Prosecution Insights
Last updated: April 19, 2026
Application No. 19/171,081

SYSTEMS AND METHODS FOR EVALUATING TUMOR FRACTION

Non-Final OA §101§103§DP
Filed
Apr 04, 2025
Examiner
VANNI, GEORGE STEVEN
Art Unit
1686
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Foundation Medicine Inc.
OA Round
2 (Non-Final)
66%
Grant Probability
Favorable
2-3
OA Rounds
4y 1m
To Grant
92%
With Interview

Examiner Intelligence

Grants 66% — above average
66%
Career Allow Rate
386 granted / 581 resolved
+6.4% vs TC avg
Strong +25% interview lift
Without
With
+25.1%
Interview Lift
resolved cases with interview
Typical timeline
4y 1m
Avg Prosecution
42 currently pending
Career history
623
Total Applications
across all art units

Statute-Specific Performance

§101
26.2%
-13.8% vs TC avg
§103
25.4%
-14.6% vs TC avg
§102
6.7%
-33.3% vs TC avg
§112
13.9%
-26.1% vs TC avg
Black line = Tech Center average estimate • Based on career data from 581 resolved cases

Office Action

§101 §103 §DP
DETAILED ACTION This application is being examined under AIA first-to-file provisions. Status of claims Canceled: none Pending: 1-30 Withdrawn: 2, 14 and 27-28 Examined: 1, 3-13, 15-26 and 29-30 Independent: 1, 13 and 30 Allowable: none Rejections applied Abbreviations 112/b Indefiniteness PHOSITA "a Person Having Ordinary Skill In The Art before the effective filing date of the claimed invention" 112/b "Means for" BRI Broadest Reasonable Interpretation 112/a Enablement, Written description CRM "Computer-Readable Media" and equivalent language 112 Other IDS Information Disclosure Statement x 102, 103 JE Judicial Exception x 101 JE(s) 112/a 35 USC 112(a) and similarly for 112/b, etc. 101 Other N:N page:line x Double Patenting MM/DD/YYYY date format Priority As detailed on the 5/9/2025 filing receipt, this application claims priority to as early as 5/20/2019. At this point in examination, all claims have been interpreted as being accorded this priority date. Withdrawal / revision of objections and/or rejections In view of the amendment and remarks: The previous 103 rejections are withdrawn, and new 103 rejection are applied. The previous double patenting rejections are withdrawn, and new rejections are applied. Rejections and/or objections not maintained from previous office actions are withdrawn. The following rejections and/or objections are either maintained or newly applied. They constitute the complete set applied to the instant application. Objection to the specification: title The title should be amended to more specifically reflect the claims, particularly referencing steps/elements: setting the context of the invention, particular to all claims, and distinguishing the instant application from any related applications (e.g. 17/612,966), for example amendment to include terms such as: allele fraction, copy number variation, subgenomic interval, etc. The title should be "descriptive" and "as... specific as possible" (MPEP 606, 1st para. and 37 CFR 1.72; also MPEP 606.01 pertains). The present title, substantively, recites "...EVALUATING TUMOR FRACTION," but there are at least 87 applications and patents with "tumor fraction" in their titles, rendering the present title insufficiently specific, in particular relative to the detailed recitation of the independent claims. This objection is maintained. Claim rejections - 112/b The following is a quotation of 35 USC 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. Claims 1, 3-13, 15-26 and 29-30 are rejected under 112/b, as indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claims depending from rejected claims are rejected similarly, unless otherwise noted, and any amendments in response to the following rejections should be applied throughout the claims, as appropriate. With regard to any suggested amendment below, for claim interpretation during the present examination it is assumed that each amendment suggested here is made. However equivalent amendments also would be acceptable. The following issues cause the respective claims to be rejected under 112/b as indefinite: Claim Recitation Comment (suggestions in bold) 1, 13 determining... a tumor fraction In the 2nd "determining" step, the relationship is unclear between this instance of "a tumor fraction" and that in the preamble. Possibly this instance should recite "the" instead of "a." Claim 13 is rejected similarly. 1, 10, 13, 30 determining... the target variable values In the 2nd "determining" step, the recitation requires but lacks clear antecedent at least because the preceding instance instantiates "value" as singular. It is not clear how the previously recited "a value for a target variable associated with each of a plurality of subgenomic intervals" (1st "determining" step) relates to this plural instance of "values." If it is intended that the original instance of "value" is plural such that different values may be associated with different intervals, then this may be clarified. Claims 13 and 13 are rejected similarly. Also, in claim 10, the recited "the plurality of target variable values" requires but lacks clear antecedent. 1, 13, 30 determining... determined by modeling In the 2nd "determining" step, the relationship is unclear between the finally recited "determined by modeling" and the preceding recitations at least because (i) it is not clear what this final clause modifies, e.g. "tumor fraction," "tumor purity" or "tumor ploidy" and (ii) it is not clear whether the recited "without" applies to this recited "determined by modeling," e.g. whether the correct interpretation is with or without some element being "determined by modeling." Claims 13 and 13 are rejected similarly. 1, 9, 12 (i)... at a corresponding locus...; (ii)... at a corresponding locus...; or (iii)... at a corresponding locus... The relationships are unclear between the instances of "a corresponding locus." Relatedly, the claim 9-recited "the corresponding locus" requires but lacks clear antecedent, and the same issue occurs in claim 12. This rejection might be overcome by amending to "first locus," "second locus," etc. and by clarifying whether the claims 9 and 12 recitations are newly instantiated or refer to previous recitations. 3, 15 a plurality of values The relationship is unclear between this instance and the claim 1 recited "the target variable values" (2nd "determining" step). Claim 15 is rejected similarly. 3, 15 wherein the determination of the tumor fraction for the sample comprises:... The relationship is unclear between claims 1 and 3, in particular the relationship between the "tumor fraction" determinations of claims 1 vs. 3. For example, claim 1 recites "determining... a tumor fraction...based on the target variable values...," but claim 3, while reciting "determination of the tumor fraction for the sample comprises:...," does not recite "target variable values." Claim 3 does not clearly narrow claim 1 at least because it is ambiguous which of the recitations of claim 1continue to apply in claim 3. Claim 15 is rejected similarly. 8, 20 an allele fraction The relationship is unclear between this instance and the two instances in claim 1 at (i) and (ii). More generally, the relationship is unclear between the claim 3 "plurality of values" and the other recitations of "allele fraction" and "values" throughout claims 1 and 3. This rejection might be overcome, for example, by more particularly reciting the "plurality of values" at its instantiation in claim 3, e.g. relative to other data elements such as "allele fraction" and "values" throughout claims 1 and 3. Claim 20 is rejected similarly. 12, 24 Not clearly interpretable due to the complexity of the grammatical construction and placement of commas. For example, it does not appear that a comma is appropriate within the recited "a ratio of the difference..., relative to abundance..." Similarly, it does not appear that the placement of commas is correct within "and the expected value comprises the expected ratio of the difference in abundance between a maternal allele and a paternal allele... relative, to abundance of the maternal allele or the paternal allele, wherein the expected value is the expected ratio for a non-tumorous sample." In otherwise apparently parallel constructions, a comma in one instance appears before "relative" and in another instance after "relative." Possibly it would help to enumerate the recited parts of each ratio. Claim 24 is rejected similarly. 12, 24 the expected ratio Requires but lacks clear antecedent. Claim 24 is rejected similarly. 12, 24 the expected ratio for a non-tumorous sample Requires but lacks clear antecedent. Claim 24 is rejected similarly. Claim rejections - 35 USC 103 In the event the determination of the status of the application as subject to AIA 35 USC 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 35 USC 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 of this title, 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. 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 USC 102(b)(2)(C) for any potential 35 USC 102(a)(2) prior art against the later invention. Claims 1, 13 and 30 Claims 1, 13 and 30 are rejected under 35 USC 103 as being unpatentable over Wu 2019b ("Plasma DNA analysis in prostate cancer: opportunities for improving clinical management." Clinical Chemistry 65.1 (2019): 100-107, as cited on the attached Form PTO-892) and Annala (as cited on the 9/10/2025 Form PTO-892). Regarding claim 1, the wet lab steps including "providing...," "ligating...," "amplifying...," "capturing...," "sequencing..." and "receiving..." read on Annala's sampling patients with prostate cancer (Annala: p. OF11, 1st col., last paragraph; p. OF11, 2nd col., 2nd paragraph; and entire document). It would have been prima facie obvious to modify Wu 2019b using Annala as further described below. Regarding the recited "determining..." and "copy number variation (CNV)...," Wu 2019b teaches determining "copy number assessment" (Wu 2019b: p. 101, last para.; also pp. 102-103; and entire document). Regarding the recited "determining... a tumor fraction...," Wu 2019b teaches "tumor-to-normal fraction" (Wu 2019b: p. 100, §"CONTENT;" also pp. 101-103 and 105; and entire document). It is not clear that Wu 2019b relies on either tumor purity or tumor ploidy in its teaching "tumor-to-normal fraction" (Wu 2019b: p. 100, §"CONTENT;" also pp. 101-103 and 105; and entire document). Also, in a BRI, the recited "without using a tumor purity or a tumor ploidy" (e.g. claim 1) reads on embodiments in which one but not the other is used. That is, in a BRI, it is sufficient to forego only one. The art is applied to claims 13 and 30 similarly to as described for claim 1. The claim 30 computational elements read on Annala's "computational analysis" (Annala: p. OF12, 2nd col.; and entire document). Combining Wu 2019b and Annala It would have been prima facie obvious to modify Wu 2019b using Annala to arrive at the claimed invention. One would have been motivated to combine the lab steps with Annala with those of Wu 2019b because Annala teaches a baseline for comparison and the importance of copy number (p. 447 1st col., 2nd para.; p. 447, 2nd col., 3rd para.). Both Wu 2019b and Annala are directed to determining tumor fraction, and therefore one of ordinary skill in the art would be expected to successfully combine their teachings. No prior art has been applied to the following claims No prior art is applied to claims 3-12, 15-26 and 29. Neither art in the search results nor art on the IDSs teaches the particularly recited use of a certainty metric in the recited context, and it is not clear that any combinable art of record would have rendered the claims obvious. Claim rejections - 101 35 USC 101 reads: 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. For each rejection below, dependent claims are rejected similarly as not remedying the rejection, unless otherwise noted. Response to arguments regarding Claim Rejections - 35 USC 101 -- Abstract idea Applicant states (original emphasis removed, bold emphasis added, applicant remarks: p. 11): ...the amended claims practically apply the alleged judicial exception, as evidenced by the technical improvement in the fields of genomics and medical diagnostics. In particular, the claimed methods allow for the determination of a tumor fraction, an important indicator for monitoring cancer in a subject, without using a tumor purity and tumor ploidy determined by modeling, which is a substantial technical advantage compared to prior tumor fraction determination methods, as further discussed below. Thus, the claims are also subject matter eligible under Step 2A, Prong Two of the Subject Matter Eligibility test. ...As explained in paragraphs [0058] and [0059] of the application: ... Traditional approaches for predicting tumor fraction can be highly unreliable for low tumor content due to poorly fit models. In some embodiments, the methods described herein can overcome certain drawbacks of the traditional approaches, for example, by determining tumor fraction (and associated confidence levels) based on the effects of tumor cell aneuploidy, e.g., as measured by the allele coverage or allele fraction at one or more subgenomic intervals in a sample. It is not yet clear what is the improvement in the form of practical application which must result for the recited "...without using a tumor purity or a tumor ploidy for the sample" (e.g. claim 1). These conditions may be true with respect to the recited process and its analyses, but it is not yet clear what improvement in the form of practical application must result. Also, it is not yet clear that the claims are limited to delivering the asserted improvements. First, it is not clear that the previous state of the technology must suffer from the asserted problems, noting for example the asserted "can be" language. Second, the asserted problem appears to be asserted in the context of "low tumor content," but the claims are not limited to this context. Third, the asserted "highly unreliable" is insufficiently specific as to "unreliable" "tumor fraction" in what sense and as to why. Fourth, to the extent that the 101 argument relies on improvement with respect to modeling, it is not yet sufficiently clear as to (i) what role modeling plays in the claims and (ii) how and why the modeling is improved and (iii) what is the effect of any improvement to modeling. It can be agreed that a Step 2A, Prong Two explanation of improvement is not limited to what is explicitly disclosed in the instant specification. Rather, arguments and evidence may be extrinsic to the original disclosure, including references available after the priority date, as long as it is clear that an argument applies to all embodiments of a properly supported claim. Judicial exceptions (JE) to 101 patentability Claims 1, 3-13, 15-26 and 29-30 are rejected under 35 USC 101 because the claimed inventions are not directed to patent eligible subject matter. After consideration of relevant factors with respect to each claim as a whole, each claim is directed to one or more JEs (i.e. an abstract idea, a natural phenomenon, a law of nature and/or a product of nature), as identified below. Any elements or combination of elements beyond the JE(s) (i.e. "additional elements") are conventional and do not constitute significantly more than the JE(s). Thus, no claim includes additional elements amounting to significantly more than the JE(s), as explained below. In Alice, citing Mayo and Bilski, two Mayo/Alice questions determine eligibility under 101: First, is a claim directed to a JE? And second, if so, does the claim recite significantly more than the JE? MPEP 2106 organizes JE analysis into Steps 1, 2A (1st & 2nd prongs) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: www.uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials. Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter? -- MPEP 2106.I and 2106.03 [Step 1: claims 1, 13 and 30: YES] Step 2A, 1st prong: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea? -- abstract idea -- MPEP 2106.I and 2106.04 Preliminarily, in a 1st prong of Step 2A, elements of independent claim 1 are interpreted as directed to the abstract idea of calculating a tumor fraction including the JE elements of "determining... a value..." and "determining... a tumor fraction...," each of which, including all recitation within each listed element, in at least some embodiments within a BRI, involves only manipulation of data. While manipulation of data is not per se directed to an abstract idea, in this instance the above-identified elements are directed to the abstract ideas identified below. Claims 13 and 30 are analyzed similarly. BRIs of the claims are analogous to an abstract idea in the form of at least a mental process, at least equivalent to a computer-implemented process, including obtaining and comparing intangible data (e.g. Cybersource, Synopsys and Electric Power Group). In a BRI, it is not clear that the claim embodiments are limited so as to require complexity precluding analogy to a mental process. BRIs of the claims also are analogous to an abstract idea in the form of a mathematical concept, including mathematical relationships and calculations, as found in the following case law, as cited and discussed above: collecting information, analyzing it, and displaying certain results of the collection and analysis (Electric Power Group) and/or obtaining and comparing intangible data (e.g. Cybersource, Ambry and Myriad CAFC) and/or execution of an algorithm to implement mathematical relationships and/or formulas, including image processing (e.g. TLI, Digitech, Benson, Flook, Diehr, FuzzySharp, In re Grams and In re Abele all as cited in MPEP 2106). Instant examples of math concepts include the recited determining, using the one or more processors, a tumor fraction for the sample based on the target variable values of claims 1, 13 and 30, as well as relationships inherent in these recitations as the only supported embodiments. The preceding case law examples are cited for the basic form of their identified abstract ideas, and analogy to these example abstract ideas need not be within the same technology field, 101 analysis generally being assumed to be neutral with respect to technology field. Regarding inherency of abstract ideas, MPEP 2106.04.II.A.1 includes: "the claims in Alice Corp. v. CLS Bank, 'described' the concept of intermediated settlement without ever explicitly using the words 'intermediated' or 'settlement'" (emphasis added, p. 1). Similarly, inherency can effectively be recitation, as in, for example, "By claiming simply 'crystalline paroxetine hydrochloride hemihydrate' with no reference to how it was produced, SKB effectively claimed 'crystalline paroxetine hydrochloride hemihydrate whether non-naturally occurring or arising through natural conversion.' Claim 1, as issued, therefore combines patentable and unpatentable subject matter, and is invalid under Section 101." (capitalization added, SmithKline Beecham Corp. v. Apotex Corp., 365 F.3d 1306, 1321-33, Fed. Cir. 2004). In the instant type of data processing claims, the specification is not merely adding background explanation as to how a claimed process works, e.g. a physical process based on, involving or further explained by abstract ideas and natural laws. Rather, the specification is detailing the only disclosed way that a programmer may proceed from the recited inputs to the recited outputs, e.g. through actual performance of the disclosed judicial exceptions (JEs). Regarding the "Meaning of 'Recites,'" MPEP 2106.04.II.A.1 states: In Prong One examiners evaluate whether the claim recites a judicial exception, i.e. whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim. While the terms "set forth" and "described" are thus both equated with "recite", their different language is intended to indicate that there are two ways in which an exception can be recited in a claim. For instance, the claims in Diehr, 450 U.S. at 178 n. 2, 179 n.5, 191-92, 209 USPQ at 4-5 (1981), clearly stated a mathematical equation in the repetitively calculating step, and the claims in Mayo, 566 U.S. 66, 75-77, 101 USPQ2d 1961, 1967-68 (2012), clearly stated laws of nature in the wherein clause, such that the claims "set forth" an identifiable judicial exception. Alternatively, the claims in Alice Corp., 573 U.S. at 218, 110 USPQ2d at 1982, described the concept of intermediated settlement without ever explicitly using the words "intermediated" or "settlement." While the "set forth" language approximates explicit recitation, it also is fundamental that all recitation must be interpreted and that to be patent eligible a claim must satisfy 101 according to its properly interpreted scope, e.g. for all embodiments on which the claim reads, e.g. according to any inherency pertinent to a given claim and disclosure accompanying that claim, i.e. consistent with the "described" meaning of "recites" as in the MPEP. Thus, within a BRI, the identified abstract idea elements read on one or more embodiments which only involve manipulation of data. It is not clear than any improvement argument clearly on the record causes a claim not to be directed to a JE for all embodiments within the scope of the claim. As in Alice (at 306, as cited in the MPEP above) and Bilski (as cited in Alice, id), an abstract idea may comprise multiple abstract elements or steps (i.e. from Alice: "a series of steps" at 306) and need not be a single equation, relationship or principle. It is not clear that the identified elements must represent other than an abstract idea according to any relevant analysis or case law. [Step 2A, 1st prong, abstract idea: claims 1, 13 and 30: YES] Step 2A, 2nd prong: If the claims recite a judicial exception under the 1st prong, then is the judicial exception integrated into a practical application? -- MPEP 2106.I and 2106.04(d) MPEP 2106.04(d).I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application: An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a); Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2); Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b); Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e). In Step 2A, 1st prong above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs). In Step 2B below, any remaining steps and/or elements are therefore in addition to the identified JE(s). Any such additional steps and additional elements are further discussed in Step 2B. Here in Step 2A, 2nd prong, no additional step or element clearly demonstrates integration of the JE(s) into a practical application. At this point in examination it is not yet the case that any of the Step 2A, 2nd prong considerations enumerated above clearly demonstrates integration of the identified JE(s) into a practical application. Referring to the considerations above, none of 1. an improvement, 2. treatment, 3. a particular machine or 4. a transformation is clear in the record. For example, regarding the first consideration at MPEP 2106.04(d)(1), the record, including for example the specification, does not yet clearly disclose an explanation of improvement over the previous state of the technology field. The claims do not yet clearly result in such an improvement (e.g. specification: [90-92, 386, 430]). [Step 2A, 2nd prong: claims 1, 13 and 30: NO] Step 2B: Do the claims recite a non-conventional arrangement of additional elements in addition to the identified JEs? -- MPEP 2106.I and 2106.05 Addressing the second Mayo/Alice question, all elements of claims 1, 13 and 30 are part of one or more identified JEs (as described above), except for elements identified here as conventional elements in addition to the above judicial exceptions: The recited "providing...," "ligating...," "amplifying...," "capturing...," "sequencing..." and "receiving..." (in claim 1 and similarly in claims 13 and 30) are conventional elements of a laboratory and/or computing environment and/or conventional data gathering/input elements, as exemplified by Annala (as cited on the attached Form PTO-892). It is emphasized that, outside of an improvement argument, analysis of what is conventional generally pertains to the above-identified additional elements and not to elements identified as part of a JE. [Step 2B: claims 1, 13 and 30: NO] Summary and conclusion regarding claims 1, 13 and 30 Summing up the above analysis of claims 1, 13 and 30, each viewed as a whole and considering all elements individually and in combination, no claim recites limitations that transform the claim, finally interpreted as directed to the identified JE(s), into patent eligible subject matter, and it is not clear that any claim is sufficiently analogous to controlling case law identifying an example of an eligible claim. Remaining claims Claims 3-12, 15-26 and 29 add elements which also are part of the identified JEs for the same reasons described above regarding the independent claims and therefore do not provide the something significantly more necessary to satisfy 101. None of the dependent claim elements provides the something significantly more than the identified JE(s) necessary to satisfy 101. Nonstatutory double patenting The nonstatutory double patenting rejection is based on a judicially created doctrine to prevent the improper timewise extension of the "right to exclude" granted by a patent and to prevent multiple suits against an accused infringer by different assignees of the same invention (MPEP 804.II.B, 1st para.). A nonstatutory double patenting rejection is appropriate where the conflicting claims (instant v. reference) are not identical, but an examined-application claim (instant claim) is not patentably distinct from a reference claim because the instant claim is either anticipated by, or would have been obvious over, the reference claim (MPEP 804.II.B, 2nd para.). In cases of double patenting rejections versus reference claims of pending applications, as opposed to claims of an issued patent, the rejections are provisional because the reference claims have not been patented. Presently, no rejections are provisional. 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 application or patent of the reference claim either is shown to be commonly owned with the instant application or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must comply fully with 37 CFR 3.73(b). Applicant may wish to consider electronically filing a terminal disclaimer (MPEP 1490.V pertains, along with https://www.uspto.gov/patents-application-process/applying-online/eterminal-disclaimer). Electronic filing may lead to faster approval of the disclaimer. Also, if filing electronically, Applicant is encouraged to notify the examiner by telephone so that examination may resume more quickly. Double patenting rejections of instant claims 1, 3-13, 15-26 and 29-30 Instant claims 1, 3-13, 15-26 and 29-30 are rejected on the grounds of nonstatutory double patenting as unpatentable over one or more claims in reference applications 17/612,966 and 18/570,600 and 19/020,349 in view of Wu 2019b (as cited on the attached Form PTO-892) and Annala (as cited on the 9/10/2025 Form PTO-892). Although the reference claims are not identical to the instant claims, in a BRI they also are not patentably distinct from the instant claims: either (i) because the instant claims recite obviously equivalent or broader limitations in comparison to the reference claims or (ii) because the instant claims recite limitations which are obvious over the cited art. It is not clear that the instant claims recite limitations which are narrower than limitations in the reference claims. Each reference application recites claims which involve analyzing tumor fraction. The instantly recited determining a tumor fraction would have been prima facie obvious in view of the cited art. It would have been obvious in view of the cited art to modify reference claims to arrive at the rejected instant claims. Either the instant limitations are interpreted as reading on a reference limitation, or the instant limitations would have been obvious in view of the cited art. That is, to the extent that any instant claims are narrower than reference claims, then any such narrowing would have been obvious over the cited art. Citations to art In the above citations to documents in the art, rejections refer to the portions of each document cited as example portions as well as to the entirety of each document, unless otherwise noted in the situation of lengthy, multi-subject documents. Other passages not specifically cited within a document may apply as well. Conclusion No claim is allowed. A shortened statutory period for reply is set to expire THREE MONTHS from the mailing date of this communication. Inquiries Information regarding the filing, management and status of patent applications which are published (available to all users) or unpublished (available to registered users) may be obtained from the Patent Center: https://patentcenter.uspto.gov. Further information is available at https://www.uspto.gov/patents/apply/patent-center, and information about filing in DOCX format is available at https://www.uspto.gov/patents/docx. The Electronic Business Center (EBC) at 866-217-9197 (toll-free) is available for additional questions, and assistance from a Customer Service Representative is available at 800-786-9199 (IN USA OR CANADA) or 571-272-1000. The examiner for this Office action, G. Steven Vanni, may be contacted at: (571) 272-3855 Tu-F 8-7 (ET). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D. Riggs, II, may be reached at (571) 270-3062. /G. STEVEN VANNI/Primary patents examiner, Art Unit 1686
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Prosecution Timeline

Apr 04, 2025
Application Filed
Sep 06, 2025
Non-Final Rejection — §101, §103, §DP
Dec 09, 2025
Response Filed
Feb 05, 2026
Non-Final Rejection — §101, §103, §DP (current)

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Prosecution Projections

2-3
Expected OA Rounds
66%
Grant Probability
92%
With Interview (+25.1%)
4y 1m
Median Time to Grant
Moderate
PTA Risk
Based on 581 resolved cases by this examiner. Grant probability derived from career allow rate.

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