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
The Examiner notes in the claim set filed April 14, 2026, Applicant has deleted Formula (I) pertaining to the election of species A discussed on pg. 2 within the non-final rejection mailed January 16, 2026.
Therefore, in view of the foregoing reason, the Examiner hereby modifies the election of species A now drawn to a species of Formula (Ia), where B is thymine; R1 is H; R2 is H; and OR3 wherein R3 is a triphosphate.
The Examiner respectfully notes the elected species reads on claims 1, 4, 8, 12-13 and 15-17.
Claim Status
The claim set and Applicant’s remarks filed April 14, 2026 have been entered.
Claims 2-3, 10, 21 and 25-28 are canceled.
Claims 5-7, 9, 11, 14, 18-20, 22-24 and 29 continue to be withdrawn from further consideration as being drawn to either a nonelected species or a nonelected invention respectively.
Thus, claims 1, 4, 8, 12-13 and 15-17 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Withdrawn Objections and Rejections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 16, 2026:
(I) The objection to claim 15 is withdrawn in view of Applicant’s amendment to claim 15.
(II) The rejection of claim 2 under 35 U.S.C. 103 is withdrawn in view of Applicant’s cancellation of claim 2.
Response to Arguments
The rejection of claims 1, 4, 8, 12-13 and 15-17 under 35 U.S.C. 103 is maintained.
Applicant argues:
(A) Li has disclosed a very broad genus of nucleoside analogues with hundreds if not thousands of possible 3’-O reversible blocking groups; and provides no reason or motivation to one skilled in the art to select the specific 3’-O reversible blocking group to arrive at the claimed nucleoside or nucleotide of instant claim 1, see Applicant’s remarks, pg. 9, last paragraph.
(B) One skilled in the art, in view of the teachings of Li, would have no reason to select Structure A and further select Ra, Rb, and Rc to be hydrogen to arrive at the claimed blocking group as its clear from the teachings that substituted alkenyl blocking groups are preferred embodiments, see Applicant’s remarks, pg. 10, first full paragraph.
With respect to Applicant’s arguments (A)-(B), the Examiner notes Li teaches the reversible blocking group R1 is a substituted or unsubstituted alkenyl; and further exemplifies the unsubstituted alkenyl includes the vinyl group as required within Formula (Ia) of instant claim 1 when the Structure A of Li contains a double bond and Ra, Rb, and Rc is each hydrogen.
The motivation and reason would be to provide a reversible blocking group for the nucleoside analogues of Li comprising the unsubstituted alkenyl which is exemplified by Structure A taught by Li.
(C) The claimed 3’-O vinyl blocking group has unexpected properties that make it particularly suitable as a reversible blocking group, where claimed blocking group demonstrated a fast deblocking rate and ease of incorporation into oligonucleotide via biosynthesis, see Applicant’s remarks, pg. 10, last paragraph – pg. 11, first paragraph.
(D) Figure 2 illustrates the vinyl group’s relatively small size may make it more compatible with enzymes capable of adding nucleotides to oligonucleotides, see Applicant’s remarks, pg. 11, second full paragraph.
(E) Usage of a 3’ vinyl blocking group allows for the usage of a tetrazine reagent to deblock, which, advantageously, requires only mild conditions, see Applicant’s remarks, pg. 11, third full paragraph.
With respect to Applicant’s arguments (C)-(E), the Examiner notes the instant specification states “The deprotection of vinyl ethers with tetrazine may involve relatively fast kinetics, approaching a 'click'-type reaction (see paragraph [0069]).
Additionally, the unexpected properties as argued above are reasonably interpreted by the Examiner to be expected properties as they relate to the vinyl group's structure and use as a 3'-O blocking agent; as since Li teaches a vinyl group as a reversible blocking group which is encompassed by structure A for use within the nucleoside analogues taught by Li as discussed above; the Examiner notes there is reason to believe the unexpected properties as argued by Applicant would be expected properties of the analogues of Li.
Furthermore, the Examiner notes the following MPEP sections:
MPEP 716.01(c)(I) states objective evidence must be factually supported by an appropriate affidavit or declaration to be of probative value and includes evidence of unexpected results;
MPEP 716.01(c)(II) states arguments presented by the applicant cannot take the place of evidence in the record;
MPEP 716.02(b)(I) states the evidence relied upon should establish that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance; and
MPEP 716.02(c)(I) states evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention; and where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness.
Thus, in view of the foregoing reasons, Applicant’s arguments (A)-(E) have been fully considered but are not found persuasive.
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, 4, 8, 12-13 and 15-17 remain rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (Published 26 October 2017, WO-2017185026-A1, also known as Complete Genomics Inc (Published 26 October 2017, WO 17/185026) in the IDS filed 09/06/2023).
Regarding claims 1, 4, 8, 12-13 and 15-17, Li teaches deoxyribose nucleoside analogues having a 3’-O reversible blocking group and a nucleobase, see pg. 17, paragraph [0047].
Li exemplifies such nucleoside analogues include those of Formula (I) represented by the structure,
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, where Li teaches R1 is the 3’-O reversible blocking group; R2 is or includes a nucleobase; and R3 is a cleavable linking moiety comprising at least three phosphates, see pg. 17, paragraph [0048].
The Examiner respectfully notes Formula I comprises a deoxyribose core and therefore fulfills the structural limitation where R1 is H and R2 is H as elected by Applicant in the species election discussed above; and as recited in claim 4 and claim 8 respectively.
Li teaches the nucleoside analogue is a nucleoside triphosphate (i.e. R3 consists of three consecutive phosphates) (e.g. OR3 is a triphosphate as elected by Applicant in the species election discussed above and corresponding to the recitation in claim 12; the nucleotide where -OR3 is triphosphate as recited in claim 17); see pg. 48, paragraph [0048]; and wherein the triphosphate structure is exemplified as evidenced by Li within Formula II on pg. 22, paragraph [0058].
Li teaches R2 can be a base selected from and including thymine (T) (e.g. B is thymine as elected by Applicant in the species election discussed above and corresponding to the fifth nucleobase recited in claim 13), see paragraph [0048], pg. 18.
Li teaches the reversible blocking group R1 is a substituted or unsubstituted alkenyl, see paragraph [0049].
Li exemplifies the unsubstituted alkenyl as the reversible blocking group which is represented by Structure A,
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, where in Structure A, Ra, Rb, and Rc are each individually selected from the group consisting of and including hydrogen. Li also teaches in Structure A
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can represent a double bond and the
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indicates where the moiety is connected to the remainer of the molecule. See pg. 18, paragraph [0050]. The Examiner notes in view of the teachings of Li, Li discloses the 3’-O vinyl group as recited in Formula (Ia) of claim 1.
Li teaches the nucleoside analogues of Formula I can be labeled with a detectable label (e.g. a fluorescent label) at the R2 position, see pg. 21, paragraph [0056].
Li exemplifies the nucleoside analogue of Formula I labeled with a detectable label as a compound of Formula IA, see pg. 21, paragraph [0057]; having the structure,
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, where R4 is a nucleobase, L is a linker, and D contains a detectable label (e.g. a fluorescent label), see pg. 22, Formula IA.
The Examiner notes the teachings of Formula IA of Li correspond to wherein B comprises a nucleobase covalently bound to a detectable label through a linker, as recited in claim 15; and when B is thymine as taught by Li above, the thymine is covalently bound to a detectable label through a linker which corresponds to the third recited structure in claim 16.
Although, Li does not exemplify the elected compound within the Election/Restrictions section above. However, Li does teach a nucleoside triphosphate comprising the limitations corresponding to B is thymine; R1 is H; R2 is H; OR3 wherein R3 is a triphosphate; and each of R4a, R4b and R4c is H as discussed above and is encompassed by the recited Formula (Ia) of claim 1.
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 select any of the disclosed options taught within Formula I or Formula IA of Li as discussed above; and thus arrive at the elected species of Formula (Ia) of claim 1 as discussed above because Li teaches all of the limitations required within the elected species of Formula (Ia) of claim 1 are possible choices within the nucleoside analogues of Formula I or Formula IA of Li 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 chosen from the limitations taught within Formula I or Formula IA of Li and thus arrive at the elected species of Formula (Ia) of instant claim 1 as within the scope of the artisan as combining prior art elements according to known compounds to yield predictable results.
One of ordinary skill in the art would have been motivated to have chosen from the limitations taught within Formula I or Formula IA of Li in order to arrive at a deoxyribose nucleoside analogue having a 3’-O reversible blocking group and a nucleobase as taught by Li above. One of ordinary skill in the art would have had a reasonable expectation of success to have chosen from the limitations within Formula I or Formula IA of Li and therefore would have arrived at the elected species of Formula (Ia) of instant claim 1, because Li teaches all of the structural limitations required within the elected species of Formula (Ia) of instant claim 1 are all possible choices within the nucleoside analogues of Formula I or Formula IA of Li 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.
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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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.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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