DETAILED ACTION
Response to Amendment
Applicant’s response to the office action filed on April 17, 2026 has been entered. The claims pending in this application are claims 44-65 wherein claims 48-51, 56, and 57 have been withdrawn due to the restriction requirement in the office action mailed on June 25, 2025. Since applicant argues that “[A]t least some of the objections and rejections in the current office action are new and could have been made against the claims as originally presented. For example, claim 44 has now been rejected under § 112(b) because of the phrase ‘the extending being continued until substantially all of the extended primers are blocked with the first blocking group. This phrase appeared in claim 44 as originally presented. The rejection could have been made in the first office action, but was not. By raising it now, the Office has introduced a new ground of rejection that was not necessitated by applicant's amendment of the claims, nor based on in IDS - contrary to MPEP § 706.07(a). Thus, the current office action should not have been made final. Applicant requests that the finality be removed” (see applicant’s remarks, page 8, fifth and sixth paragraphs), the examiner agrees to withdraw the final office action mailed on January 6, 2026.
Claims 44-47, 52-55, and 58-65 will be examined.
Specification
The substituted specification filed on April 17, 2026 has been entered. However, although applicant stated that “[A]lso enclosed is an ST.26 compliant sequence listing” (applicant’s remarks, page 8, seventh paragraph), the examiner cannot locate the ST.26 compliant sequence listing mentioned by applicant. Applicant is required to file the ST.26 compliant sequence listing.
Claim Objections
Claim 44 is objected to because of the following informalities: (1) “the rephasing” in line 5 should be “the method” because “the rephasing” is not a complete phrase; (2) “corresponding to” in steps (i) and (iii) should be “is complementary to”; (3) “the sequencing primers from step (ii)” in item (iii) should be “extended sequencing primers without the first blocking group from step (ii)” because the sequencing primers in item (iii) is extended sequencing primers without the first blocking group and are different from the sequencing primers in item (ii); and (4) “said first and second blocking groups are each” in the last “wherein” phrase should be “said first blocking group and said second blocking group are”.
Response to Arguments
In page 10, third to fifth paragraph of applicant’s remarks, applicant argues that “[T]he objections to claim 44 include the assertion that the term ‘corresponding to’ should be ‘complementary to’. This is not correct, because the perspective of the claim is from the strand being synthesized and detected. Step (a)(i) includes ‘further extending the sequencing primers using a first mixture that contains a DNA polymerase and four nucleotide triphosphates selected from A, T, C, and G and/or analogs thereof, wherein one of nucleotide triphosphates or analogs in the first mixture corresponds to the first nucleotide (X) of the selected dinucleotide. Thus, if the selected dinucleotide XY is, for example, AG, the nucleotide triphosphate or analog that corresponds to the first nucleotide is ‘A’. The meaning of ‘corresponds’ in this context is [[is]] explained (for example) in ¶ [0131] of the specification. Applicant respectfully declines to make any of the word changes proposed in the objections. The proposed word changes are stylistic rather than substantive, and potentially less clear than the current wording”.
These arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection. Applicant argues that the meaning of “corresponds” is defined in paragraph [0131] of the specification and paragraph [0113] of US 2023/0129228 A1, which is US publication of the instant application, states that “[A]s noted, the nucleotide at the 5′ position of the oligonucleotide is fixed, and corresponds to the second nucleotide of the selected dinucleotide. A nucleotide at the 5’ position of the oligonucleotide ‘corresponds’ to the second nucleotide of the selected dinucleotide if the 5′ nucleotide of the oligo and the second nucleotide both can form a base pair with the same base in the template. For example, if the second nucleotide is A, T, G or C, respectively, the 5’ nucleotide can be A, T, G or C, respectively”, this paragraph indicates that a nucleotide at the 5’ position of the oligonucleotide ‘corresponds’ to the second nucleotide of the selected dinucleotide means that the 5’ nucleotide of the oligo and the second nucleotide can form a base pair with the same base in the template and the definition for “correspond to” in the specification only limits to 5’ nucleotide of the oligo and the second nucleotide. Since one of nucleotide triphosphates or analogs in claim 44 is from the first mixture and a single nucleotide triphosphate selected from A, T, C, or G and analogs thereof in claim 44 is from a second mixture, the definition “correspond to” in paragraph [0113] of US 2023/ 0129228 A1 cannot be used for claim 44 and the phrase “correspond to” in claim 44 should be only defined as its plain meaning.
Claim 45 is objected to because of the following informality: “the only nucleotide triphosphate” should be “the single nucleotide triphosphate” because no phrase “only nucleotide triphosphate” in claim 44. Note that applicant has not addressed this issue.
Claim 46 is objected to because of the following informality: this claim should be deleted since claims 44 and 45 have all limitations recited in the claim. Note that applicant has not addressed this issue.
Claim 47 is objected to because of the following informality: “one of the first and second blocking groups is an O-azidomethyl group, and one of the first and second blocking groups is an O-NH₂ group” should be “one of the first blocking group and the second blocking group is an O-azidomethyl group, and another of the first blocking group and the second blocking group is an O-NH₂ group”. Note that applicant has not addressed this issue.
Claim 52 is objected to because of the following informality: “five to fifteen of said cycles are performed in step (a)” should be “the multiple cycles are five to fifteen cycles”. Note that applicant has not addressed this issue.
Claim 55 is objected to because of the following informality: “the cleaving in step (ii)” should be “step (ii)”. Note that applicant has not addressed this issue.
Claim 58 is objected to because of the following informality: “resuming cycles of
the sequencing of the clonal population of DNA templates after the rephasing” should be
“sequencing the clonal population of DNA templates after said rephasing the sequencing primers in the clonal population of DNA templates” because there is no cycles of the sequencing of the clonal population of DNA templates in claim 44. Note that applicant has not addressed this issue.
Claim 59 is objected to because of the following informality: “performing multiple cycles of sequencing of a plurality of clonal populations of DNA templates in which a sequencing primer hybridized to each DNA template is extended by one nucleotide per cycle, thereby identifying a complementary nucleotide in the DNA template; after a number of such sequencing cycles, rephasing the sequencing primers according to the method of claim 44; then resuming cycles of the sequencing to identify further nucleotides in the DNA template” should be “performing multiple cycles of sequencing a plurality of clonal populations of DNA templates in which a sequencing primer hybridized to each of the DNA templates is extended by one nucleotide in each of the multiple cycles, thereby identifying a complementary nucleotide in each of the DNA templates; after a number of the multiple cycles, rephasing the sequencing primers according to the method of claim 44; then sequencing the plurality of clonal populations of DNA templates to identify further nucleotides in each of the DNA templates”. Note that applicant has not addressed this issue.
Claim 60 or 61 or 62 or 65 is objected to because of the following informality: “the rephasing” should be “said rephasing the sequencing primers” since “the rephasing” is not a complete phrase. Note that applicant has not addressed this issue.
Claim 60 is objected to because of the following informality: the phrase “within the first 800 of said multiple cycles” should be deleted because there is no phrase “first 800 of said multiple cycles first 800 of said multiple cycles” in claims 44 and 59. Note that applicant has not addressed this issue.
Claim 61 is objected to because of the following informality: “the rephasing extends the number of clonal populations of DNA templates in the plurality having a discordance percentage of less than 2% by at least 1.5-fold” should be “the method increases at least 1.5-fold of clonal populations of DNA templates having a discordance percentage of less than 2% in the plurality clonal populations of DNA templates”. Note that applicant has not addressed this issue.
Claim 62 is objected to because of the following informality: “the phrasing extends the number of clonal populations of DNA templates in the plurality having a discordance percentage of less than 2% by at least 200 cycles” should be “the method extends clonal populations of DNA templates having a discordance percentage of less than 2% in the plurality clonal populations of DNA templates for at least 200 cycles”. Note that applicant has not addressed this issue.
Claim 65 is objected to because of the following informality: “during the sequencing” should be deleted since the claim does not indicate sequencing for what. Note that applicant has not addressed this issue.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 44-47, 52-55, and 58-65 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 44 is rejected as vague and indefinite in view of the preamble of the claim because it is unclear that a method of dinucleotide frequency rephasing (DFR) what is used to restore phase at a selected dinucleotide XY from where during a process of sequencing-by-synthesis. Please clarify.
Response to Arguments
In page 10, last paragraph bridge to page 11, first paragraph of applicant’s remarks, applicant argues that “[I]n the preamble to claim 44, the meaning of dinucleotide frequency rephasing is defined in the preamble as a method ‘to restore phase at a selected dinuclcotide XY during a process of sequencing-by-synthesis.’ As described in the specification, sequencing primers get out of phase when individual sequencing primers become one or more nucleotides ahead or behind in their position over the template being sequenced, in comparison with most of the sequencing primers in the reaction mixture. As explained in the specification, out-of-phase primers can be rephased according to this invention at any position within a sequence read of the operator's choosing. Accordingly, the ‘selected dinucleotide’ referred to in claim 44 is a particular dinucleotide selected by the operator during the sequencing where the claimed method is performed to restore phase”.
These arguments have been fully considered but they are not persuasive toward the withdrawal of the rejection because the preamble of claim 44 does not indicate that a method of dinucleotide frequency rephasing (DFR) what is used to restore phase at a selected dinucleotide XY from where during a process of sequencing-by-synthesis. In other word, it is unclear that a selected dinucleotide XY is from where.
Claim 44 is rejected as vague and indefinite because the phrase “the extending being continued until substantially all of the extended sequencing primers are blocked with the first blocking group” in step (i) does not make sense since it is unclear whether the first blocking groups is located on 3’ ends of extended sequencing primers or not. Does this phrase mean that “said extending the sequencing primers being stopped until 3’ ends of extended sequencing primers are blocked with the first blocking group”? Please clarify. Note that applicant has not addressed this issue.
Claim 44 is rejected as vague and indefinite in view of step (ii) because it is unclear that the first blocking group located in where is unblocked. Please clarify. Note that applicant has not addressed this issue
Claim 54 is rejected as vague and indefinite because the claim does not make sense because “the readjusting” is not a complete phrase in view of claim 53 and “the sequencing a uracil triphosphate or analog thereof that can be incorporated into the sequencing primer in place of thymine triphosphate” lack an antecedent basis. Does this claim mean that “wherein said readjusting the 3’ end of the sequencing primers to an upstream position comprises cleaving uracil bases from the sequencing primers and the uracil bases are the analogs which are incorporated to the sequencing primers before readjusting step”? Please clarify. Note that applicant has not addressed this issue
Claim 65 is rejected as vague and indefinite because it is unclear that a read length of at least 800 bases is obtained from where. Please clarify.
Response to Arguments
In page 11, fifth paragraph of applicant’s remarks, applicant argues that “the read length of 800 bases is obtained from the sequencing by synthesis referred to in claim 44, with rephasing being done two to four times during the 800 bases of sequencing”.
This argument has been fully considered but it is not persuasive toward the withdrawal of the rejection because the claim does not indicate where at least 800 bases come from.
Conclusion
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.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph. D., whose telephone number is (571)272-0746. The examiner can normally be reached Monday to Friday, 9 AM to 5 PM.
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/FRANK W LU/
Primary Examiner, Art Unit 1683
April 23, 2026
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