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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 11/10/2025 has been entered.
Claim Status
Applicant’s amendment filed 11/10/2025 has been entered. Claims 2, 8, and 15 are cancelled. Claims 1, 3-7, 9-14, and 16-21 are pending. Claims 1, 6-7, 10-11, 13, 16-19 are amended. Claim 21 is new. Claims 1, 3-7, 9-14, and 16-21 are examined herein.
Applicant amended claims 1 and 19 to require the limitations of “bodily fluid” for the sample comprising a target nucleic acid from canceled claim 2, which was rejected in the Final Office action mailed 5/2/2025.
Applicant further amended claim 1 to require previously unexamined limitations of “two or more” Cas endonucleases binding to the “ends of the” target nucleic acid to a particle to form “two or more” particle “complexes” which are introduced directly to the bodily fluid sample. Rejection of claim 1 (and dependent claims 1-5, 7-8, 10-14, and 16-20) under 35 U.S.C. 102(a)(1) as being anticipated by Cann (US20160017396A1, published January 21, 2016) is withdrawn in view of Applicant’s amendment to claim 1 (and to cancel claims 2 and 8).
Applicant cancelled claim 8 (“the target nucleic acid comprises cDNA, cfDNA, or ctDNA”) to overcome a 112(d) rejection for failing to further limit the subject matter of the claim from which it depends. The 112(d) rejection of record is withdrawn.
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.
Claim Rejections - 35 USC § 103 – new 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.
Claims 1, 3-5, 7, 10-14, and 16-21 are rejected under 35 U.S.C. 103 as being
unpatentable over Cann (US20160017396A1, published January 21, 2016, of
record). This rejection is modified as necessitated by Applicant’s amendment to claim 1 to require the limitation of “bodily fluid” for the sample comprising a target nucleic acid from canceled claim 2 and to require previously unexamined limitations of “two or more” Cas endonucleases being introduced directly to bodily fluid sample to bind to the “ends of the” target DNA and further to cancel claim 8.
Regarding claims 1 and 7, Cann teaches using CRISPR-Cas systems to form a complex with the target nucleic acids, separating the complex, and thereby enriching the target nucleic acid (see abstract, para 0006, and Example 1). Cann teaches bodily fluid samples comprising plasma and serum (see claim 22) and maternal plasma and blood (see paras 0164 and 0168). Cann further teaches methods of enriching target nucleic acids comprising obtaining the target DNA from a subject’s plasma or serum (see claim 22). Claim 1 recites “the method comprising”, which allows additional steps to achieve enriching a sample. Cann teaches isolating target nucleic acids before introducing Cas endonuclease (para 0164) and after introducing Cas endonuclease (claim 1, para 0006, and Example 1). Cann further teaches that the guide RNA is biotinylated (particle; see Fig. 1) or the Cas protein is labeled with a capture tag (see para 009 and see Example 1). Cann teaches that “a protein” includes a mixture of “two or more proteins” and teaches methods of enriching a target nucleic acid including providing a population of Cas9 proteins programmed with a set of crRNAs (see paras 0020, 0026, 0033, 0052-0057, 0093, 0213, and 0234). Cann further teaches that Cas9 protein remains on the target nucleic acid binding site following DNA cleavage, therefore, Cas9 proteins binding and cleaving target nucleic acids can then be bound to the “ends” of the target nucleic acid upon cleavage (see paras 0138 and 0217-0218; Example 1).
However, Cann does not specifically teach using the enrichment methods
wherein the target nucleic acid is present at no more than about 0.01% of cell-free DNA
in the bodily fluid.
Cann teaches more sensitive methods of enriching and detecting single nucleotide variants (SNV), including point mutations and SNPs, present in cell free DNA sample in the 0.01% to 0.1% frequency range (see para 0166). Cann teaches the target nucleic acid comprising cell free DNA (cfDNA) (see claim 22 and para 0157). Cann further teach methods of enriching and/or detecting target nucleic acids in circulating tumor DNA (ctDNA) from cancer patients (see paras 0156 and 0165).
It would have been obvious to one of ordinary skill in the art before the effective
filing date of the claimed invention to have modified the Cann’s method of enriching
nucleic acids with Cas endonucleases specifically to target nucleic acids present in cell free DNA samples at 0.01% as also taught in Cann because it would have amounted to a simple combination of prior art elements according to known methods to yield predictable results. Cann teaches methods of enriching and detecting target nucleic acids using Cas endonucleases to bind the target nucleic acid and further teaches more sensitive methods of enriching and detecting point mutations and SNPs present in cell free DNA sample in the 0.01% to 0.1% frequency range (see para 0166). Cann further teaches particles bound to the guide RNA or the two or more Cas9 proteins (particle; see Fig. 1; para 009; and Example 1) programmed with a set of guide RNAs (see paras 0020, 0026, 0033, 0052-0057, 0093, 0213, and 0234) to form two or more particles complexes that target the nucleic acid in a sample. One would have had a reasonable expectation of success because Cann teaches several compositions and different uses of Cas endonucleases to bind target nucleic acids in samples collected from subjects. Thus, the claimed invention as a whole is prima facie obvious.
Regarding claims 3 and 4, Cann teaches that the particle is magnetic streptavidin
beads (see paras 0038 and Example 7).
Regarding claim 5, Cann teaches that the guide RNA is biotinylated (see Fig. 1).
Regarding claim 10, Cann teaches isolating the target nucleic acid from the CRISPR-Cas and gRNA complex and further teaches isolating the target nucleic acid
from the polynucleotide population (see para 0122 and 0152).
Regarding claim 11, Cann teaches separating the target nucleic acid from the
particle by applying a magnetic field to the particle complex, then treating the complex
with proteases or a detergent washing step (see paras 0138, 0155 and 0167; claim 22).
Regarding claims 12-14, Cann teaches methods for sequencing target DNA sequences from ctDNA isolated from cancer patients, wherein the variant comprises a mutation specific to a tumor (see para 0156 and 0167) to obtaining sequence reads
(see para 204). Cann further teaches analyzing the sequence reads to identify variants
to monitor tumor progression and/or test a tumor patient’s response to targeted drug
treatments (see para 0165).
Regarding claim 16, Cann teaches detection of target nucleic acids where Cas9
complexes with fragmented target BRAF DNA are isolated using streptavidin coated
magnetically responsive beads (see para 0058, Fig. 14, and Example 7).
Regarding claim 17, Cann teaches detecting the presence of target nucleic acids
by applying a magnetic field to separate the particle complex from the sample (see
paras 0166-0167).
Regarding claim 18, Cann teaches methods for detecting target nucleic acids
and further amplifying the target nucleic acid sequences (see paras 0024 and 0158).
Regarding claim 19, Cann teaches a method for detecting a variant in a nucleic
acid sample, the method comprising obtaining cfDNA from a subject's plasma or serum
from a subject suspected of having a variant in a target nucleic acid (see claims 22 and
23 and para 0028. Cann further teaches enriching the sample using CRISPR-Cas
systems to form a complex with the target nucleic acids and separating the complex
(see abstract and para 0006). Cann teaches more sensitive methods of enriching and
detecting single nucleotide variants (SNV), including point mutations and SNPs, present in cell free DNA sample in the 0.01% to 0.1% frequency range (see para 0166). Cann teaches that “a protein” includes a mixture of “two or more proteins” and teaches methods of enriching a target nucleic acid including providing a population of Cas9 proteins programmed with a set of crRNAs (see paras 0020, 0026, 0033, 0052-0057, 0093, 0213, and 0234). Cann further teaches that Cas9 protein remains on the target nucleic acid binding site following DNA cleavage, therefore, Cas9 proteins binding and cleaving target nucleic acids can then be bound to the “ends” of the target nucleic acid upon cleavage (see paras 0138 and 0217-0218; Example 1).
Regarding claim 20, Cann further teaches detecting the variant in the target
nucleic acid sample with gel electrophoresis (see para 0261).
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Claims 6, 9, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Cann (US20160017396A1, published January 21, 2016) as applied to claims 1, 3-5, 7, 10-14, and 16-20 above, and further in view of Gourguechon
(WO2016100955A2; published June 23, 2016; as cited as #34 in the 17 page IDS
filed on August 9, 2024).
The teachings of Cann are applied to claims 6 and 9 as they are applied to claims 1, 3-5, 7, 10-14, and 16-20 under U.S.C. §103 above.
However, Cann does not teach introducing an exonuclease to the bodily fluid sample to digest unbound nucleic acid (claims 6 and 21). Cann further does not teach that the target nucleic acid is from a genome of a pathogen (claim 9).
Gourguechon's disclosure is directed to methods and compositions for depleting targeted nucleic acid sequences from a sample, enriching for sequences of interest from a sample, and/or partitioning of sequences from a sample using CRISPR-Cas system protein-gRNA complexes (see abstract and para 0010). Gourguechon teaches embodiments with catalytically active Cas9 endonuclease (see para 0160).
Regarding claims 6 and 21, Gourguechon teaches a method of enriching a sample by contacting target nucleic acids with a plurality of CRISPR-Cas system protein-gRNA complexes and treating the sample with exonucleases to enrich the bound nucleic acids (see paras 0181-0182).
Regarding claim 9, Gourguechon teaches a method of enriching a sample wherein the target nucleic acid is obtained from the genome of a pathogen (see paras 0086 and 0105).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the methods of enriching and detecting target nucleic acids disclosed by Cann with introducing exonucleases described by Gourguechon because it would have amounted to a simple combination of prior art elements according to known methods to yield predictable results. Gourguechon teaches enriching for sequences from a sample by treating the sample with exonucleases, as discussed above. One would have been motivated to combine the methods of Cann and Gourguechon to provide improved methods of enriching and detecting tumor mutations in cancer patients with increased sensitivity by digesting and removing unwanted nucleic acids. It would have been further obvious to have applied the Cann’s methods to enrich and detect a target nucleic acid from a genome of a pathogen instead of tumor mutations or other nucleic acid variants, as described by Cann, as it is a simple substitution of known DNA elements for another that would obtain predictable results. The ordinary artisan would have had a reasonable expectation of success because both Cann and Gourguechon are directed to improved methods of detecting target nucleic acids and can be used to diagnose and/or treat patients. Thus, the claimed invention as a whole is prima facie obvious.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Response to Arguments
Applicant's arguments filed 11/10/2025 have been fully considered but they are not persuasive. Applicant argues on pages 7-8 that Cann does not teach or disclose two or more Cas endonucleases or two or more Cas endonuclease guide RNA particles directly into the bodily fluid sample to bind to the ends of the target nucleic acid, nor does the Office Action allege that Cann does.
The Office disagrees. The newly added limitations for claim 1 were not previously examined. Accordingly, a new U.S.C. §103 rejection necessitated by amendment details Cann’s teachings regarding using at least two Cas proteins and binding the ends of a target nucleic acid.
Applicant argues, regarding claims 6 and 9, rejected under U.S.C. §103 as being unpatentable over Cann and further in view of Gourguechon that the cited disclosures of Gourguechon do not teach or disclose using at least two Cas proteins to bind to the ends of a target nucleic acid. Applicant further argues that the cited disclosures of Cann and Gourguechon, either individually or in combination, fail to disclose or render obvious claims 1 and 19, as amended. Therefore, claims 1 and 19 are nonobvious in view of the cited references and the dependent claims depend from independent claim 1 or claim 19, directly or indirectly, and therefore are nonobvious over the cited references for at least the same reasons.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Furthermore, as previously discussed, the newly added limitations for claims 1 and 19 were not previously examined and a new U.S.C. §103 rejection necessitated by amendment details Cann’s teachings regarding using at least two Cas proteins and binding the ends of a target nucleic acid and Gourguechon teaches treating the sample with exonucleases to enrich the bound nucleic acids (see para 0181-0182) and that the target nucleic acid is from a genome of a pathogen (paras 0086 and 0105).
Double Patenting – withdrawn
Provisionally rejection of claims 1-14 and 16-20 on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 14-19 of copending Application No. 18/128698, in view of Cann (US20160017396A1) and Gourguechon (WO2016100955A2; published June 23, 2016; as cited as #34 in the 17 page IDS filed on August 9, 2024) is withdrawn in view of the Notice of Abandonment of the co-pending application mailed 05/04/2026.
Double Patenting – modified in view of Applicant’s amendment to claims
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, 3-7, 9-14, and 16-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-11, and 13-20 of copending Application No. 18/121,328, in view of Cann (US20160017396A1; of record) and Gourguechon (WO2016100955A2; of record).
Claims 1-5, 7-11, and 13-20 of the ‘328 application encompass a method for enriching a sample, the method comprising: obtaining a biological sample (bodily fluid) comprising a target nucleic acid; binding Cas endonuclease and guide RNA that targets the target nucleic acid to a particle to form a particle complex; introducing the particle complex to the sample to bind to the target nucleic acid and that the target nucleic acid is present at no more than about 0.01% of cell-free DNA in the bodily fluid sample (instant claims 1 and 19). Claims 1-5, 7-11, and 13-20 of the ‘328 application teach digesting unbound nucleic acids with exonucleases (instant claims 6 and 21), using magnetic particles (instant claims 3-4), and isolating target nucleic acids by applying a magnetic field to separate the target nucleic acid from the particle (instant claims 10-11). Claims 1-5, 7-11, and 13-20 of the ‘328 application further teach the bodily fluid sample comprising bile, blood, plasma, serum, sweat, saliva, urine, feces, phlegm, mucus, sputum, tears, cerebrospinal fluid, synovial fluid, pericardial fluid, lymphatic fluid, semen, vaginal secretion, products of lactation or menstruation, amniotic fluid, pleural fluid, rheum, or vomit (instant claim 7). Claims 1-5, 7-11, and 13-20 of the ‘328 application teach amplifying the target nucleic acid sequence (instant claim 17), sequencing the target nucleic acid to obtain sequence reads (instant claim 12), analyzing the sequence reads to identify one or more variants in the biological sample (instant claim 13), wherein the variant comprises a mutation specific to a tumor (instant claim 14), amplifying the target nucleic acid sequence (instant claim 17), and detecting the target nucleic acid in the sample comprising gel electrophoresis (instant claims 16 and 20).
The copending claims do not teach that the guide RNA is biotinylated (instant claim 5) and that the target nucleic acid is from a genome of pathogen (instant claim 9).
However, the teachings of Cann and Gourguechon are discussed above. In particular, the teachings of Cann regarding the guide RNA that is biotinylated and Gourguechon regarding the target nucleic acid being from a genome of a pathogen are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the method of the copending claims to include a guide RNA that is biotinylated as taught by Cann and further to apply the methods to a target nucleic acid that is a from a genome of a pathogen as taught by Gourguechon because Cann and Gourguechon also teaches methods of enriching nucleic acids with Cas endonuclease and detecting nucleic acids from bodily fluid samples.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-7, 9-14, and 16-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/385,649, in view of Cann (US20160017396A1; of record) and Gourguechon (WO2016100955A2; of record).
Claims 1-20 of the ‘649 application encompass a method for enriching a sample, the method comprising: obtaining a biological sample (bodily fluid) comprising a target nucleic acid; binding Cas endonuclease and guide RNA that targets the target nucleic acid to a particle to form a particle complex; introducing the particle complex to the sample to bind to the target nucleic acid and that the target nucleic acid is present at no more than about 0.01% of cell-free DNA in the bodily fluid sample (instant claims 1 and 19). Claims 1-20 of the ‘649 application teach digesting unbound nucleic acids with exonucleases (instant claims 6 and 21), using magnetic particles (instant claims 3-4), and isolating target nucleic acids by applying a magnetic field to separate the target nucleic acid from the particle (instant claims 10-11). Claims 1-20 of the ‘649 application further teach the bodily fluid sample comprising bile, blood, plasma, serum, sweat, saliva, urine, feces, phlegm, mucus, sputum, tears, cerebrospinal fluid, synovial fluid, pericardial fluid, lymphatic fluid, semen, vaginal secretion, products of lactation or menstruation, amniotic fluid, pleural fluid, rheum, or vomit (instant claim 7). Claims 1-20 of the ‘649 application teach amplifying the target nucleic acid sequence (instant claim 17), sequencing the target nucleic acid to obtain sequence reads (instant claim 12), analyzing the sequence reads to identify one or more variants in the biological sample (instant claim 13), wherein the variant comprises a mutation specific to a tumor (instant claim 14), amplifying the target nucleic acid sequence (instant claim 17), and detecting the target nucleic acid in the sample comprising gel electrophoresis (instant claims 16 and 20).
The copending claims do not teach that the guide RNA is biotinylated (instant claim 5) and further do not teach that the target nucleic acid is from a genome of pathogen (instant claim 9).
However, the teachings of Cann and Gourguechon are discussed above. In particular, the teachings of Cann regarding the guide RNA that is biotinylated and Gourguechon regarding the target nucleic acid being from a genome of a pathogen are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the method of the copending claims to include a guide RNA that is biotinylated as taught by Cann and further to apply the methods to a target nucleic acid that is a from a genome of a pathogen as taught by Gourguechon because Cann and Gourguechon also teaches methods of enriching nucleic acids with Cas endonuclease and detecting nucleic acids from bodily fluid samples.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-7, 9-14, and 16-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 14-19 of copending Application No. 18/514,333, in view of Cann (US20160017396A1; of record) and Gourguechon (WO2016100955A2; of record).
Claims 1-12 and 14-19 of the ‘333 application encompass a method for enriching a sample, the method comprising: obtaining a biological sample (bodily fluid) comprising a target nucleic acid; binding Cas endonuclease and guide RNA that targets the target nucleic acid to a particle to form a particle complex; introducing the particle complex to the sample to bind to the target nucleic acid; and digesting unbound nucleic acids with exonucleases (instant claims 1, 6, 16, and 21). Claims 1-12 and 14-19 of the ‘333 application further teach that the sample comprises a liquid biopsy sample and that the sample is from a patient (instant claims 1 and 7). Claims 1-12 and 14-19 of the ‘333 application further teach that the target nucleic acid includes a mutation specific to a tumor, and is present at no more than about 0.01% of cell-free DNA in the bodily fluid sample (instant claims 1, 14, and 19). Claims 1-12 and 14-19 of the ‘333 application teach amplifying the target nucleic acid sequence (instant claim 18).
The copending claims do not teach that using magnetic beads (instant claims 3-4), the guide RNA is biotinylated (instant claim 5), that the target nucleic acid is from a genome of pathogen (instant claim 9), isolating target nucleic acids by applying a magnetic field to separate the target nucleic acid from the particle (instant claims 10-11), sequencing the target nucleic acid to obtain sequence reads (instant claim 12), analyzing the sequence reads to identify one or more variants in the biological sample (instant claim 13), and detecting the target nucleic acid in the sample comprising gel electrophoresis (instant claim 20).
However, the teachings of Cann and Gourguechon are discussed above. In particular, the teachings of Cann regarding using magnetic beads (instant claims 3-4), that the guide RNA is biotinylated (instant claim 5), that the target nucleic acid is from a genome of pathogen (instant claim 9), isolating target nucleic acids by applying a magnetic field to separate the target nucleic acid from the particle (instant claim 11), sequencing the target nucleic acid to obtain sequence reads (instant claim 12), analyzing the sequence reads to identify one or more variants in the biological sample (instant claim 13), and detecting the target nucleic acid in the sample comprising gel electrophoresis (instant claim 20) and Gourguechon regarding the target nucleic acid being from a genome of a pathogen (instant claim 9) are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the method of the copending claims to include isolating steps using a guide RNA that is biotinylated, magnetic beads complexed with the guide RNA and Cas, and applying a magnetic field to separate the target nucleic acid from the particle, and further to include sequencing and analyzing steps to identify the variants in the biological sample as taught by Cann. It would have been further obvious to one of ordinary skill in the art to have modified the method of the copending claims to apply the methods to a target nucleic acid that is a from a genome of a pathogen as taught by Gourguechon because Cann and Gourguechon also teaches methods of enriching nucleic acids with Cas endonuclease and detecting nucleic acids from bodily fluid samples.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-7, 9-14, and 16-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 and 21-22 of copending Application No. 18/519,589, in view of Cann (US20160017396A1; of record).
Claims 1-18 and 21-22 of the ‘589 application encompass a method for enriching a sample, the method comprising: obtaining a biological sample (bodily fluid) comprising a target nucleic acid; binding Cas endonuclease and guide RNA that targets the target nucleic acid to a particle to form a particle complex; and introducing the particle complex to the sample to bind to the target nucleic acid, and teach that the target nucleic acid is present at no more than about 0.01% of cell-free DNA in the bodily fluid sample (instant claims 1 and 19). Claims 1-18 and 21-22 of the ‘589 application teach digesting unbound nucleic acids with exonucleases (instant claims 6 and 21), using magnetic particles (instant claims 3-4) and the guide RNA is biotinylated (instant claim 5). Claims 1-18 and 21-22 of the ‘589 application further teach the bodily fluid sample comprising bile, blood, plasma, serum, sweat, saliva, urine, feces, phlegm, mucus, sputum, tears, cerebrospinal fluid, synovial fluid, pericardial fluid, lymphatic fluid, semen, vaginal secretion, products of lactation or menstruation, amniotic fluid, pleural fluid, rheum, or vomit (instant claim 7). Claims 1-18 of the ‘589 application teach the target nucleic acid is from a genome of pathogen (instant claim 9) and isolating target nucleic acids by applying a magnetic field to separate the target nucleic acid from the particle (instant claims 10-11 and 17). Claims 1-18 of the ‘589 application teach sequencing the target nucleic acid to obtain sequence reads (instant claim 12), analyzing the sequence reads to identify one or more variants in the biological sample (instant claim 13), and that the variant comprises a mutation specific to a tumor (instant claim 14). Claims 1-18 of the ‘589 application teach the target nucleic acid is present at no more that about 0.01% of cell-free DBA in the bodily fluid sample (instant claim 15), detecting the target nucleic acid in the sample (instant claim 16) and amplifying the target nucleic acid sample (instant claim 18).
The copending claims do not teach a method of detecting a variant in a nucleic acid sample comprising obtaining a biological sample comprising nucleic acid from a patient suspected of having a variant in a target nucleic acid; enriching the sample by introducing a Cas endonuclease guide RNA particle complex directly into the sample to bind to the target nucleic acid wherein the guide RNA targets the target nucleic acid; separating the particle complex with the bound target nucleic acid from the sample; and detecting the variant in the target nucleic acid sample (instant claim 19) and that the detecting step comprises gel electrophoresis (instant claim 20).
However, the teachings of Cann are discussed above. In particular, the teachings of Cann regarding a method for detecting a variant in a nucleic acid sample, the method comprising obtaining cfDNA from a subject's plasma or serum from a subject suspected of having a variant in a target nucleic acid (instant claim 19) and detecting the variant in the target nucleic acid sample with gel electrophoresis (instant claim 20) are discussed above.
It would have been obvious to one of ordinary skill in the art to have modified the method of the copending claims to include the methods of detecting a variant in a nucleic acid sample comprising gel electrophoresis as taught by Cann because Cann also teaches methods of enriching nucleic acids with Cas endonuclease and detecting nucleic acids from bodily fluid samples.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 11/10/2025 have been fully considered but they are not persuasive. Applicant requests that the non-statutory double patenting rejections be held in abeyance until the claims are otherwise deemed allowable, at which stage Applicant will consider filing a terminal disclaimer to overcome the non-statutory double patenting rejections. However, such a response is not a proper reply to the outstanding rejection of record.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHALEDA B HASAN whose telephone number is (571)272-0239. The examiner can normally be reached IFP, Monday - Friday 7:30am-5pm.
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KHALEDA B HASAN/Examiner, Art Unit 1636
/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636
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