DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendments and arguments filed 8/3/2026 have been entered and carefully considered but are not completely persuasive.
Claims 19-28 are pending and under examination.
The IDS filed 8/3/2026 has been entered and considered.
The substitute specification filed 8/3/2026 has been entered.
The rejection under 35 USC 112 (b) and (d) have been withdrawn.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 19-28 is/are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental steps, mathematic concepts, organizing human activity, or a natural law without significantly more.
Applicant is directed to MPEP 2106 and the Federal Register notice (FR89, no 137 (7/17/2024) p 58128-58138) for the most current and complete guidelines in the analysis of patent- eligible subject matter. The current MPEP is the primary source for the USPTO’s patent eligibility guidance.
With respect to step (1): YES, the claims are drawn to statutory categories: The claims recite processes.
With respect to step (2A) (1): YES, the claims recite an abstract idea, law of nature and/or natural phenomenon. The claims explicitly recite elements that, individually and in combination, constitute one or more judicial exceptions (JE).
Mathematic concepts, Mental Processes or Elements in Addition (EIA) in the claim(s) include:
19. (New) A method of classifying a test subject as having cancer or not having cancer, the method comprising:
(Preamble, indicating a method, and the goal of the method.)
(a) obtaining a test sample comprising cfDNA from the test subject,
(EIA- a step of data gathering: obtaining a sample, of any type, by any means as long as it comprises cfDNA)
(b) obtaining sequences of at least a portion of cfDNA molecules present in the test sample from the test subject, wherein the sequences have endpoints and the sequences are mappable to genomic locations;
(EIA- a step of data gathering: sequencing the sample, by any means, and a description of the sequences obtained.)
(c) calculating a set of test sample values indicative of the frequency of cfDNA endpoints mapping to single base genomic locations in a defined genome region comprising a plurality of single base genomic locations, wherein the test sample values are calculated using a mathematical transformation of a count of cfDNA endpoints mapping to the single base genomic locations in the genomic region and representing the distribution of the number of cfDNA endpoints occurring at multiple single base locations in the genome region;
(Mathematic Concept: calculating values “indicative of frequency” using a transformation which accounts for counts and a distribution. MPEP 2106.04(a)(2) Section I)
(d) determining a likelihood that the test sample contains tumor DNA by comparing the test sample values calculated from the frequency of cfDNA endpoints in step (c), with a plurality of reference values, wherein the reference values are calculated as in step (c), and the genome region used in the calculation is the same as the genome region in step (c), wherein the reference values are determined from cfDNA in a plurality of reference samples obtained from individuals known to not have cancer or known to have cancer; and
(Mathematic concept of comparing the data values and calculating a likelihood; Alternatively, a mental process of observing the data values, comparing them, and making a judgement as to whether they correlate or not. MPEP 2106.04(a)(2) Sections I and III.)
(e) classifying the test subject as (i) having cancer when the test sample is classified as containing tumor DNA or (ii) not having cancer when the test sample is classified as not containing tumor DNA, wherein the test sample is classified as containing or not containing tumor DNA using the likelihood determined in step (d), wherein the classification of the test sample is dependent upon meeting a classification threshold.
(Mental process of observing a calculated likelihood value, comparing it to a threshold, and making a judgement as to whether the sample contains tumor DNA, or not. Alternatively, a mathematic concept of whether the likelihood value is greater than, or less than, a threshold value. MPEP 2106.04(a)(2) Sections I and III.)
20. The method of claim 19, wherein the plurality of reference samples is obtained from individuals known to not have cancer and from individuals known to have cancer.
(EIA- a step related to data gathering: describing sample data gathered from reference individuals.)
21. The method of claim 19, wherein steps (c) and (d) are performed for a plurality of genome regions.
(Mathematic concepts and mental processes: iterating steps b) and c).)
22. The method of claim 19, wherein at least one genome region comprises a transcription factor binding site.
(Mental Process/ mathematic concept modification: spelling out the type of region to which the sequence reads should map.)
23. The method of claim 19, wherein at least one genome region comprises a CTCF binding site.
(Mental Process/ mathematic concept modification: spelling out the type of region to which the sequence reads should map.)
24. The method of claim 19, wherein the cfDNA sequenced comprises DNA derived from hematopoietic cells and non-hematopoietic cells, and wherein at least a portion of the non-hematopoietic cells are tumor cells.
(EIA- related to data gathering: describing the sample gathered.)
25. The method of claim 19, wherein the test values and reference values are calculated for a plurality of genomic locations.
(Mathematic concepts and mental processes: iterating steps b) and c) at different locations.)
26. The method of claim 19, wherein the cfDNA is sequenced on a massively parallel DNA sequencer.
(EIA- data gathering, specifying a type of sequencer to be utilized in sequencing the sample.)
27. The method of claim 19, wherein the test sample is a blood sample.
(EIA- data gathering, describing the type of sample to be gathered.)
28. The method of claim 27 wherein the reference samples are blood samples.
(EIA- data gathering, describing the type of sample to be gathered.)
Natural law embraced by claim(s) 19-28:
The claims embrace the naturally occurring correlation between naturally occurring changes in genetic material, and a naturally occurring phenotype of cancer.
With respect to step 2A (2): NO, the claims do not integrate any JE into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone, or in combination to determine if the JE is integrated into a practical application (MPEP 2106.05(a-c, e, f and h)).
Claim(s) 19-20, 24, 26-28 recite the additional non-abstract element(s) of data gathering, or a description of the data gathered.
Data gathering steps are not an abstract idea, they are extra-solution activity, as they collect the data needed to carry out the JE. The data gathering does not impose any meaningful limitation on the JE, or how the JE is performed. The additional limitation (data gathering) must have more than a nominal or insignificant relationship to the identified judicial exception. (MPEP 2106.04/.05, citing Intellectual Ventures LLC v. Symantec Corp, McRO, TLI communications, OIP Techs. Inc. v. Amason.com Inc., Electric Power Group LLC v. Alstrom S.A.).
Dependent claim(s) 21-23, 25 recite(s) an abstract limitation to the JE reciting additional mathematic concepts, or mental processes. Additional abstract limitations cannot provide a practical application of the JE as they are a part of that JE.
In combination, the limitations of data gathering, for the purpose of carrying out the JE, using a general-purpose computer merely provide extra-solution activity, and fail to integrate the JE into a practical application.
With respect to step 2B: NO. The claims recite a JE, do not integrate that JE into a practical application, and thus are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). The additional elements were considered individually and in combination to determine if they provide significantly more than the judicial exception. (MPEP 2106.05.A i-vi).
With respect to claim(s) 19-20, 24, 26-28: The limitation(s) identified above as non-abstract elements (EIA) related to data gathering do not rise to the level of significantly more than the judicial exception.
Chudova (US 2016/0019338 A1) obtains samples comprising cfDNA, and sequences them, providing mappable reads with endpoints.
Lo et al. (US 2013/0040824 A1) obtains samples comprising cfDNA, and sequences them, providing mappable reads, with endpoints.
Song et al. (US 2012/0164646 A1) obtains samples comprising cfDNA, from samples that may contain normal and tumor/ cancer cells, sequences the cfDNA, providing mappable reads with endpoints.
Benz et al. (US 2013/0017958 A1) obtains samples comprising cfDNA, sequences them, providing mappable reads with endpoints.
Quake et al. (US 2012/0295810 A1) obtains samples of plasma comprising cfDNA, sequences them, and provides mappable reads with endpoints.
Schuetz et al. (US 2013/0116127 A1) obtains samples of plasma, blood or serum which comprise cfDNA, sequences the samples, providing mappable reads with endpoints to diagnose cancer.
Rabinowitz et al. (US 2011/0288780) obtain samples of blood or plasma which comprise cfDNA, sequences them to provide mappable reads with endpoints.
Scholl et al. (US 2012/0021919 A1) obtains samples of plasma which comprise cfDNA, sequences them, and provides mappable reads with endpoints which map to genomic regions.
These elements meet the BRI of the identified data gathering limitations. As such, the prior art recognizes that this data gathering element is routine, well understood and conventional in the art (as in Alice Corp., CyberSource v. Retail Decisions, Parker v. Flook).
In the specification at [0166-0167] it is disclosed that the steps identified as data gathering can be met using the publicly available sequence read datasets.
Activities such as data gathering do not improve the functioning of a computer, or comprise an improvement to any other technical field. The limitations do not require or set forth a particular machine, they do not effect a transformation of matter, nor do they provide an unconventional step (citing McRO and Trading Technologies Int’l v. IBG). Data gathering steps constitute a general link to a technological environment. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception are insufficient to provide significantly more (as discussed in Alice Corp.,).
Dependent claim(s) 21-23, 25 each recite a limitation requiring additional mathematic concepts or mental processes. Additional abstract limitations cannot provide significantly more than the JE as they are a part of that JE (MPEP 2106.05).
In combination, the data gathering steps providing the information required to be acted upon by the JE, performed in a generic computer or generic computing environment fail to rise to the level of significantly more than that JE. The data gathering steps provide the data for the JE, which is carried out by the general-purpose computers. No non-routine step or element has clearly been identified.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. For these reasons, the claims, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Applicant’s arguments:
Applicant’s arguments have been carefully considered but are not persuasive.
The examiner acknowledges Applicant’s arguments which set forth that the claims lead to an improvement in the determining the presence or absence of cancer. According to the guidance set forth in MPEP 2106, this is an improvement to the judicial exception itself and is not reflected back into a specific technological environment or practically applied process.
An improvement in the judicial exception itself is not an improvement in technology. For example, in In re Board of Trustees of Leland Stanford Junior University, 989 F.3d 1367, 1370, 1373 (Fed. Cir. 2021) (Stanford I), Applicant argued that the claimed process was an improvement over prior processes because it ‘‘yields a greater number of haplotype phase predictions,’’ but the Court found it was not ‘‘an improved technological process’’ and instead was an improved “mathematical process.’’ The court explained that such claims were directed to an abstract idea because they describe ‘‘mathematically calculating alleles’ haplotype phase,’’ like the ‘‘mathematical algorithms for performing calculations’’ in prior cases. Notably, the Federal Circuit found that the claims did not reflect an improvement to a technological process, which would render the claims eligible (FR89 no.137, p58137, 7/17/2024).
Here, Applicant has provided an improved mathematical process of calculating a likelihood that the test sample includes tumor DNA.
The improvement in calculating a likelihood that the test sample includes tumor DNA (carried out by the judicial exception) does not provide an improvement in the technology of receiving a test sample or obtaining sequences of at least a portion of cfDNA molecules. The collection of samples and sequence data is carried out, unchanged, whether or not the judicial exception is applied. (Cleveland Clinic Foundation: using well-known or standard laboratory techniques is not sufficient to show an improvement (MPEP2106.05(a)).
The improvement in calculating a likelihood that the test sample includes tumor DNA (achieved by the judicial exception) does not require a non-conventional interaction with a specific element of a computer as was required in Enfish. The disputed claims in Enfish were patent-eligible because they were "directed to a specific improvement to the way computers operate, embodied in [a] self-referential table." Enfish, 822 F.3d at 1336. The court found that the "plain focus of the claims" there was on an improvement to computer functionality itself-a self-referential table for a computer database, designed to improve the way a computer carries out its basic functions of storing and retrieving data- not on a task for which a computer is used in its ordinary capacity. Id. at 1335-36. The court noted that the specification identified additional benefits conferred by the self-referential table (e.g., increased flexibility, faster search times, and smaller memory requirements), which further supported the court's conclusion that the claims were directed to an improvement of an existing technology. Id. at 1337 (citation omitted).
The improvement in calculating a likelihood that the test sample includes tumor DNA (carried out by the judicial exception) does not improve the functionality of the computer itself as in Finjan, Visual Memory, or SRI Int’l. In Finjan, claims to virus scanning were found to be an improvement in computer technology. In Visual Memory, claims to an enhanced computer memory system were found to be directed to an improvement in computer capabilities. In SRI Int'l, claims to detecting suspicious activity by using network monitors and analyzing network packets were found to be an improvement in computer network technology.
The improvement in calculating a likelihood that the test sample includes tumor DNA does not provide an improvement in computer animation and use rules to automate a subjective task of humans to create a sequence of synchronized, animated characters as in McRo. In McRO, it was not the mere presence of unconventional rules that led to patent eligibility. In McRO, "[t]he claimed improvement was to how the physical display operated (to produce better quality images)." SAP Am. v. InvestPic, LLC, 898 F.3d 1161, 1167 (Fed. Cir. 2018). The claims in McRO recited a step of applying the data sets generated using the specific claimed rules to a sequence of animated characters to produce lip synchronization and facial expression control of those animated characters. McRO, 837 F.3d at 1308. Thus, the claims were directed to an improvement in computer animation and used rules to automate a subjective task of humans to create a sequence of synchronized, animated characters. Id. at 1314--15.
In the claims at issue here, there is no such application of specifically claimed rules to produce an improved technological result. The process of calculating a likelihood that the test sample includes tumor DNA is not a technological process; it is information evaluation.
It is noted the claims are not computer-implemented, thus any arguments about improvement to a computer are not persuasive.
The MPEP sets forth that “if the examiner concludes the disclosed invention does not improve technology, the burden shifts to applicant to provide persuasive arguments supported by any necessary evidence to demonstrate that one of ordinary skill in the art would understand that the disclosed invention improves technology. Any such evidence submitted under 37 CFR 1.132 must establish what the specification would convey to one of ordinary skill in the art and cannot be used to supplement the specification.” Applicant’s arguments cannot take the place of evidence.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 19-28 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,352,670. Although the claims at issue are not identical, they are not patentably distinct from each other because the steps representing the invention are the same with the difference being that the application actively obtains a sample, and the method is intended to diagnose cancer.
Conclusion
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARY K ZEMAN whose telephone number is 5712720723. The examiner can normally be reached on 8am-2pm M-F. Email may be sent to mary.zeman@uspto.gov if the appropriate permissions have been filed.
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, Larry Riggs can be reached on 571 270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARY K ZEMAN/ Primary Examiner, Art Unit 1686
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