DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
2. Applicant’s response filed on November 6, 2025 has been entered.
Claims 40, 41, 43, 51-59, and 61-74 are pending. Claims 40, 41, 43, 51-53, 55-59, 62, and 69-74 are under examination. Claims 54, 61, and 63-68 remain withdrawn from consideration as being drawn to a non-elected invention or species.
Response to Arguments
3. Applicant’s arguments filed on November 6, 2025 have been fully considered.
Rejection of claims 69 and 70 under 35 U.S.C. 112(b)
Applicant argues that the rejection should be withdrawn in view of the amendments to claims 69 and 70 (Remarks, page 7).
This argument was persuasive. The rejection has been withdrawn.
Rejection of claims 40, 41, 43, 51-53, 62, and 69 under 35 U.S.C. 103 as being unpatentable over Islam in view of Frisen
Applicant argues that the rejection should be withdrawn because the cited references fail to teach or suggest that “the composition is a soluble composition” as required by amended independent claim 40 (Remarks, pages 9-14).
This argument, and especially Applicant’s remarks at page 13, last paragraph – page 14, first full paragraph, was persuasive. Islam in view of Frisen fails to teach or suggest the required soluble composition and only suggests a composition in which the different oligonucleotides and nucleic acids are immobilized, directly or indirectly, on a solid phase. The rejection has been withdrawn accordingly.
Rejections of claims 55-59 and 70-72 citing Islam and Frisen as the primary combination of references
Applicant argues that the rejections should be withdrawn because the cited references fail to remedy the deficiencies in the primary combination of references with respect to amended claim 40, from which claims 55-59 and 70-72 depend (Remarks, pages 14-16).
This argument was persuasive. The rejections have been withdrawn.
Information Disclosure Statements
4. Applicant’s submission of an Information Disclosure Statement (IDS) on November 6, 2025 and also on January 22, 2026 is acknowledged. All of the references cited in the IDSs have been considered.
Claim Rejections - 35 USC § 102
5. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
6. Claims 40, 41, 51-53, 62, 69, and 73 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bower and Johnston (Nucleic Acids Research 2010; 38: e194; newly cited).
The instant claims are drawn to a soluble composition comprising a template nucleic acid, a template switch oligonucleotide (TSO), a single product nucleic acid, and a sequencing platform adapter construct. The claims additionally require the template nucleic acid and the template switch oligonucleotide to be hybridized to adjacent regions of the single nucleic acid product. As well, the TSO and single product nucleic acid contain at least one exo-sample nucleotide at a particular region of the nucleic acids. Lastly, Applicant has previously elected the following species for examination: (i) RNA template nucleic acid, and (ii) the 3’ hybridization domain of the template switch oligonucleotide comprises a homo-trinucleotide.
Regarding claims 40, 53, 62, and 69, Bower and Johnston disclose a soluble composition containing the following elements (see, e.g., Fig. 1 on p. 3): (i) an RNA template nucleic acid; and (ii) a TSO comprising a 3’ hybridization domain that includes a 3’ homo-trinucleotide (GGG) and one or more exo-sample nucleotides (dUTP) located 5’ of the 3’ hybridization domain (i.e., dUTP adapter B in Fig. 1). The TSO also contains a sequencing platform adapter construct since the “Adapter B” sequence contained in the TSO is capable of functioning in the required manner. See also the “First-strand cDNA synthesis incorporating dUTP and 5’ and 3’ adapter sequences” section on page 2 for additional discussion of the method shown in Figure 1.
Further regarding claims 40 and 73, the soluble composition of Bower and Johnston also contains a single product nucleic acid that (i) comprises a sequence complementary to the template RNA, and (ii) contains one or more exo-sample nucleotides (dUTP) located 5’ of the sequence complementary to the template RNA (see Fig. 1 and Table 1, where the first strand cDNA synthesis product contains a plurality of dUTPs 5’ of the sequence complementary to the template RNA. As well, as can be seen in Figure 1 and the accompanying discussion in the figure legend, the TSO and template nucleic acid hybridize to adjacent portions of the single product nucleic acid.
Regarding claims 40, 41, and 52, the sequencing adapter construct in the TSO of Bower and Johnston is capable of functioning as a sequencing primer domain since it can function as a sequencing primer. The sequencing adapter construct in the TSO of Bower and Johnston can also bind to a complementary surface-attached sequencing platform oligonucleotide.
Regarding claims 40, 41, and 51, the single product nucleic acid in the soluble composition of Bower and Johnston also contains a sequencing adapter platform construct since the “Adapter A” sequence at the 5’ end of the reverse transcription primer is capable of functioning in the required manner. As with the sequencing platform adapter construct contained in the TSO of Bower and Johnston, the sequencing platform adapter construct in the reverse transcription primer of Bower and Johnston is capable of functioning as a sequencing primer domain since it can function as a sequencing primer. It can also bind to a complementary surface-attached sequencing platform oligonucleotide.
Thus, claims 40, 41, 51-53, 62, 69, and 73 are anticipated by Bower and Johnston.
Claim Rejections - 35 USC § 103
7. 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.
8. 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.
9. Claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over Bower and Johnston (Nucleic Acids Research 2010; 38: e194; newly cited).
As discussed above, the teachings of Bower and Johnston anticipate the compositions of claims 40, 41, 51-53, 62, 69, and 73.
Bower and Johnston do not specify the reaction vessel in which the method depicted in Figure 1 is conducted, but it would have been prima facie obvious to perform this reaction in a reaction tube (i.e., to provide the soluble composition of claim 40 in a reaction tube). More specifically, the ordinary artisan would have recognized that the soluble composition of Bower and Johnston could be provided in any known reaction vessel, and accordingly, would have been motivated to select the well-known option of a reaction tube with a reasonable expectation of success. Thus, the composition of claim 43 is prima facie obvious over Bower and Johnston.
10. Claims 55-59 and 71 are rejected under 35 U.S.C. 103 as being unpatentable over Bower and Johnston (Nucleic Acids Research 2010; 38: e194; newly cited) in view of Kapteyn et al. (BMC Genomics 2010; 11: 413; cited previously).
As discussed above, the teachings Bower and Johnston anticipate the compositions of claims 40, 41, 51-53, 62, 69, and 73.
Bower and Johnston do not teach that the TSO contains a modification (e.g., an iso-nucleotide base) that prevents a polymerase from switching from the TSO to a different template nucleic acid as required by claims 55 and 56.
Bower and Johnston also do not teach that the TSO contains a modification as required by claims 57-59 and 71.
Prior to the effective filing date of the claimed invention, though, it would have been prima facie obvious to design the TSO of Bower and Johnston such that it includes iso-nucleotides at the 5’ end. Kapteyn provides motivation to do so by teaching that the presence of such nucleotides at the 5’ end of a TSO “inhibit MMLV-RT from extending the cDNA beyond the TS oligo, thus increasing cDNA yield by reducing formation of concatemers of the TS oligo that are the sources of significant background” (abstract; see also pages 2 and 5-7 as well as Fig. 1). The ordinary artisan would have recognized that reducing background resulting from undesirable TSO concatemer formation would also benefit the method practiced using the compositions of Bower and Johnston, and accordingly, would have been motivated to the design the TSO of Bower and Johnston to contain the beneficial 5’ iso-nucleotides discussed in Kapteyn. The ordinary artisan would have had a reasonable expectation of success since Kapteyn described how to design such nucleotides (see, e.g., pages 5-6 and 8). Thus, the compositions of claims 55-59 and 71 are prima facie obvious.
11. Claims 57-59, 71, and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Bower and Johnston (Nucleic Acids Research 2010; 38: e194; newly cited) in view of Linnarson et al. (US 2012/0010091 A1; cited previously).
As discussed above, the teachings Bower and Johnston anticipate the compositions of claims 40, 41, 51-53, 62, 69, and 73.
Bower and Johnston do not teach that the TSO contains a modification as required by claims 57-59, 71, and 72.
Linnarson also discloses compositions comprising an RNA template, a TSO, and a sequencing adaptor construct, where the TSO and RNA template are hybridized adjacent to one another on a nucleic acid (see, e.g., Example 1 on pp. 9-10, esp. para. 84 and Table 1; see also Fig. 3 and paras. 15, 67, and 89-90). The TSO in Linnarson has the same general structural features as that of Bower and Johnston since it also contains three 3’-terminal ribonucleotides as a hybridization domain and a 5’ sequencing adaptor construct (see, e.g., Table 1, Fig. 3, and paras. 15, 67, 84, and 88-90).
Regarding claims 57-59, 71, and 72, Linnarson teaches that the TSO may contain one or more modifications (see, e.g., paras. 52 and 57-63). The modification(s) may be linkage modifications, end modifications, and/or nucleotide analogs (paras. 52 and 57-63). The modifications may include an amino modification at the 5’ position of a 5’-terminal nucleotide (para. 60).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for the ordinary artisan to modify the TSO of Bower and Johnston to include one or more of the modifications (e.g., the nucleotide analogs, linkage modifications, and/or end modification) disclosed in Linnarson. The ordinary artisan would have recognized that, given the similarity between the TSO of Bower and Johnston and the TSO of Linnarson, the modifications disclosed in Linnarson would offer the same benefits to the TSO of Bower and Johnston. For example, the benefits of exonuclease resistance, increased thermal stability of duplexes, improved hybridization kinetics, and universal base pairing discussed in paras. 58-59 and 62 of Linnarson would have been reasonably considered to apply to the TSO of Bower and Johnston.
As well, the ordinary artisan would have recognized that, given the similarity between the TSO of Bower and Johnston and the TSO of Linnarson, the modifications disclosed in Linnarson would be suitable for incorporation into the TSO of Bower and Johnston, and accordingly, would have been motivated to incorporate any desired modification disclosed in Linnarson at any suitable location in the TSO (e.g., at the 5’ end or 5’ of the 3’ hybridization domain), recognizing its suitability for the intended purpose. As discussed in MPEP 2144.07, selecting a known material or method based on its suitability for the intended purpose is prima facie obvious in the absence of unexpected results. In this case, the TSO of Bower and Johnston and the TSO of Linnarson are quite similar, and no evidence of unexpected results has been presented. Thus, the compositions of claims 57-59, 71, and 72 are prima facie obvious.
12. Claims 70 and 74 are rejected under 35 U.S.C. 103 as being unpatentable over Bower and Johnston (Nucleic Acids Research 2010; 38: e194; newly cited) in view of Duck et al. (US 4,876,187; cited previously) and further in view of Mauger et al. (Nucleic Acids Research 2007; 35: e62; newly cited).
As discussed above, the teachings Bower and Johnston anticipate the compositions of claims 40, 41, 51-53, 62, 69, and 73.
Regarding claim 70, Bower and Johnston do not teach that the exo-sample nucleotides (i.e., dUs) located 5’ of the 3’ hybridization domain of the TSO include a ribonucleotide.
Regarding claim 74, Bower and Johnston do not teach that the exo-sample nucleotides (i.e., dUs) located 5’ of the template RNA-complementary portion of the single product nucleic acid include a ribonucleotide.
Prior to the effective filing date of the claimed invention, though, it would have been prima facie obvious for the ordinary artisan to substitute the exo-sample nucleotides (i.e., dUs) in the 5’ portion of the TSO and in the single product nucleic acid of Bower and Johnston with ribonucleotides. As discussed in MPEP 2144.06 and 2144.07, respectively, in the absence of unexpected results, it is prima facie obvious to substitute equivalents known to be useful for the same purpose or to select a known material or method based on its suitability for the intended purpose. In this case, Bower and Johnston teach that the exo-sample nucleotides (uracils) are present in the disclosed olignucleotides to permit later cleavage via uracil DNA glycosylase (UDG) (see Figs. 1-2; see also the first para. of the “Results and Discussion” section on p. 4). Duck teaches that uracil-containing nucleic acids may be cleaved using DNA glycosylase and either an AP endonuclease or basic conditions, whereas ribonucleotide-containing nucleic acids may be cleaved using RNase (see, e.g., col. 2, ll. 14-25 and col. 11, ll. 3-52; see also Fig. 1). Therefore, the prior art of Duck discloses equivalent methods for cleaving a nucleic acid. As well, the teachings of Duck concerning RNase-mediated cleavage would have indicated to the ordinary artisan that the uracils in the TSO and single product nucleic acid of Bower and Johnston could be substituted with ribonucleotides to obtain an alternate method for cleavage. The ordinary artisan would have had a reasonable expectation of success in replacing all uracils in the composition of Bower and Johnston with ribonucloetides since Mauger disclosed a polymerase capable of incorporating both ribonucleotides and deoxyribonucleotides (abstract; p. 2, col. 2; and pp. 5-6). Further, no evidence of unexpected results has been presented with respect to the inclusion of ribonucleotides in the recited positions of the claimed nucleic acids. Thus, the compositions of claims 70 and 74 are prima facie obvious.
Conclusion
13. No claims are currently allowable.
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 Angela Bertagna whose telephone number is (571)272-8291. The examiner can normally be reached 8-5, M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached on 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANGELA M. BERTAGNA/Primary Examiner, Art Unit 1637