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 .
Application Status
This action is written in response to applicant’s correspondence received on 6/25/2026. Claims 44, 46, 50-57, and 88-90 are pending. Claims 44, 46, 50-51, 53, and 88 have been amended. Claim 90 is newly added. Claims 1-43, 45, 47-49, and 58-87 have been cancelled. All pending claims are currently under examination.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow. This Office Action is Final.
Claim Rejections - 35 USC § 112 – New Rejection Necessitated by Amendment
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 44, 46, 50-57, and 88-90 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.
Regarding claim 44, claim 44 recites “does not comprise a sequence that is capable of binding to a primer immobilized to the substrate by hybridization,” (see lines 5-6 of step d). Step d therefore recites “a primer,” where previously “a first primer” immobilized to the a substrate is recited in step b. Furthermore, step d later recites “a second primer.” Claim 44 therefore recites multiple primers, and recitation in line 5 of step d of “a primer” lacks proper antecedent basis, as it is unclear to which primer is being referred (i.e., the first immobilized primer? The second primer?). It is furthermore unclear if additional primers, for instance three immobilized primers, are recited in the claim because both first and second primers are recited but step d further recites “a primer” without reference to the primer being either the first or second primer. It is unclear if line 5 of step d is in reference to a third, separate primer on the substrate because the language is not clear.
Claims 46, 50-57, and 88-90 depend from claim 44 and do not resolve this issue and are therefore also rejected under 112(b).
Claim Rejections - 35 USC § 103 – New Rejection Necessitated by Amendment
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.
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 44, 46, 50-57, and 88-90 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (WO 2017/218979 A1, of record) in view of Kozarewa (Kozarewa I et al. Nat Methods. 2009 Apr;6(4):291-5).
Regarding these claims, Zhang is a patent document which teaches labelling and detecting double-strand breaks (DSBs) in nucleic acids (Title, Abstract, and see document).
Regarding claim 44, Zhang teaches a method of sample preparation for identifying DNA double-strand breaks (DSB) in a nucleic acid sample, where the preparation comprises modifying DSB-associated nucleic acids to be suitable for binding to a substrate comprising immobilized primers (e.g., paragraphs 121 and 128, Figure 3). Zhang teaches a method of a) providing a plurality of nucleic acids, b) ligating an adaptor to the 3’ terminus of a DSB (see Figure 3A-3B). Zhang teaches fragmenting the oligos, where such fragmenting/cutting leaves one end exposed for ligation of an additional adaptor at the fragment/cut site (Figure 3C-3D). Furthermore, Zhang teaches that the adapters comprise Illumina RA3 sequences and are therefore “complementary” to primer sequences (see Figure 3, paragraphs 121 and 188). Zhang further teaches fragmenting the nucleic acids by teaching that the adapter-ligated nucleic acids are cut by Cas9 enzymes (step 4, paragraphs 121 and 188). Zhang teaches exposing the nucleic acids to a second adapter (step 6 of paragraph 121, and further the “third adapter” which can be ligated paragraphs 120 and 123). Furthermore, Zhang teaches that the second adapter is not ligatable to the first adaptor because the first adaptor is ”blocked” (e.g., step 2 of paragraph 121 and 188). Zhang teaches using different adaptors (e.g., RA3 and RA5, paragraph 121); thus, Zhang teaches a second adaptor that does not bind to the first primer immobilized on the substrate. Furthermore, Figure 3 of Zhang teaches the ligation of blocked adaptors, which prevent further ligation (i.e., where the second adaptor is not capable of being ligated to the first adaptor). Zheng further teaches that sequencing is performed on platforms such as Illumina sequencing platforms (e.g., paragraphs 67 and 87).
Zheng does not teach that the second adaptor is an adaptor which comprises a sequence identical to a region of a second primer but does not comprise a sequence complementary to the region of the second primer (i.e., Zheng’s adaptors are complementary and double-stranded and not partially complementary, as required by the claim).
Kozarewa is a research article which focuses on improved methods of genomic mapping and sequencing using Illumina platforms (Title, Abstract, and throughout). Zhang and Kozarewa therefore overlap in subject matter and field of endeavor because both teach Illumina sequencing and methods of mapping sequencing reads. Kozarewa teaches a method of improved mapping where the method does not require prior amplification (e.g., Title, throughout). Kozarewa teaches that it is known in the art that library prep amplification steps introduce unwanted biases, unevenly distributed read coverages, and create amplification artifacts. To remedy this known problem, Kozarewa teaches a method of directly amplifying fragmented nucleic acids on a flow cell using cluster amplification (i.e., bridge amplification), where ligation of specially designed adaptors allow such an approach (Abstract, and page 2, final paragraph).
Kozarewa teaches that:
“In our no-PCR protocol, partially double stranded adapters are also added to end-repaired, template DNA with a 3’ A overhang, by ligation (Figure 1). Unlike the standard Illumina adapters, no-PCR adapters contain additional sequences that allow hybridization of templates directly to the flow cell surface. Incompletely ligated fragments are inert in the cluster amplification step. Thus it is not necessary to retain the PCR step to enrich for properly ligated fragments,” (page 2, final paragraph).
Kozarewa depicts such cluster/bridge amplification using no-PCR strategies in Figure 1, and further teaches:
“Whereas standard adapters consist only of sections to which read 1 and read 2 sequencing primers hybridize (R1 and R2′), no-PCR adapters also contain sequences that facilitate hybridization to oligonucleotides attached to the flow cell surface (FP1 and FP2′). The standard library prep uses PCR to add these sections, and to enrich for fully ligated templates which then amplify on the flow cell surface. With the no-PCR approach, the flow cell itself is used to select for fully ligated template molecules. All no-PCR templates hybridize to the flow cell in the same orientation, because only the FP2′ sequence is reverse complementary to a flow cell oligonucleotide,” (caption beneath Figure 1).
Thus, Kozarewa teaches that partially complementary adaptors are known in the art and are useful in no-PCR methods of unbiased DNA amplification (above).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed application to modify the adaptor sequences taught by Zhang to comprise a region identical to a second primer and not comprise a sequence identical to a region of a second primer (i.e., partially complementary) because such design of adaptors are already known in the art as taught by Kozarewa. The practitioner would be motivated to adopt the teachings of Kozarewwa to those of Zhang because Kozarewa teaches that such no-PCR cluster amplification which occurs directly on the flow cell has advantages such as reduced amplification artefacts, results in better mapping of genomic reads, and has a more even distribution across read coverage (Abstract of Kozarewa).
Regarding claim 46, Zhang teaches that during bridge amplification, first and second primers are immobilized, the sequences attached to libraries prepared in their methods bind to the immobilized primers (paragraph 231
Regarding claim 50, Zhang teaches that the blocked protective feature prevents other nucleic acids from ligating to the first adapter (paragraph 121, step 2).
Regarding claim 51, Kezarewa teaches that the sequence identical to the second primer is capable of carrying out cluster amplification, and is therefore reasonably identical to the second primer at least 5 or more bases (e.g., Figure 1).
Regarding claim 52, Zhang teaches denaturing nucleic acids to generate single-stranded DNA as a step in sequencing (e.g., paragraph 16).
Regarding claim 53, Zhang teaches contacting the nucleic acids with a substrate comprising immobilized primers under conditions suitable for hybridization of the immobilized primers to complementary nucleic acids (e.g., paragraph 16).
Regarding claim 54, Zhang teaches sequencing nucleic acid molecules to obtain sequence information (e.g., paragraph 32). Kezarewa similarly teaches hybridizing the nucleic acids to the substrate using hybridization of the adaptors and nucleic acids (Figure 1).
Regarding claim 55, Zhang teaches that the plurality of nucleic acids is gDNA (e.g., paragraph 33, final sentence).
Regarding claim 56, Zhang teaches the order to perform the method in the steps a), b), c), and d) (e.g., the methods taught in paragraphs 121 and 188). Note that although the methods taught by Zhang in paragraphs 121 and 188 begin with fragmentation, they also include an additional fragmentation step where the nucleic acids are cut by Cas9 (step 6, paragraphs 121 and 188). The instant method is recited to “comprise” the steps, and therefore allow for additional steps and reagents, such as those taught by Zhang in paragraphs 121 and 188. Also see Figure 3.
Regarding claim 57, Zhang teaches that the nucleic acids are exposed to Cas9, which can cause DSBs in a nucleic acid sample (step 4, paragraph 121).
Regarding claim 88, Zhang teaches preparing samples for amplification using immobilized primers and the second primer (e.g., Zhang teaches Illumina sequencing and bridge amplification, paragraph 231). Zhang teaches bridge amplification (paragraph 231). Kazarewa also teaches bridge/cluster amplification (Figure 1).
Regarding claim 89, Zhang teaches that the method is carried out in vitro (e.g., step 8 of paragraph 188).
Regarding claim 90, Zhang teaches that bridge amplification occurs as a part of their sequencing method (paragraph 231). Kazarewa also teaches that cluster amplification (i.e., bridge amplification) is carried out on the flow cell using the two primers (Figure 1).
Response to Arguments
The Applicant’s arguments filed 6/25/2026 have been considered but are not persuasive. The Applicant argues that Zhang does not anticipate the claimed subject matter. This argument is persuasive. Upon Applicant’s amendments, which clarify the subject matter of the claims, a new search has been conducted to address the clarified claims and new limitations with respect to the nature of the second adaptor. Upon searching of the subject matter, Kozarewa was found, where Kazarewa does teach partially complementary adaptor sequences which are known to be useful in no-PCR amplification for the purposes of refining sequencing reads using Illumina flow cell technology. Given that Zhang is also drawn to sequencing using Illumina sequencing technologies, the methods and teachings are applicable to the teachings of Zhang. Thus, the presently viewed invention can be viewed as the combination of known prior art elements, where furthermore there is a known advantage to using the adaptor designs presently recited, as such partially complimentary adaptors are taught by Kozarewa and are known to have advantages in no-PCR sequencing methods. Thus, while the Applicant’s arguments regarding the teachings of the adaptors of Zhang are persuasive, the search prompted by Applicant amendments yielded Kozarewa, who teaches that partially complementary adaptor sequences used in flow cell sequencing such as used by Zhang is a known, advantageous design of adaptors.
Double Patenting – Maintained/Updated in Response to Amendment
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 44, 46, 50-57, and 88-90 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,421,544 (‘544). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 44, claim 1 of ‘544 recites:
“A method of sample preparation for identifying DNA double-strand breaks (DSBs) in a nucleic acid sample, wherein the preparation comprises modifying DSB-associated nucleic acids to be capable of binding to a substrate comprising at least a first immobilised primer, the method comprising:
providing a sample comprising a plurality of nucleic acids;
exposing the plurality of nucleic acids to a first adaptor pair under conditions conducive to ligation, wherein the first adaptor pair comprises first and second oligonucleotides that are at least partially complementary to each other, and the first oligonucleotide is ligatable to a 3′ terminus of a strand of a DSB and comprises a sequence that is capable of binding to the first immobilised primer by hybridisation;
fragmenting the plurality of nucleic acids; and
d) exposing the plurality of nucleic acids to a second adaptor pair under conditions conducive to ligation, wherein the second adaptor pair is capable of being ligated to at least a 5′ terminus of a strand at a break induced by fragmentation but is not capable of being ligated to the first oligonucleotide of the first adaptor pair, wherein the second adaptor pair comprises first and second oligonucleotides that are partially complementary to each other, and the first oligonucleotide is ligatable to a 5′ terminus and comprises a sequence identical to a region of a second primer, and the second oligonucleotide does not comprise a sequence that is complementary to said sequence identical to a region of the second primer.”
Note that, regarding step (b), ‘544 recites “a first adaptor pair” which reasonably includes “a first adaptor” as recited in instant claim 1 step (d). This minor difference in wording of step (b) between ‘544 and step (b) of the instant application is insignificant, as both claims are drawn to the same subject matter comprising a first adaptor.
Similarly, step (d) of ‘544 recites “a second adaptor pair” which reasonably includes a “second adaptor” as recited in instant claim 1 step (d). This minor difference in wording of step (d) between ‘544 and step (d) of the instant application is insignificant, as both are drawn to the same subject matter comprising a second adaptor.
Furthermore, claims 3-4 of ‘544 recite
“3. The method of claim 1, wherein the second primer is a second immobilised primer comprised by the substrate.
4. The method of claim 3, wherein the method comprises modification of the DSB-associated nucleic acids to be capable of amplification, wherein the amplification comprises the use of the first immobilised primer and the second immobilised primer.”
Thus, claim instant claim 44 is drawn to the same subject matter as claim 1 of the ‘544 patent and anticipates the present subject matter of claim 44.
Regarding claim 46, claims 3-4 of ‘544 recite:
“3. The method of claim 1, wherein the second primer is a second immobilised primer comprised by the substrate.
4. The method of claim 3, wherein the method comprises modification of the DSB-associated nucleic acids to be capable of amplification, wherein the amplification comprises the use of the first immobilised primer and the second immobilised primer.”
Claims 3-4 of ‘544 therefore recite that the substrate comprises first and second immobilized primers.
Regarding claim 50, claim 9 of ‘544 recites: “The method of claim 1, wherein the second adaptor pair is not capable of being ligated to the first adaptor pair due to the presence of a 3′ modification of the first adaptor pair.”
Regarding claim 51, claim 10 of ‘544 recites: “The method of claim 1, wherein the oligonucleotide of the second adaptor pair that is ligatable to a 5′ terminus comprises a sequence identical to 5, 10, 15, 20, 21, 24, or more bases of the second primer.”
Regarding claim 52, claim 11 of ‘544 recites: “11. The method of claim 1, further comprising denaturing the plurality of nucleic acids to form a plurality of single-stranded nucleic acids.”
Regarding claim 53, claim 12 of ‘544 recites: “12. The method of claim 1, further comprising contacting the plurality of nucleic acids with the substrate comprising immobilised primers under conditions suitable for hybridisation of the immobilised primers to complementary nucleic acids.”
Regarding claim 54, claim 13 of ‘544 recites: “13. The method of claim 12, further comprising obtaining sequence information for any nucleic acids hybridised to the substrate.”
Regarding claim 55, claim 14 of ‘544 recites: “14. The method of claim 1, wherein said sample comprising a plurality of nucleic acids is genomic DNA (gDNA).”
Regarding claim 56, claims 15-17 of ‘544 recite:
15. The method of claim 1, wherein the steps are performed in the order a), b), c), and then d).
16. The method of claim 15, wherein the sample is exposed to conditions capable of causing a DSB at a feature in the nucleic acid sample prior to step b).
17. The method of claim 1, wherein the steps are performed in the order a), c), d), and then b), wherein the sample is exposed to conditions capable of causing or suspected of being capable of causing a DSB between steps d) and b).
Regarding claim 57, claim 18 of ‘544 recites: “18. The method of claim 17, wherein the sample is exposed to conditions capable of causing a DSB at a feature in the nucleic acid sample.”
Regarding claim 88, claims 2-5 of ‘544 recite:
2. The method of claim 1, wherein the method comprises modification of the DSB-associated nucleic acids to be capable of amplification, wherein the amplification comprises the use of the first immobilised primer and the second primer.
3. The method of claim 1, wherein the second primer is a second immobilised primer comprised by the substrate.
4. The method of claim 3, wherein the method comprises modification of the DSB-associated nucleic acids to be capable of amplification, wherein the amplification comprises the use of the first immobilised primer and the second immobilised primer.
5. The method of claim 4, wherein the amplification is bridge amplification.
Regarding claim 89, claim 19 of ‘544 recites: “19. The method of claim 1, wherein said ligation in step b) occurs in situ or in vitro using a cell or tissue sample.”
Regarding claim 90, claim 5 of ‘544 recites that amplification is performed (bridge amplification).
Thus, the claims of ‘544 recites nearly identical subject matter to what is being claimed in the instant application and therefore anticipates the claimed subject matter.
Claims 44, 46, 50-57, and 88-90 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,428,683 (‘683). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 44, claim 1 of ‘683 recites:
A method for identifying DNA double-strand breaks (DSBs) in a sample comprising a nucleic acid, comprising
exposing the sample of nucleic acid suspected of containing DSBs, under ligation conditions, to a first pair of oligonucleotides, wherein a first oligonucleotide of the first pair of oligonucleotides comprises a 5′ binding feature that enables ligation of said first oligonucleotide to a first strand of a DSB, a first hybridization site to which a first sequencing primer can bind, and a binding sequence for separating said DSB from a pool of DSBs; and a second oligonucleotide of the first pair of oligonucleotides that is complementary to said first oligonucleotide of the first pair and comprises a 3′ binding feature that enables ligation of said second oligonucleotide to a second strand of said DSB; wherein either or both of said oligonucleotides comprise, a 3′ and/or 5′ protective feature;
fragmenting the nucleic acid of said sample into fragments;
exposing said fragments, under ligation conditions, to a second pair of oligonucleotides, wherein a first oligonucleotide of the second pair of oligonucleotides comprises a 5′ binding feature, that enables ligation of said first oligonucleotide to a first strand of a fragmented nucleic acid and a second hybridization site to which a second sequencing primer can bind; and a second longer oligonucleotide of the second pair of oligonucleotides that is in part complementary to said first oligonucleotide of the second pair and comprises a 3′ binding feature for binding to a second strand of said fragmented nucleic acid, a sequence complimentary to said second hybridization site, and a further sequence; and wherein either or both of said oligonucleotides comprise a 3′ and/or 5′ protective feature;
denaturing the fragments to provide single strand nucleic acids;
v) separating the single strand nucleic acids of part iv) into two groups: group A strands that are associated with a DSB and have ligated at a first end the first hybridization site and the binding sequence provided by the first oligonucleotide of the first pair of oligonucleotides and at another end the second hybridization site and the further sequence provided by the second oligonucleotide of the second pair of oligonucleotides and group B strands that are not associated with a DSB and do not have ligated at a first end the hybridization site and the binding sequence provided by the first oligonucleotide of the first pair of oligonucleotides, wherein the separating comprises hybridizing the binding sequence provided by the first oligonucleotide of the first pair of oligonucleotides to a complementary binding strand anchored to a substrate in order to retain group A strands, and
removing group B strands from the substrate; and
vi) sequencing the strands of group A using at least the first sequencing primers where each sequence is equivalent to a DSB, wherein the number and nature of base pair deletions can be determined by comparing each sequence with a genome representative of a species from which the sample was taken.
Claim 1 of ‘683 therefore recites a method for identifying DSBs by providing a sample of plurality of nucleic acids, exposing the nucleic acids to a pair of oligonucleotides ligatable to the 3’ end which are complementary, fragmenting the nucleic acids, and exposing the nucleic acids to a second pair of nucleotides. Furthermore, claim 2 of ‘683 recites that the sequences comprise a sequence enabling bridge amplification, which implies that the sequences are to be sequenced on a substrate comprising immobilized primers. Claims 1 and 2 of ‘683 therefore anticipates the claim limitations recited in claim 44 of the present application.
Regarding claim 46, claim 2 of ‘683 recites that the sequences comprise a sequence enabling bridge amplification, which implies that the sequences are to be suitable for amplification, where the nucleic acids are sequenced on a substrate comprising immobilized primers (i.e., sequencing on NGS sequencing platforms using bridge amplification). Bridge amplification depends on a substrate comprising immobilized first and second primers, where nucleic acids to be sequenced hybridize to the immobilized primers. Furthermore, recitation of “identical to a region” regarding the second primer can be as few as one or two nucleotides, where a second adaptor inherently reads on such a primer.
Regarding claim 50, claim 9 of ‘683 recites that the end-modifications resist ligation.
Regarding claim 51, claim 1 of ‘683 recites that the second sequencing primer binds to a hybridization region of the 5’ ligation region of the second pair of oligonucleotides.
Regarding claim 52, step iv) of claim 1 of ‘683 recites denaturing fragments to provide single-strand nucleic acids (step iv) of claim 1, ‘683).
Regarding claim 53, claim 2 of ‘683 recite bridge amplification, which uses immobilized primers on a substrate in conditions suitable for hybridization of immobilized primers to complementary nucleic acids.
Regarding claim 54, step vi) of claim 1 of ‘683 recites obtaining sequence information.
Regarding claim 55, claim 5 of ‘683 recites that the nucleic acid sample is gDNA.
Regarding claim 56, the steps of claim 1 of ‘683 are recited in the same order as those recited in instant claim 1; a practitioner could therefore immediately envision that the steps are taken in the order recited.
Regarding claim 57, claim 1 of ‘683 recites that the method is intended for identifying DSBs, where the site of any DSB can reasonably be interpreted to be a “feature of interest” simply because such DSBs could be mapped using the method of claim 1 of ‘683, where any mapped DSB could be a “feature of interest.”
Regarding claim 88, claim 2 of ‘683 recites that the sequences comprise a sequence enabling bridge amplification.
Regarding claim 89, claim 17 of ‘683 recites that ligation occurs in situ or in vitro using a cell or tissue sample.
Regarding claim 90, given that ‘683 recites that the sequences are suitable for bridge amplification (claim 2), and that such bridge amplification relies on immobilized primers, the claims of ‘683 anticipate instant claim 90 because a practitioner can immediately envision using the first and second immobilized primers for amplification such as bridge amplification as recited in claim 2 of ‘683.
Response to Arguments
The Applicant’s arguments filed 6/25/2026 have been considered but are not persuasive. The Applicant argues that the statutory rejection of the instant claims in view of ‘544 was misapplied. This argument is persuasive. However, in light of the Applicant’s amendments, the present claims have been reconsidered. Based upon the Applicant’s amendments, a non-statutory double patenting rejection is given for the instant claims based upon ‘544.
The Applicant states that a terminal disclaimer will be considered for ‘683 but has not filed a terminal disclaimer or offered an argument against the non-statutory double patenting rejection based upon ‘683. The rejection is therefore maintained.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOUGLAS CHARLES RYAN whose telephone number is (571)272-8406. The examiner can normally be reached M-F 8AM - 5PM.
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/D.C.R./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
