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 .
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed on 07/02/2026 has been considered by the Examiner inasmuch as foreign documents have been submitted into the file wrapper in English.
Claim Status
The claim set and Applicant remarks filed April 29, 2026 have been entered.
Claims 1-21 are canceled.
Thus, claims 22-42 as amended are examined on the merits herein.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action on January 30, 2026:
(I) The objection of claims 22, 24, 26, 29, 31, 33, 36 and 41-42 is withdrawn in view of Applicant’s amendments to these claims.
(II) Applicant’s arguments, see paragraph , filed April 29, 2026, with respect to the 112(d) rejection of have been fully considered and are persuasive. The rejection has been withdrawn.
Response to Arguments
The Examiner has reviewed and considered Applicant’s arguments, see Applicant’s remarks, paragraph #4, The Rejection under 35 U.S.C. § 103 on pp. 17-22.
However, the Examiner maintains the 103 rejection of record in view of the reasons below.
The Examiner notes Sugawara teaches their compounds as represented by the generic formula (II) as a pseudo solid phase-protecting group, and when L1 is a single bond; L2 is single bond or -O-; L3 is a C1-6 alkylene group; and L4 is a single bond as discussed below corresponds to when c is 0 or 1 and a is 1-3 of formula (II) of instant claim 22.
The Examiner also notes within instant claim 22 the recited formula (II) of instant claim 22 is a generic formula.
Moreover, Sugawara teaches their compounds of formula (II) are used for producing oligonucleotides.
The Examiner further notes instant claim 36 is drawn to synthesizing oligonucleotides using the compounds of instant claim 22.
Furthermore, Sugawara teaches formula (XI) which is an oligonucleotide which comprises a pseudo solid phase protecting group and overlaps with the compounds recited in generic formula (I) of instant claim 29.
Accordingly, in view of these considerations, the Examiner notes an anticipatory rejection (e.g. a 102 rejection) was not made against the instant claims using the Sugawara reference, rather an obviousness rejection (e.g. a 103 rejection) was made as Sugawara’s teachings correspond to and encompass the pseudo solid phase protecting groups recited in generic formula (II) of instant claim 22 and the compound of generic formula (I) of instant claim 29; and Sugawara further teaches the use of their compounds within synthesis methods to produce oligonucleotides as recited within instant claim 36.
Finally, MPEP 2144.08(II)(A)(4)(a) states “There is no absolute correlation between the size of the prior art genus and a conclusion of obviousness. See, e.g., Baird, 16 F.3d at 383, 29 USPQ2d at 1552”; and particularly in view of the fact that Sugawara already teaches all possible combinations comprised within formula (II) are pseudo solid phase protecting groups used for oligonucleotide synthesis; it then stands to reason that all possible combinations comprised within formula (II) of Sugawara are pseudo solid phase protecting groups used for the same purpose.
Thus, absent secondary considerations, the Examiner reasonably concludes that it would have been well within the scope of the artisan to have selected from the possibilities as taught within formula (II) of Sugawara as discussed above in order to arrive at the claimed invention as recited in independent claims 22, 29, 36 and 41-42.
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 22-42 remain rejected under 35 U.S.C. 103 as being unpatentable over Sugawara (Published 06 June 2019, US-20190169223-A1, PTO-892 mailed 01/30/2026).
Regarding claims 22-42, Sugawara teaches [25] the compound or salt thereof described in [24], wherein the pseudo solid phase-protecting group is represented by the following formula (II),
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, see pg. 3, paragraph [0068], formula (II) is on pg. 4, left column.
Sugawara teaches wherein
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indicates a bond to a group protected by the pseudo solid phase-protecting group, see paragraph [0069]; L1 is chosen from and includes a single bond, see paragraph [0070]; L2 is chosen from and includes a single bond, or -O-, see paragraph [0071]; L3 is chosen from and includes a C1-6 alkylene group, see paragraph [0073]; L4 is chosen from and includes a single bond, see paragraph [0074]; R1 is a C1-40 alkyl group and s is an integer of 1 to 5, see paragraph [0070].
(I) The Examiner respectfully notes when:
L1 is a single bond;
L2 is -O-;
L3 is a C1-6 alkylene group;
L4 is a single bond;
R1 is a C8-40 alkyl group; and
s is an integer from 1 to 4; the compound of formula (II) of Sugawara corresponds to formula (II) of instant claim 22 when:
c is 1, see claim 22, line 9;
a is an integer from 1 to 3, see claim 22, line 10;
R3 is H, see claim 22, line 11;
R5 is O-R6 or H, see claim 22, line 12;
each of R4 is independently O-R6, see claim 22, line 13;
R6 is at each occurrence independently a C8-C40 aliphatic hydrocarbon group, see claim 22, line 14;
b is an integer of 1 to 3, see claim 22, line 15;
with the proviso that if b is 1, at least one of R3 and R5 is not H, see claim 22, lines 16; and
with the further proviso that the sum of all carbon atoms contained in the R3, R4, R5 moieties present is greater than 23 and less than 200, see claim 22, lines 17-18.
The Examiner further notes the teachings of L1-L4, R1 and s of Formula (II) of Sugawara correspond to all structural limitations within instant claims 23-27.
(II) The Examiner also respectfully notes when:
L1 is a single bond;
L2 is a single bond;
L3 is a C1-6 alkylene group;
L4 is a single bond;
R1 is a C8-40 alkyl group; and
s is an integer from 1 to 4; the compound of formula (II) of Sugawara corresponds to formula (II) of instant claim 22 when:
c is 0, see claim 22, line 9;
a is an integer from 1 to 3, see claim 22, line 10;
R3 is H, see claim 22, line 11;
R5 is O-R6 or H, see claim 22, line 12;
each of R4 is independently O-R6, see claim 22, line 13;
R6 is at each occurrence independently a C8-C40 aliphatic hydrocarbon group, see claim 22, line 14;
b is an integer of 1 to 3, see claim 22, line 15;
with the proviso that if b is 1, at least one of R3 and R5 is not H, see claim 22, lines 16; and
with the further proviso that the sum of all carbon atoms contained in the R3, R4, R5 moieties present is greater than 23 and less than 200, see claim 22, lines 17-18.
(III) The Examiner further notes the teachings of L1-L4, R1 and s of Formula (II) of Sugawara correspond to all structural limitations within instant claims 23-26 and 28 as discussed above.
(IV) The Examiner also particularly respectfully notes all structural limitations within formulae III to VII of claim 26 are met by the teachings of Sugawara as discussed above.
Sugawara teaches [24] a compound represented by the following formula (XI), or a salt thereof, depicted as,
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, see pg. 3, paragraph [0061], formula (XI).
Sugawara teaches Z is a pseudo solid phase-protecting group, see paragraph [0066]. The Examiner respectfully notes the “
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” referred in Formula (II) of Sugawara is Z which is bonded to the hydroxyl moiety of the oligonucleotide to be protected as depicted in Formula (IX) of Sugawara above.
Therefore, the Examiner respectfully notes the limitation of “the attachment point to an oxygen atom of a hydroxyl moiety of the oligonucleotide to be protected” as required in claim 22, lines 6-8 is met by the teachings of Sugawara as discussed above.
Sugawara teaches the oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of the 2’-position, 3’-position, and 5’-position (e.g. R1 is a protecting group, see claim 29, pg. 6, line 3), see abstract.
The Examiner respectively notes Formula XI of Sugawara depicted above teaches hydroxyl groups at each of the 5’-positions of each nucleoside within the oligonucleotide of Formula XI (e.g. X is independently at each position O, see claim 29, pg. 6, line 4).
Sugawara teaches “n-1” within Formula XI as depicted above, additionally Sugarwa teaches wherein “n” in Formula XI above is an integer of 1 or greater (e.g. n is an integer equal to or greater than 0, see claim 29, pg. 6, line 5), see paragraph [0062].
Sugawara teaches Y is chosen from and includes a hydrogen, a hydroxyl or a thiol (e.g. Z is H or an electron withdrawing group, see claim 29, pg. 6, line 6), see paragraph [0065].
The Examiner respectfully notes within Formula XI of Sugawara above it teaches an =O atom directly connected to the phosphorous atom which the Examiner notes correspond to the Y limitation within Formula I of instant claim 29 (e.g. Y is independently, for each repetitive unit, O, see claim 29, pg. 6, line 7).
Sugawara teaches BaseZ is a nucleobase (e.g. each of the nucleoside x0 to xn may be the same or different, see claim 29, pg. 6, line 8), see paragraph [0063].
The Examiner respectfully notes when Formula (II) of Sugawara is applied to Formula (XI) of Sugawara, for example when the Examiner noted that Formula (II) corresponds to “Z” within Formula (XI) of Sugawara as discussed above, the limitation of CA is a single bond is met (e.g. CA is a single bond, see claim 29, pg. 6, line 9).
The Examiner also respectfully reiterates the teachings of Formula (II) of Sugawara specifically said teachings of Sugawara above meeting all structural limitations of “c”, “a”, “R3”, “R5”, “R4, “R6”, “b” and both provisions as outlined in claim 29, pg. 6, line 10 – pg. 7, line 2.
Therefore, the teachings of Sugawara above correspond to the compound of formula (I) of instant claims 29-30.
The Examiner also respectfully notes the teachings of Sugawara above correspond to all structural limitations of the compound of formula I-b as recited and required within claims 31-32; the formulae VIII-XII as recited and required within claim 33; as well as the structural limitations required in claims 34-35, respectively.
Sugawara teaches a novel method for producing oligonucleotides (e.g. synthesis of oligonucleotides, required in claim 36, line 1), see paragraph [0001].
Sugawara teaches the production method of an oligonucleotide includes a step of subjecting a nucleoside or oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of and including the 2’-position and 3’-position, see paragraph [0015].
Sugawara teaches [1] deprotecting a first nucleoside or first oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of 2’-position and the 3’-position and having a 5’-hydroxyl group protected with a temporary protecting group (e.g. a backbone hydroxyl protected by a protecting group R1, required in claim 36, lines 5-6) to remove the temporary protecting group to form a 5’-hydroxyl group (e.g. cleaving the protecting group thereby generating a free backbone hydroxyl group, required in claim 36, lines 7-8), see paragraph [0018].
The Examiner respectfully notes the two previous paragraphs correspond to the limitations of lines 2-8 of claim 36.
Sugawara teaches [2] converting the resulting 5’-hydroxyl group into an H-phosphonated form using an H-phosphonate reagent, see paragraph [0019].
Sugawara teaches [3] forming an oligomer of the first nucleoside or first oligonucleotide with a second nucleoside or second oligonucleotide having a 3’-hydroxyl group and having a 5’-hydroxyl group protected with a temporary protecting group, by forming a phosphite diester bond from the 5’-hydroxyl group now converted to the H-phosphonated form of the first nucleoside or first oligonucleotide and the 3’-hydroxyl group of the second nucleoside or second oligonucleotide, see paragraph [0020].
The Examiner respectfully notes the two previous paragraphs correspond to the limitations of claim 36, pg. 12, lines 1-5.
Sugawara teaches [8] wherein in any one of [3]-[7], further including [6] removing all of the basic protecting groups, the temporary protecting groups and the pseudo solid-phase protecting group (e.g. cleaving the oligonucleotide from the pseudo solid phase protecting group, see claim 36, pg. 12, line 8), see paragraph [0025].
Sugawara teaches in any one of [1] to [6], wherein the pseudo solid phase-protecting group is represented by Formula (II), see paragraph [0050].
The Examiner respectfully notes the two previous paragraphs correspond to the limitation of claim 36, pg. 12, line 8.
Sugawara teaches [4] further including the step of converting the phosphite diester bond of the oligomer into and including a phosphodiester bond or a thiophosphodiester bond, see paragraph [0021].
The Examiner respectfully notes the limitations of (i) the phosphate moiety is a phosphorous (III) moiety, required in claim 37, lines 2-3; (ii) oxidizing or sulfurizing the phosphorous (III) atom to a phosphorous (V) atom, required in claim 37, lines 4-5; and (iii) reacting the free backbone hydroxyl group of step b) with a phosphoramidite nucleoside or oligonucleotide building block to form a phosphite triester bond and comprising oxidizing or sulfurizing the phosphite triester bond as required in claim 38; are all reasonably interpreted by the Examiner to be physical limitations that result from converting the phosphite diester bond into either a phosphodiester bond, if the bond is oxidized, or a thiophosphodiester bond, if the bond is sulfurized. Therefore, since Sugawara teaches converting the phosphite diester bond of the oligomer into and including a phosphodiester bond or a thiophosphodiester bond, the Examiner reasonably interprets all physical limitations as recited above within claims 37-38 are met by the teachings of Sugawara discussed above.
Sugawara teaches the pseudo solid phase-protecting groups on the phosphodiester bonds or thiophosphodiester bonds may be all removed by treatment with a mixture of ammonia, water and an aqueous methylamine solution (e.g. a base selected from the group consisting of ammonia, a C1-C6-alkyl amine and a source of hydroxide ions, required in claim 39), see paragraph [0473] of Sugawara; as evidenced by the Specification which discloses a C1-C6-alkyl amine is in particular methylamine, see pg. 73, lines 14-20; and discloses a person skilled in the art knows that an aqueous solution of ammonia may also be referred to as an ammonium hydroxide solution since it comprises ammonium ions and hydroxide ions, see pg. 73, lines 25-30.
Sugawara teaches [11] the production method described in [2] the elongation reaction, see paragraph [0028]-[0031]; and [12] the production method described in [11] further including converting the phosphite diester bond of the oligomer into and including a phosphodiester bond or a thiophosphodiester bond, see paragraph [0032].
Sugawara teaches the production method described in [12] further comprising adding a polar solvent to a reaction mixture to form a precipitate and collecting the precipitate by solid liquid separation (e.g. isolating the support-cleaved oligonucleotide, required in claim 40), see paragraph [0034].
Sugawara teaches a nucleoside or a oligonucleotide (e.g. the nucleoside or oligonucleotide, required in claim 42, line 3) having the solid phase-protecting group of the formula (I) in which m is 0 may be obtained by, for example the reaction (e.g. preparing the compound of claim 29, required in claim 42, line 1) of a carboxylic acid represented by Formula (X-1),
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, see pg. 31, left column, with a hydroxyl group (e.g. the first free backbone hydroxyl moiety, required in claim 42, line 4), see paragraph [00488].
The Examiner respectfully notes the structure of Formula (X-1) meets all structural limitations of formula XIV of instant claim 42 as recited and required in claim 42, pg. 14, lines 1-13.
The Examiner respectfully notes when Sugawara teaches L1 and L2 are a single bond; L3 is a C1-6 alkyl; and L4 is a single bond, these teachings correspond to when c is 0 as required in claim 42, line 1; and Formula (XIV) as recited in claim 42, pg. 14, lines 3-15.
The Examiner also respectfully reiterates Sugawara teaches the oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of the 2’-position, 3’-position, and 5’-position, see abstract; or the first oligonucleotide having a pseudo solid phase-protecting group in at least one location selected from the group consisting of the 2’-position and the 3’-position and having a 5’-hydroxyl group protected with a temporary protecting group, see paragraph [0018]; and wherein the Examiner respectfully notes these limitations correspond to the limitation a second backbone hydroxyl which is protected by a protecting group R1 as required in claim 42, lines 4-5.
With particular respect to the limitation of under conditions suitable to form an ester bond between the oxygen atom of the first free backbone moiety of the compound of step I), required in claim 42, lines 7-9; the Examiner reasonably interprets this limitation as a physical limitation that is met by reacting the oligonucleotide with the -OH group of RL of Formula XIV, as recited in claim 42, line 9 – pg. 14, line 3. Since Sugawara teaches the oligonucleotide and Formula XIV as required in claim 42, the physical limitation is met by the teachings of Sugawara.
Additionally, the Examiner also respectfully notes formula (XI) of Sugawara teaches “Z” is a pseudo solid phase-protecting group, for example Formula (X-1), which again the Examiner notes is bonded to the oxygen atom of the 3’ hydroxyl group of the sugar which results in the formation of an ester bond between the oxygen atom of the oligonucleotide and the carbonyl of Formula (X-1) as taught by Sugawara above.
Therefore, the Examiner respectfully notes the teachings of Sugawara meet all structural limitations and method steps recited and required within claim 42 as discussed above.
With respect to claim 41, the Examiner respectfully notes when Sugawara teaches L1 is a single bond and L2 is -O- within Formula (X-I) as discussed above, the Examiner again respectfully notes this teaching of Sugawara corresponds to c is 1 as required in claim 41, line 1.
Sugawara also teaches when the carboxylic acid is used for the introduction of the pseudo solid phase-protecting group, the pseudo solid phase-protecting group may be introduced into the nucleoside or oligonucleotide in a solvent using a condensing agent such as and including carbonyldiimidazole (e.g. the activated carbonic acid derivative, required in claim 41, pg. 13, line 4), see paragraph [0490]; as evidenced by the Specification which discloses the activated carbonic acid derivative used in step ii) may be 1,1’-carbonyldiimidazole, see pg. 54, lines 15-20.
With particular respect to the limitation of reacting the product of step ii) with a compound of Formula XIII, required in claim 41, pg. 13, line 5; Sugawara exemplifies the formula (X-6),
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, see paragraph [0495], where the symbols are the same as defined above, see paragraph [0496].
The Examiner respectfully reiterates Sugawara teaches L1 is chosen from and includes a single bond, see paragraph [0070]; L2 is chosen from and includes -O-, see paragraph [0071]; L3 is chosen from and includes C1-6 alkylene group, see paragraph [0073]; L4 is chosen from and includes a single bond, see paragraph [0074]; R1 is a C1-40 alkyl group and s is an integer of 1 to 5, see paragraph [0070].
The Examiner also particularly notes when:
L1 is a single bond;
L2 is -O-;
L3 is a C1-6 alkylene group; and
L4 is a single bond; the compound of formula (II) of Sugawara corresponds to Formula (XIII) of instant claim 41.
Although, the Examiner respectfully notes Sugawara does not explicitly teach reacting the first free hydroxyl moiety of either the nucleoside or oligonucleoside with an activated carbonic acid derivative, as required in claim 41, pg. 13, line 4.
However, the Examiner respectfully reiterates Sugawara teaches when the carboxylic acid is used for the introduction of the pseudo solid phase-protecting group, the pseudo solid phase-protecting group may be introduced into the nucleoside or oligonucleotide in a solvent using a condensing agent such as and including carbonyldiimidazole as discussed above.
Moreover, Sugawara teaches Formula (XIII) of instant claim 41 as discussed above. Therefore, in view of these teachings it would have been well within the scope of the artisan to have decided to react the hydroxyl group of Formula X-6 with the free hydroxyl group of the nucleoside or oligonucleotide thus incorporating any of the pseudo solid phase-protecting groups as taught by Sugawara above; as Sugawara explicitly teaches using the recited condensing agent, carbonyldiimidazole, in the method of incorporating the pseudo solid phase-protecting group into the nucleoside or oligonucleotide which has a hydroxyl group as taught by Sugawara above.
Therefore, the artisan could have decided based on these teachings to react the carbonyldiimidazole with the nucleoside or oligonucleotide first and then to have reacted the resulting product with Formula (X-6) of Sugawara and arrived at the claimed invention of claim 41 as within the scope of the artisan based on the prior art teachings of Sugawara above. See MPEP 2144.04(IV)(C) which recites “selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results”.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have made this modification to the reaction method of Sugawara above in view of the teachings of Sugawara above as within the scope of the artisan as combining prior art elements according to known compositions and methods to yield predictable results. One of ordinary skill in the art would have been motivated to provide a novel method for producing oligonucleotides as taught by Sugawara above.
One of ordinary skill in the art would have had a reasonable expectation of success to have included such a modification into the method of Sugawara, as Sugawara already teaches the use of the condensing agent, carbonyldiimidazole, with the pseudo solid phase-protecting group of Sugawara for incorporation into the nucleoside or oligonucleotide of Sugawara as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the 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.
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.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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