DETAILED ACTION
Status of the Claims
Claims 23-35 and 37-45 are currently pending and are examined herein.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections – 35 U.S.C. 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 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.
Accuragen, Inc.
Claims 23-35 and 37-45 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Accuragen, Inc. (WO 2015/089333 A1, published 06/18/2015, cited in IDS of 08/01/2023).
Regarding claim 23, Accuragen discloses a method of identifying a sequence variant in a nucleic acid sample comprising a plurality of polynucleotides, each polynucleotide of the plurality having a 5' end and a 3' end (e.g., Accuragen claims 1-2 and/or para [0060]), the method comprising:
(a) circularizing individual polynucleotides of said plurality to form a plurality of circular polynucleotides, each of which having a junction between the 5' end and 3' end (e.g., Accuragen claims 1-2 and/or para [0060]);
(b) amplifying the circular polynucleotides of (a) to produce amplified polynucleotides (e.g., Accuragen claims 1-2 and/or para [0060]);
(c) shearing the amplified polynucleotides to produce sheared polynucleotides, each sheared polynucleotide comprising one or more shear points at a 5' end and/or a 3' end (e.g., as per Fig. 12 and/or 14 and/or para [0030]);
(d) sequencing the sheared polynucleotides to produce a plurality of sequencing reads (e.g., Accuragen claims 1-2 and/or para [0060]);
(e) identifying sequence differences between sequencing reads and a reference sequence (e.g., Accuragen claims 1-2 and/or para [0060]); and
(f) calling a sequence difference as the sequence variant when the sequence difference occurs in at least two different sheared polynucleotides (e.g., as per the Abstract and/or Accuragen claims 1-2 and/or para [0060]).
Regarding claim 24, Accuragen discloses the above method, wherein calling the sequence difference as the sequence variant occurs further when (i) the sequence difference is identified on both strands of a double-stranded input molecule; and/or (ii) the sequence difference occurs in a consensus sequence for a concatemer formed by amplification comprising rolling circle amplification (e.g., as per Accuragen claim 7 and/or para [0061]).
Regarding claim 25, Accuragen discloses the above method, wherein the plurality of polynucleotides is single-stranded (e.g., as per Accuragen claim 3 and/or para [0007]).
Regarding claim 26, Accuragen discloses the above method, wherein circularizing is effected by subjecting the plurality of polynucleotides to a ligation reaction (e.g., as per Accuragen claim 4 and/or para [0006]-[0009]).
Regarding claim 27, Accuragen discloses the above method, wherein the sequence variant is a single nucleotide polymorphism (e.g., as per Accuragen claim 6 and/or para [0062]).
Regarding claim 28, Accuragen discloses the above method, wherein the reference sequence is a consensus sequence formed by aligning the sequencing reads with one another (e.g., as per Accuragen claim 7 and/or para [0061]).
Regarding claim 29, Accuragen discloses the above method, wherein the reference sequence is a sequencing read (e.g., as per Accuragen claims 7-8 and/or para [0061]).
Regarding claim 30, Accuragen discloses the above method, wherein circularizing comprises the step of joining an adapter polynucleotide to the 5' end, the 3' end, or both the 5' end and the 3' end of a polynucleotide in the plurality of polynucleotides (e.g., as per Accuragen claim 9 and/or para [0007]).
Regarding claim 31, Accuragen discloses the above method, wherein amplifying is effected by using a polymerase having strand-displacement activity (e.g., as per Accuragen claim 10 and/or para [0007]).
Regarding claim 32, Accuragen discloses the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising random primers (e.g., as per Accuragen claim 11 and/or para [0007]).
Regarding claim 33, Accuragen discloses the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising one or more primers, each of which specifically hybridizes to a different target sequence via sequence complementarity (e.g., as per Accuragen claim 12 and/or para [0007]).
Regarding claim 34, Accuragen discloses the above method, wherein the amplified polynucleotides are subjected to the sequencing step without enrichment (e.g., as per Accuragen claim 13 and/or para [0008]).
Regarding claim 35, Accuragen discloses the above method, further comprising enriching one or more target polynucleotides among the amplified polynucleotides by performing an enrichment step prior to sequencing (e.g., as per Accuragen claim 14 and/or para [0008]).
Regarding claim 37, Accuragen discloses the above method, wherein the sample is a sample from a subject (e.g., as per Accuragen claim 41 and/or para [0016]).
Regarding claim 38, Accuragen discloses the above method, wherein the sample is urine, stool, blood, saliva, tissue, or bodily fluid (e.g., as per Accuragen claim 42 and/or para [0016]).
Regarding claim 39, Accuragen discloses the above method, wherein the sample comprises tumor cells (e.g., as per Accuragen claim 43 and/or para [0016]).
Regarding claim 40, Accuragen discloses the above method, wherein the sample is a formalin-fixed paraffin embedded (FFPE) sample (e.g., as per Accuragen claim 44 and/or para [0016]).
Regarding claim 41, Accuragen discloses the above method, further comprising diagnosing, and optionally treating, said subject based on the calling step (e.g., as per Accuragen claim 45 and/or para [0016]).
Regarding claim 42, Accuragen discloses the above method, wherein the sequence variant is a causal genetic variant (e.g., as per Accuragen claim 46 and/or para [0016]).
Regarding claim 43, Accuragen discloses the above method, wherein the sequence variant is associated with a type or stage of cancer (e.g., as per Accuragen claim 47 and/or para [0016]).
Regarding claim 44, Accuragen discloses the above method, wherein the plurality of polynucleotides comprises cell-free polynucleotides (e.g., as per Accuragen claim 48 and/or para [0016]).
Regarding claim 45, Accuragen discloses the above method, wherein the cell-free polynucleotides comprise circulating tumor DNA (e.g., as per Accuragen claim 49 and/or para [0016]).
Lou et al.
Claims 23-29 and 31-34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lou et al. (Proc. Natl. Acad. Sci., 2013, 110(49):19872-19877).
Regarding claim 23, Lou discloses a method of identifying a sequence variant in a nucleic acid sample comprising a plurality of polynucleotides, each polynucleotide of the plurality having a 5' end and a 3' end (e.g., Abstract), the method comprising:
(a) circularizing individual polynucleotides of said plurality to form a plurality of circular polynucleotides, each of which having a junction between the 5' end and 3' end (e.g., as per the C. Circularization section on pp. 1-2 of the Supporting Information Materials and Methods);
(b) amplifying the circular polynucleotides of (a) to produce amplified polynucleotides (e.g., as per the D. Rolling circle amplification section on p. 2 of the Supporting Information Materials and Methods);
(c) shearing the amplified polynucleotides to produce sheared polynucleotides, each sheared polynucleotide comprising one or more shear points at a 5' end and/or a 3' end (e.g., as per the 15. Shear RCA products to 1,500 bp using Covaris S220 section on p. 2 of the Supporting Information Materials and Methods);
(d) sequencing the sheared polynucleotides to produce a plurality of sequencing reads (e.g., using standard Illumina MiSeq sequencing as per the Error Rate of Circle Sequencing section on pp. 19874-19875);
(e) identifying sequence differences between sequencing reads and a reference sequence (e.g., compared to a reference sequence as per the Error Rate of Circle Sequencing section on pp. 19874-19875); and
(f) calling a sequence difference as the sequence variant when the sequence difference occurs in at least two different sheared polynucleotides (e.g., based on consensus sequence as per the Error Rate of Circle Sequencing section on pp. 19874-19875).
Regarding claim 24, Lou discloses the above method, wherein calling the sequence difference as the sequence variant occurs further when the sequence difference occurs in a consensus sequence for a concatemer formed by amplification comprising rolling circle amplification (e.g., based on consensus sequence as per the Error Rate of Circle Sequencing section on pp. 19874-19875).
Regarding claim 25, Lou discloses the above method, wherein the plurality of polynucleotides is single-stranded (e.g., as per Fig. 1B).
Regarding claim 26, Lou discloses the above method, wherein circularizing is effected by subjecting the plurality of polynucleotides to a ligation reaction (e.g., as per Fig. 1B and/or as per the Circle Sequencing section on p. 19877).
Regarding claim 27, Lou discloses the above method, wherein the sequence variant is a single nucleotide polymorphism (e.g., as per the Error Rate of Circle Sequencing section on pp. 19874-19875).
Regarding claim 28, Lou discloses the above method, wherein the reference sequence is a consensus sequence formed by aligning the sequencing reads with one another (e.g., as per the Bioinformatic Processing section on p. 19877 and the Circle-Sequencing Computational Workflow section of the Supporting Information Materials and Methods section pp. 2-14).
Regarding claim 29, Lou discloses the above method, wherein the reference sequence is a sequencing read (e.g., as per the Bioinformatic Processing section on p. 19877 and the Circle-Sequencing Computational Workflow section of the Supporting Information Materials and Methods section pp. 2-14).
Regarding claim 31, Lou discloses the above method, wherein amplifying is effected by using a polymerase having strand-displacement activity (e.g., Phi29 as per the D. Rolling circle amplification section on p. 2 of the Supporting Information Materials and Methods).
Regarding claim 32, Lou discloses the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising random primers (e.g., random primers as per the D. Rolling circle amplification section on p. 2 of the Supporting Information Materials and Methods).
Regarding claim 33, Lou discloses the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising one or more primers, each of which specifically hybridizes to a different target sequence via sequence complementarity (e.g., annealing primers as per the D. Rolling circle amplification section on p. 2 of the Supporting Information Materials and Methods).
Regarding claim 34, Lou discloses the above method, wherein the amplified polynucleotides are subjected to the sequencing step without enrichment (e.g., using standard Illumina MiSeq sequencing as per the Error Rate of Circle Sequencing section on pp. 19874-19875).
Claim Rejections – 35 U.S.C. 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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Lou et al. and Accuragen, Inc.
Claims 23-35 and 37-45 are rejected under 35 U.S.C. 103 as being unpatentable over Lou et al. (Proc. Natl. Acad. Sci., 2013, 110(49):19872-19877) in view of Accuragen, Inc. (WO 2015/089333 A1, published 06/18/2015, cited in IDS of 08/01/2023).
Lou is relied on as above, however, while the reference discloses a proof-of-concept example using a Saccharomyces cerevisiae reference genome (e.g., as per the Error Rate of Circle Sequencing section on pp. 19874-19875), the reference is silent on the use of adapter use, enrichment methods, diagnosis, and the specific types of samples and variants detected, as set forth in claims 30, 35, and 37-45.
Regarding claim 30, Accuragen discloses circularizing that comprises the step of joining an adapter polynucleotide to the 5' end, the 3' end, or both the 5' end and the 3' end of a polynucleotide in the plurality of polynucleotides (e.g., as per Accuragen claim 9 and/or para [0007]).
Regarding claim 35, Accuragen discloses enriching one or more target polynucleotides among the amplified polynucleotides by performing an enrichment step prior to sequencing (e.g., as per Accuragen claim 14 and/or para [0008]).
Regarding claim 37, Accuragen discloses a sample from a subject (e.g., as per Accuragen claim 41 and/or para [0016]).
Regarding claim 38, Accuragen discloses that the sample is urine, stool, blood, saliva, tissue, or bodily fluid (e.g., as per Accuragen claim 42 and/or para [0016]).
Regarding claim 39, Accuragen discloses a sample that comprises tumor cells (e.g., as per Accuragen claim 43 and/or para [0016]).
Regarding claim 40, Accuragen discloses a sample that is a formalin-fixed paraffin embedded (FFPE) sample (e.g., as per Accuragen claim 44 and/or para [0016]).
Regarding claim 41, Accuragen discloses diagnosing, and optionally treating, said subject based on the calling step (e.g., as per Accuragen claim 45 and/or para [0016]).
Regarding claim 42, Accuragen discloses that the sequence variant is a causal genetic variant (e.g., as per Accuragen claim 46 and/or para [0016]).
Regarding claim 43, Accuragen discloses that the sequence variant is associated with a type or stage of cancer (e.g., as per Accuragen claim 47 and/or para [0016]).
Regarding claim 44, Accuragen discloses that the plurality of polynucleotides comprises cell-free polynucleotides (e.g., as per Accuragen claim 48 and/or para [0016]).
Regarding claim 45, Accuragen discloses that cell-free polynucleotides comprise circulating tumor DNA (e.g., as per Accuragen claim 49 and/or para [0016]).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to utilize the specifics of circle sequencing as per Lou using the adapters, enrichment, samples, and variant types as per Accuragen. One of ordinary skill in the art would have been motivated to do so since Lou teaches the greatly reduced error rates obtained using their methodologies (e.g., as per the Discussion section).
Further, as per MPEP 2143(I)(A), the rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. In the instant case, all of the elements of circle sequencing and various samples were well known in the art, as per Lou and Accuragen, the mere combining of the individual elements in one embodiment in the manner of the claimed invention results in no change in the elements respective functions, and the combination yields nothing more than predictable results.
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since both references are drawn to similar circularization and rolling circle amplification library preparation methods.
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
U.S. 18/955,777
Claims 23-35, 37-39, and 41-42 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-6, 8, 10, 12-14, 18, and 21-23 of copending Application No. 18/955,777 (the ‘777 application). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 23, The claims of the ‘777 application a method of identifying a sequence variant in a nucleic acid sample comprising a plurality of polynucleotides, each polynucleotide of the plurality having a 5' end and a 3' end, the method comprising (a) circularizing individual polynucleotides of said plurality to form a plurality of circular polynucleotides, each of which having a junction between the 5' end and 3' end; (b) amplifying the circular polynucleotides of (a) to produce amplified polynucleotides; (c) shearing the amplified polynucleotides to produce sheared polynucleotides, each sheared polynucleotide comprising one or more shear points at a 5' end and/or a 3' end; (d) sequencing the sheared polynucleotides to produce a plurality of sequencing reads; (e) identifying sequence differences between sequencing reads and a reference sequence; and (f) calling a sequence difference as the sequence variant when the sequence difference occurs in at least two different sheared polynucleotides (e.g., as per claim 1 of the ‘777 application).
Regarding claim 24, The claims of the ‘777 application the above method, wherein calling the sequence difference as the sequence variant occurs further when (i) the sequence difference is identified on both strands of a double-stranded input molecule; and/or (ii) the sequence difference occurs in a consensus sequence for a concatemer formed by amplification comprising rolling circle amplification (e.g., as per claim 1 of the ‘777 application).
Regarding claim 25, The claims of the ‘777 application the above method, wherein the plurality of polynucleotides is single-stranded (e.g., as per claim 14 of the ‘777 application).
Regarding claim 26, The claims of the ‘777 application the above method, wherein circularizing is effected by subjecting the plurality of polynucleotides to a ligation reaction (e.g., as per claim 8 of the ‘777 application).
Regarding claim 27, The claims of the ‘777 application the above method, wherein the sequence variant is a single nucleotide polymorphism (e.g., as per claim 21 of the ‘777 application).
Regarding claim 29, The claims of the ‘777 application the above method, wherein the reference sequence is a sequencing read (e.g., as per claim 1 of the ‘777 application).
Regarding claim 30, The claims of the ‘777 application the above method, wherein circularizing comprises the step of joining an adapter polynucleotide to the 5' end, the 3' end, or both the 5' end and the 3' end of a polynucleotide in the plurality of polynucleotides (e.g., as per claim 2 of the ‘777 application).
Regarding claim 31, The claims of the ‘777 application the above method, wherein amplifying is effected by using a polymerase having strand-displacement activity (e.g., as per claim 10 of the ‘777 application).
Regarding claim 32, The claims of the ‘777 application the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising random primers (e.g., as per claim 12 of the ‘777 application).
Regarding claim 33, The claims of the ‘777 application the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising one or more primers, each of which specifically hybridizes to a different target sequence via sequence complementarity (e.g., as per claim 13 of the ‘777 application).
Regarding claim 34, The claims of the ‘777 application the above method, wherein the amplified polynucleotides are subjected to the sequencing step without enrichment (e.g., as per claim 1 of the ‘777 application).
Regarding claim 35, The claims of the ‘777 application the above method, further comprising enriching one or more target polynucleotides among the amplified polynucleotides by performing an enrichment step prior to sequencing (e.g., as per claims 5-6 of the ‘777 application).
Regarding claim 37, The claims of the ‘777 application the above method, wherein the sample is a sample from a subject (e.g., as per claim 23 of the ‘777 application).
Regarding claim 38, The claims of the ‘777 application the above method, wherein the sample is urine, stool, blood, saliva, tissue, or bodily fluid (e.g., as per claim 23 of the ‘777 application).
Regarding claim 39, The claims of the ‘777 application the above method, wherein the sample comprises tumor cells (e.g., as per claim 18 of the ‘777 application).
Regarding claim 41, The claims of the ‘777 application the above method, further comprising diagnosing, and optionally treating, said subject based on the calling step (e.g., as per claim 22 of the ‘777 application).
Regarding claim 42, The claims of the ‘777 application the above method, wherein the sequence variant is a causal genetic variant (e.g., as per claim 22 of the ‘777 application).
U.S. 11,643,683 B2
Claims 23-35, 37-40, and 42-45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,643,683 B2 (the ‘683 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding claim 23, The claims of the ‘683 patent a method of identifying a sequence variant in a nucleic acid sample comprising a plurality of polynucleotides, each polynucleotide of the plurality having a 5' end and a 3' end, the method comprising (a) circularizing individual polynucleotides of said plurality to form a plurality of circular polynucleotides, each of which having a junction between the 5' end and 3' end; (b) amplifying the circular polynucleotides of (a) to produce amplified polynucleotides; (c) shearing the amplified polynucleotides to produce sheared polynucleotides, each sheared polynucleotide comprising one or more shear points at a 5' end and/or a 3' end; (d) sequencing the sheared polynucleotides to produce a plurality of sequencing reads; (e) identifying sequence differences between sequencing reads and a reference sequence; and (f) calling a sequence difference as the sequence variant when the sequence difference occurs in at least two different sheared polynucleotides (e.g., as per claims 1, 2, and 19 of the ‘683 patent).
Regarding claim 24, The claims of the ‘683 patent the above method, wherein calling the sequence difference as the sequence variant occurs further when (i) the sequence difference is identified on both strands of a double-stranded input molecule; and/or (ii) the sequence difference occurs in a consensus sequence for a concatemer formed by amplification comprising rolling circle amplification (e.g., as per claim 4 of the ‘683 patent).
Regarding claim 25, The claims of the ‘683 patent the above method, wherein the plurality of polynucleotides is single-stranded (e.g., as per claim 2 of the ‘683 patent).
Regarding claim 26, The claims of the ‘683 patent the above method, wherein circularizing is effected by subjecting the plurality of polynucleotides to a ligation reaction (e.g., as per claim 1 of the ‘683 patent).
Regarding claim 27, The claims of the ‘683 patent the above method, wherein the sequence variant is a single nucleotide polymorphism (e.g., as per claim 3 of the ‘683 patent).
Regarding claim 28, The claims of the ‘683 patent the above method, wherein the reference sequence is a consensus sequence formed by aligning the sequencing reads with one another (e.g., as per claim 4 of the ‘683 patent).
Regarding claim 29, The claims of the ‘683 patent the above method, wherein the reference sequence is a sequencing read (e.g., as per claim 4 of the ‘683 patent).
Regarding claim 30, The claims of the ‘683 patent the above method, wherein circularizing comprises the step of joining an adapter polynucleotide to the 5' end, the 3' end, or both the 5' end and the 3' end of a polynucleotide in the plurality of polynucleotides (e.g., as per claim 5 of the ‘683 patent).
Regarding claim 31, The claims of the ‘683 patent the above method, wherein amplifying is effected by using a polymerase having strand-displacement activity (e.g., as per claim 6 of the ‘683 patent).
Regarding claim 32, The claims of the ‘683 patent the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising random primers (e.g., as per claim 7 of the ‘683 patent).
Regarding claim 33, The claims of the ‘683 patent the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising one or more primers, each of which specifically hybridizes to a different target sequence via sequence complementarity (e.g., as per claim 8 of the ‘683 patent).
Regarding claim 34, The claims of the ‘683 patent the above method, wherein the amplified polynucleotides are subjected to the sequencing step without enrichment (e.g., as per claim 9 of the ‘683 patent).
Regarding claim 35, The claims of the ‘683 patent the above method, further comprising enriching one or more target polynucleotides among the amplified polynucleotides by performing an enrichment step prior to sequencing (e.g., as per claim 10 of the ‘683 patent).
Regarding claim 37, The claims of the ‘683 patent the above method, wherein the sample is a sample from a subject (e.g., as per claim 12 of the ‘683 patent).
Regarding claim 38, The claims of the ‘683 patent the above method, wherein the sample is urine, stool, blood, saliva, tissue, or bodily fluid (e.g., as per claim 13 of the ‘683 patent).
Regarding claim 39, The claims of the ‘683 patent the above method, wherein the sample comprises tumor cells (e.g., as per claim 14 of the ‘683 patent).
Regarding claim 40, The claims of the ‘683 patent the above method, wherein the sample is a formalin-fixed paraffin embedded (FFPE) sample (e.g., as per claim 15 of the ‘683 patent).
Regarding claim 42, The claims of the ‘683 patent the above method, wherein the sequence variant is a causal genetic variant (e.g., as per claim 3 of the ‘683 patent).
Regarding claim 43, The claims of the ‘683 patent the above method, wherein the sequence variant is associated with a type or stage of cancer (e.g., as per claim 16 of the ‘683 patent).
Regarding claim 44, The claims of the ‘683 patent the above method, wherein the plurality of polynucleotides comprises cell-free polynucleotides (e.g., as per claim 17 of the ‘683 patent).
Regarding claim 45, The claims of the ‘683 patent the above method, wherein the cell-free polynucleotides comprise circulating tumor DNA (e.g., as per claim 18 of the ‘683 patent).
U.S. 10,724,088 B2
Claims 23-35, 37-40, and 42-45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 10,724,088 B2 (the ‘088 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding claim 23, The claims of the ‘088 patent a method of identifying a sequence variant in a nucleic acid sample comprising a plurality of polynucleotides, each polynucleotide of the plurality having a 5' end and a 3' end, the method comprising (a) circularizing individual polynucleotides of said plurality to form a plurality of circular polynucleotides, each of which having a junction between the 5' end and 3' end; (b) amplifying the circular polynucleotides of (a) to produce amplified polynucleotides; (c) shearing the amplified polynucleotides to produce sheared polynucleotides, each sheared polynucleotide comprising one or more shear points at a 5' end and/or a 3' end; (d) sequencing the sheared polynucleotides to produce a plurality of sequencing reads; (e) identifying sequence differences between sequencing reads and a reference sequence; and (f) calling a sequence difference as the sequence variant when the sequence difference occurs in at least two different sheared polynucleotides (e.g., as per claims 1 and 21-22 of the ‘088 patent).
Regarding claim 24, The claims of the ‘088 patent the above method, wherein calling the sequence difference as the sequence variant occurs further when (i) the sequence difference is identified on both strands of a double-stranded input molecule; and/or (ii) the sequence difference occurs in a consensus sequence for a concatemer formed by amplification comprising rolling circle amplification (e.g., as per claim 1 of the ‘088 patent).
Regarding claim 25, The claims of the ‘088 patent the above method, wherein the plurality of polynucleotides is single-stranded (e.g., as per claim 3 of the ‘088 patent).
Regarding claim 26, The claims of the ‘088 patent the above method, wherein circularizing is effected by subjecting the plurality of polynucleotides to a ligation reaction (e.g., as per claim 1 of the ‘088 patent).
Regarding claim 27, The claims of the ‘088 patent the above method, wherein the sequence variant is a single nucleotide polymorphism (e.g., as per claim 4 of the ‘088 patent).
Regarding claim 28, The claims of the ‘088 patent the above method, wherein the reference sequence is a consensus sequence formed by aligning the sequencing reads with one another (e.g., as per claims 2 and 5 of the ‘088 patent).
Regarding claim 29, The claims of the ‘088 patent the above method, wherein the reference sequence is a sequencing read (e.g., as per claim 6 of the ‘088 patent).
Regarding claim 30, The claims of the ‘088 patent the above method, wherein circularizing comprises the step of joining an adapter polynucleotide to the 5' end, the 3' end, or both the 5' end and the 3' end of a polynucleotide in the plurality of polynucleotides (e.g., as per claim 7 of the ‘088 patent).
Regarding claim 31, The claims of the ‘088 patent the above method, wherein amplifying is effected by using a polymerase having strand-displacement activity (e.g., as per claim 8 of the ‘088 patent).
Regarding claim 32, The claims of the ‘088 patent the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising random primers (e.g., as per claim 9 of the ‘088 patent).
Regarding claim 33, The claims of the ‘088 patent the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising one or more primers, each of which specifically hybridizes to a different target sequence via sequence complementarity (e.g., as per claim 10 of the ‘088 patent).
Regarding claim 34, The claims of the ‘088 patent the above method, wherein the amplified polynucleotides are subjected to the sequencing step without enrichment (e.g., as per claim 11 of the ‘088 patent).
Regarding claim 35, The claims of the ‘088 patent the above method, further comprising enriching one or more target polynucleotides among the amplified polynucleotides by performing an enrichment step prior to sequencing (e.g., as per claim 12 of the ‘088 patent).
Regarding claim 37, The claims of the ‘088 patent the above method, wherein the sample is a sample from a subject (e.g., as per claim 14 of the ‘088 patent).
Regarding claim 38, The claims of the ‘088 patent the above method, wherein the sample is urine, stool, blood, saliva, tissue, or bodily fluid (e.g., as per claim 15 of the ‘088 patent).
Regarding claim 39, The claims of the ‘088 patent the above method, wherein the sample comprises tumor cells (e.g., as per claim 16 of the ‘088 patent).
Regarding claim 40, The claims of the ‘088 patent the above method, wherein the sample is a formalin-fixed paraffin embedded (FFPE) sample (e.g., as per claim 17 of the ‘088 patent).
Regarding claim 42, The claims of the ‘088 patent the above method, wherein the sequence variant is a causal genetic variant (e.g., as per claim 18 of the ‘088 patent).
Regarding claim 43, The claims of the ‘088 patent the above method, wherein the sequence variant is associated with a type or stage of cancer (e.g., as per claim 18 of the ‘088 patent).
Regarding claim 44, The claims of the ‘088 patent the above method, wherein the plurality of polynucleotides comprises cell-free polynucleotides (e.g., as per claim 19 of the ‘088 patent).
Regarding claim 45, The claims of the ‘088 patent the above method, wherein the cell-free polynucleotides comprise circulating tumor DNA (e.g., as per claim 20 of the ‘088 patent).
U.S. 10,155,980 B2
Claims 23-34, 37-40, and 42-45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,155,980 B2 (the ‘980 patent). Although the claims at issue are not identical, they are not patentably distinct from each other because the rejected claims of the present invention would be anticipated and/or rendered obvious by the subject matter in the claims of the reference patent.
Regarding claim 23, The claims of the ‘980 patent a method of identifying a sequence variant in a nucleic acid sample comprising a plurality of polynucleotides, each polynucleotide of the plurality having a 5' end and a 3' end, the method comprising (a) circularizing individual polynucleotides of said plurality to form a plurality of circular polynucleotides, each of which having a junction between the 5' end and 3' end; (b) amplifying the circular polynucleotides of (a) to produce amplified polynucleotides; (c) shearing the amplified polynucleotides to produce sheared polynucleotides, each sheared polynucleotide comprising one or more shear points at a 5' end and/or a 3' end; (d) sequencing the sheared polynucleotides to produce a plurality of sequencing reads; (e) identifying sequence differences between sequencing reads and a reference sequence; and (f) calling a sequence difference as the sequence variant when the sequence difference occurs in at least two different sheared polynucleotides (e.g., as per claims 1 and 13 of the ‘980 patent).
Regarding claim 24, The claims of the ‘980 patent the above method, wherein calling the sequence difference as the sequence variant occurs further when (i) the sequence difference is identified on both strands of a double-stranded input molecule; and/or (ii) the sequence difference occurs in a consensus sequence for a concatemer formed by amplification comprising rolling circle amplification (e.g., as per claims 16-18 of the ‘980 patent).
Regarding claim 25, The claims of the ‘980 patent the above method, wherein the plurality of polynucleotides is single-stranded (e.g., as per claim 3 of the ‘980 patent).
Regarding claim 26, The claims of the ‘980 patent the above method, wherein circularizing is effected by subjecting the plurality of polynucleotides to a ligation reaction (e.g., as per claim 1 of the ‘980 patent).
Regarding claim 27, The claims of the ‘980 patent the above method, wherein the sequence variant is a single nucleotide polymorphism (e.g., as per claim 21 of the ‘980 patent).
Regarding claim 28, The claims of the ‘980 patent the above method, wherein the reference sequence is a consensus sequence formed by aligning the sequencing reads with one another (e.g., as per claims 16-17 of the ‘980 patent).
Regarding claim 29, The claims of the ‘980 patent the above method, wherein the reference sequence is a sequencing read (e.g., as per claims 16-17 of the ‘980 patent).
Regarding claim 30, The claims of the ‘980 patent the above method, wherein circularizing comprises the step of joining an adapter polynucleotide to the 5' end, the 3' end, or both the 5' end and the 3' end of a polynucleotide in the plurality of polynucleotides (e.g., as per claim 5 of the ‘980 patent).
Regarding claim 31, The claims of the ‘980 patent the above method, wherein amplifying is effected by using a polymerase having strand-displacement activity (e.g., as per claims 1 and 16-18 of the ‘980 patent).
Regarding claim 32, The claims of the ‘980 patent the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising random primers (e.g., as per claim 7 of the ‘980 patent).
Regarding claim 33, The claims of the ‘980 patent the above method, wherein amplifying comprises subjecting the circular polynucleotides to an amplification reaction mixture comprising one or more primers, each of which specifically hybridizes to a different target sequence via sequence complementarity (e.g., as per claim 7 of the ‘980 patent).
Regarding claim 34, The claims of the ‘980 patent the above method, wherein the amplified polynucleotides are subjected to the sequencing step without enrichment (e.g., as per claim 1 of the ‘980 patent).
Regarding claim 37, The claims of the ‘980 patent the above method, wherein the sample is a sample from a subject (e.g., as per claim 8 of the ‘980 patent).
Regarding claim 38, The claims of the ‘980 patent the above method, wherein the sample is urine, stool, blood, saliva, tissue, or bodily fluid (e.g., as per claim 9 of the ‘980 patent).
Regarding claim 39, The claims of the ‘980 patent the above method, wherein the sample comprises tumor cells (e.g., as per claim 10 of the ‘980 patent).
Regarding claim 40, The claims of the ‘980 patent the above method, wherein the sample is a formalin-fixed paraffin embedded (FFPE) sample (e.g., as per claim 11 of the ‘980 patent).
Regarding claim 42, The claims of the ‘980 patent the above method, wherein the sequence variant is a causal genetic variant (e.g., as per claim 21 of the ‘980 patent).
Regarding claim 43, The claims of the ‘980 patent the above method, wherein the sequence variant is associated with a type or stage of cancer (e.g., as per claim 22 of the ‘980 patent).
Regarding claim 44, The claims of the ‘980 patent the above method, wherein the plurality of polynucleotides comprises cell-free polynucleotides (e.g., as per claim 12 of the ‘980 patent).
Regarding claim 45, The claims of the ‘980 patent the above method, wherein the cell-free polynucleotides comprise circulating tumor DNA (e.g., as per claim 15 of the ‘980 patent).
Conclusion
No claims are allowed.
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/JEREMY C FLINDERS/
Primary Examiner, Art Unit 1684
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