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 .
Claim Status
Applicant’s claims filed 6/4/2024 has been entered. Claims 19-20 are cancelled. Claims 1-18 and 21-22 are pending and examined herein.
Priority
This application is a CON of 18/131,634 (filed 04/06/2023), which is a CON of 16/179,523 (filed 11/02/2018; ABN), which is a CIP of 16/018,926 (filed 06/26/2018; ABN), and has PRO 62/672,217 (filed 05/16/2018) and PRO 62/526,091 (filed 06/28/2017). Accordingly, the EFD is 06/28/2017.
Claim Objections
Claim 15 is objected to because of the following informalities: Claim 15 appears to have a typographical error where “DBA” should read “DNA”. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-18 and 21-22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “A method for enriching a sample, the method comprising: obtaining a biological sample comprising a target nucleic acid” followed by “enriching for the target nucleic acid directly within the sample” and “introducing the particle complex to the sample to bind to the target nucleic acid”. It is unclear whether the “biological sample” of line 2 is the same as the “sample” of lines 1, 3, and/or 6. It is unclear whether the “sample” of line 1 comprises a sample other than a biological sample. It is further unclear whether the “enriching” step is applied to the “sample” of line 1 (comprising more than a biological sample) or the “biological sample” of line 2, or if they are the same sample. Therefore, the claim is indefinite.
Claims 2, 6, 16-17, and 21-22 recite “the sample” and directly or indirectly depend from claim 1. It is unclear whether “the sample” is limited to a “biological sample” or if it comprises more components.
Claim 2 recites the limitation “the sample comprises bodily fluid”. It unclear whether the “sample” refers to “biological sample” or a “sample” comprising other components.
Claim 7 depends from claim 2 and recites “the bodily fluid sample”. It is unclear whether the “sample” of claim 1 comprises a “biological sample” that is different or the same as “the bodily fluid sample”. It is further unclear whether the “biological sample” is limited to “bodily fluid”.
Claim 15 recites the limitation "bodily fluid sample" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 15, depending from claim 2, recites the limitation "bodily fluid sample" in line 2. It is unclear whether the “bodily fluid sample” is refers to “biological sample” or “sample” comprising other components.
Claim 17, depending from claim 1, recites the limitation "sample” in line 2. It is unclear whether the “sample” is limited to a “biological sample” or “sample” comprising other components.
Claim 17, depending from claim 1, recites the limitation "sample” in line 2. It is unclear whether the “sample” is limited to a “biological sample” or “sample” comprising other components.
Claim 17 recites the limitation "The method of claim 15, wherein the detection step" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 21, depending from claim 1, recites the limitation "sample” in line 2. It is unclear whether the “sample” is limited to a “biological sample” or “sample” comprising other components. Claim 22 recites “the sample” and directly or indirectly depend from claim and is similarly rejected for indefiniteness.
Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
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 1-18 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Cann (US20160017396A1, published 1/21/2016; Cite No. 14 in the 17 page IDS filed 7/30/2024), in view of Gourguechon et al. (WO2016100955A2; published 6/23/2016; Cite No. 34 in the 17 page IDS filed 7/30/2024).
Cann’s disclosure is directed to enriching polynucleotides using CRISPR-Cas systems and teaches a variety of methods for enriching target nucleic acids (entire document).
Regarding claim 1, Cann teaches a method for enriching a target nucleic acid in a population of cell free DNA (cfDNA) from a subject's plasma or serum and providing a target-specific crRNA and a Cas protein variant and contacting the target nucleic acid with the endonuclease system to form a complex (see claim 22; paras 0023 and 0157).
However, Cann does not specifically teach introducing the Cas endonuclease to the biological sample directly.
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 (abstract).
Regarding claim 1, Gourguechon teaches the method comprising obtaining a biological sample comprising a target nucleic acid, enriching for the target nucleic acid directly within the sample by contacting the sample with a plurality of CRISPR/Cas system protein-gRNA particle complexes that bind the target nucleic acids (claims 51-54; Example 9).
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 target nucleic acids in biological samples by introducing the CRISPR-gRNA particle complexes directly to the sample to bind the target nucleic acid, as described by Gourguechon because it would have amounted to a simple combination of prior art elements according to known methods to yield predictable results. One would have had a reasonable expectation of success because Cann and Gourguechon are directed to 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.
Regarding claim 2, Cann teaches samples comprising bodily fluids of plasma and serum (claim 22) and maternal plasma and blood (paras 0164 and 0168).
Regarding claims 3-4, Cann teaches particles comprising streptavidin coated magnetically responsive beads (paras 0009-0014, 0058; Fig. 14; and Example 7).
Regarding claim 5, Cann teaches biotinylated guide RNA (para 0009-0014, 0019; Examples 1, 3, and 7).
Regarding claim 6, 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 para 0181-0182).
Regarding claim 7, Cann teaches bodily fluids comprising plasma and serum (claim 22) and maternal plasma and blood (paras 0164 and 0168) and Gourguechon further teaches bodily fluid samples comprising whole blood, plasma, serum, tears, saliva, mucous, cerebrospinal fluid, feces or urine (claims 51-54).
Regarding claim 8, Cann teaches the target nucleic acid comprising cell free DNA (cfDNA) (claim 22; paras 0023 and 0157). Cann further teach methods of enriching and/or detecting target nucleic acids in circulating tumor DNA (ctDNA) from cancer patients (paras 0156 and 0165).
Regarding claim 9, Gourguechon teaches that the target nucleic acid is obtained from the genome of a pathogen (para 0086 and 0105).
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 (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 (paras 0138, 0155 and 0167; and 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 (para 0156 and 0167) to obtaining sequence reads (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 (para 0165).
Regarding claim 15, 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).
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 21, Gourguechon teaches using the Cas endonuclease of the particle complex within the sample to cut the target nucleic acid (claims 1, 54; paras 0010, 0014-0019).
Regarding claim 22, the method made obvious by Cann and Gourguechon would
inherently result in the claimed limitation because it made obvious the claimed method
steps and materials recited in the instant claim.
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.
Double Patenting
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 1-18 and 21-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3-7, 9-14, and 16-21 of copending Application No. 18/131,634). Although the claims at issue are not identical, they are not patentably distinct from each other because there is significant overlap in the claims.
Claims 1, 3-7, 9-14, and 16-21 of the ‘634 application encompass a method of enriching a sample, the method comprising: obtaining a bodily fluid sample comprising a target nucleic acid; binding Cas endonuclease (which encompasses catalytically active and inactive) and guide RNA that targets the target nucleic acid to a particle to form a particle complex; digesting unprotected nucleic acids with an exonuclease; isolating the target nucleic acid; and introducing the particle complex to the sample to bind to the target nucleic acid. Claims 1, 3-7, 9-14, and 16-21 of the ‘634 application further teach that the bodily fluid sample comprises 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, that the target nucleic acid comprises cDNA, cfDNA, or ctDNA, and that the target nucleic acid is present at no more than about 0.01% of cell-free DNA in the bodily fluid sample. Claims 1, 3-7, 9-14, and 16-21 of the '634 application further teach detecting tumor mutations from the sample, amplifying the target nucleic acid, analyzing sequence reads, and applying magnetic fields to separate the target nucleic acids from the particle.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-18 and 21-22 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. 18/128,328, in view of Cann (US20160017396A1, published 1/21/2016; Cite No. 14 in the 17 page IDS filed 7/30/2024) and Gourguechon et al. (WO2016100955A2; published 6/23/2016; Cite No. 34 in the 17 page IDS filed 7/30/2024).
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; and introducing the particle complex to the sample to bind to the target nucleic acid. Claims 1-5, 7-11, and 13-20 of the ‘328 application teach digesting unbound nucleic acids with exonucleases, using magnetic particles, and isolating target nucleic acids by applying a magnetic field to separate the target nucleic acid from the particle. 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. Claims 1-5, 7-11, and 13-20 of the ‘328 application further teach that the target nucleic acid comprises cDNA, cfDNA, or ctDNA, and is present at no more than about 0.01% of cell-free DNA in the bodily fluid sample. Claims 1-5, 7-11, and 13-20 of the ‘328 application teach detecting the target nucleic acid in the sample comprising gel electrophoresis, amplifying the target nucleic acid sequence, sequencing the target nucleic acid to obtain sequence reads, and analyzing the sequence reads to identify one or more variants in the biological sample, wherein the variant comprises a mutation specific to a tumor.
The copending claims do not teach that the guide RNA is biotinylated (claim 5) and further do not teach that the target nucleic acid is from a genome of pathogen (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 1-18 and 21-22 are provisionally 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, published 1/21/2016; Cite No. 14 in the 17 page IDS filed 7/30/2024) and Gourguechon et al. (WO2016100955A2; published 6/23/2016; Cite No. 34 in the 17 page IDS filed 7/30/2024).
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; and introducing the particle complex to the sample to bind to the target nucleic acid. Claims 1-20 of the ‘649 application teach digesting unbound nucleic acids with exonucleases, using magnetic particles, and isolating target nucleic acids by applying a magnetic field to separate the target nucleic acid from the particle. 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. Claims 1-20 of the ‘649 application further teach that the target nucleic acid comprises cDNA, cfDNA, or ctDNA, and is present at no more than about 0.01% of cell-free DNA in the bodily fluid sample. Claims 1-20 of the ‘649 application teach detecting the target nucleic acid in the sample comprising gel electrophoresis, amplifying the target nucleic acid sequence, sequencing the target nucleic acid to obtain sequence reads, and analyzing the sequence reads to identify one or more variants in the biological sample, wherein the variant comprises a mutation specific to a tumor.
The copending claims do not teach that the guide RNA is biotinylated (claim 5) and further do not teach that the target nucleic acid is from a genome of pathogen (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 1-18 and 21-22 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, published 1/21/2016; Cite No. 14 in the 17 page IDS filed 7/30/2024) and Gourguechon et al. (WO2016100955A2; published 6/23/2016; Cite No. 34 in the 17 page IDS filed 7/30/2024).
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. 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. Claims 1-12 and 14-19 of the ‘333 application further teach that the target nucleic acid comprises cDNA, cfDNA, or ctDNA, 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. Claims 1-12 and 14-19 of the ‘333 application teach amplifying the target nucleic acid sequence.
The copending claims do not teach that using magnetic beads (claims 3-4), the guide RNA is biotinylated (claim 5), that the target nucleic acid is from a genome of pathogen (claim 9), isolating target nucleic acids by applying a magnetic field to separate the target nucleic acid from the particle (claim 11), sequencing the target nucleic acid to obtain sequence reads (claim 12), and analyzing the sequence reads to identify one or more variants in the biological sample (claim 13).
However, the teachings of Cann and Gourguechon are discussed above. In particular, the teachings of Cann regarding using magnetic beads (claims 3-4), that the guide RNA is biotinylated (claim 5), that the target nucleic acid is from a genome of pathogen (claim 9), isolating target nucleic acids by applying a magnetic field to separate the target nucleic acid from the particle (claim 11), sequencing the target nucleic acid to obtain sequence reads (claim 12), and analyzing the sequence reads to identify one or more variants in the biological sample (claim 13) and Gourguechon regarding the target nucleic acid being from a genome of a pathogen (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.
Conclusion
No claim is allowed.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636
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