DETAILED ACTION
CONTINUED EXAMINATION UNDER 37 CFR 1.114 AFTER FINAL REJECTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission of RCE and amendment filed on September 11, 2025 have been entered. The claims pending in this application are claims 32-34, 36-38, 41-45, 49, 50, 58, 59, 61, and 62. The objection and rejection not reiterated from the previous office action is hereby withdrawn in view of applicant’s amendment filed on September 11, 2025. Claims 32-34, 36-38, 41-45, 49, 50, 58, 59, 61, and 62 will be examined.
Claim Objections
Claim 32 is objected to because of the following informality: “on the 5’ end” in line 10 should be “on its 5’ end”.
Claim 37 is objected to because of the following informality: “on the 5’ end” in line 14 should be “on its 5’ end”.
Claim 50 is objected to because of the following informality: “the nucleic acid” in line 4 should be “the nucleic acid strand”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
New Matter
Claims 37, 38, 41-45, 50, 59, and 61 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
A limitation “a forward primer that specifically hybridizes to the sequencing platform adaptor construct of the template switch oligonucleotide and comprises SEQ ID NO: 03 or SEQ ID NO: 04; a reverse primer that specifically hybridizes to the sequencing platform adaptor construct of the first-strand synthesis primer and comprises SEQ ID NO: 03 or SEQ ID NO: 04”
is added to independent claim 37, a limitation “the nucleic acid domain of the nucleic acid strand comprises SEQ ID NO: 03 or SEQ ID NO: 04” is added to dependent claim 50, and a newly added claim 61 contains a limitation “the forward primer further comprises one or more of SEQ ID NO: 1, 2, 5, or 6 and the reverse primer comprises one or more of SEQ ID NO: 1, 2, 5, or 6.” Although the specification describes that “[I]n certain aspects, the sequencing platform
adapter construct includes a nucleic acid domain selected from: a domain (e.g., a ‘capture site’ or ‘capture sequence’) that specifically binds to a surface-attached sequencing platform oligonucleotide (e.g., the P5 or P7 oligonucleotides attached to the surface of a flow cell in an Illumina® sequencing system); a sequencing primer binding domain (e.g., a domain to which the Read 1 or Read 2 primers of the Illumina® platform may bind); a barcode domain (e.g., a domain that uniquely identifies the sample source of the nucleic acid being sequenced to enable sample multiplexing by marking every molecule from a given sample with a specific barcode or ‘tag’); a barcode sequencing primer binding domain (a domain to which a primer used for sequencing a barcode binds); a molecular identification domain (e.g., a molecular index tag, such as a randomized tag of 4, 6, or other number of nucleotides) for uniquely marking molecules of interest to determine expression levels based on the number of instances a unique tag is sequenced; or any combination of such domains. In certain aspects, a barcode domain (e.g., sample index tag) and a molecular identification domain (e.g., a molecular index tag) may be included in the same nucleic acid”, “[T]he nucleic acid domains may have a length and sequence that enables a polynucleotide (e.g., an oligonucleotide) employed by the sequencing platform of interest to specifically bind to the nucleic acid domain, e.g., for solid phase amplification and/or sequencing by synthesis of the cDNA insert flanked by the nucleic acid domains. Example nucleic acid domains include the P5 (5’-AATGATACGGCGACCACCGA-3’) (SEQ ID NO:01), P7 (5’-CAAGCAGAAGACGGCATACGAGAT-3’) (SEQ ID NO:02), Read 1 primer (5’-ACACTCTTTCCCTACACGACGCTCTTCCGATCT-3’) (SEQ ID NO:03) and Read 2 primer (5’-GTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT-3’) (SEQ ID NO:04) domains employed on the Illumina®-based sequencing platforms. Other example nucleic acid domains include the A adapter (5’-CCATCTCATCCCTGCGTGTCTCCGACTCAG-3’) (SEQ ID NO:05) and P1 adapter (5’-CCTCTCTATGGGCAGTCGGTGAT-3’) (SEQ ID NO:06) domains employed on the Ion Torrent™-based sequencing platforms”, “cDNA on the beads was eluted by addition of 50 μl PCR Mastermix (5 μl 10 Advantage2 buffer, 5 μl GC Melt reagent, 1 μl 10 mM dNTPs, 1 μl Advantage2 polymerase (Clontech), 240 nM forward PCR primer, 240 nM reverse PCR primer , and 36.8 μl water). Samples were thermocycled for 12 PCR cycles with the settings 95° C. 1 minute, 12X (95° C. 15 seconds, 65° C. 30 seconds, 68° C. 1 minute)”,
“cDNA on the beads was eluted by addition of 50 μl PCR Mastermix (5 μl 10 Advantage2 buffer, 5 μl GC Melt reagent, 1 μl 10 mM dNTPs, 1 μl Advantage2 polymerase (All Clontech), 240 nM forward PCR primer, 240 nM reverse PCR primer, and 36.8 μl water). Samples were thermocycled for 12 PCR cycles with the settings 95° C. 1 minute, 12X (95° C. 15 seconds, 65° C. 30 seconds, 68° C. 1 minute)”, and “[F]irst strand reactions were diluted with 40 μl TE buffer. 5 μl diluted cDNA was combined with 45 μl PCR Mastermix (5 μl 10 Advantage2 buffer, 1 μl 10 mM dNTPs, 1 μl Advantage2 polymerase (All Clontech), 240 nM forward PCR primer, 240 nM reverse PCR primer (and 36 μl water). Samples were thermocycled for 20 PCR cycles with the settings 95° C. 1 minute, 20X (95° C. 15 seconds, 65° C. 30 seconds)” (see paragraphs [0041], [0043], [0089], [0093], and [0102] of US 2021/0155922 A1, which is US application of this instant application), nowhere in the specification describes such limitations recited in claims 37, 50 and 61 since, although a nucleotide sequence at 5’ end of the nucleic acid strand can be considered as a sequence platform adapter construct and the specification does not describe that the sequencing platform adapter construct of the nucleic acid strand comprises SEQ ID NO: 03 or SEQ ID NO: 04, page 15, lines 20-31 and page 28, lines 8-23 and original claims 28 and 58 suggested by applicant do not describe a forward primer that specifically hybridizes to the sequencing platform adaptor construct of the template switch oligonucleotide and comprises SEQ ID NO: 03 or SEQ ID NO: 04 and a reverse primer that specifically hybridizes to the sequencing platform adaptor construct of the first-strand synthesis primer and comprises SEQ ID NO: 03 or SEQ ID NO: 04, and page 14, line 20 to page 15, line 10 of the specification suggested by applicant do not describe that the forward primer comprising SEQ ID NO. 3 or 4 further comprises one or more of SEQ ID NO: 1, 2, 5, or 6 and the reverse primer comprising SEQ ID NO. 3 or 4 further comprises one or more of SEQ ID NO: 1, 2, 5, or 6.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application.” MPEP 2163.06 further notes “When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicant should therefore specifically point out the support for any amendments made to the disclosure” (emphasis added).
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.
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 32-34, 36, and 49 are rejected under 35 U.S.C. 103 as being unpatentable over Kapteyn et al., (BMC Genomics, 11, 413, 2010) in view of Chenchik et al., (US Patent No. 5,962,272, published on October 5, 1999).
Regarding claims 32-34, 36, 49, and 58, Kapteyn et al., teach that a composition comprising a template ribonucleic acid (RNA) and a template switch oligonucleotide (ie., the iso3TS oligonucleotide), wherein each of the template RNA and the template switch oligonucleotide is hybridized to adjacent regions of a nucleic acid strand (ie., the first strand of the cDNA), wherein the template switch oligonucleotide comprises a 3’ hybridization domain (ie., (rG) (rG) (rG) on 3’ of iso3TS Oligo for template switching) and a sequencing platform adapter construct comprising a sequencing primer binding domain (eg., some nucleotide sequence of TS Oligo) and the nucleic acid strand comprises a sequencing platform adapter construct at the 5’ end of the nucleic acid strand, wherein: the sequencing platform adapter construct of the nucleic acid strand is different from the sequencing platform adapter construct of the template switch oligonucleotide; and the template switch oligonucleotide comprises a modification (ie., iso-nucleotides at 5’ end of the iso3TS oligonucleotide) on its 5’ end that prevents a template switching polymerase from switching from the template switch oligonucleotide to a different template nucleic acid after synthesizing the complement of the 5’ end of the template switch oligonucleotide, and the modification is selected from the group consisting of: an abasic lesion, a nucleotide adduct, an isocytosine, an isoguanine, and combinations thereof as recited in claim 32 wherein the sequencing platform adapter construct of the template switch oligonucleotide and/or the nucleic acid strand further comprises a nucleic acid domain selected from the group consisting of: a domain that specifically binds to a surface-attached sequencing platform oligonucleotide, a barcode domain, a barcode sequencing primer binding domain, a molecular identification domain, and combinations thereof as recited in claim 33, the 3’ hybridization domain comprises a homonucleotide stretch (ie., (rG) (rG) (rG) on 3’ of iso3 TS Oligo for template switching) as recited in claim 34, the composition is present in a reaction tube (ie., a reaction tube for the first strand cDNA synthesis) as recited in claim 36,and the sequencing platform adapter construct of the template switch oligonucleotide comprises at least a portion (ie., GTG) of a nucleic acid domain comprising SEQ ID NO: 03 or SEQ ID NO: 04 and the sequencing platform adapter construct of the nucleic acid strand comprises at least a portion (ie., CCG) of a nucleic acid domain comprising SEQ ID NO: 03 or SEQ ID NO: O4 as recited in claim 49 (see Figure 1 in page 3 and pages 7 and 8).
Kapteyn et al., do not disclose that the template switch oligonucleotide is attached directly or indirectly to a solid support as recited in claim 32.
Chenchik et al., teach a template switching oligonucleotide comprising a hapten group such as biotin in its 5’end and incubating said RNA-cDNA-hapten intermediate with a binding ligand of said hapten group wherein said binding ligand is conjugated to a support (see column 6, second paragraph and claims 1 and 16).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the composition as recited in claim 32 wherein the composition comprises a template RNA, a template switch oligonucleotide comprising a hapten group in its 5’ end, a nucleic acid strand, and a support conjugated with a binding agent for the hapten group such that, in the composition, each of the template RNA and the template switch oligonucleotide is hybridized to adjacent regions of the nucleic acid strand and the template switch oligonucleotide is attached indirectly to the solid support in view of the prior arts of Kapteyn et al., and Chenchik et al.. One having ordinary skill in the art would have been motivated to do so because Chenchik et al., teach a template switching oligonucleotide comprising a hapten group such as biotin in its 5’end and incubating said RNA-cDNA-hapten intermediate with a binding ligand of said hapten group wherein said binding ligand is conjugated to a support (see column 6, second paragraph and claims 1 and 16). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the composition recited in claim 32 by incorporating a hapten group to 5’ end of the template switch oligonucleotide taught by Kapteyn et al., and adding a support conjugated with a binding agent for the hapten group into the composition taught by Kapteyn et al., in view of the prior arts of Kapteyn et al., and Chenchik et al., in order to purify a template RNA-cDNA complex from the composition of claim 32.
Claim 58 is rejected under 35 U.S.C. 103 as being unpatentable over Kapteyn et al., in view of Chenchik et al., as applied to claims 32-34, 36, and 49 above, and further in view of Liu et al., (US 2001/0039014 A1, published on November 8, 2001).
The teachings of Kapteyn et al., and Chenchik et al., have been summarized previously, supra.
Kapteyn et al., and Chenchik et al., do not disclose that the modification is an abasic lesion as recited in claim 58. However, the modification of the template switch oligonucleotide taught by Kapteyn et al., is a combination of isocytosine and isoguanine (see Figure 1C).
Liu et al., teach that “[T]he PCR stopper may be essentially any moiety which prevents read-through of the polymerase to be used for the amplification reaction. Suitable PCR stoppers include, but are not limited to, hexaethylene glycol (HEG), abasic sites, and any non-natural or modified nucleotide which prevents read-through of the polymerase, including DNA analogues such as peptide nucleic acid (PNA)” (see paragraph [0080]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the composition as recited in claim 58 wherein the modification is an abasic lesion in view of the prior arts of Kapteyn et al., Chenchik et al., and Liu et al., One having ordinary skill in the art would have been motivated to do so because Liu et al., teach that “[T]he PCR stopper may be essentially any moiety which prevents read-through of the polymerase to be used for the amplification reaction. Suitable PCR stoppers include, but are not limited to, hexaethylene glycol (HEG), abasic sites, and any non-natural or modified nucleotide which prevents read-through of the polymerase, including DNA analogues such as peptide nucleic acid (PNA)” (see paragraph [0080]) and the simple substitution of one kind of modification (ie., the non-natural nucleotides such as a combination of isocytosine and isoguanine taught by Kapteyn et al.,) from another kind of modification (ie., abasic sites taught by Liu et al.,) during the process of making the template switching oligonucleotide recited in claim 32, in the absence of convincing evidence to the contrary, would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made since the non-natural nucleotides such as a combination of isocytosine and isoguanine taught by Kapteyn et al., and the abasic site taught by Liu et al., are used for the same purpose (ie., preventing read-through of a polymerase from switching from the template switch oligonucleotide to a different template nucleic acid) and are exchangeable. One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the composition recited in claim 58 by substituting the modification on the template switch oligonucleotide such as a combination of isocytosine and isoguanine taught by Kapteyn et al., from the abasic sites taught by Liu et al., during the process of making the template switching oligonucleotide recited in claim 58 in view of the prior arts of Kapteyn et al., Chenchik et al., and Liu et al..
Furthermore, the motivation to make the substitution cited above arises from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. Support for making the obviousness rejection comes from the M.P.E.P. at 2144.06, 2144.07 and 2144.09.
Also note that there is no invention involved in combining old elements is such a manner that these elements perform in combination the same function as set forth in the prior art without giving unobvious or unexpected results. In re Rose 220 F.2d. 459, 105 USPQ 237 (CCPA 1955).
Claim 62 is rejected under 35 U.S.C. 103 as being unpatentable over Kapteyn et al., in view of Chenchik et al., as applied to claims 32-34, 36, and 49 above, and further in view of Bass et al., (US 2001/0039014 A1, published on November 8, 2001).
The teachings of Kapteyn et al., and Chenchik et al., have been summarized previously, supra.
Kapteyn et al., and Chenchik et al., do not disclose that the solid support is a bead as recited in claim 62. However, Chenchik et al., teach that “the term ‘solid support’ refers to any known substrate which can be used for the immobilization of a binding ligand” (see column 13, fourth paragraph).
Bass et al., teach that a solid substrate used for localizing nucleic acids and one or more moiety recognition agents is a bead or a chip or a slide (see paragraph [0086]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have made the composition as recited in claim 62 wherein the solid support is a bead in view of the prior arts of Kapteyn et al., Chenchik et al., and Bass et al., One having ordinary skill in the art would have been motivated to do so because Chenchik et al., teach that “the term ‘solid support’ refers to any known substrate which can be used for the immobilization of a binding ligand” (see column 13, fourth paragraph) while Bass et al., teach that a solid substrate used for localizing nucleic acids and one or more moiety recognition agents is a bead or a chip or a slide (see paragraph [0086]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to make the composition recited in claim 62 using a bead as a support for conjugating the binding agent taught by Chenchik et al., during the process of making the support recited in claim 32 in view of the prior arts of Kapteyn et al., Chenchik et al., and Bass et al..
Response to Arguments
Applicant’s arguments with respect to claims 32-34, 36-38, 41-46, 49, 50, and 58-60 have been considered but are moot because the new ground of rejection does not rely on any teaching or matter specifically challenged in the argument.
Conclusion
No claim is allowed.
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/FRANK W LU/
Primary Examiner, Art Unit 1683
January 9, 2026