussed above.
With respect to limitation (b), the Examiner reasonably interprets this limitation to be a physical limitation that is well within the scope of the artisan through routine experimentation and optimization as the combination of Aoki and Pitsch teach all structural limitations of the solvent required in limitation (b).
Additionally, 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 well within the scope of the artisan through routine experimentation and optimization to arrive at an oxidation solution with the recited volume ratios as required in claims 13-14 for the oxidation step (step A4) as taught by Aoki above, as Aoki teaches iodine, water, pyridine and tetrahydrofuran are components within the oxidation solution, and teaches acetonitrile can be used in the reaction solvent to form compound (206) of Aoki, which the Examiner also respectfully notes is the reactant within step A4 of Aoki as discussed above.
Thus, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included limitations (a)-(b) into the method of Aoki above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results with respect to limitation (a); or through routine experimentation and optimization with respect to limitation (b) as discussed above. One of ordinary skill in the art would have been motivated to include limitations (a)-(b) into the method of Aoki in order to create compound (208) of Aoki as discussed above. One of ordinary skill in the art would have had a reasonable expectation of success to have included limitations (a)-(b) into the method of Aoki, as both Aoki and Pitsch are drawn to using an oxidation solution including iodine, water, pyridine and tetrahydrofuran to synthesize oligonucleotides as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(II) Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Aoki et al. (Published 24 July, 2014, US-20140206856-A1, IDS filed 10/27/2022) and Pitsch et al. (Published Year 2001, "Chemical synthesis of RNA sequences with 2′-O-[(triisopropylsilyl)oxy]methyl-protected ribonucleoside phosphoramidites" in: Beaucage S.L. et al., Current Protocols in Nucleic Acid Chemistry (New York, John Wiley & Sons, Inc, 2001), pp. 3.8.1-3.8.15, PTO-892) as applied to claims 1-3, 6-9, 11-14, 18-20 and 23-28 above, and further in view of Ohgi et al. (Filed 30 March 2018, US-20200038427-A1, PTO-892 mailed 08/14/2025).
Aoki and Pitsch address claims 1-3, 6-9, 11-14, 18-20 and 23-28 as written above. Aoki further teaches a production method of nucleic acids, see paragraph [0001]. Aoki teaches the nucleic acid is produced by the production method discussed above, and that use thereof is broad, for example, it is suitable for use in the production of a medicament, see paragraph [0278].
Although Aoki and Pitsch do not teach the non-linker nucleotide, required in claims 4-5.
However, in the same field of endeavor of nucleic acid synthesis, Ohgi teaches cyclic nucleic acid molecules having gene expression control function, see title, Ohgi teaches the cyclic nucleotide molecule is useful as a pharmaceutical product, see abstract. Ohgi teaches a cyclic nucleotide molecule represented by the formula (A) containing a linker (L), see paragraph [0016].
Ohgi teaches the linker is a molecule of a non-nucleotide structure, see paragraph [0071].
Ohgi teaches the linker may be represented by formula (II), see paragraph [0128]; wherein Ohgi exemplifies formula (II) as formula (II-8a) represented by the structure,
PNG
media_image5.png
225
515
media_image5.png
Greyscale
, see paragraph [0144]. The Examiner notes that formula (II-8a) corresponds to formula (A14-1) of instant claim 5.
Ohgi teaches the cyclic nucleotides can be synthesized easily, see paragraph [0071].
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have included the linker as recited above into the nucleic acids produced by Aoki 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 use the method of producing nucleic acids of Aoki in the production of a medicament as discussed above; for example in the production of a cyclic nucleotide as a pharmaceutical product as taught by Oghi as discussed above. One of ordinary skill in the art would have had a reasonable expectation of success of inserting the linker as taught by Oghi into the nucleic acids produced by Aoki, as both Aoki and Oghi are drawn to producing nucleic acids, Oghi teaches their nucleic acids can contain linkers; and Oghi teaches their cyclic nucleotides can be synthesized easily 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.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691