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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-3, 6, 7, 9, 12, 16, 17, 19, 27, 28, 49, 52, 55, 60, 63, 89 and 114, in the reply filed on 04/03/2026 is acknowledged.
Claim 121 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-3, 6, 7, 9, 12, 16, 17, 19, 27, 28, 49, 52, 55, 60, 63, 89, 114 and 121 are pending.
Claims 1-3, 6, 7, 9, 12, 16, 17, 19, 27, 28, 49, 52, 55, 60, 63, 89 and 114 are under examination on the merits.
Priority
This application 18/339,126 filed on 06/21/2023 is a CON of 371 national phase of PCTUS2021/073101 filed on 12/23/2021, and claims the benefit of provisional U.S. Patent Application No. 63/199,467, filed on 12/30/2020.
The priority date of claim 1 and its dependent claims 2-3, 6, 7, 9, 12, 16, 17, 19, 27, 28, 49, 52, 55, 60, 63, 89 and 114 is determined to be 12/30/2020, the filing date of provisional U.S. Patent Application No. 63/199,467.
Specification
The use of terms which are trade names or marks used in commerce (including IIlumina®, NovaSeq™, and Thermo Fisher Scientific® among others), has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because of the following informalities: The term "MethylMinder" in paragraph 211 appears to be a typographical error intended to be "MethylMiner". Appropriate correction is required.
Claim Interpretation
Claims 63 and 89 include the term “optionally” to describe limitations. Claim scope is not limited by claim language that makes optional but does not require specific structural features. MPEP 2111.04.
Claim Rejections - 35 USC § 112(b)
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 1-3, 6, 7, 9, 12, 16, 17, 19, 27, 28, 49, 52, 55, 60, 63, 89, and 114 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 the limitation “a procedure that affects a first nucleobase in the DNA differently from a second nucleobase in the DNA of the sample, wherein the first nucleobase is a modified or unmodified nucleobase, the second nucleobase is a modified or unmodified nucleobase different from the first nucleobase and the first nucleobase and the second nucleobase have the same base pairing specificity, thereby producing a converted sample”. The claim further recites “sequence-specifically degrading a plurality of the target sequences in the converted sample having a first epigenetic status” and “detecting the presence or absence of a target sequence having a second epigenetic status”. However, the claim does not require a different specific affect to the first and second nucleobase. Accordingly, both the first and second nucleobase could be affected in the same way, resulting in sequences containing nucleobases that are identical and cannot be specifically degraded or detected. The claims do not limit or define any structural changes necessary for the distinction of sequences having the first or second epigenetic status
Claims 2, 3, 6, 7, 9, 12, 16, 17, 19, 27, 28, 49, 52, 55, 60, 63, 89, and 114 are similarly indefinite because they directly or indirectly depend from claim 1.
Claim 114 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. Claim 114 recites the limitation “determining a likelihood that the subject has cancer”. Claim 114 depends from claim 1 which recites “a) subjecting the sample or a subsample thereof to a procedure that affects a first nucleobase in the DNA differently from a second nucleobase in the DNA of the sample --; b) sequence-specifically degrading a plurality of the target sequences ---; and c) detecting the presence or absence of a target sequence ---“. The omitted steps appear to be: active steps that determine a likelihood that the subject has cancer. Claims should clearly delineate all active steps required for performing the claimed methods.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 89 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 89 recites the limitation “wherein the first nucleobase is a modified or unmodified cytosine and the second nucleobase is a modified or unmodified cytosine”. As written, both the first and second nucleobase can be the same modified or unmodified cytosine. The claim fails to include all the limitations of the claim upon which it depends. Claim 1 requires “the second nucleobase is a modified or unmodified nucleobase different from the first nucleobase”.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 114 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106, part II.
Based upon consideration of the claims as a whole, as well as consideration of elements/steps recited in addition to the judicial exception, the present claims fail to meet the elements required for patent eligibility.
Step 1
The claimed invention is directed to the statutory category of a process.
Step 2A, Prong One
The claim is (claims are) taken to be directed to an abstract idea, a judicial exception.
Claim 114 is directed to a method comprising “determining a likelihood that the subject has cancer”. This limitation is an abstract mental process (see MPEP 2106.04(a)(2)(III)). As written, the determining step encompasses the mental step of looking at data and making mental judgements.
Step 2A, Prong Two
The exception is not integrated into a practical application of the exception. The claims do not recite any additional elements that integrate the exception into a practical application of the exception.
While claim 1, which claim 114 depends from, recites “a) subjecting the sample or a subsample thereof to a procedure that affects a first nucleobase in the DNA differently from a second nucleobase in the DNA of the sample --; b) sequence-specifically degrading a plurality of the target sequences ---; and c) detecting the presence or absence of a target sequence ---”, these are not an integration of the exception into a practical application. Instead, these elements are data gathering required to perform the method.
Step 2B
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. The claim does not add a specific limitation other than what is well-understood, routine, and conventional in the field. Steps directed to subjecting a sample to a procedure that affects a first nucleobase in the DNA differently from a second nucleobase in the DNA of the sample, sequence-specifically degrading target sequences, and detecting the presence or absence of a target sequence are techniques that are routine, conventional, and well-known in the art as demonstrated in the 102 and 103 rejections documented below.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 6, 9, 12, 28, 49, 52, 55, 60, 89, and 114 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Liu et al. (Methylation-sensitive enrichment of minor DNA alleles using a double-strand DNA-specific nuclease. 2017. Nucleic Acids Research. 45(6): 1-11).
Regarding claim 1, Liu teaches a method of methylation-sensitive enrichment of DNA alleles. Regarding a), Liu teaches performing bisulfite conversion on DNA samples (p. 2, col. 2) and converting unmethylated cytosines (a first nucleobase) to uracil, while methylated cytosines (a second nucleobase) remain as methylated cytosines (Fig. 1) , which reads on a procedure that affects a first nucleobase in the DNA differently from a second nucleobase in the DNA of the sample, the second nucleobase is a modified or unmodified nucleobase different from the first nucleobase, and the first nucleobase and the second nucleobase have the same base pairing specificity, thereby producing a converted sample.
Regarding b), Liu teaches using double-strand-specific DNA nuclease on bisulfite converted DNA to target and degrade sites that were formerly unmethylated (a first epigenetic status) (Fig. 1, p. 2, col. 2), which reads on sequence-specifically degrading a plurality of the target sequences in the converted sample having a first epigenetic status, thereby producing a treated sample.
Regarding c), Liu teaches performing downstream detection technologies to detect methylation changes in DNA with methylated cytosines (a second epigenetic status) (Abstract and Fig. 1), which reads on detecting the presence or absence of a target sequence having a second epigenetic status in the treated sample.
Regarding claim 2, Liu teaches bisulfite converted DNA with unmethylated cytosines converted to uracil (Fig. 1), i.e. target sequences with a first epigenetic status comprising a conversion product of the first nucleobase.
Regarding claim 3, Liu teaches bisulfite converted DNA with unmethylated cytosines converted to uracil (Fig. 1), i.e. target sequences with a first epigenetic status comprising a conversion product of the first nucleobase.
Regarding claim 6, Liu teaches detection methods include sequencing (Abstract and p.4, col. 1).
Regarding claim 9, Liu teaches the use of probes for sequences of Ataxia Telangiectasia Mutated gene (ATM) which is often hypermethylated in breast cancer (p. 4, col. 1). Liu teaches probes for unmethylated sequences (a first epigenetic status) (p. 4, col. 2) and further teaches plasma-circulating DNA samples from healthy donors which were unmethylated in ATM promoter (Fig. 4 legend), which reads on a first epigenetic status that is a reference epigenetic status, that is prevalent in cell-free DNA from a healthy subject .
Regarding claim 12, Liu teaches DNA with methylated cytosines (a second epigenetic status) (Abstract and Fig. 1) is found in lung tumor samples (Table 1), which reads on a second epigenetic status that is a non-reference epigenetic status, wherein non-reference epigenetic status is a status prevalent in a cancerous tissue.
Regarding claim 28, Liu teaches using double-strand-specific DNA nuclease on bisulfite converted DNA to target and degrade sites that were formerly methylated or unmethylated (Fig. 1, p. 2, col. 2), which reads contacting the converted sample with a sequence-specific nuclease.
Regarding claim 49, Liu teaches applying the method to four targets (p. 5, col. 1).
Regarding claim 52, Liu teaches applying the method to four different genes (p. 5, col. 1).
Regarding claim 55, Liu teaches downstream detection by amplifying sequences from DNA samples after bisulfite conversion and nuclease degradation (i.e. sequences in treated DNA samples) (Fig. 1 and p. 2, col. 1).
Regarding claim 60, Liu teaches the DNA sample is circulating DNA (cfDNA) obtained from donors (p. 2, col. 1-2).
Regarding claim 89, Liu teaches performing bisulfite conversion on DNA samples (p. 2, col. 2) which reads on “wherein the procedure to which the sample or a subsample thereof is subjected comprises: a) bisulfite conversion”
Regarding claim 114, Liu teaches using the method to screen for methylation in lung tumor cancer samples (TL) or normal lung samples (NL) and teaches the method detects cancer in samples (Table 1 and p. 9, col. 2), which reads on determining a likelihood that the subject has cancer.
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, 7, 16, 17, 19, 27, and 63 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Methylation-sensitive enrichment of minor DNA alleles using a double-strand DNA-specific nuclease. 2017. Nucleic Acids Research. 45(6): 1-11) in view of Mortimer et al. (WO2017181146).
The teachings of Liu as they relate to claim 1 are stated in the 102 rejection above in this office action.
Liu does not teach capturing at least one target region set from the treated sample, wherein the presence or absence of a target sequence having a second epigenetic status is detected in the at least one captured target region set (claim 7); the at least one target region set comprises a sequence-variable target region set and an epigenetic target region set (claim 16); DNA molecules corresponding to the sequence-variable target region set are captured in the treated sample with a greater capture yield than DNA molecules corresponding to the epigenetic target region set (claim 17); the at least one target region set comprises a hypermethylation variable target region set,
a hypomethylation variable target region set, and/or a fragmentation variable target region set (claim 19); or the sequence-variable target region set comprises at least one sequence that is not prevalent in cell-free DNA from a healthy subject (claim 27).
Mortimer teaches methods for analyzing cfDNA for tumor markers with mutations or changes in methylation patterns (para 10).
Regarding claim 7, Mortimer teaches enriching target sequences and regions of interest with capture probes before sequencing (paras 152, 240) and detecting features such as epigenetic signatures or modifications such as methylation (paras 124, 236), which reads on detecting the presence or absence of a target sequence having a second epigenetic status.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liu and Mortimer to arrive at the instantly claimed invention. The modification would have entailed using the capture probes of Mortimer on the nuclease treated sample of Liu to enrich target sequences having a second epigenetic status. One of skill in the art would have been motivated by the further enrichment of a small methylated allele population for analysis. Liu states that one goal of heir method is to enrich minor methylation levels (p. 8, col. 1-2) and the probes of Mortimer would have increased enrichment of target sequences and regions of interest. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 16, Mortimer teaches targeting regions such as single-nucleotide variants (sequence-variable target regions) (para 240) or epigenetic signatures (para 236). Mortimer further teaches using information regarding somatic or genetic variants in combination with epigenetic signatures (para 236).
Mortimer teaches that combined analysis of DNA and DNA modifications enhances sensitivity and specificity to the detection of cancer (para 236). It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liu and Mortimer to arrive at the instantly claimed invention. The modification would have entailed capturing both DNA with sequence variants and methylated regions with the capture method of Mortimer. One would have been motivated to capture and combine analysis of both sequence and epigenetic variants for the increased ability to detect cancer. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 17, neither Liu nor Mortimer teach DNA molecules corresponding to the sequence-variable target region set are captured in the treated sample with a greater capture yield than DNA molecules corresponding to the epigenetic target region set.
However, Mortimer teaches differential bait concentrations (para 115) and varying the concentration of probes or baits to capture more of particular nucleic acid molecules within a sample (para 198).
Thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liu and Mortimer to arrive at the instantly claimed invention. Varying the concentrations of bait as in Mortimer to capture a greater yield of sequence-variable target regions compared to epigenetic target regions would have been a matter of routine optimization to one of skill in the art. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 19, Mortimer teaches selecting regions that are differentially methylated (para 13), which reads on hypermethylation and hypomethylation variable target regions.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liu and Mortimer to arrive at the instantly claimed invention.
The modification would have entailed using the capture probes of Mortimer on the nuclease treated sample of Liu to enrich target sequences having hypermethylated or hypomethylated regions. One of skill in the art would have been motivated by the further enrichment of methylated alleles. Liu states that one goal of heir method is to enrich minor methylation levels (p. 8, col. 1-2) and the probes of Mortimer would have increased enrichment of differentially methylated target sequences and regions of interest. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 27, Mortimer teaches SNVs (sequence-variable target region) associated with cancer (para 152).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liu and Mortimer to arrive at the instantly claimed invention. The modification would have entailed selecting sequence-variable target region associated with cancer as taught by Mortimer. One would have been motivated by ability to detect mutations associated with cancer in addition to changes in methylation patterns. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 63, Liu does not teach target sequences are captured from the treated sample or ligating barcode-containing adapters.
Mortimer teaches enriching target sequences and regions of interest with capture probes before sequencing (paras 152, 240).
Mortimer teaches performing sequencing, including next generation sequencing on sequences of interest (para 153). Mortimer further teaches using molecular barcodes that tag individual cfDNA molecules derived from the subject (para 37). Mortimer teaches tags or adapters are ligated to sequences (para 105).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Liu and Mortimer to arrive at the instantly claimed invention. The modification would have entailed capture target sequences with the capture probes of Mortimer, and, further, adding the barcoded tags of Mortimer to the treated sample of Liu and performing the sequencing method of Mortimer. One would have been motivated by the ability to identify individual samples or target regions by barcode while performing sequencing.
There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
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.
(I). Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,891,653 in view of Liu et al. (Methylation-sensitive enrichment of minor DNA alleles using a double-strand DNA-specific nuclease. 2017. Nucleic Acids Research. 45(6): 1-11..
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims substantially anticipate the identified claims of this application. The additional limitations of the ‘653 claims are encompassed by the open claim language "comprising" found in the instant claims.
Regarding instant claim 1, claim 1 of the ‘653 patent requires (b) subjecting the first subsample to a procedure that affects a first nucleobase in the cfDNA differently from a second nucleobase in the cfDNA of the first subsample, wherein the first nucleobase is a modified or unmodified nucleobase, the second nucleobase is a modified or unmodified nucleobase different from the first nucleobase, the first nucleobase and the second nucleobase have the same base pairing specificity, and the first nucleobase is a modified or unmodified cytosine and the second nucleobase is a modified or unmodified cytosine; thereby providing converted cfDNA of the first subsample; and (f) sequencing captured cfDNA of the first subsample corresponding to the epigenetic target set and the sequence-variable target set and (ii) the captured cfDNA of the second subsample corresponding to the epigenetic target set and the sequence-variable target set in a manner that distinguishes the first nucleobase from the second nucleobase in the captured cfDNA of the first subsample.
Therefore claim 1 of the ‘653 patent requires elements of
Claims of the ‘653 patent do not require sequence-specifically degrading a plurality of the target sequences in the converted sample having a first epigenetic status, thereby producing a treated sample.
The teachings of Liu as they relate to these claims are given previously in this office action and are fully incorporated here.
(II). Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 12,234,518.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims substantially anticipate the identified claims of this application. The additional limitations of the ‘518 claims are encompassed by the open claim language "comprising" found in the instant claims.
Regarding instant claim 1, claim 1 of the ‘518 patent requires b) subjecting the second subsample to a base conversion procedure that affects a first nucleobase in the DNA differently from a second nucleobase in the DNA of the second subsample, wherein the first nucleobase is a modified or unmodified nucleobase, the second nucleobase is a modified or unmodified nucleobase different from the first nucleobase, and the first nucleobase and the second nucleobase have the same base pairing specificity, thereby producing a treated subsample; and sequencing DNA in the target region set and DNA from the first subsample, wherein DNA from the second subsample is sequenced in a manner that distinguishes the first nucleobase from the second nucleobase in the DNA of the target region set. Claim 2 of the ‘518 patent requires the DNA of the first subsample is contacted with a methylation-sensitive nuclease, thereby degrading nonspecifically partitioned DNA in the first subsample, which reads on sequence-specifically degrading a plurality of the target sequences in the converted sample having a first epigenetic status.
(III). Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/325,759 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims substantially anticipate the identified claims of this application. The additional limitations of the ‘759 claims are encompassed by the open claim language "comprising" found in the instant claims.
Regarding instant claim 1, copending claim 1 requires a) subjecting the sample to a procedure that affects a first nucleobase in the DNA differently from a second nucleobase in the DNA of the sample, wherein the first nucleobase is a modified or unmodified nucleobase, the second nucleobase is a modified or unmodified nucleobase different from the first nucleobase, and the first nucleobase and the second nucleobase have the same base pairing specificity; and c) sequencing DNA in at least one of the first and second subsamples in a manner that distinguishes the first nucleobase from the second nucleobase.
Claims of the copending application do not require sequence-specifically degrading a plurality of the target sequences in the converted sample having a first epigenetic status, thereby producing a treated sample.
The teachings of Liu as they relate to these claims are given previously in this office action and are fully incorporated here.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
(IV). Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 21 of copending Application No 18/433,345. (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims substantially anticipate the identified claims of this application. The additional limitations of the ‘345 claims are encompassed by the open claim language "comprising" found in the instant claims.
Regarding instant claim 1, copending claim 21 requires (b) subjecting the first subsample to a procedure that affects a first nucleobase in the cfDNA differently from a second nucleobase in the cfDNA of the first subsample, wherein the first nucleobase is a modified or unmodified nucleobase, the second nucleobase is a modified or unmodified nucleobase different from the first nucleobase, the first nucleobase and the second nucleobase have the same base pairing specificity, and the first nucleobase is a modified or unmodified cytosine and the second nucleobase is a modified or unmodified cytosine; thereby providing converted cfDNA of the first subsample; and (e) sequencing (i) the captured cfDNA of the first subsample in a manner that distinguishes the first nucleobase from the second nucleobase in the captured cfDNA of the first subsample and (ii) the captured cfDNA of the second subsample.
Claims of the copending application do not require sequence-specifically degrading a plurality of the target sequences in the converted sample having a first epigenetic status, thereby producing a treated sample.
The teachings of Liu as they relate to these claims are given previously in this office action and are fully incorporated here.
Note: copending application 18/433,345 has been granted a patent. However, the patent (12,655,469) has not yet been published.
(V). Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7 of copending Application No. 18/922,116 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims substantially anticipate the identified claims of this application. The additional limitations of the ‘116 claims are encompassed by the open claim language "comprising" found in the instant claims.
Regarding instant claim 1, copending claim 1 requires c) subjecting the second subsample to a base conversion procedure that affects a first nucleobase in the DNA differently from a second nucleobase in the DNA of the second subsample, wherein the first nucleobase is a modified or unmodified nucleobase, the second nucleobase is a modified or unmodified nucleobase different from the first nucleobase, and the first nucleobase and the second nucleobase have the same base pairing specificity, thereby producing a treated subsample; and d) sequencing DNA from the first subsample and DNA from the second subsample, wherein DNA from the second subsample is sequenced in a manner that distinguishes the first nucleobase from the second nucleobase in the DNA of the target region set. Copending claim 7 requires the DNA of the first subsample is contacted with a methylation-sensitive nuclease, thereby degrading nonspecifically partitioned DNA in the first subsample.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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