DETAILED ACTION
Status of the Claims
Claims 1-30 are pending.
Claim 20 is amended.
Claims 1-30 are the subject of this Office Action
The following Office Action is in response to Applicant’s communication dated 07/01/2026. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Maintained Claim Objections
Claim 19 is objected to as being dependent upon a rejected base claim, but would be free from the prior art if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Appropriate correction is required.
New Claim Rejection(s) – 35 USC § 112(a)
Necessitated by Amendments
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 20-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. This rejection concerns “new matter.”
Claim 20 has been amended to include the limitation “(ii) at least two single nucleotide polymorphisms that are within 0.1 kb of each other and are phased alleles”, however, the specification as originally filed does not provide adequate written description support for such a limitation. Specifically, no sufficient written description support was found for identified SNPs that are within 0.1 kb of each other on phased alleles in the context of tumor-specific targeted sequencing data. While the specification does discuss loci that are within 0.1 kb of one another, this was only found to be in the context of alleles at nearby loci in phased parental genetic data used to determine that in fetal genomic data.
Claims 21-25 depend from claim 20 and are therefore similarly rejected.
Applicants are reminded, as per 37 C.F.R. 1.121, that no amendment may introduce new matter into the disclosure of an application, and that in accordance with MPEP § 2163(II)(A)(3)(b), when filing an amendment an applicant should show support in the original disclosure for new or amended claims.
MPEP §2163(I) states that to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. MPEP §2163(I)(B) explains the written description matter as it relates to new and amended claims, stating that the written description requirement prevents an applicant from claiming subject matter that was not adequately described in the specification as filed.
MPEP 2163.06(I) notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).”
Modified Claim Rejections – 35 U.S.C. 103
Necessitated by Amendments
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.
Diehn et al. and Schmitt et al. and/or Kinde et al.
Claims 1-18 and 20-30 are rejected under 35 U.S.C. 103 as being unpatentable over Diehn et al. (U.S. PGPub 2024/0392387 A1) in view of Schmitt et al. (Proc. Natl. Acad. Sci., 2012, 109(36):14508-14513) and/or Kinde et al. (Proc. Natl. Acad. Sci., 2011, 108(23):9530-9535).
Regarding claim 1(in part), Diehn discloses a method comprising:
(a) selectively enriching 100 to 100,000 target loci from a first cell-free DNA sample obtained from a first biological sample of the subject (e.g., cell-free DNA as per ¶¶0691-0692) to obtain a first set of selectively enriched DNA molecules, wherein the 100 to 100,000 target loci span 100 to 100,000 tumor-specific variants previously identified from a tumor biopsy sample of the subject (e.g., as per Example 2, ¶0264, ¶¶0273-0274, ¶¶0508-0509, and/or ¶0728); and
(b) determining the sequence of at least some of the first set of selectively enriched DNA molecules and obtaining sequence reads for target loci (e.g., sequencing the enriched DNA as per ¶0699 and/or Example 2 and/or ¶¶0732-0733), and identifying one or more of the tumor-specific variants present in the first cell-free DNA sample from the sequence reads (e.g., “allowing the tracking and quantitation of those mutations originally discovered in the primary tumor” as per Example 2), wherein the tumor-specific variants comprise one or more duplications, deletions, inversions, translocations, or a combination thereof (e.g., as per Example 2 and ¶¶0508-0509).
However, it is noted that the reference does not explicitly disclose the limitation of obtaining sequence reads with a depth of read of 20,000 to 500,000 per target locus for at least 100 of the target loci, as set forth in claims 1, 10, 14, and 25. However, Applicant is directed to In re Aller, Lacey, and Hall, 105 USPQ 233 (C.C.P.A. 1955), where the court found "More particularly, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." Routine optimization is not considered inventive and no evidence has been presented that the selection of 20,000x-500,000x sequencing depth was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art. In support of this, it is noted that Schmitt (e.g., as per the Mutant Recovery section on p. 14511) and Kinde (e.g., as per Table 1), both of which are drawn to detection of ultra-rare mutants through high-throughput sequencing, each disclose sequencing depths in the claimed range.
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 perform the next-generation sequencing in Diehn using the sequencing read depths as per Kinde and/or Schmittt. One of ordinary skill in the art would have been motivated to do so since increasing of sequencing depth was known to increase sensitivity of detecting ultra-rate mutations. 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 increasing sequencing depth for detection of rare mutations were well known in the art, as per Diehn, Kinde, and Schmitt, 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.
Regarding claim 2, Diehn discloses the above method, wherein the tumor biopsy sample of the subject includes a tumor tissue from a solid tumor (e.g., as per ¶0014).
Regarding claim 3, Diehn discloses the above method, wherein the first cell-free DNA sample is obtained from a blood, plasma, serum, or urine sample of the subject (e.g., as per ¶¶0698-0699 and/or ¶0733 and/or Example 2).
Regarding claim 4, Diehn discloses the above method, wherein the first cell-free DNA sample comprises circulating tumor DNA (e.g., as per ¶¶0691-0694).
Regarding claim 5, Diehn discloses the above method, wherein step (a) comprises selectively enriching 100 to 1,000 target loci, wherein the 100 to 1,000 target loci span 100 to 1,000 tumor-specific variants previously identified from a tumor biopsy sample of the subject, wherein the selective enrichment of the target loci is performed using target locus-specific primers or probes in one reaction volume, wherein the first set of selectively enriched DNA molecules are tagged with a plurality of different molecular barcodes (e.g., as per ¶0234, “[t]he selector set may comprise information pertaining to a plurality of genomic regions comprising 25, 30, 35, 40,45, 50, 55, 60, 65,70,75, 80, 85, 90, 95,100,110,120, 130, 140, 150, 160, 170, 180, 190, 200 or more mutations present in at least one subject suffering from a cancer”).
Regarding claim 6, Diehn discloses the above method, wherein step (a) comprises selectively enriching 100 to 200 target loci (e.g., as per ¶0234, “[t]he selector set may comprise information pertaining to a plurality of genomic regions comprising 25, 30, 35, 40,45, 50, 55, 60, 65,70,75, 80, 85, 90, 95,100,110,120, 130, 140, 150, 160, 170, 180, 190, 200 or more mutations present in at least one subject suffering from a cancer”), wherein the 100 to 200 target loci span 100 to 200 tumor-specific variants previously identified from a tumor biopsy sample of the subject (e.g., in creating a ‘personalized selector’ set of tumor-specific mutations to measure/monitor as per Example 2 and/or ¶0273 and/or ¶0728), wherein the selective enrichment of the target loci is performed using target locus-specific primers or probes in one reaction volume (e.g., as per ¶¶0698-0699 and/or ¶0733 and/or Example 2), wherein the first set of selectively enriched DNA molecules are tagged with a plurality of different molecular barcodes (e.g., as per Example 2 and/or ¶¶0056-0057 and/or ¶¶0122-0124).
Regarding claim 7, Diehn discloses the above method, wherein step (b) comprises identifying at least one duplication or deletion present in the first cell-free DNA sample from the sequence reads (e.g., as per Example 2 and ¶¶0508-0509).
Regarding claim 8, Diehn discloses the above method, wherein step (b) comprises identifying at least one inversion or translocation present in the first cell-free DNA sample from the sequence reads (e.g., as per Example 2 and ¶¶0508-0509).
Regarding claim 9, Diehn discloses the above method, wherein step (b) further comprises identifying at least one single nucleotide variant present in the first cell-free DNA sample from the sequence reads (e.g., as per Example 2 and ¶¶0508-0509).
Regarding claim 11, Diehn discloses the above method, wherein the subject is a human subject (e.g., Example 2, wherein the subject may be human as per ¶0761).
Regarding claim 12, Diehn discloses the above method, wherein the cancer is colorectal cancer, lung cancer, bladder cancer, or breast cancer (e.g., as per ¶0029 and/or ¶0065).
Regarding claim 13, Diehn discloses the above method, wherein the method further comprises performing barcoding PCR prior to step (b) (e.g., as per ¶0123).
Regarding claim 15, Diehn discloses the above method, wherein the first biological sample and the second biological sample are taken from the same subject at different points in time (e.g., as per ¶¶0141-0142).
Regarding claim 16, Diehn discloses the above method, wherein the first biological sample and the second biological sample are taken from the same subject from different sources (e.g., as per ¶¶0141-0142).
Regarding claim 17, Diehn discloses the above method, wherein the method further comprises detecting recurrence and/or metastases of the cancer from the tumor-specific variants detected in the first cell-free DNA sample or the second cell-free DNA sample (e.g., as per ¶0018 and/or ¶0147).
Regarding claim 18, Diehn discloses the above method, wherein the method identifies a tumor-specific variant present in the first cell-free DNA sample or the second cell-free DNA sample at a limit of detection of less than or equal to 0.015% (e.g., as per ¶0471, ¶0733, and/or Fig. 5A).
Regarding claim 20, Diehn discloses a method comprising:
(a) selectively enriching 100 to 100,000 target loci from a first cell-free DNA sample obtained from a biological sample of the subject (e.g., as per ¶¶0698-0699 and/or ¶0733 and/or Example 2) to obtain a first set of selectively enriched DNA molecules, wherein the 100 to 100,000 target loci span 100 to 100,000 tumor-specific variants previously identified from a tumor biopsy sample of the subject (e.g., as per ¶0234, “[t]he selector set may comprise information pertaining to a plurality of genomic regions comprising 25, 30, 35, 40,45, 50, 55, 60, 65,70,75, 80, 85, 90, 95,100,110,120, 130, 140, 150, 160, 170, 180, 190, 200 or more mutations present in at least one subject suffering from a cancer” by creating a ‘personalized selector’ set of tumor-specific mutations to measure/monitor as per Example 2 and/or ¶0273 and/or ¶0728); and
(b) determining the sequence of at least some of the first set of selectively enriched DNA molecules and obtaining sequence reads (e.g., sequencing the enriched DNA as per ¶0699 and/or Example 2 and/or ¶¶0732-0733), and identifying one or more of the tumor-specific variants present in the first cell-free DNA sample from the sequence reads (e.g., “allowing the tracking and quantitation of those mutations originally discovered in the primary tumor” as per Example 2), wherein the method identifies a tumor-specific variant present in the first cell-free DNA sample at a limit of detection of less than or equal to 0.015% (e.g., as per ¶0471, ¶0733, and/or Fig. 5A), wherein the tumor-specific variants comprise one or more duplications, deletions, inversions, translocations, or a combination thereof (e.g., as per ¶0485 and/or ¶¶0508-0509).
However, it is noted that Diehn is silent regarding the explicit limitation of “wherein … at least two single nucleotide polymorphisms that are within 0.1 kb of each other and are phased alleles”.
As per MPEP 2111.04(I) regarding “wherein/whereby” clauses, “the court noted that a ‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’ Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003))”. In the present case, the SNPs that are within 0.1 kb of each other and are phased alleles would be highly dependent on the cfDNA sample used in selectively enriching the target loci and also on the presence and/or type of tumor that may be present. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). In the instant case, it is noted that some cancers or tumors may yield SNPs that are within 0.1 kb of one another, such is the case in Diehn, as shown in Fig. 17A for the intron between exons 19 and 20 of the ALK gene on chromosome 2 as well as countless examples in Tables 6-18 of Diehn. In other words, the finding of SNPs within 0.1 kb of one another is not uncommon (e.g., as shown by Diehn in Tables 6-18) and therefore there is reason to believe that such SNPs are to be included in sets of 100 to 100,000 tumor-specific variants as per the instant claim.
Regarding claim 21, Diehn discloses the above method, wherein the tumor biopsy sample of the subject includes a tumor tissue from a solid tumor (e.g., as per ¶0014), wherein the first cell-free DNA sample is obtained from a blood, plasma, serum, or urine sample of the subject (e.g., as per ¶¶0698-0699 and/or ¶0733 and/or Example 2).
Regarding claim 22, Diehn discloses the above method, wherein step (b) comprises identifying at least one duplication or deletion present in the first cell-free DNA sample from the sequence reads (e.g., as per Example 2 and ¶¶0508-0509).
Regarding claim 23, Diehn discloses the above method, wherein step (b) comprises identifying at least one inversion or translocation present in the first cell-free DNA sample from the sequence reads (e.g., as per Example 2 and ¶¶0508-0509).
Regarding claim 24, Diehn discloses the above method, wherein step (b) further comprises identifying at least one single nucleotide polymorphism present in the first cell-free DNA sample from the sequence reads (e.g., as per Example 2 and ¶¶0508-0509).
Regarding claim 26, Diehn discloses the above method, further comprising identifying the tumor-specific variants from the tumor biopsy sample by whole genome sequencing (e.g., in creating a ‘personalized selector’ set of tumor-specific mutations to measure/monitor as per Example 2 and/or ¶0273 and/or ¶0728, which may be done via whole exome genome or whole exome sequencing as per ¶0274).
Regarding claim 27, Diehn discloses the above method, further comprising identifying the tumor-specific variants from the tumor biopsy sample by whole exome sequencing (e.g., in creating a ‘personalized selector’ set of tumor-specific mutations to measure/monitor as per Example 2 and/or ¶0273 and/or ¶0728, which may be done via whole exome genome or whole exome sequencing as per ¶0274).
Regarding claim 28, Diehn discloses the above method, wherein step (b) comprises identifying at least 10 tumor-specific variants from the sequence reads (e.g., as per ¶¶0514-0519).
Regarding claim 29, Diehn discloses the above method, wherein step (b) comprises identifying from the sequence reads at least two of the tumor-specific variants that are phased alleles and less than 0.01 kb from each other (e.g., as shown in Table 5).
Regarding claim 30, Diehn discloses the above method, wherein the tumor-specific variants comprise clonal tumor-specific variants identified by sequencing nucleic acids from multiple regions of the tumor biopsy sample (e.g., from measuring ratios of different mutations found in the same tumor, as per ¶¶0781-0782).
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Response to Arguments
The 07/01/2026 remarks argue: not all elements are taught.
Applicant's arguments have been fully considered but they are not persuasive for at least the following reasons.
Specifically, the remarks at pages 8-9 assert that “Diehn fails to teach or suggest the claimed combination, including tumor-informed identification of 100 to 100,000 tumor-specific variants followed by selective enrichment of corresponding cfDNA loci. Diehn repeatedly criticizes the prior art for being patient-specific and for requiring a personalized assay to be designed for each patient.”
This is not persuasive, at least because Diehn does not discourage the use of a personalized selector set, but rather instruct how to apply its use in their method. Example 2 states, inter alia, “[t]he personalized selector would then be applied for capture of the fragments of interest, sequenced and analyzed in the same manner as the 'off-the-shelf' CAPP-Seq workflow, allowing the tracking and quantitation of those mutations originally discovered in the primary tumor within the corresponding cfDNA”).
Furthermore, assuming, arguendo, that this were a nonpreferred embodiment (with which the Examiner does not agree), as per MPEP § 2123, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989), which states “[t]hat the [prior art] discloses a multitude of effective combinations does not render any particular formulation less obvious. This is especially true because the claimed composition is used for the identical purpose taught by the prior art.”
Further, Applicant points to embodiments of Diehn not relied on in the rejection (e.g., ¶¶0771-0773) to assert that “[t]hose population-selector disclosures may describe recurrent regions useful for a broad CAPP-Seq platform, but they do not disclose selecting 50 to 2,000 tumor biopsy-specific SNVs identified by WES or WGS in the tumor biopsy sample of the same subject.” At least because Applicant is relying on an embodiment not used in the rejection, and there is no indication that it would be relevant to the embodiments that are relied on, such arguments are not persuasive.
Next, the remarks contend that “Diehn does not disclose ‘generating sequence reads with a depth of read of at least 10,000 per target locus,’ as recited in claim 1” and that “Diehn's disclosure can at most incidentally include some values of 10,000 reads, but it is not clear whether the 10,000 reads are per target locus”. The remarks acknowledge that Diehn discusses in several locations sequencing read depths of at least 10,000x for the targeted loci, but allege that these discussions in are strictly for non-personalized selector sets. This has been fully considered but is not persuasive at least because Diehn is clear about the sequencing and analysis being the same, whether the selector set is for personalized or off-the-shelf sets (e.g., as per Example 2, Diehn discloses that assays using personalized selector sets are to be “sequenced and analyzed in the same manner as the ‘off-the-shelf’ CAPP-Seq workflow”).
Further, the remarks at pages 9-10 assert that “Diehn does not teach that increasing per-locus depth of reads would predictably achieve the claimed method” and that “Schmitt and Kinde do not cure Diehn's deficiency because they do not teach the claimed scale or context”. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Maintained 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. 17/692,469
Claims 1-18 and 20-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-38 of copending Application No. 17/692,469 (the ‘469 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 claims 1-18 and 20-30, the claims of the ‘469 application disclose a method comprising selectively enriching and barcoding 100 to 100,000 target loci from a cfDNA sample (from blood, serum, plasma, or urine) comprising ctDNA which span 100 to 100,000 tumor-specific variants previously identified from a solid tumor biopsy from the subject, sequencing to a read depth of 20,000x to 500,000x, and identifying the tumor-specific variants and with a LOD less than or equal to 0.015% (e.g., as per claims of the ‘469 application).
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Applicant’s Response
The 07/01/2026 reply includes Applicant’s response to the nonstatutory double patenting rejection of record: “Applicant respectfully traverses these rejections and requests that the Office hold the double patenting rejections in abeyance until such time as the claims at issue are deemed otherwise allowable. If any double patenting concern remains at that time, Applicant will address it at the appropriate time.”
This request is not the filing of a terminal disclaimer, or filing of a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, as the required response in accordance with MPEP 804 I.B.1.
Applicant’s request is expressly contrary to MPEP 804 I.B.1. (see also MPEP 714.03 and 37 C.F.R. 1.111).
U.S. 19/327,573
Claims 1-18 and 20-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23-50 of copending Application No. 19/327,573 (the ‘573 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 claims 1-18 and 20-30, the claims of the ‘573 application disclose a method comprising selectively enriching and barcoding 100 to 100,000 target loci from a cfDNA sample (from blood, serum, plasma, or urine) comprising ctDNA which span 100 to 100,000 tumor-specific variants previously identified from a solid tumor biopsy from the subject, sequencing to a read depth of 20,000x to 500,000x, and identifying the tumor-specific variants and with a LOD less than or equal to 0.015% (e.g., as per claims of the ‘753 application).
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Applicant’s Response
The 07/01/2026 reply includes Applicant’s response to the nonstatutory double patenting rejection of record: “Applicant respectfully traverses these rejections and requests that the Office hold the double patenting rejections in abeyance until such time as the claims at issue are deemed otherwise allowable. If any double patenting concern remains at that time, Applicant will address it at the appropriate time.”
This request is not the filing of a terminal disclaimer, or filing of a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, as the required response in accordance with MPEP 804 I.B.1.
Applicant’s request is expressly contrary to MPEP 804 I.B.1. (see also MPEP 714.03 and 37 C.F.R. 1.111).
U.S. 19/410,320
Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 19/410,320 (the ‘320 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 claims 1-30, the claims of the ‘320 application disclose a method comprising selectively enriching and barcoding 100 to 100,000 target loci from a cfDNA sample (from blood, serum, plasma, or urine) comprising ctDNA which span 100 to 100,000 tumor-specific variants previously identified from a solid tumor biopsy from the subject, sequencing to a read depth of 20,000x to 500,000x, and identifying the tumor-specific variants and with a LOD less than or equal to 0.015% (e.g., as per claims of the ‘320 application).
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Applicant’s Response
The 07/01/2026 reply includes Applicant’s response to the nonstatutory double patenting rejection of record: “Applicant respectfully traverses these rejections and requests that the Office hold the double patenting rejections in abeyance until such time as the claims at issue are deemed otherwise allowable. If any double patenting concern remains at that time, Applicant will address it at the appropriate time.”
This request is not the filing of a terminal disclaimer, or filing of a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, as the required response in accordance with MPEP 804 I.B.1.
Applicant’s request is expressly contrary to MPEP 804 I.B.1. (see also MPEP 714.03 and 37 C.F.R. 1.111).
U.S. 11,530,454 B2
Claims 1-18 and 20-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,530,454 B2 (the ‘454 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 claims 1-18 and 20-30, the claims of the ‘454 patent disclose a method comprising selectively enriching and barcoding 100 to 100,000 target loci from a cfDNA sample (from blood, serum, plasma, or urine) comprising ctDNA which span 100 to 100,000 tumor-specific variants previously identified from a solid tumor biopsy from the subject, sequencing to a read depth of 20,000x to 500,000x, and identifying the tumor-specific variants and with a LOD less than or equal to 0.015% (e.g., as per claims of the ‘454 patent).
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Applicant’s Response
The 07/01/2026 reply includes Applicant’s response to the nonstatutory double patenting rejection of record: “Applicant respectfully traverses these rejections and requests that the Office hold the double patenting rejections in abeyance until such time as the claims at issue are deemed otherwise allowable. If any double patenting concern remains at that time, Applicant will address it at the appropriate time.”
This request is not the filing of a terminal disclaimer, or filing of a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, as the required response in accordance with MPEP 804 I.B.1.
Applicant’s request is expressly contrary to MPEP 804 I.B.1. (see also MPEP 714.03 and 37 C.F.R. 1.111).
U.S. 12,492,429 B2
Claims 1-18 and 20-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,492,429 B2 (the ‘429 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 claims 1-18 and 20-30, the claims of the ‘429 patent disclose a method comprising selectively enriching and barcoding 100 to 100,000 target loci from a cfDNA sample (from blood, serum, plasma, or urine) comprising ctDNA which span 100 to 100,000 tumor-specific variants previously identified from a solid tumor biopsy from the subject, sequencing to a read depth of 20,000x to 500,000x, and identifying the tumor-specific variants and with a LOD less than or equal to 0.015% (e.g., as per claims of the ‘429 patent).
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Applicant’s Response
The 07/01/2026 reply includes Applicant’s response to the nonstatutory double patenting rejection of record: “Applicant respectfully traverses these rejections and requests that the Office hold the double patenting rejections in abeyance until such time as the claims at issue are deemed otherwise allowable. If any double patenting concern remains at that time, Applicant will address it at the appropriate time.”
This request is not the filing of a terminal disclaimer, or filing of a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, as the required response in accordance with MPEP 804 I.B.1.
Applicant’s request is expressly contrary to MPEP 804 I.B.1. (see also MPEP 714.03 and 37 C.F.R. 1.111).
U.S. 12,203,142 B2
Claims 1-18 and 20-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,203,142 B2 (the ‘142 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 claims 1-18 and 20-30, the claims of the ‘142 patent disclose a method comprising selectively enriching and barcoding 100 to 100,000 target loci from a cfDNA sample (from blood, serum, plasma, or urine) comprising ctDNA which span 100 to 100,000 tumor-specific variants previously identified from a solid tumor biopsy from the subject, sequencing to a read depth of 20,000x to 500,000x, and identifying the tumor-specific variants and with a LOD less than or equal to 0.015% (e.g., as per claims of the ‘142 patent).
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Applicant’s Response
The 07/01/2026 reply includes Applicant’s response to the nonstatutory double patenting rejection of record: “Applicant respectfully traverses these rejections and requests that the Office hold the double patenting rejections in abeyance until such time as the claims at issue are deemed otherwise allowable. If any double patenting concern remains at that time, Applicant will address it at the appropriate time.”
This request is not the filing of a terminal disclaimer, or filing of a showing that the claims subject to the rejection are patentably distinct from the reference application’s claims, as the required response in accordance with MPEP 804 I.B.1.
Applicant’s request is expressly contrary to MPEP 804 I.B.1. (see also MPEP 714.03 and 37 C.F.R. 1.111).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEREMY FLINDERS whose telephone number is (571)270-1022. The examiner can normally be reached M-F 10-6:00 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached on (571)272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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