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 .
Status of the Application
The Amendment and Response filed June 4, 2026 is acknowledged.
Claims 65-84 were pending. Claims 65-74 and 77-84 are being examined on the merits. Claims 75-76 are canceled.
Response to Arguments
Applicant’s arguments filed June 4, 2026 have been fully considered.
The following objections and rejections are WITHDRAWN in view of Applicant’s arguments and the amendments to the specification and claims:
Objections to the Drawings
Objections to the Specification – embedded hyperlink
Objections to the Specification – Cross-Reference to Related Applications
Rejection of claim 66 under 35 USC § 112(b), indefiniteness
The following rejections are MODIFIED in view of the instant claim amendments:
Prior art rejections
Response to arguments regarding prior art rejections
Applicant argues that the prior art rejections should be withdrawn for several reasons. First, Applicant argues that the secondary reference, Jacobson, “teaches circularization only as a means to obtain barcode association information independent of construct length, not as a teaching to generate circular sequencing templates of the type recited in amended claim 65” (Remarks, pp. 7-8).
The Examiner disagrees. MPEP 2144 (IV) states “[t]he reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant”. Thus, while Jacobson may teach circularization to obtain barcode information, that does not preclude the ordinary artisan from circularizing a linear construct for another reason.
Applicant further argues that the Office has not articulated why the ordinary artisan would have been motivated to circularize Gormley’s disclosed library constructs, and also has not explained why there would be a reasonable expectation of success in doing so. Applicant also states that the Office has not articulated how the ordinary artisan would have circularized Gormley’s library constructs, and, more specifically, that “the Office does not explain why a person of ordinary skill would have modified Gormley’s solid-support constructs and processing, which are expressly concerned with linearizing bridged surface products to facilitate primer access, by adopting Jacobson’s barcode-association circularization maneuver, which is expressly used to juxtapose tag ends for tag sequencing and optional restriction-digest excision” (Remarks, p. 8).
The Examiner disagrees. The discussion of the motivation to combine and the expectation of success are in the Non-Final Office Action mailed November 5, 2025 (p. 7, para. 1). As to how the ordinary artisan would have done so, the Examiner notes that this is not relevant to instant claims as they are product claims. Rather, independent claim 65 merely recites that the polynucleotide is circular, but does not explicitly or implicitly require any method of circularizing the polynucleotide.
Applicant additionally argues that the combination of Gormley and Jacobson also fails to teach or suggest the cleavable site requirement of instantly amended claim 65 “in the claimed structural context”, and further that “even where Gormley mentions certain cleavage chemistries that overlap with portions of Applicant’s claimed cleavable-site list, Gormley teaches them as techniques for processing and linearizing immobilized bridge surface amplification products to create primer-accessible, partially single-stranded sequencing templates, not as first and second cleavable sites embedded within a circular polynucleotide as structure elements of the circular construct”. Finally, Applicant argues that Jacobson also does not cure the deficiencies as to the cleavage sites (Remarks, pp. 8-9).
The Examiner disagrees. First, it is not clear what Applicant is referring to as the “structural context” of the claim and if or how they intend for that to limit the claim construction. Second, Applicant’s intended use of the claimed construct with the recited cleavage chemistries may differ from the use in the cited art. The Examiner notes again that MPEP 2144 (IV) states “[t]he reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant”. Further, the Non-Final Office Action mailed November 5, 2025 states that Jacobson, not Gormley, teaches circular constructs, and that Gormley, not Jacobson, teaches the cleavage sites.
Regarding dependent claim 66, Applicant argues that the Office has not articulated why the ordinary artisan would have been motivated to incorporate the teachings of Guan as to SEQ ID NO: 178 into the Gormley plus Jacobson constructs, and also has not explained why there would be a reasonable expectation of success in doing so (Remarks, p. 10).
The Examiner disagrees. The discussion of the motivation to combine and the expectation of success are in the Non-Final Office Action mailed November 5, 2025 (p. 8, para. 3).
Regarding dependent claim 68-72, Applicant argues that the Office has not articulated why the ordinary artisan would have been motivated to incorporate the teachings of Glezer into the Gormley plus Jacobson constructs, and also has not explained why there would be a reasonable expectation of success in doing so (Remarks, pp. 10-11).
The Examiner disagrees. The discussion of the motivation to combine and the expectation of success are in the Non-Final Office Action mailed November 5, 2025 (p. 10, para. 1).
Regarding dependent claim 74 and 81-84, Applicant argues that the Office has not articulated why the ordinary artisan would have been motivated to incorporate the teachings of Duenwald into the Gormley plus Jacobson constructs, and also has not explained why there would be a reasonable expectation of success in doing so (Remarks, p. 11).
The Examiner disagrees. The discussion of the motivation to combine and the expectation of success are in the Non-Final Office Action mailed November 5, 2025 (p. 11, para. 3; p. 12, para. 3 through p. 13, para. 1).
These arguments are not persuasive. The rejections are modified in view of the instant claim amendments.
Information Disclosure Statement
The Information Disclosure Statement submitted March 3, 2026 has been considered.
Claim Interpretation
Claim 65 recites in the preamble “[a] circular polynucleotide”. Any terminology in the preamble that limits the structure of the claimed invention must be treated as a claim limitation. MPEP 2111.02 (I). Thus, the “circular” term here is being interpreted as limiting the claimed polynucleotides to those with a circular structure.
The claims recite various “primer sequence[s]”, including “sequencing” and “platform” primers. However, any primer can be used for sequencing or as a platform primer, and thus “sequencing” and “platform” do not structurally limit the polynucleotide sequence. Consequently, these terms are being construed as statements of intended use that do not distinguish the art.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 80 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 80 recites that the first and second cleavable site independently comprise “a
sequence specifically recognized by an [endo/exo]nuclease enzyme”. However, claim 65, from which claim 80 depends, limits the first and second cleavable sites to a diol, disulfide or photocleavable linker, an abasic site, a uracil nucleotide, deoxy-8-oxo-guanine nucleotide, a methylated nucleotide or a ribonucleotide. Since claim 80 recites a cleavable site that is different from any of those recited in claim 65, it does not incorporate all of the limitations of claim 65, and is in improper dependent form.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 65, 67, 73 and 77-80 are rejected under 35 U.S.C. 103 as being unpatentable over Gormley (US Patent App. Pub. No. 2010/0273662 A1) in view of Jacobson (US Patent App. Pub. No. 2014/0141982 A1).
Regarding independent claim 65, Gormley teaches …
A polynucleotide comprising:
a first sequencing primer sequence, wherein the first sequencing primer sequence
comprises SEQ ID NO: 152 (para. 144: Oligo A adapter sequence is identical to instant SEQ ID NO: 152; para. 77: Oligo A comprises a universal sequencing primer sequence; Figs. 1A, 1E);
a template polynucleotide sequence (Fig. 2A; para. 80: an adapter comprising Oligo A is joined to the target DNA fragments/template polynucleotide);
Regarding the limitations “a first cleavable site” and “a second cleavable site”, it is noted that any unmodified phosphodiester bond is a cleavable bond (para. 98), thus the bond between any two nucleotides in the construct is a cleavable site. Further, Gormley additionally teaches that the first and second cleavable sites independently comprise a diol linker, a photocleavable linker, an abasic site, and ribonucleotides (which may comprise uracil) (para. 116).
Further, Jacobson teaches a “circular polynucleotide” construct. Specifically, Jacobson teaches that constructs can be circularized to improve sequencing reactions, e.g., attaching a barcode to the linear construct and then “the barcoded constructs … can be circularized so as to get a barcode association which is independent of the length of the nucleic acid constructs” (para. 112).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to modify the Gormley polynucleotide construct to circularize it, as taught by Jacobson. Gormley teaches the need to increase throughput for various nucleic acid sequencing methods, and teaches generating constructs which comprise the target sequences, and which are suitable for high throughput sequencing. Jacobson teaches that circularizing constructs can simplify and improve data generation in sequencing assays. The ordinary artisan would have been motivated to modify the Gormley construct by circularizing it with the expectation that doing so would result in a more efficient construct for high throughput sequencing. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid constructs is well-known in the art.
Regarding dependent claim 67, Gormley additionally teaches that the polynucleotide construct comprises additional primer sequences (paras. 13, 19, 26, 33-36, 39, 53, 55, 77). These sequences could be used as “platform” sequences.
Regarding dependent claim 73, Gormley additionally teaches that the template comprises genomic DNA or a fragment thereof (para. 29).
Regarding dependent claims 77-80, Gormley additionally teaches that the cleavage sites independently comprise an abasic site, ribonucleotides (which may comprise uracil) and an endonuclease enzyme sequence (para. 116).
Claim 66 is rejected under 35 U.S.C. 103 as being unpatentable over Gormley (US Patent App. Pub. No. 2010/0273662 A1) in view of Jacobson (US Patent App. Pub. No. 2014/0141982 A1) as applied to claim 65 above, and further in view of Guan (US Patent App. Pub. No. 2016/0194696 A1).
Regarding dependent claim 66, as noted above, the claim language is indefinite.
However, Gormley teaches that the construct has additional primer sequences, which could be used as sequencing primer binding sequences, and Guan teaches a sequence comprising SEQ ID NO: 178, which is an adapter sequence for high-throughput sequencing (Table 2, SEQ ID NO: 11).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to further modify the modified Gormley polynucleotide, discussed above, to include the Guan sequence. Gormley teaches the need to increase throughput for various nucleic acid sequencing methods, and teaches generating constructs which comprise the target sequences which are attached to various additional known sequences. Guan teaches an adapter sequence which is useful for such a purpose. The ordinary artisan would have been motivated to try the Gormley construct with the Guan sequence in order to optimize the Gormley construct as desired through routine experimentation, and because Guan teaches that the adapter sequence is useful for such a purpose. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid constructs is well-known in the art.
Claims 68-72 are rejected under 35 U.S.C. 103 as being unpatentable over Gormley (US Patent App. Pub. No. 2010/0273662 A1) in view of Jacobson (US Patent App. Pub. No. 2014/0141982 A1) as applied to claims 65 and 67 above, and further in view of Glezer1 (US Patent App. Pub. No. 2021/0277461).
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Regarding dependent claim 68, as noted above, Gormley teaches that the construct has additional primer sequences, which could be used as platform primer sequences, and Glezer teaches a sequence that comprises SEQ ID NO: 92 (Table 1, SEQ ID NO: 1).
Regarding dependent claims 69-72, as noted above, Gormley teaches that the construct has additional primer sequences, which could be used as platform primer sequences, and Glezer teaches sequences that comprise SEQ ID NO: 104, SEQ ID NO: 4 and SEQ ID NO: 106. Specifically, each of these three sequences is comprised within each of Glezer SEQ ID NOs: 11-13 (Table 2).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to further modify the modified Gormley polynucleotide, discussed above, to include the Glezer sequences. Gormley teaches the need to increase throughput for various nucleic acid sequencing methods, and teaches generating constructs which comprise the target sequences which are attached to various additional known sequences. Glezer teaches various adapter sequences which are useful for such a purpose. The ordinary artisan would have been motivated to try the Gormley construct with the Glezer sequences in order to optimize the Gormley construct as desired through routine experimentation, and because Glezer teaches that the adapter sequences are useful for such a purpose. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid constructs is well-known in the art.
Claims 74 and 81-84 are rejected under 35 U.S.C. 103 as being unpatentable over Gormley (US Patent App. Pub. No. 2010/0273662 A1) in view of Jacobson (US Patent App. Pub. No. 2014/0141982 A1) as applied to claims 65 and 67 above, and further in view of Duenwald (US Patent App. Pub. No. 2017/0220735 A1), as evidenced by Illumina (Illumina Adapter Sequences, 2025).
Regarding dependent claim 74, Duenwald teaches that the template polynucleotide
sequence comprises a cancer associated gene, or fragment thereof (paras. 407, 455).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to further modify the modify Gormley polynucleotide, discussed above, to include the Duenwald target sequence. Gormley teaches the need to increase throughput for various nucleic acid sequencing methods, and teaches generating constructs which comprise the target sequences, and which are suitable for high throughput sequencing. Duenwald teaches that it is useful to sequence cancer associated genes with high throughput sequencing methods. The ordinary artisan would have been motivated to modify the Gormley construct by including the Duenwald target sequence with the expectation that doing so would result in an efficient construct and corresponding method for high throughput sequencing of cancer nucleic acids. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid constructs is well-known in the art.
Regarding dependent claims 81-83, Duenwald teaches that first and second index
sequences (para. 597), as recited in claim 81, and teaches that such dual indexing has several advantages, including, e.g., that it allows “samples [to] be multiplexed at a high-level allowing normalization and correction of run-to-run variation with high statistical confidence” (para. 597). Further, regarding claims 82-83, Duenwald teaches using the Illumina TruSeq index sequences (para. 571), which are 6 nucleotides long, as evidenced by Illumina (p. 80: indexes are 6 nucleotides long).
Regarding dependent claim 84, as noted above, Gormley teaches that the construct has additional primer sequences, which could be used as platform primer or sequencing primer sequences, and Duenwald teaches index sequences. Duenwald does not specifically teach that the index has to be between two known primer sequences, but it does teach that the index sequence does have to be placed in the construct in a position such that it will be amplified with the target sequence to provide labels to identify samples (para. 398). The ordinary artisan would be able to optimize the design of the construct accordingly.
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to further modify the modify Gormley polynucleotide, discussed above, to include the Duenwald dual indexing, and to optimize the location of the index sequences in the construct. Gormley teaches the need to increase throughput for various nucleic acid sequencing methods, and teaches generating constructs which comprise the target sequences, and which are suitable for high throughput sequencing. Duenwald teaches that including dual indexing in the construct can improve multiplexing capability. The ordinary artisan would have been motivated to modify the Gormley construct by including dual indexes in appropriate positions with the expectation that doing so would result in a more efficient construct for high throughput sequencing. The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid constructs is well-known in the art.
Prior Art and Patent Eligibility
Regarding compliance with 35 USC § 101, circular polynucleotides comprising SEQ ID NO: 152 and template polynucleotide sequences are not found in naturally occurring sequences. Thus, independent claim 65 and dependent claims 66-74 and 77-84 are patent eligible.
Other prior art that is relevant to SEQ ID NO: 92 is Homburger2 (US Patent No. 6,703,491). Homburger is directed to Drosophila gene sequences and methods of their use, and teaches a nucleic acid sequence having 80.9% sequence identity to SEQ ID NO: 92 (Homburger SEQ ID NO: 2214).
Other prior art that is relevant to SEQ ID NOs: 4, 104 and 136 is Fotin-Mleczek3 (US
Patent App. Pub. No. 2016/0331844). Fotin-Mleczek is directed to RNA containing compositions for use in the treatment of cancer, and teaches a nucleic acid sequence comprising a sequence with approximately 90% homology to each of SEQ ID NOs: 4, 104 and 106 (Fotin-Mleczek SEQ ID NO: 2130).
Conclusion
Claims 65-74 and 77-84 are being examined and are rejected. No claims are allowed.
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 CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 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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/CAROLYN L GREENE/Examiner, Art Unit 1681 /GARY BENZION/Supervisory Patent Examiner, Art Unit 1681
1 Glezer was cited in the Information Disclosure Statement submitted February 28, 2024.
2 Homburger was cited in the Information Disclosure Statement submitted February 28, 2024.
3 Fotin-Mleczek was cited in the Information Disclosure Statement submitted February 28, 2024.
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