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 .
The Response of 6 July 2026 has been entered.
Claims 1-11, 15, 16, 19, 20, 25-27, 30 and 31 are currently pending.
Election/Restrictions
Applicant’s election without traverse of the invention of Group I, claims 1-11, 15, 16, 19 and 20, and the species of a recombinase encoded by the host genome, a type II restriction endonuclease as the cleavage enzyme, a polynucleotide sequence bordered by cleavage domains which are bordered by recombinase sites as the first domain of the plasmid, and SEQ ID 1 as the plasmid sequence, in the reply filed on 6 July 2026 is acknowledged. As noted by Applicant, Groups II and III in the Restriction Requirement of 6 May 2026 should include claims 25-27 and 30 in Group II and claim 31 in Group III.
Claims 4, 7, 25-27, 30 and 31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (claims 4 and 7) and invention (claims 25-27, 30 and 31), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6 July 2026.
Claims 1-3, 5, 6, 8-11, 15, 16, 19 and 20 are considered herein with respect to the elected species of a recombinase encoded by the host genome and a type II restriction endonuclease as the cleavage enzyme (the remaining species elections pertain to unelected Groups II and III).
Claim Rejections - 35 USC § 102
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.
Claims 1, 8-11, 15, 16 and 20 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative (in the case of claims 9-10), under 35 U.S.C. 103 as obvious over Ducani et al., Nature methods 10.7 (2013): 647-652 (cited in IDS of 24 Aug. 2022), optionally (in the case of claims 9-10) in view of Ali et al., Chemical Society Reviews 43.10 (2014): 3324-3341.
Regarding claim 1, Ducani teaches a method for producing a plurality of single stranded DNA polynucleotides comprising: a) providing a DNA minicircle comprising the polynucleotide sequence to be produced bordered by cleavage domains; b) performing a rolling circle amplification (RCA) reaction with the DNA minicircle of (a) as a template to produce an RCA product comprising a plurality of copies of the polynucleotide sequence to be produced, bordered by cleavage domains; and c) cleaving the RCA product at the cleavage domains to release the plurality of single stranded DNA polynucleotides (p. 648, under The MOSIC method; Fig. 1; under ONLINE METHODS, including under Pseudogene in vitro amplification).
Regarding the recitation in claim 1 of “a DNA minicircle obtained from a parental minicircle plasmid”, the above recitation is a product-by-process limitation which is limiting to the claimed DNA minicircle only to the extent of any structure necessarily implied by the recited process (see MPEP 2113). The recited process of being “obtained from a parental minicircle plasmid” does not necessarily imply any particular structure to the claimed plasmid (e.g., the method does not recite any particular structural features derived from the parental plasmid, and the method also does not preclude subsequent processing steps that could remove any such derived sequences). As such, the recitation that the DNA minicircle is obtained from a parental minicircle plasmid does not patentably distinguish Ducani.
Regarding claim 8, Ducani teaches nicking (cleaving a single strand of) the minicircle DNA with the nicking endonuclease Nb.Bsr.Di (under ONLINE METHODS, under Pseudogene in vitro amplification).
Regarding claims 9-10, while Ducani does not expressly disclose the protocol for carrying out RCA, Ali evidences that RCA involves binding/hybridizing of a primer to the DNA minicircle (under 2. Fundamentals of RCA) and the method of Ducani would have thus involved such a hybridization. Alternatively, it would have been obvious in view of Ali to carry out RCA using established methods including binding/hybridizing of a primer to the DNA minicircle. Regarding claim 10, it would have been prima facie obvious that the primer could bind any portion of the DNA minicircle. Moreover, the claimed method does not require a step of forming the DNA minicircle from a parental plasmid (see product-by-process analysis, above), and as such any sequence within the minicircle of Ducan could be formed by a recombination step.
Regarding claims 11 and 15, Ducani teaches that the cleavage domains are adjacent to the target polynucleotide sequence, are capable of being recognized by a cleavage enzyme (a type II restriction enzyme) and form hairpin structures (p. 648, under The MOSIC method; Fig. 1; under ONLINE METHODS, under Pseudogene designs).
Regarding claim 16, Ducani teaches that the cleavage domains can be cleaved by the same restriction enzyme and that the construct can include multiple polynucleotide sequences (the same or different) bordered by cleavage domains (p. 648, under The MOSIC method; Fig. 1; under ONLINE METHODS, under Pseudogene designs).
Regarding claim 20, Ducani teaches isolating the single stranded oligonucleotides yielded by the method (under ONLINE METHODS, under Oligonucleotide production).
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.
Claims 1-3, 5, 6, 8-11, 15, 16 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Ducani, as applied to claims 1, 8-11, 15, 16 and 20 above, in view of Kay et al., Nature biotechnology 28.12 (2010): 1287-1289 (cited in IDS of 29 Nov. 2022).
Claims 1-3, 5, 6, 8-11, 15, 16 and 20 differ from Ducani, as applied to claims 1, 8-11, 15, 16 and 20 above, in that: the DNA minicircle is obtained from a parental minicircle plasmid (claim 1; while the product-by-process language of claim 1 is not considered to distinguish Ducani, the limitation is further addressed as being obvious in the instant rejection); step (a) comprises providing a host cell comprising the parental minicircle plasmid, wherein the host cell is capable of expressing a site-specific recombinase enzyme that acts on recombinase attachment sites in the parental minicircle plasmid (claim 2); the site-specific recombinase enzyme is encoded by the host cell genome (claim 3); the method further comprises a step of inducing expression of the site-specific recombinase in the host cell to promote formation of the DNA minicircle in the cell (claim 5); and the method further comprises a step of isolating the DNA minicircle from the host cell (claim 6).
Kay teaches a method for efficiently producing minicircle DNA, comprising expressing a parental minicircle plasmid comprising recombinase attachment sites bordering a target polynucleotide sequence in a host cell having a heterologous site-specific recombinase enzyme that acts on recombinase attachment sites in the parental minicircle plasmid stably incorporated into the host cell genome such that expression of the plasmid results in excision and circularization of the target polynucleotide sequence, yielding a DNA minicircle comprising the target polynucleotide sequence (under ONLINE METHODS, under Minicircle production protocol; Fig. 1). The host cell with integrated recombinase enhances efficiency by reducing the amount of unwanted plasmid products yielded by the method (p. 1288, 2nd full ¶ to p. 1289, 1st ¶).
Regarding claim 5, Kay teaches that the recombinase expression is inducible via L-arabinose (under Abstract; under ONLINE METHODS, under Minicircle production protocol).
Regarding claim 6, Kay teaches isolating the DNA minicircle product (under ONLINE METHODS, under Minicircle production protocol).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Ducani to produce single-stranded polynucleotides of interest by carrying out RCA on a minicircle DNA wherein the minicircle is produced via a parental minicircle plasmid in a recombinase-integrated host cell as taught by Kay because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to use the method of Kay to produce minicircle DNA for use in the method of Ducani because Kay teaches that such method can be used to efficiently produce minicircle DNA in a timeframe and quantity similar to that of routine plasmid preparation (Kay, Abstract). Using the method of Kay to produce minicircle DNA for use in the method of Ducani would have led to predictable results with a reasonable expectation of success because Ducani teaches use of minicircle DNA for the RCA amplification step and one of ordinary skill would have recognized that such minicircle DNA could be produced by any known method for producing minicircle DNA (there is no disclosure in Ducani or evident rationale indicating that the particular plasmid excision/ligation strategy used to produce the minicircle DNA in Ducani would have been critical to the method; moreover, the method of Kay is a general purpose method and one ordinary skill in the art would have recognized that the DNA minicircles yielded thereby could be used for any purpose for which such DNA is used in the art).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Ducani in view of Kay, as applied to claims 1-3, 5, 6, 8-11, 15, 16 and 20 above, further in view of Linck et al., Analytical methods 4.5 (2012): 1215-1220.
Claim 19 differs from the combination of Ducani in view of Kay, as applied to claims 1-3, 5, 6, 8-11, 15, 16 and 20 above, in that: he RCA reaction is performed in the presence of one or more functionalized nucleotides (dNTPs).
Linck teaches that polynucleotide products of RCA are commonly fluorescently labeled for visualization, e.g. in diagnostic applications, and that such labeling can be accomplished directly via performing RCA using a fluorophore-functionalized dNTP (entire doc, including under 1. Introduction; under 3. Results and Discussion). The direct labeling method was advantageous in that it allowed for fewer handling steps and more higher labeling density relative to alternative methods involving hybridized probes and/or post-synthesis labeling (under Abstract; and 4. Conclusion).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Ducani in view of Kay to produce single-stranded polynucleotides of interest by carrying out RCA on a minicircle DNA wherein the RCA uses functionalized dNTPs as taught by Linck because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to use functionalized dNTPs as taught by Linck in carrying out the RCA in the method of Ducani in view of Kay because Linck teaches that doing so can directly label RCA products in a manner that is more effective and/or efficient than post-RCA labeling strategies. Using functionalized dNTPs as taught by Linck in carrying out the RCA in the method of Ducani in view of Kay would have led to predictable results with a reasonable expectation of success because Linck teaches that such dNTPs can be utilized in RCA as used in the method of Ducani in view of Kay. Moreover, one of ordinary skill in the art would have recognized that the RCA step of Ducani is distinct from the step(s) of deriving the minicircle DNA via a parental minicircle plasmid, and as such the RCA step(s) could be carried out using any known modifications/protocols known in the RCA art.
Conclusion
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657
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