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 Claims / Response to Amendment
This office action is in response to an amendment filed on May 20, 2026.
Claims 1-13 were previously pending. Applicant amended claim 1.
Claims 1-13 are currently pending, with claims 4, 6-7 and 9-10 withdrawn.
Claims 1-3, 5, 8 and 11-13 are under consideration.
All of the amendment and arguments have been thoroughly reviewed and considered.
Applicant's submission of the replacement drawings obviated the previously presented objection.
All of the previously presented rejections have been withdrawn as being addressed or obviated by the amendment of the claims, which added new limitations to the claims, that were not considered in the previous rejections.
The previously set forth prior art rejections have been withdrawn in view of the recent claim amendment filed on May 20, 2026, which added new limitations to the claims (e.g., the newly amended kits in claim 1 now recites "wherein the pool of TACS is fixed to a solid support" and "wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs" which are new limitations not previously considered).
Thus, the scope of the claims has been changed in a manner that were not considered in the previous rejections.
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 contains new grounds for rejection necessitated by amendment.
Priority
The priority date of the instant claims 1-3, 5, 8 and 11-13 is 07/07/2017, filling date of the US provisional application NO. 62/529,790.
Claim Interpretation
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP§ 2111.
For the purpose of applying prior art, claim 1 recites "a pool of TArget Capture Sequences (TACS)."
The specification provides definition for the term "TArget Capture Sequences (TACS)" as follows:
"As used herein, the term “TArget Capture Sequences” or “TACS” refers to short DNA sequences that are complementary to the region(s) of interest on a genomic sequence(s) of interest (e.g., chromosome(s) of interest) and which are used as “bait” to capture and enrich the region of interest from a large library of sequences, such as a whole genomic sequencing library prepared from a biological sample. " (page 50, lines 1-5)
Accordingly, "a pool of TArget Capture Sequences (TACS)" is interpreted as a collection of at least two short DNA nucleic acids.
For the purpose of applying prior art, claim 1 recites a "reference coordinate system," which is a term not expressly defined by the specification.
The specification at page 53, lines 23-27 provides the following relevant description:
"In one embodiment, the pool of TACS comprises a plurality of TACS families directed to different genomic sequences of interest. Each TACS family comprises a plurality of members that bind to the same genomic sequence of interest but having different start and/or stop positions with respect to a reference coordinate system for the genomic sequence of interest.
Typically, the reference coordinate system that is used for analyzing human genomic DNA is the human reference genome built hg19, which is publically available in the art, but other coordinate systems may also be used. Alternatively, the reference coordinate system can be an artificially created genome based on built hg19 that contains only the genomic sequences of interest."
Thus, under BRI and in light of the specification, the term "reference coordinate system" is interpreted to encompass any sequence or collection of sequences that can be used as reference for nucleotide positions.
For the purpose of applying prior art, claim 1 recites "wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs."
The application's disclosure describes staggered TACs as follows:
”Furthermore, in certain embodiments, the TACS used in the methods are families of TACS, comprising a plurality of members that bind to the same genomic sequence but with differing start and/or stop positions, such that enrichment of the genomic sequences of interest is significantly improved compared to use of a single TACS binding to the genomic sequence. The configuration of such families of TACS is illustrated schematically in FIG. 3 , showing that the different start and/or stop positions of the members of the TACS family when bound to the genomic sequence of interest results in a staggered binding pattern for the family members. “ (page 47, lines 1-7)
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Accordingly, TACs having staggered start and stop positions are interpreted to mean oligonucleotides with hybridization sites to a target sequence that partially overlap, with the staggered portion being the portion that does not overlap. For example, if oligo 1 hybridizes to nucleotide positions 1-20 of a reference sequence, oligo 2 hybridizes nucleotide positions 5-25, the probes are staggered by 5 base pairs at both start and stop positions.
New Grounds of 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.
Claims 1-3, 5, 11 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over
Koumbaris1 (US20160340733A1 - Multiplexed parallel analysis of targeted genomic regions for non-invasive prenatal testing; published 2016-11-24; cited as U.S. patent document “M” in IDS filed on IDS - 05/11/2023) , in view of
Lee (Lee, Tin-Lap, and Alfred Chun Shui Luk, eds. Tiling arrays: methods and protocols. Humana Press, 2013); and
Teer (Teer et al; ; NISC Comparative Sequencing Program; Margulies EH, Green ED, Collins FS, Mullikin JC, Biesecker LG. Systematic comparison of three genomic enrichment methods for massively parallel DNA sequencing. Genome Res. 2010 Oct;20(10):1420-31. doi: 10.1101/gr.106716.110. Epub 2010 Sep 1. PMID: 20810667; PMCID: PMC2945191) ; as evidenced by
Schott (Schott et al., Targeted Capture of Complete Coding Regions across Divergent Species. Genome Biol Evol. 2017 Feb 1;9(2):398-414. doi: 10.1093/gbe/evx005. PMID: 28137744; PMCID: PMC5381602); and
McCormack (McCormack et al., Applications of next-generation sequencing to phylogeography and phylogenetics. Mol Phylogenet Evol. 2013 Feb;66(2):526-38. doi: 10.1016/j.ympev.2011.12.007. Epub 2011 Dec 14. PMID: 22197804.).
A) Koumbaris1 discloses a kit comprising a pool of TArget Capture Sequences (TACS) that largely overlap in scope with the claimed kit.
Regarding claim 1, Koumbaris1 teaches a kit comprising a container comprising a pool of TArget Capture Sequences (TACS) ([0088]; [00094]),
wherein the pool of TACS is fixed to a solid support ([0088] TACS are provided in a form that allows them to be bound to a solid support, such as biotinylated TACS. In another embodiment, the TACS are provided together with a solid support, such as biotinylated TACS provided together with streptavidin-coated magnetic beads) ,
wherein the pool of TACS comprises a plurality of TACS families ([0094]” chromosomal regions used to design primers to amplify suitable loci on chromosomes 13, 18, 21 and X, to thereby prepare the pool of TACS for analysis of chromosomes 13, 18, 21 and X, are shown in FIG. 2”; Fig. 2 shows a number of regions for each chromosome, thus each TACS family is designed for targeting each chromosome comprising multiple target regions),
wherein each TACS family comprises a plurality of member sequences ([0094]; Fig. 2),
wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions ([0094]; Fig. 2, the TACS generated via amplifying the different chromosomal regions having different start and/or stop codons, as shown in FIG. 2, also have different start and/or stop positions),
further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length ([0094] “TACS range from 100-260 bp in size and are generated through a PCR-based approach”; Fig. 2; claim 1),
each member sequence having a 5' end and a 3' end (claim 1);
(ii) each member sequence binds to the same genomic sequence of interest (FIG. 2),
wherein the 5' end and the 3' end of each member sequence are each at least 50 base pairs away from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements ( [0014]; [0055]); and
(iii) the GC content of the pool of TACS is between 19% and 80%, as determined by calculating the GC content of each member within the pool of TACS ([0015]; [0059]).
The only feature Koumbaris1 does not explicitly teach is that ꟷ the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs, newly added in the recent claim amendment. However, this feature encompasses tiled probe design, which is obvious in view of the knowledge in the prior art, especially within the context of hybridization capture.
Tiled probes are oligonucleotides with hybridization sites to a target sequence that partially overlap, they are well-known in the art.
Lee teaches the degree of overlap is a key factor for optimizing resolution:
"Thus, proper probe length is important to improve the signal-to-noise ratio. The interval (degree of overlap) of the probes, which is decided by the genome size of the target organism and the number of probes mounted on the array slide, determines the resolution of expressed regions on the genome (Fig. 1 ). " (page 26, part 3, lines 5-9)
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Tiled hybridization capture probes, which increases the diversity of probes sequences available for hybridization, have known advantages over individual probes, such as compensation for hybridization issues with individual probes (e.g., secondary structure, GC content) and allowing capture across divergent regions; thereby increasing capture of complete region. See Schott (Page 402, right-hand col; lines 22-28).
Additionally, McCormack teaches (page 532, left-hand col, para 2, lines 1-6):
“A final benefit of target enrichment is that probes can be tiled such that short reads from many tiled sections can later be assembled into larger contigs, obviating the problem of SNPs versus gene trees. This design maximizes the advantages of depth of coverage on a platform like Illumina, while minimizing the drawback of short read length.”
The claimed specific stagger space of 5-10 base pairs is not only an obvious result of routine optimization in the design of tiled probes, but is also expressly taught by the prior art.
Teer teaches a target enrichment scheme (MGS) for massively parallel sequencing using tiled probes, wherein within each region of interest, the probes are staggered every 5-11 bases. (page 1429, right-hand col, para 3, "MGS array design").
Teer also teaches that the MGS approach is highly effective, with the highest sensitivity and most uniform capture (Abstract; page 1427, left-hand col, para 5, lines 5-6).
Therefore, a skilled artisan, motivated by the known benefit of tiled probes, such as complete capture of region of interest, and maximize depth of coverage for sequencing, as suggested by Schott and McCormack, would have found it prima facie obvious, before the effective filing date of the claimed invention, to utilize tiled probes with staggered start and end positions for hybridization capture targeting the chromosomal regions in Koumbaris1.
A skilled artisan would also have found it obvious to utilize the specific probe design as claimed with 5-10 staggered bases, for the potential benefit of superior sensitivity and uniformity, as suggested by Teer.
Teer teaches probes are staggered every 5-11 bases. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05
A skilled artisan would have had reasonable expectation of success because a skilled artisan would readily understand that the degree of overlap (i.e. number of staggered bases) in tiled probes is a known variable for optimization, meaning a smaller overlap in base pairs between probes hybridization sites in a given region means higher probe density, leading to higher coverage and resolution, as explained by Lee.
Modifying the probes set in Koumbaris1 to include tiled probes targeting each region of interest is within the skill of a person of ordinary skill in the art, as tiled probes are well-known in the art, and the 250 bp chromosome regions in Koumbaris1 (FIG. 2) are compatible target regions for tiled probes, according to Teer (page 1429, right-hand col, para 2, ROI segment at least 200 bp in length).
B) Regarding claim 2, Teer teaches wherein the start and/or stop positions of the member sequences are staggered by at least 3 base pairs (page 1429, right-hand col, para 2).
Regarding claim 3, Koumbaris1 teaches wherein the pool of TACS comprises at least 2 TACS families (Fig.2 ).
Regarding claim 5, Koumbaris1 teaches wherein each TACS family comprises at least 2 member sequences (Fig. 2).
Regarding claim 11, Koumbaris1 teaches wherein the different member sequences have different % GC content ([0059]).
Regarding claim 13, Koumbaris1 teaches wherein the kit further comprises one or more of the following:(i) one or more components for isolating cell free DNA from a biological sample and (ii) one or more components for preparing the sequencing library comprising primers, adapters, buffers, linkers, restriction enzymes, ligation enzymes and polymerase enzymes ([0088]).
Claims 8 and 12 is rejected under 35 U.S.C. 103 as being unpatentable over Koumbaris1, in view of Lee and Teer, as applied to claim 1 above and further in view of
Majumdar (Majumdar et al. Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis. J Hum Reprod Sci. 2016 Apr-Jun;9(2):94-100. doi: 10.4103/0974-1208.183512. PMID: 27382234; PMCID: PMC4915293).
A) The teachings of Koumbaris1 are recited above and applied as for base claim 1.
Regarding claim 8, while Koumbaris1 teaches an prenatal assay for the detection of fetal aneuploidies of any chromosomes, such as chromosomes 13, 18, 21, X and Y([0009]; [0019]; [0021]), via the binding of TACS sequences to target chromosomes ; it does not explicitly teach assaying all chromosomes within the human genome.
Majumdar teaches a need for improved methods for preimplantation genetic screening, noting that methods capable of analyzing all 24 human chromosomes would likely remedy the shortcomings of earlier approaches that screened only a subset of chromosomes (page 95, left-hand col, paras. 1-3).
Accordingly, it would have been prima facie obvious to a person of ordinary skill in the art, in view of Koumbaris2 and Majumdar, before the effective filing date of the claimed invention to expand the TACS library in the assay of Koumbaris2 to include all 24 chromosomes as binding targets. Majumdar provides a clear motivation ꟷ such modification would improve detection of aneuploidies in prenatal assays and also enable broader applications in preimplantation genetic screening.
B) Regarding claim 12, Majumdar teaches in IVF Pre-implantation Genetic Screening (PGS) (entire document).
Double Patenting- Obvious Type -- New Grounds
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 1-3, 5 and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6, 10 of copending Application No. 18/926,874 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over the claims (filed on10/25/2024) of the '874 application.
Instant claim 1 recites:
A kit comprising a container comprising a pool of TArget Capture Sequences (TACS) (‘874 Application, claim 1, 10),
wherein the pool of TACS is fixed to a solid support (‘874 Application, claim 6),
wherein the pool of TACS comprises a plurality of TACS families (‘874 Application, claim 2, 10),
wherein each TACS family comprises a plurality of member sequences (‘874 Application, claim 2, 10),
wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions (‘874 Application, claim 2, 10),
wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs (‘874 Application, claim 5; ""[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." See MPEP 2144.05"), and
further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length (‘874 Application, claim 1, 10),
each member sequence having a 5' end and a 3' end (‘874 Application, claim 1, 10);
(ii) each member sequence binds to the same genomic sequence of interest (‘874 Application, claim 1, 10),
wherein the 5' end and the 3' end of each member sequence are each at least 50 base pairs away from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements (‘874 Application, claim 1, 10); and
(iii) the GC content of the pool of TACS is between 19% and 80%, as determined by calculating the GC content of each member within the pool of TACS (‘874 Application, claim 1, 10).
Therefore, instant claims 1-3, 5 and 13 are obvious over claims 1-2, 6, 10 of the '874 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, 5 and 11 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 3, 8 and 13-18 of U.S. Patent No. 11111538B2 in view of Teer (Teer et al; ; NISC Comparative Sequencing Program; Margulies EH, Green ED, Collins FS, Mullikin JC, Biesecker LG. Systematic comparison of three genomic enrichment methods for massively parallel DNA sequencing. Genome Res. 2010 Oct;20(10):1420-31. doi: 10.1101/gr.106716.110. Epub 2010 Sep 1. PMID: 20810667; PMCID: PMC2945191).
Instant claim 1 recites:
A kit comprising a container comprising a pool of TArget Capture Sequences (TACS),
wherein the pool of TACS is fixed to a solid support (‘538 Patent, claim 8),
wherein the pool of TACS comprises a plurality of TACS families (‘538 Patent, claim 1),
wherein each TACS family comprises a plurality of member sequences (‘538 Patent, claim 1),
wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions,
wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs, and
further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length(‘538 Patent, claim 1),
each member sequence having a 5' end and a 3' end (‘538 Patent, claim 1);
(ii) each member sequence binds to the same genomic sequence of interest,
wherein the 5' end and the 3' end of each member sequence are each at least 50 base pairs away from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements (‘538 Patent, claim 1); and
(iii) the GC content of the pool of TACS is between 19% and 80% (‘538 Patent, claim 1), as determined by calculating the GC content of each member within the pool of TACS.
The claims of the ‘538 patent largely overlap with the instant claim 1. While the ‘538 patent discloses TArget Capture Sequences (TACS), it does not specifically claim TACS member sequence binds to the same genomic sequence of interest but has different start and/or stop positions that are staggered.
Teer teaches a target enrichment scheme (MGS) for massively parallel sequencing using tiled probes, wherein the tiled probes bind to the same genomic sequence and have different start/stop positions, within each region of interest, the probes are staggered every 5-11 bases. (page 1429, right-hand col, para 3, "MGS array design").
Therefore, it would have been obvious for one of ordinary skill in the art to use tiled probes design with staggered start/stop positions as taught by Teer while preparing the TArget Capture Sequences in '538 patent, because both references are in the overlapping field of molecular biology assays, specifically target enrichment via hybridization. The use of tiled probe design in preparing '538 patent's TArget Capture Sequences represents a predictable use of prior art elements according to known methods to yield predictable results (see MPEP §2143).
Therefore, instant claim1 is obvious over claims 1 and 8 of the '538 patent, in view of Teer. Instant claims 3, 5 and 11 are obvious over claims 1, 3 and 13-18 of the '538 patent, in view of Teer.
Claims 1, 3 and 5 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-2 and 6-7 of U.S. Patent No. 12421551B2 in view of Teer (Teer et al; ; NISC Comparative Sequencing Program; Margulies EH, Green ED, Collins FS, Mullikin JC, Biesecker LG. Systematic comparison of three genomic enrichment methods for massively parallel DNA sequencing. Genome Res. 2010 Oct;20(10):1420-31. doi: 10.1101/gr.106716.110. Epub 2010 Sep 1. PMID: 20810667; PMCID: PMC2945191).
Instant claim 1 recites:
A kit comprising a container comprising a pool of TArget Capture Sequences (TACS),
wherein the pool of TACS is fixed to a solid support (‘551 Patent, claim 2),
wherein the pool of TACS comprises a plurality of TACS families (‘551 Patent, claim 1),
wherein each TACS family comprises a plurality of member sequences (‘551 Patent, claim 1),
wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions,
wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs, and
further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length,
each member sequence having a 5' end and a 3' end;
(ii) each member sequence binds to the same genomic sequence of interest,
wherein the 5' end and the 3' end of each member sequence are each at least 50 base pairs away from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements (‘551 Patent, claim 1); and
(iii) the GC content of the pool of TACS is between 19% and 80% (‘551 Patent, claim 6), as determined by calculating the GC content of each member within the pool of TACS.
The claims of the ‘551 patent largely overlap with the instant claim 1. While the ‘551 patent discloses TArget Capture Sequences (TACS), it does not specifically claim TACS member sequence having length of 100-500 base pairs, and binds to the same genomic sequence of interest but has different start and/or stop positions that are staggered.
Teer teaches a target enrichment scheme (MGS) for massively parallel sequencing using 104 base pair tiled probes, wherein the tiled probes bind to the same genomic sequence and have different start/stop positions, within each region of interest, the probes are staggered every 5-11 bases. (page 1429, right-hand col, para 3, "MGS array design").
Therefore, it would have been obvious for one of ordinary skill in the art to use tiled probes design with staggered start/stop positions as taught by Teer while preparing the TArget Capture Sequences in '551 patent, because both references are in the overlapping field of molecular biology assays, specifically target enrichment via hybridization. The use of tiled probe design in preparing '551 patent's TArget Capture Sequences represents a predictable use of prior art elements according to known methods to yield predictable results (see MPEP §2143).
Therefore, instant claim 1 is obvious over claims 1-2 and 6 of the '551 patent, in view of Teer. Instant claims 3 and 5 are obvious over claims 1 and 7 of the '551 patent, in view of Teer.
Claims 1, 3, 5 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-2, 7-12 of U.S. Patent No. 12480160B2 in view of Teer (Teer et al; ; NISC Comparative Sequencing Program; Margulies EH, Green ED, Collins FS, Mullikin JC, Biesecker LG. Systematic comparison of three genomic enrichment methods for massively parallel DNA sequencing. Genome Res. 2010 Oct;20(10):1420-31. doi: 10.1101/gr.106716.110. Epub 2010 Sep 1. PMID: 20810667; PMCID: PMC2945191).
Instant claim 1 recites:
A kit comprising a container comprising a pool of TArget Capture Sequences (TACS),
wherein the pool of TACS is fixed to a solid support (‘160 Patent, claim 2) ,
wherein the pool of TACS comprises a plurality of TACS families (‘160 Patent, claim 1),
wherein each TACS family comprises a plurality of member sequences (‘160 Patent, claim 1),
wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions,
wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs, and
further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length (‘160 Patent, claim 1),
each member sequence having a 5' end and a 3' end (‘160 Patent, claim 1);
(ii) each member sequence binds to the same genomic sequence of interest,
wherein the 5' end and the 3' end of each member sequence are each at least 50 base pairs away from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements (‘160 Patent, claim 1); and
(iii) the GC content of the pool of TACS is between 19% and 80% (‘160 Patent, claim 1), as determined by calculating the GC content of each member within the pool of TACS.
The claims of the ‘160 patent largely overlap with the instant claim 1. While the ‘160 patent discloses TArget Capture Sequences (TACS), it does not specifically claim TACS member sequence binds to the same genomic sequence of interest but has different start and/or stop positions that are staggered.
Teer teaches a target enrichment scheme (MGS) for massively parallel sequencing using tiled probes, wherein the tiled probes bind to the same genomic sequence and have different start/stop positions, within each region of interest, the probes are staggered every 5-11 bases. (page 1429, right-hand col, para 3, "MGS array design").
Therefore, it would have been obvious for one of ordinary skill in the art to use tiled probes design with staggered start/stop positions as taught by Teer while preparing the TArget Capture Sequences in '160 patent, because both references are in the overlapping field of molecular biology assays, specifically target enrichment via hybridization. The use of tiled probe design in preparing '160 patent's TArget Capture Sequences represents a predictable use of prior art elements according to known methods to yield predictable results (see MPEP §2143).
Therefore, instant claim1 is obvious over claims 1-2 of the ‘160 patent, in view of Teer. Instant claims 3 and 5 are obvious over claims 1 and 7-12 of the ‘160 patent, in view of Teer.
Claims 1-3, 5 and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 4, 7, 9, 13 and 18 of U.S. Patent No. 11879157B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over claims of the '157 patent.
Instant claim 1 recites:
A kit comprising a container comprising a pool of TArget Capture Sequences (TACS),
wherein the pool of TACS is fixed to a solid support (‘157 patent, claim 7),
wherein the pool of TACS comprises a plurality of TACS families (‘157 patent, claim 18),
wherein each TACS family comprises a plurality of member sequences (‘157 patent, claims 2, 18),
wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions (‘157 patent, claims 2, 18),
wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs (‘157 patent, claim 4), and
further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length (‘157 patent, claims 2, 18),
each member sequence having a 5' end and a 3' end (‘157 patent, claims 2, 18);
(ii) each member sequence binds to the same genomic sequence of interest,
wherein the 5' end and the 3' end of each member sequence are each at least 50 base pairs away from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements (‘157 patent, claims 2, 18); and
(iii) the GC content of the pool of TACS is between 19% and 80% (‘157 patent, claims 2, 18), as determined by calculating the GC content of each member within the pool of TACS.
Therefore, instant claim 1 is obvious over claims 2, 7, 18 of the '157 patent. Instant claims 2; 3, 5; 8 are obvious over claims 4; 9; 13 of the '157 patent.
Claims 1-3, 5, 8 and 12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, 7 of U.S. Patent No. 11649500B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over claims of the '500 patent.
Instant claim 1 recites:
A kit comprising a container comprising a pool of TArget Capture Sequences (TACS),
wherein the pool of TACS is fixed to a solid support (‘500 Patent, claim 7) ,
wherein the pool of TACS comprises a plurality of TACS families (‘500 Patent, claim 1),
wherein each TACS family comprises a plurality of member sequences(‘500 Patent, claim 1),
wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions(‘500 Patent, claim 1),
wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs (‘500 Patent, claim 1), and
further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length (‘500 Patent, claim 1),
each member sequence having a 5' end and a 3' end (‘500 Patent, claim 1);
(ii) each member sequence binds to the same genomic sequence of interest,
wherein the 5' end and the 3' end of each member sequence are each at least 50 base pairs away from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements (‘500 Patent, claim 1); and
(iii) the GC content of the pool of TACS is between 19% and 80% (‘500 Patent, claim 1), as determined by calculating the GC content of each member within the pool of TACS.
Therefore, instant claims 1 and 2 are anticipated by claims 1 and 7 of the '500 patent. Instant claims 3, 5; 8; 12 are anticipated by claims 5; 4; 2 of the '500 patent, respectively.
Claims 1-3 and 5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 4 of U.S. Patent No. 12435374B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over claims of the '374 patent.
Instant claim 1 recites:
A kit comprising a container comprising a pool of TArget Capture Sequences (TACS),
wherein the pool of TACS is fixed to a solid support (‘374 Patent, claim 4) ,
wherein the pool of TACS comprises a plurality of TACS families (‘374 Patent, claim 1),
wherein each TACS family comprises a plurality of member sequences (‘374 Patent, claim 1),
wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions (‘374 Patent, claim 1),
wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs (‘374 Patent, claim 1), and
further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length (‘374 Patent, claim 1),
each member sequence having a 5' end and a 3' end (‘374 Patent, claim 1);
(ii) each member sequence binds to the same genomic sequence of interest,
wherein the 5' end and the 3' end of each member sequence are each at least 50 base pairs away from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements (‘374 Patent, claim 1); and
(iii) the GC content of the pool of TACS is between 19% and 80% (‘374 Patent, claim 1), as determined by calculating the GC content of each member within the pool of TACS.
Therefore, instant claims 1 and 2 are anticipated by claims 1 and 4 of the '374 patent. Instant claims 3 and 5 are anticipated by claim 2 of the '374 patent, respectively.
Claims 1-3 and 5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 and 5 of U.S. Patent No. 12270069B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are obvious over claims of the '069 patent.
Instant claim 1 recites:
A kit comprising a container comprising a pool of TArget Capture Sequences (TACS),
wherein the pool of TACS is fixed to a solid support (‘069 Patent, claim 5),
wherein the pool of TACS comprises a plurality of TACS families (‘069 Patent, claim 1),
wherein each TACS family comprises a plurality of member sequences (‘069 Patent, claim 1),
wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions (‘069 Patent, claim 1),
wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs (‘069 Patent, claim 1), and
further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length (‘069 Patent, claim 1),
each member sequence having a 5' end and a 3' end (‘069 Patent, claim 1);
(ii) each member sequence binds to the same genomic sequence of interest (‘069 Patent, claim 1),
wherein the 5' end and the 3' end of each member sequence are each at least 50 base pairs away from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements (‘069 Patent, claim 1); and
(iii) the GC content of the pool of TACS is between 19% and 80% (‘069 Patent, claim 1), as determined by calculating the GC content of each member within the pool of TACS.
Therefore, instant claims 1-2 are anticipated by claims 1 and 5 of the '069 patent. Instant claims 3; 5 are anticipated by claims 3; 2 of the '069 patent, respectively.
Claims 1-3 and 5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 41-42, 44-47 and 52 of copending Application No. 18/398,421 ('421 application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims (Amended claims filed on 12/28/2023) of the '421 application.
Instant claim 1 recites:
A kit comprising a container comprising a pool of TArget Capture Sequences (TACS),
wherein the pool of TACS is fixed to a solid support (‘421 Application, claim 44),
wherein the pool of TACS comprises a plurality of TACS families (‘421 Application, claim 41, 52),
wherein each TACS family comprises a plurality of member sequences (‘421 Application, claim 41, 52),
wherein each member sequence binds to the same genomic sequence of interest but has different start and/or stop positions (‘421 Application, claim 42, 52),
wherein the start and/or stop positions for the member sequences within a TACS family, with respect to a reference coordinate system for the genomic sequence of interest are staggered by 5-10 base pairs (‘421 Application, claim 47), and
further wherein:
(i) each member sequence within each TACS family is between 100-500 base pairs in length (‘421 Application, claim 41, 52),
each member sequence having a 5' end and a 3' end (‘421 Application, claim 41, 52);
(ii) each member sequence binds to the same genomic sequence of interest,
wherein the 5' end and the 3' end of each member sequence are each at least 50 base pairs away from regions harboring Copy Number Variations (CNVs), Segmental duplications or repetitive DNA elements (‘421 Application, claim 41, 52); and
(iii) the GC content of the pool of TACS is between 19% and 80% (‘421 Application, claim 41, 52), as determined by calculating the GC content of each member within the pool of TACS.
Therefore, instant claim 1 is anticipated by claims 41-42, 44, 52 of the '421 application. Instant claims 2; 3; 5 are anticipated by claims 47; 45; 46 of the '421 application, respectively.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Prior Art
Below are relevant prior art not used in rejection but pertinent to the claims or disclosure.
Staggered tiled probes for hybridization capture are well-known in the art and commercially before 2017.
See Tewhey et al. Enrichment of sequencing targets from the human genome by solution hybridization. Genome Biol. 2009;10(10):R116. doi: 10.1186/gb-2009-10-10-r116. Epub 2009 Oct 16. PMID: 19835619; PMCID: PMC2784331.; see FIG. 2 ;
See Simon MD. Capture hybridization analysis of RNA targets (CHART). Curr Protoc Mol Biol. 2013;Chapter 21:Unit 21.25.. doi: 10.1002/0471142727.mb2125s101. PMID: 23288463. (see page 4, step 11, “The tiled nucleotides are 20-mers that are complementary to the target RNA and overlap each other by 10 nt (e.g., Oligo 1 targets nucleotides 1 to 20; Oligo 2 targets nucleotides 10 to 30; Oligo 3 targets nucleotides 20 to 40; etc.)”);
See Samorodnitsky et al., Evaluation of Hybridization Capture Versus Amplicon-Based Methods for Whole-Exome Sequencing. Hum Mutat. 2015 Sep;36(9):903-14. doi: 10.1002/humu.22825. Epub 2015 Jul 15. PMID: 26110913; PMCID: PMC4832303. (see Fig. 1, SeqCap, commercialized by Roche);
See Lemmon et al. Anchored hybrid enrichment for massively high-throughput phylogenomics. Syst Biol. 2012 Oct;61(5):727-44. doi: 10.1093/sysbio/sys049. Epub 2012 May 17. PMID: 22605266. (see Page 729, left-hand col, lines 28-31“Probes were tiled across each of the probe regions. For each of the five model species, a new 120-bp probe began every 5bp”).
Conclusion
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.
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/TIAN NMN YU/Examiner , Art Unit 1681 /AARON A PRIEST/Primary Examiner, Art Unit 1681
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