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 .
Applicant’s reply to the April 22, 2026 Office Action, filed July 14, 2026, is acknowledged. Claims 1-27 are currently pending. Claims 1-4, 6-7, 9-11, 13-15, 17-18 and 20-27 remain withdrawn as being drawn to a nonelected invention. Claims 5, 8, 12, 16 and 19 are under examination. Any objection or rejection of record in the previous Office Action, which is not addressed in this action has been withdrawn in light of Applicant’s amendments and/or arguments. This action is Final.
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 5 and 8 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. This is a new rejection as necessitated by amendments.
Claim 5 is vague and indefinite for the following reasons:
In claim 5, the limitations “the transposon end sequence" in line 14 are unclear and confusing. It is unclear which transposon end sequence the limitation is referencing? Is this the 3’ transposon end sequence of the first transposon, the transposon end of the second transposon sequence or an additional transposon end sequence?
Claim 8 depends from claim 5 and is therefore included in this rejection.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 5, 8 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Cann et al. (WIPO International Application Publication WO 2016/014409 A1, published January 28, 2016), cited on the IDS filed February 16, 2023, in view of Zhang et al. (U.S. Patent Application Publication US 2022/0220469 A1, published July 14, 2022, effectively filed May 20, 2019). This is a new rejection as necessitated by amendments.
Regarding claim 5, Cann teaches a method of targeted generation of 5' tagged fragments of a target nucleic acid (Page 25, [00104] and [00102], Pages 26-27, [00106]-[00107] and Pages 40-41, [00149]). Cann teaches a transposome complex with a transposase comprising a first transposon comprising a 3’ transposon end sequence and a 5’ adaptor sequence (Pages 24-28, [00101]-[00108], Pages 40-41, [0149] and Figs. 4B-D). Cann teaches a catalytically inactive endonuclease associated with a guide RNA that can direct endonuclease binding to one or more nucleic acid sequences of interest (Abstract, Pages 6-7, [0026], Pages 8-9, [0033], Page 75, [00257] and Figs. 4A-D). Cann teaches a second transposon comprising the complement of the transposon end sequence (Pages 26-27, [00106]-[00107] and Pages 40-41, [00149]). Cann teaches combining a sample comprising a double-stranded nucleic acid and a transposome complexes of claim 1, that is a targeted transposome complex (Pages 24-28, [00101]—[00108], Pages 40-41, [0149] and Figs. 4B-D). Cann teaches fragmenting the nucleic acid into a plurality of fragments by the transposase, by joining the 3' end of the first transposon to the 5' ends of the fragments to produce a plurality of 5' tagged fragments (Page 24, [00101], Page 25, [00104], Page 26-27, [00106]-[00107], Pages 40-41, [00149] and Figs. 4B-D). Cann teaches any transposition system that is capable of inserting a transposon end in a random manner can be used in the present invention (Pages 26-27, [00107]).
Regarding claim 8, Cann teaches combining a sample comprising a double- stranded nucleic acid with one or more transposome complex that is targeted (Pages 24-28, [00101]—[00108], Pages 40-41, [0149] and Figs. 4B-D). Cann teaches combining the sample with a catalytically inactive endonuclease, wherein the catalytically inactive endonuclease is bound to a first binding partner (Pages 3-4, [0015], Page 5, [0020], Pages 6-7, [0025]-[0026], Pages 8-9, [0033], Pages 30-31, [00114], Page 47, [00165] and Page 75, [00258]). Cann teaches adding the transposase and first and second transposons and the transposase is bound to a second binding partner (Pages 24-28, [00101]—[00108], Pages 40-41, [0149], Pages 30-31, [00114], Page 47, [00165] and Page 75, [00258] and Figs. 4B-D). Cann teaches the transposase can bind to catalytically inactive endonuclease by pairing of the first and second binding partners (Pages 24-28, [00101]—[00108], Pages 40-41, [0149], Pages 30-31, [00114], Page 47, [00165] and Page 75, [00258] and Figs. 4B-D).
Regarding claim 19, Can teaches a method of targeted generation of 5' tagged fragments of nucleic acid (Page 25, [00104] and [00102], Pages 26-27, [00106]-[00107] and Pages 40-41, [00149]). Cann teaches hybridizing one or more targeting oligonucleotides to a sample comprising single-stranded nucleic acid (Page 1, [0003], Page 11, [0045], Page 19, [0088], Page 24 [00101], and Page 56, [00193]). Cann teaches one or more targeting oligonucleotides can each bind to a sequence of interest in the single-stranded nucleic acid (Page 3, [0014] Page 24, [00101], Pages 31-32, [00119], Page 52, [0183] and Page 56, [0193]). Cann teaches hybridizing the one or more targeting oligonucleotides to the sample generates a region of double-stranded nucleic acid (Page 14, [0053], Page 22, [0097], Page 52, [0183] and Page 61, [0211]). Cann teaches applying a transposome complex comprising a transposase and a first transposon comprising a 3' transposon end sequence and a 5' adaptor sequence (Pages 24-28, [00101]—[00108], Pages 40-41, [0149] and Figs. 4B-D). Can teaches a second transposon comprising a 5' transposon end sequence and the 5' transposon end sequence is complementary to the 3' transposon end sequence (Pages 26-27, [00106]-[00107] and Pages 40-41, [00149]). Cann teaches fragmenting the nucleic acid having the region generated by hybridizing the one or more targeting oligonucleotides into a plurality of fragments by the transposase, by joining the 3' end of the first transposon to the 5' ends of the fragments to produce a plurality of 5' tagged fragments (Page 24, [00101], Page 25, [00104], Page 26-27, [00106]-[00107], Pages 40-41, [00149], Page 52, [0183], Page 61, [0211] and Figs. 4B-D).
Cann does not teach or suggest the catalytically inactive endonuclease is from cyanobacteria Scytonema hofmanni (ShCAST).
Zhang teaches a method of targeted generation of 5’ tagged fragments of a target nucleic acid (Page 20, [0156] and Page 86, [0718]). Zhang teaches a transposome complex comprising a transposase and a transposon comprising a 3’ transposon end sequence, an adapter (Page 72, [0618]-[0620], Page 73, [0631]-[0632], Page 84, [0706] and Pages 105-106, [0835]). Zhang teaches using a catalytically inactive endonuclease associated with a guide RNA, wherein the guide RNA can direct endonuclease binding to one or more nucleic acid sequences of interest, wherein the catalytically inactive endonuclease is from cyanobacteria Scytonema hofmanni (ShCAST) (Page 1, [0016], Page 6, [0062], Page s 24-25, [0185], Page 60, [0509], Page 71, [0616], Page 72, [0621], Page 119, [0935] and Page 189, [1321]). Zhang teaches hybridizing the one or more targeting oligonucleotides to the sample generates a region of double-stranded nucleic acid (Page 38, [0328], Page 47, [0408] and Page 60, [0510]). Zhang teaches a second transposon comprising the complement of the transposon end sequence (Page 105, [0835]). Zhang teaches a transposition system that is capable of inserting a transposon end in a random manner (Page 72, [0620] and Page 73, [0629]).
It would have been prima facie obvious to one having ordinary skill in the art at the time of the invention to modify the method of Cann by substituting the transposition system of Zhang, using a catalytically inactive endonuclease being from cyanobacteria Scytonema hofmanni (ShCAST) and hybridizing the one or more targeting oligonucleotides to the sample generates a region of double-stranded nucleic acid because it has been held that the simple substitution of one known element for another to obtain predictable results is obvious. In re Fout, 213 USPQ 532 (CCPA 1982), In re O'Farrell, 7 USPQ2d 1673 (Fed. Cir. 1988). Simply substituting the transposition system of Cann with the transposition system of Zhang would obtain predictable results because both Cann and Zhang disclose methods using transposome complexes. Additionally, the transposition system of Zhang are well suited for the system of Cann because Cann teaches that any transposition system that is capable of inserting a transposon end in a random manner can be used in the present invention (Pages 26-27, [00107]) and Zhang teaches a transposition system that is capable of inserting a transposon end in a random manner (Page 72, [0620] and Page 73, [0629]).
Claims 12 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Cann et al. (WIPO International Application Publication WO 2016/014409 A1, published January 28, 2016), cited on the IDS filed February 16, 2023, in view of Mir et al. (U.S. Patent Application Publication US 2022/0073980 A1, published March 10, 2022, effectively filed November 27, 2019), previously cited in the April 22, 2026 Office Action. This rejection is modified as necessitated by amendments.
Regarding claim 12, Cann teaches a method of targeted generation of 5' tagged fragments of a target nucleic acid (Page 25, [00104] and [00102], Pages 26-27, [00106]-[00107] and Pages 40-41, [00149]). Cann teaches a transposase, a first transposon comprising a 3' transposon end sequence and a 5' adaptor sequence (Pages 24-28, [00101]-[00108], Pages 40-41, [0149] and Figs. 4B-D). Cann teaches the targeting oligonucleotide can bind to one or more nucleic acid sequences of interest (Page 3, [0014], Page 24, [00101], Pages 31-32, [00119]). Cann teaches a second transposon comprising a 5' transposon end sequence, wherein the 5' transposon end sequence is complementary to the 3' transposon end sequence (Pages 26-27, [00106]-[00107] and Pages 40-41, [00149]). Cann teaches combining a sample comprising a double-stranded nucleic acid and a transposome complex, that is a targeted transposome complex (Pages 24-28, [00101]-[00108], Pages 40-41, [0149] and Figs. 4B-D). Cann teaches fragmenting the nucleic acid into a plurality of fragments by the transposase, by joining the 3' end of the first transposon to 5' ends of the fragments to produce a plurality of 5' tagged fragments (Page 24, [00101], Page 25, [00104], Page 26-27, [00106]-[00107], Pages 40-41, [00149] and Figs. 4B-D). Cann teaches the content of Grunenwald et al. United States Patent Application Publication 2010/0120098 A1, published May 13, 2010, (cited on the instant IDS filed 02/16/2023) is incorporated in its entirety by reference, and exemplifies the transposome complexes used in the invention (Page 26, [00106]).
Regarding claim 16, Cann teaches the fragmenting is performed at 45 °C to 65 °C (Page 79, [00269] and Example 3).
Cann does not teach or suggest a targeting oligonucleotide coated with a recombinase. Cann does not teach or suggest initiating strand invasion of the nucleic acid by the recombinase. Cann does not teach or suggest a first temperature used for initiating strand invasion is below a second temperature for fragmenting by the transposase.
Mir teaches identifying and storing the identity and positions of differently labelled nucleotides incorporated into each of a plurality of sequence fragments (Abstract and Page 3, [0019]). Mir teaches using CRISPR cas9-guide RNA complexes to target sequences (Page 14, [0162]). Mir teaches target transposome complexes comprising a transposase and a transposon end (Pages 14-15, [0162]-[0169]). Mir teaches a targeting oligonucleotide coated with a recombinase (Page 12, [0148] and Page 14, [0159]). Mir teaches initiating strand invasion of the nucleic acid by the recombinase (Page 12, [0148] and Page 14, [0159]). Mir teaches a first temperature used for initiating strand invasion is below a second temperature for fragmenting by the transposase (Pages 40-41, [0610], Pages 42, [0628] and Page 16, [0187]). Mir teaches the content of Grunenwald et al. United States Patent Application Publication 2010/0120098 A1, published May 13, 2010, (cited on the instant IDS filed 02/16/2023) is incorporated in its entirety by reference, and exemplifies the transposome complexes used in the invention (Page 14, [0162]).
It would have been prima facie obvious to one having ordinary skill in the art at the time of the invention to modify the method of Cann by substituting the transposome complexes that use strand invasion and a recombinase, of Mir because it has been held that the simple substitution of one known element for another to obtain predictable results is obvious. In re Fout, 213 USPQ 532 (CCPA 1982), In re O'Farrell, 7 USPQ2d 1673 (Fed. Cir. 1988). Simply substituting the transposome complexes that use strand invasion and a recombinase of Mir with the transposome complex of Cann would obtain predictable results because both Mir and Cann disclose methods using transposome complexes. Additionally, the transposome complexes of Mir are well suited for the system of Cann because both Mir and Cam disclose that the transposome complexes may be exemplified by Grunewald.
Response to arguments
Applicant’s arguments and amendments filed July 14, 2026, with respect to the rejections under U.S.C. § 112(b) have been fully considered and are persuasive, therefore these
rejections have been withdrawn.
However, upon further consideration new grounds of rejection under 35 U.S.C. § 112 are made, as discussed above in view of Applicant’s amendments.
Applicant’s arguments and amendments filed July 14, 2026, with respect to the rejections under U.S.C. § 102 have been fully considered and are persuasive in part, therefore these
rejections have been withdrawn.
However, upon further consideration new grounds of rejection under 35 U.S.C. § 103 are made in view of Applicant’s amendments.
As discussed above, newly cited Zhang discloses a catalytically inactive endonuclease associated with a guide RNA, wherein the guide RNA can direct endonuclease binding to one or more nucleic acid sequences of interest and the catalytically inactive endonuclease is from cyanobacteria Scytonema hofmanni (ShCAST). It would have been prima facie obvious to one having ordinary skill in the art at the time of the invention to modify the method of Cann by substituting the transposition system of Zhang, using a catalytically inactive endonuclease being from cyanobacteria Scytonema hofmanni (ShCAST) and hybridizing the one or more targeting oligonucleotides to the sample generates a region of double-stranded nucleic acid because it has been held that the simple substitution of one known element for another to obtain predictable results is obvious. In re Fout, 213 USPQ 532 (CCPA 1982), In re O'Farrell, 7 USPQ2d 1673 (Fed. Cir. 1988). Simply substituting the transposition system of Cann with the transposition system of Zhang would obtain predictable results because both Cann and Zhang disclose methods using transposome complexes. Additionally, the transposition system of Zhang are well suited for the system of Cann because Cann teaches that any transposition system that is capable of inserting a transposon end in a random manner can be used in the present invention (Pages 26-27, [00107]) and Zhang teaches a transposition system that is capable of inserting a transposon end in a random manner (Page 72, [0620] and Page 73, [0629]).
Applicant’s arguments and amendments filed July 14, 2026, with respect to the rejections of claims 12 and 16 under U.S.C. § 103 have been fully considered but they are not persuasive.
Applicant asserts “Cann is silent regarding “recombinase”…[and] Mir fails to remedy these deficiencies of Cann at least because Mire is also silent with respect to “recombinase” and a “targeting oligonucleotide coated with recombinase”.
However, as discussed above, while Mir does not explicitly use the word “recombinase” Mir discloses on Page 14, [0159] and Page 12, [0148] “binding of synthetic sequences to the target polynucleotide. This can occur by strand invasion of modified oligos into double stranded DNA, and can include a Rec protein (e.g. RecA) mediated invasion” and “The origins can also be created by binding of oligo primers across the length of the polynucleotide… It can also be done by invasion of a duplex by an oligo facilitated by a protein, such as RecA”; as defined by the instant specification at Page 5, [0024] and Page 50, [00379], the recombinase being used in the instant invention may be RecA. Therefore, Mir does in fact disclose the use of recombinase and a targeting oligonucleotide coated with recombinase.
Therefore, for these reasons and those listed above, Cann, in view of Zhang as well as Cann in view of Mir, are deemed to render the instant invention obvious.
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.
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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
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