Prosecution Insights
Last updated: August 15, 2026
Application No. 17/144,021

BITERMINAL DNA FRAGMENT TYPES IN CELL-FREE SAMPLES AND USES THEREOF

Final Rejection §101
Filed
Jan 07, 2021
Priority
Jan 08, 2020 — provisional 62/958,676
Examiner
HAYES, JONATHAN EDWARD
Art Unit
1685
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Grail LLC
OA Round
5 (Final)
38%
Grant Probability
At Risk
6-7
OA Rounds
0m
Est. Remaining
61%
With Interview

Examiner Intelligence

Grants only 38% of cases
38%
Career Allowance Rate
27 granted / 72 resolved
-22.5% vs TC avg
Strong +24% interview lift
Without
With
+23.5%
Interview Lift
resolved cases with interview
Typical timeline
4y 8m
Avg Prosecution
35 currently pending
Career history
105
Total Applications
across all art units

Statute-Specific Performance

§101
41.3%
+1.3% vs TC avg
§103
24.7%
-15.3% vs TC avg
§102
6.1%
-33.9% vs TC avg
§112
23.8%
-16.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 72 resolved cases

Office Action

§101
DETAILED ACTION Applicant’s response, filed 06 April 2026, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. 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 . Claim Status Claims 1-9, 11, 12, 23, 25, 29, 30, and 47-49 are pending and examined herein. Claims 1-9, 11, 12, 23, 25, 29, 30, and 47-49 are rejected. Priority Claims 1-9, 11, 12, 23, 25, 29, 30, and 47-49 are granted the claim to the benefit of priority to U.S. Provisional application 62/958676 filed 08 January 2020. Thus, the effective filling date of claims 1-9, 11, 12, 23, 25, 29, 30, and 47-49 is 08 January 2020. Information Disclosure Statement The information disclosure statements (IDS) were received on 18 November 2025, 26 January 2026, 16 April 2026, and 11 June 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner. 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. The rejection below has been modified necessitated by amendment. Claims 1-9, 11, 12, 23, 25, 29, 30, and 47-49 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. (Step 1) Claims 1-9, 11, 12, 23, 25, 29, 30, 47, and 49 falls under the statutory category of a process and claim 48 falls under the statutory category of a machine. (Step 2A Prong 1) Under the BRI, the instant claims recite judicial exceptions that are an abstract idea of the type that is in the grouping of a “mental process”, such as procedures for evaluating, analyzing or organizing information, and forming judgement or an opinion. The instant claims recite judicial exceptions that are an abstract idea of the type that is in the grouping of a “mathematical concept”, such as mathematical relationships and mathematical equations. The instant claims recite judicial exceptions that are an abstract idea of the type that is in the grouping of a “law of nature”. Independent claims 1 and 48 recite a mental process of for each of the at least 10,000 cell free DMA fragments, determining a pair of sequence motifs for the ending sequences of the cell-free DNA fragment, determining a pattern of a set of sequence motif pairs corresponding to the ending sequences of the at least 10,000 cell-free fragments, wherein the pattern provides a relationship of the plurality of cell-free DNA fragments that have a pair of ending sequences among the set of sequence motif pairs, generating, using a machine learning model, an output value by processing the pattern of the set of sequence motif pairs, the machine learning model having been trained to generate output values based on patterns of sequence motif pairs of training samples having a known classification of a pathology, determining a classification of a level of the pathology for the subject based on comparison of the output value to a reference value. Independent claims 1 and 48 recite mathematical concepts of determining a pattern of a set of sequence motif pairs corresponding to the ending sequences of the at least 10,000 cell-free fragments, wherein the pattern provides a relationship of the plurality of cell-free DNA fragments that have a pair of ending sequences among the set of sequence motif pairs and generating, using a machine learning model, an output value by processing the pattern of the set of sequence motif pairs, the machine learning model having been trained to generate output values based on patterns of sequence motif pairs of training samples having a known classification of a pathology. Independent claim 12 recites a mental process of for each of the at least 10,000 cell free DNA fragments, determining a pair of sequence motifs for the ending sequences of the cell-free DNA fragment, determining a pattern of a set of sequence motif pairs corresponding to the ending sequences of the at least 10,000 cell-free fragments, wherein the pattern provides a relationship of the plurality of cell-free DNA fragments that have a pair of ending sequences among the set of sequence motif pairs, generating, using a machine learning model, an output value by processing the pattern of the set of sequence motif pairs, the machine learning model having been trained to generate output values based on patterns of sequence motif pairs of training samples having a known fractional concentration of the clinically-relevant DNA, and determining a classification of the fractional concentration of clinically-relevant DNA in the biological sample using the output value. Independent claim 12 recites mathematical concepts of determining a pattern of a set of sequence motif pairs corresponding to the ending sequences of the at least 10,000 cell-free fragments, wherein the pattern provides a relationship of the plurality of cell-free DNA fragments that have a pair of ending sequences among the set of sequence motif pairs, and generating, using a machine learning model, an output value by processing the pattern of the set of sequence motif pairs, the machine learning model having been trained to generate output values based on patterns of sequence motif pairs of training samples having a known fractional concentration of the clinically-relevant DNA. Dependent claim 2 recites a mental process of filtering the cell-free DNA using one or more criteria to identify the plurality of cell-free DNA fragments. Dependent claim 9 recites mental processes of determining an additional pattern of a set of additional sequence motif pairs corresponding to the ending sequences of the plurality of cell-free DNA fragments, determining an additional output value of the additional pattern of the set of additional sequence motif pairs, determining a stage of the cancer for the subject based on a comparison of the additional output value to an additional reference value. Dependent Claim 9 further recites mathematical concepts of determining an additional pattern of a set of additional sequence motif pairs corresponding to the ending sequences of the plurality of cell-free DNA fragments, determining an additional output value of the additional pattern of the set of additional sequence motif pairs. Dependent claim 29 recites a mental process of determining one or more additional classifications for one or more additional sets of sequence motif pairs, and determining a final classification using the first classification and the one or more additional classifications. Dependent claim 49 recites a mental process of comparing the pattern of the set of sequence motif pairs to a reference pattern. The claims recite a process of for each of the at least 10,000 cell-free DNA fragments, determining a pair of sequence motifs for the ending sequences of the cell-free DNA fragment encompasses making observations and evaluating sequence data (which encompasses sequences of any length represented by letters to distinguish bases in the sequence) to determine a pair of sequence motifs for the ending sequences of the cell-free DNA fragment (which encompasses making an observation of the first base of the sequence of the fragment and the last base of the sequence of the fragment and extracting this information as a pair) for at least 10,000 cell-free DNA fragments (which encompasses repeating this observation and evaluation for each cell-free DNA fragment in the at least 10,000 cell-free DNA fragments), determining a pattern of a set of sequence motif pairs corresponding to the ending sequences of the at least 10,000 cell-free fragments (which encompasses generating a relative frequency represented as a fraction of a sequence motif pair see instant disclosure [0063], [0081], and [0082]), generating, using a machine learning model, an output value by processing the pattern of the set of sequence motif pairs encompass generating and output value using a fitted logistic regression model (i.e., the trained machine learning model see instant disclosure [0081]) by processing numerical values of relative frequencies of sequence motif pairs (which encompass numerical values of fractions) through multiplication, subtraction and addition. Further, the human mind is capable of processing numerical values with mathematical operations of multiplication, subtraction and addition according to a fitted logistical regression model (which encompasses a logistical regression equation), determining a classification of a level of the pathology using the output value. The human mind is capable of make observations, evaluating data based on the observations, and making a judgment based on the evaluated data. Though the claim requires 10,000 cell-free fragments to be analyzed, the action of determining a pair of sequence motifs for the ending sequences of the cell-free DNA fragment is a mental process of making an observation about data. The amount of data requires multiple repetitions of performing the mental process but does not change the nature of the step in a manner that excludes a human observing particular aspects of data. The MPEP states are 2106.04(a)(2)(I)(C) that “There is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, a claim does not have to recite the word "calculating" in order to be considered a mathematical calculation. For example, a step of "determining" a variable or number using mathematical methods or "performing" a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation”. The BRI of the step of determining a pattern of a set of sequence motif pairs corresponding to the ending sequences of the at least 10,000 cell-free DNA fragments, wherein the pattern provides a relationship of the plurality of cell-free DNA fragments that have a pair of ending sequences among the set of sequence motif pairs encompasses calculating a relative frequency which is a mathematical calculation (see instant disclosure [0081] and [0082]) and as shown by the instant disclosure at [0063] a relative frequency may refer to a proportion (a percentage or fraction)).The BRI of generating, using a machine learning model, an output value by processing the pattern of the set of sequence motif pairs encompass generating and output value using a fitted logistic regression model (i.e., the trained machine learning model see instant disclosure [0081]) by processing numerical values of relative frequencies of sequence motif pairs (which encompass numerical values of fractions) through multiplication, subtraction and addition which is a series of mathematical calculations. Dependent claims 3-8, 11, 12, 23, 25, 30, and 47 further limit the mental process/mathematical concept recited in the independent claim but do not change their nature as a mental process/mathematical concept. Thus, claims 1-9, 11, 12, 23, 25, 29, 30, and 47-49 recite abstract ideas. (Step 2A Prong 2) Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). Integration into a practical application is evaluated by identifying whether there are any additional elements recited in the claim and evaluating those additional elements to determine whether they integrate the exception into a practical application. The additional element of claims 1, 12, and 48 of performing using a sequencing platform an assay on a plurality of cell-free DNA fragments from the biological sample to obtain sequence reads, wherein performing the assay includes performing sequencing to obtain sequence to obtain the sequence reads does not integrate the judicial exceptions into a practical application because this is adding insignificant extra solution activity of data gathering. This additional element constitutes as data gathering because the sequencer configured to perform an assay and the step of performing the assay only interact with the judicial exceptions in a manner by providing data to the judicial exceptions to analyze. The additional element in claims 1, 12, and 48 of using a generic computer to perform judicial exceptions does not integrate the judicial exception into a practical application because this is applying the exception to a generic computer without an improvement to a computer technology. Thus, the additional elements do not integrate the judicial exceptions into a practical application and claims 1-9, 11, 12, 23, 25, 29, 30, and 47-49 are directed to the abstract idea. (Step 2B) Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because: The additional element in claims 1, 12, and 48 of using a generic computer to perform judicial exceptions is conventional see MPEP 2106.05(b) and MPEP 2106.05(d)(II). The additional element of claims 1, 12, and 48 of performing using a sequencing platform an assay on a plurality of cell free DNA fragments form the biological sample to obtain sequence reads, wherein performing the assay includes performing sequencing to obtain the sequence reads is conventional as shown on pages 904-905 of Volik et al. (Mol Cancer Res. 2016 Oct;14(10):898-908; previously cited) and online methods of Cristiano et al. (Nature 570, 385–389 (2019); previously cited). Thus, the additional elements are not sufficient to amount to significantly more than the judicial exception because they are conventional. Response to Arguments Applicant's arguments filed 06 April 2026 have been fully considered but they are not persuasive. Argument 1: Applicant argues that the limitations of for each of the at least 10,000 cell-free DNA fragments, determining a pair of sequence motifs for the ending sequences of the cell-free DNA fragment and determining a pattern of a set of sequence motif pairs corresponding to the ending sequences of the at least 10,000 cell-free DNA fragments are additional elements because the human mind is not capable of performing these operations (Reply p. 10). Applicant provides that the previous office action appears to assert as long as one component of a step, e.g. performing for one fragment, can be practically performed mentally, then the entire step can be practically be performed mentally (Reply p. 9). Applicant further argues by such logic every single software operation can be practically be done mentally, regardless of the complexity, as the operation can be broken down to identify at least one component that can be done mentally under such as rule (Reply p. 10). Applicant provides that during an interview the example in MPEP 2106.04(a)(2)(III)(A) of comparing BRCA sequences and determining the existence of alterations where the claims cover any way of comparing BRCA sequences such that the comparison steps can be practically be performed in the human mind was provided. Applicant argues that this example relates to identifying one allele in one small sequence and not to whether a large amount of operations can be practically be performed in a persons mind (Reply p. 10). This argument has been fully considered but found to be not persuasive. The BRI of limitation of for each of the at least 10,000 cell-free DNA fragments, determining a pair of sequence motifs for the ending sequences of the cell-free DNA fragment encompasses making observations and evaluating sequence data (which encompasses sequences of any length represented by letters to distinguish bases in the sequence) to determine a pair of sequence motifs for the ending sequences of the cell-free DNA fragment (which encompasses making an observation of the first base of the sequence of the fragment and the last base of the sequence of the fragment and extracting this information as a pair) for at least 10,000 cell-free DNA fragments (which encompasses repeating this observation and evaluation for each cell-free DNA fragment in the at least 10,000 cell-free DNA fragments). It is noted that the operation itself (i.e., determining a pair of sequence motifs) is not broken down to identify one component that can be done mentally, rather the operation itself encompasses a mental process and repeatedly performing this operation on data does not change its nature of being a mental process because the human mind can repeatedly make observations and evaluations on sequencing data. It is noted that the BRI of the limitation of “for each of the at least 10,000 cell-free DNA fragments” encompasses sequentially repeating the step of determining a pair of sequence motifs for the ending sequences of the cell-free DNA fragments for each of the at least 10,000 cell-free DNA fragments. The human mind is capable of sequentially repeating the step of determining a pair of sequence motifs for the ending sequences of the cell-free DNA fragments. The example in MPEP 2106.04(a)(2)(III)(A) of comparing BRCA sequences and determining the existence of alterations where the claims cover any way of comparing BRCA sequences such that the comparison steps can be practically be performed in the human mind was provided to show that making an observation and evaluating sequence data to determine existence of alterations was considered as a mental process. It is recognized that this example does not provided iterations of this process. The MPEP 2106.04(a)(2)(III)(A) provides examples of claims that do not recite a mental process because they cannot be practically performed in the human mind of: “a claim to a method for calculating an absolute position of a GPS receiver and an absolute time of reception of satellite signals, where the claimed GPS receiver calculated pseudoranges that estimated the distance from the GPS receiver to a plurality of satellites, SiRF Tech., 601 F.3d at 1331-33, 94 USPQ2d at 1616-17” (see 2106.04(a)(2)(III)(A)). “a claim to detecting suspicious activity by using network monitors and analyzing network packets, SRI Int’l, 930 F.3d at 1304” (see 2106.04(a)(2)(III)(A)). “a claim to a specific data encryption method for computer communication involving a several-step manipulation of data, Synopsys., 839 F.3d at 1148, 120 USPQ2d at 1481 (distinguishing the claims in TQP Development, LLC v. Intuit Inc., 2014 WL 651935 (E.D. Tex. 2014))” (see 2106.04(a)(2)(III)(A)). “a claim to a method for rendering a halftone image of a digital image by comparing, pixel by pixel, the digital image against a blue noise mask, where the method required the manipulation of computer data structures (e.g., the pixels of a digital image and a two-dimensional array known as a mask) and the output of a modified computer data structure (a halftoned digital image), Research Corp. Techs., 627 F.3d at 868, 97 USPQ2d at 1280” (see 2106.04(a)(2)(III)(A)). In view of these examples provided by the MPEP there is no indication that the repetition of a step which when only performed once (or a certain amount of times in which the step is still deemed practical to be performed in the humans mind) is a mental process but passes a threshold of not being a mental process due to being repeated a certain amount of times. All examples provided by the MPEP includes claims where the operations themselves recited in the claims cannot be performed in the human mind. Thus, it is interpreted that the repetition of a mental process (e.g., determining a sequence motif pair) does not change the nature of this limitation as being a mental process. Argument 2: Applicant argues that the limitation of generating, using a machine learning model, an output value by processing the pattern of the set of sequence motif pairs, the machine learning model having been trained to generate output values based on patterns of sequence motif pairs of training samples having a known classification of a pathology is an additional element of the claim and does not recite a mental process (Reply p. 11). This argument has been fully considered but found to be not persuasive. The BRI of generating, using a machine learning model, an output value by processing the pattern of the set of sequence motif pairs encompass generating and output value using a fitted logistic regression model (i.e., the trained machine learning model see instant disclosure [0081]) by processing numerical values of relative frequencies of sequence motif pairs (which encompass numerical values of fractions) through multiplication, subtraction and addition. Further, the human mind is capable of processing numerical values with mathematical operations of multiplication, subtraction and addition according to a fitted logistical regression model (which encompasses a logistical regression equation). It is noted that the limitation of “generating, using a machine learning model, an output value by processing the pattern of the set of sequence motif pairs, the machine learning model having been trained to generate output values based on patterns of sequence motif pairs of training samples having a known classification of a pathology” was also identified as reciting a mathematical concept. The MPEP states at 2106.04(a)(2)(I)(C) that “there is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, a claim does not have to recite the word "calculating" in order to be considered a mathematical calculation. For example, a step of "determining" a variable or number using mathematical methods or "performing" a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation”. Argument 3: Applicant argues that the limitation of determining a pattern of a set of sequence motif pairs does not recite a mathematical calculation but rather merely involves mathematical concepts (Reply p. 11). This argument has been fully considered but found to be not persuasive. The MPEP states at 2106.04(a)(2)(I)(C) that “there is no particular word or set of words that indicates a claim recites a mathematical calculation. That is, a claim does not have to recite the word "calculating" in order to be considered a mathematical calculation. For example, a step of "determining" a variable or number using mathematical methods or "performing" a mathematical operation may also be considered mathematical calculations when the broadest reasonable interpretation of the claim in light of the specification encompasses a mathematical calculation”. The step of determining a pattern of a set of sequence motif pairs corresponding to the ending sequences of the at least 10,000 cell-free DNA fragments, wherein the pattern provides a relationship of the plurality of cell-free DNA fragments that have a pair of ending sequences among the set of sequence motif pairs encompasses calculating a relative frequency which is a mathematical calculation (see instant disclosure [0081] and [0082]) and as shown by the instant disclosure at [0063] a relative frequency may refer to a proportion (a percentage or fraction). Thus, the step of determining a pattern encompasses calculating a proportion (a percentage or fraction) representing the relative frequency of a pair of ending sequences among the set of sequence motif pairs. Argument 4: Applicant argues that the previous Office Action contained inconsistencies to identify improvement (Reply p. 11-12). This argument has been fully considered but found to be not persuasive. Further clarification of the reasons the claims are interpreted as not providing an improvement to technology are provided below. The MPEP states “It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements. See the discussion of Diamond v. Diehr, 450 U.S. 175, 187 and 191-92, 209 USPQ 1, 10 (1981)) in subsection II, below. In addition, the improvement can be provided by the additional element(s) in combination with the recited judicial exception” (see MPEP 2106.05(a)). In the instant case, the identified additional elements are performing, using a sequencing platform of the pathology measurement system, an assay on a plurality of cell-free DNA fragments from the biological sample to obtain sequence reads, wherein performing the assay includes performing sequencing to obtain the sequence reads and a generic computer system. As set out above, the step of performing an assay in this manner to produce sequence reads does not integrate the judicial exceptions into a practical application because this step is insignificant extra solution activity of data gathering. This step is identified as data gathering because the only interaction between this additional element and the judicial exceptions is to provide data to the judicial exceptions to analyze. Due to this additional element being interpreted as being insignificant extra solution activity of data gathering because of how this step interacts with the judicial exceptions, it is interpreted that the combination of this additional element and the judicial exception does not provide an improvement. Further, it is noted that the argued improvement of better detection accuracy with smaller sample sizes is not provided by this additional element due to this additional element reciting the assay in a manner which encompasses conventional assay steps for producing sequencing reads from cell-free DNA fragments. As set out above, the recitation of a generic computer does not integrate the judicial exceptions into a practical application because this is applying the judicial exceptions to a generic computer. This additional element is identified as applying the judicial exceptions to a generic computer because the only interaction between this additional element and the judicial exceptions is performing the steps identified as judicial exceptions on a generic computer system which is interpreted as invoking a computer as tool to perform these identified judicial exceptions, rather than an improvement in computer capabilities (see MPEP 2106.05(a)(I) which states “In computer-related technologies, the examiner should determine whether the claim purports to improve computer capabilities or, instead, invokes computers merely as a tool. Enfish, LLC v. Microsoft Corp., 822 F.3d 1327, 1336, 118 USPQ2d 1684, 1689 (Fed. Cir. 2016)”). Due to this additional element being interpreted as invoking a generic computer as a tool to perform judicial exceptions because of how this step interacts with the judicial exceptions, it is interpreted that the combination of this additional element and the judicial exception does not provide an improvement. Further, it is noted that the argued improvement of better detection accuracy with smaller sample sizes is not provided by this additional element alone due to this additional element being a generic computer system. The improvement is not provided by the one or more identified additional elements (which includes the combination of the generic computer and the step of performing the assay to produce sequence reads from cell-free DNA fragments) or in combination with the judicial exceptions. Therefore, the improvement is provided by the identified judicial exceptions alone which does not constitute as an improvement to technology (see MPEP 2106.05(a)). Argument 5 Applicant argues that the increased accuracy as explained in the last amendment, which referred to FIG. 47, provides an improvement a technical field for a “measurement system” for similar reasons as the device in CardioNet provided an improvement (Reply p. 12-13). This argument has been fully considered but found to be not persuasive. As described immediately above, the claims do not reflect an improvement to a technology or technical field because the improvement is provided by the identified judicial exceptions alone. Further, the instant claims are not analogous to those in CardioNet, because the instant claims do not serve to improve a cardiac monitoring device, or any other device. It is interpreted that the sequencing device is not improved because the sequencing device is not operating in a different manner (i.e., the sequencing device produces sequence reads from cell-free DNA fragments which is routine). The sequencing device only interacts with the judicial exceptions in a manner by providing sequencing data to a series of abstract ideas which links this abstract data to cancer. Although, the abstract idea of how the sequencing data is analyzed provides an improvement in the accuracy of cancer detection this improvement comes solely from the abstract idea of how the sequence read data is analyzed. Argument 6: Applicant provides that the previous Office Action asserts that the claim does not recite the sample is limited to fewer compared to other methods. Applicant argues that the improvement does not need to be recited in the claims and points to the August 4th memo (“The claim itself does not need to explicitly recite the improvement described in the specification.”). Applicant argues that for a given desired accuracy, a smaller sample can be used and such an improvement is not limited to one single desired accuracy or single size of a sample (Reply p. 13). This argument has been fully considered but found to be not persuasive. The MPEP states “After the examiner has consulted the specification and determined that the disclosed invention improves technology, the claim must be evaluated to ensure the claim itself reflects the disclosed improvement in technology. Intellectual Ventures I LLC v. Symantec Corp., 838 F.3d 1307, 1316, 120 USPQ2d 1353, 1359 (Fed. Cir. 2016) (patent owner argued that the claimed email filtering system improved technology by shrinking the protection gap and mooting the volume problem, but the court disagreed because the claims themselves did not have any limitations that addressed these issues). That is, the claim must include the components or steps of the invention that provide the improvement described in the specification. However, the claim itself does not need to explicitly recite the improvement described in the specification (e.g., "thereby increasing the bandwidth of the channel"). The full scope of the claim under the BRI should be considered to determine if the claim reflects an improvement in technology (e.g., the improvement described in the specification) (See MPEP 2106.05(a)). This section shows that although the claim does not need to explicitly recite the improvement described in the specification (which in view of the example provided in the section would be akin to a recitation of the what the improvement is such as “thereby increasing accuracy at smaller sample sizes”), the claim does need to reflect the improvement in the claim and that the full scope of the claim under the BRI should be considered to determine if the claim reflects an improvement in the technology. The improvement of desired accuracy based on sample size is interpreted as being an improvement in the abstract idea of how the sequencing data is analyzed. Argument 7: Applicant argues that the combination of the following limitations, that were argued above as being additional limitations, are unconventional: “for each of the at least 10,000 cell-free DNA fragments, determining…”, “determining, by the computer system, a pattern…”, and “generating, using a machine learning model…” (Reply p. 13-14). This argument has been fully considered but found to be not persuasive. As set out above, the arguments that these limitations are additional elements were not persuasive and these limitations are interpreted as falling under the judicial exception. The MPEP states at 2106.05 “Another consideration when determining whether a claim recites significantly more than a judicial exception is whether the additional element(s) are well-understood, routine, conventional activities previously known to the industry” which shows the analysis for conventionality is reserved for additional elements. Therefore, these limitations do not amount to significantly more than the judicial exceptions because these limitations are judicial exceptions (i.e. not additional elements). 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 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 JONATHAN EDWARD HAYES whose telephone number is (571)272-6165. The examiner can normally be reached M-F 9am-5pm. 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, Olivia Wise can be reached at 571-272-2249. 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. /J.E.H./Examiner, Art Unit 1685 /KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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Prosecution Timeline

Show 10 earlier events
Feb 03, 2025
Interview Requested
Feb 20, 2025
Examiner Interview Summary
Mar 21, 2025
Request for Continued Examination
Mar 24, 2025
Response after Non-Final Action
Nov 05, 2025
Non-Final Rejection mailed — §101
Apr 01, 2026
Examiner Interview Summary
Apr 06, 2026
Response Filed
Jul 16, 2026
Final Rejection mailed — §101 (current)

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6-7
Expected OA Rounds
38%
Grant Probability
61%
With Interview (+23.5%)
4y 8m (~0m remaining)
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