DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) 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.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/12/2025 has been entered.
Applicant's response, filed on 12/12/2025, is 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.
Status of claims
Canceled:
none
New:
none
Amended:
1, 6
Pending:
1-6
Withdrawn:
none
Examined:
1-6
Independent:
1, 6
Allowable:
none
Priority
Acknowledgement is made that this application claims priority as early as 07/27/2020 (Foreign Application EP20187813.9).
Information Disclosure Statement
The Information Disclosure Statements filed on 09/30/2025 and on 02/13/2026 are compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of the list of references cited from each IDS is included with this Office Action.
Withdrawn Rejections/Objections
The rejection of claims 1-6 under 35 U.S.C. §103 over Bell in view of Wang, in the Office action mailed 09/17/2025 is withdrawn in view of the amendments and remarks filed 12/12/2025.
The rejection of claims 1-6 on the ground of nonstatutory double patenting as being unpatentable over 1, 8-9, 13 and 22 of copending Application No. 17386255 (reference application, 04/01/2025 claims) in view of Bell (as cited on the 05/25/2023 "Notice of References Cited" form 892) is withdrawn in view of the remarks filed 12/12/2025.
The rejection of 1, 2, 3 and 5-6 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 20 of copending Application No. 17534368 (reference application, 07/25/2025 claims) in view of Bell (as cited on the 05/25/2023 "Notice of References Cited" form 892) is withdrawn in view of the amendments and remarks filed 12/12/2025.
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.
Judicial exceptions (JEs) to 101 patentability
Claims 1-6 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 judicially-recognized exceptions to patentability (JEs), i.e. an abstract idea, a natural phenomenon, a law of nature and/or a product of nature, as identified below. As set forth below, it is not clear that any element or combination of elements in addition to the JE(s), i.e. and "additional elements," either integrate the identified JE(s) into a practical application and/or is a non-conventional additional element, such that it is not clear that any claim is directed to significantly more than the identified JE(s).
MPEP 2106 organizes JE analysis into Steps 1, 2A (1st prong & 2nd prong) and 2B as analyzed 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.
Analysis of claims 1-6
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Independent claim 1 is directed to a 101 process, here a "method," with process steps such as "inputting..."
Independent claim 6 is directed to a 101 process, here a "method," with process steps such as "selecting..."
[Step 1: claims 1-6: YES]
Step 2A, 1st prong: Do the claims recite a judicially-recognized exception (JE), e.g. a law of nature, a natural phenomenon or product, or an abstract idea (MPEP 2106.04.II.A.1 & .04(a))?
The MPEP at 2106.I, 2nd para. explains that JEs have been court-recognized as occurring in at least four types: abstract ideas, laws of nature and natural phenomena (including natural products).
MPEP § 2106.04(a)(2) further explains that abstract ideas may be grouped as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
• certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people);
and/or
• mental processes (procedures for observing, evaluating, analyzing/ judging and
organizing information).
Regarding the instant claims and with respect to Step 2A, 1st prong, at least preliminarily these claims recite JEs in the form of abstract ideas as follows.
Mental processes recited include:
Claims 1 and 6 recite: that the method for training a machine learning algorithm is for "determining the homologous recombination deficiency (HRD) status of a subject DNA sample..." and
“d) aligning the sequencing reads of the subject DNA sample to a reference genome, wherein the reference genome is divided into a plurality of bins, each bin belonging to a same genomic region of a chromosome arm in the reference genome to be analyzed, wherein the reference genome is divided into a first set of at most 100 kbp bins and further comprising a step of collapsing the 100 kbp bins into a second set of bins of at least 500 kbp prior to arranging the coverage signals of the chromosome arm into the coverage signal array.”
Further, at the “wherein” clauses describing the input data, the claim recites that the coverage data signal array from samples with known positive HRD status and the coverage signal array from samples with known negative HRD status are “arranged into a 1D coverage data signal vector or a 2D coverage data signal array” and "wherein arranging the 2D coverage data signal array comprises aligning in rows a coverage data signal for each chromosome with respect to a centromeric bin of each chromosome arm, that is the bin adjacent to the centromere region of the chromosome arm."
Claim 6 also recites: selecting a plurality of real samples with a known homologous recombination deficiency status and wherein the portion of the plurality of real samples with the same homologous recombination deficiency status is a random number drawn from an exponential distribution using: N=K*exp(-K*x) where x is a random number and K=1/3.
The process of determining, aligning and selecting are acts of analyzing, evaluating and judging information that could be practically performed in the human mind and/or with pen and paper. Drawing a random number from an exponential distribution equate to a process of selecting a number and arranging and aligning involves ordering and comparing chromosome signals that could be practically performed in the human mind and/or with pen and paper.
Mathematical concepts recited include:
Claim 1 recites: The method is for "training a machine learning algorithm...," and "a machine learning supervised training algorithm". Training a machine learning algorithm requires formulas for performing the calculations needed to train the model. Similarly, “a machine learning algorithm” itself represents mathematical concepts.
Claim 6 recites: wherein the portion of the plurality of real samples with the same homologous recombination deficiency status is a random number drawn from an exponential distribution using: N=K*exp(-K*x) where x is a random number and K=1/3; inputting to a machine learning supervised training algorithm a coverage data signal array from the data augmented training sample, to generate a trained machine learning model. Training and generating a trained machine learning model requires formulas for performing the calculations needed to train and generate the model.
Claim 2 recites: "wherein the trained machine learning model is a random forest model, a neural network model, a deep learning classifier or a convolutional neural network model." Training a machine learning algorithm requires formulas for performing the calculations needed to train the model. The different types of models listed are different mathematical formulas that make up the models, i.e., mathematical concepts.
Claim 3 recites: "wherein the neural network model is a convolutional neural network trained..." Training a machine learning algorithm requires formulas for performing the calculations needed to train the model.
Claim 4 recites: "wherein the trained machine learning model has been trained in semi-supervised mode..." Training a machine learning algorithm requires formulas for performing the calculations needed to train the model.
[Step 2A, 1st prong: claims 1-6: YES]
Step 2A, 2nd prong: Are the above-identified JEs integrated into a practical application (MPEP 2106.04.II.A.2 & .04(d))?
Generally regarding Step 2A, 2nd prong
MPEP 2106.04(d).I lists the following considerations for evaluating whether additional elements integrate a judicial exception into a practical application:
An improvement in the functioning of a computer, or an improvement to other technology or technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to affect 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).
Additionally, the courts have also identified limitations that did not integrate a judicial exception into a practical application:
Merely reciting a phrase such as "apply it" (or an equivalent) along with the judicial exception, or merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea, as discussed in MPEP 2106.05(f);
Adding insignificant extra-solution activity to the judicial exception, as discussed in MPEP 2106.05(g); and
Generally linking the use of a judicial exception to a particular technological environment or field of use, as discussed in MPEP 2106.05(h).
In Step 2A, 1st prong above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
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 are recited such to clearly demonstrate 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 does not clearly disclose an explanation of improvement over the previous state of the technology field. An explanation of improvement requires detailed explanation applicable to all embodiments reasonably within the claim scope. In particular, such an explanation of improvement over the previous state of technology may include: identification of the technology field, the particular improvement, as particular as possible identification of any asserted improvements, explanation of a clear difference from the technology field, explanation that reasonably all embodiments within the claim scope result in the asserted improvement, and an extension of the explanation as far as possible to include the result of an identified practical application. The claims do not clearly result in such an improvement (e.g. specification: para. [09]). See MPEP 2106.04(d) and (d)(1).
[Step 2A, 2nd prong: claims 1-6: NO]
Step 2B: Do the claims recite a non-conventional arrangement of additional elements (i.e. elements in addition to any identified JE) (MPEP 2106.05)?
All elements of claims 1-6 are part of one or more identified JEs (as described above), except for elements identified here as conventional elements in addition to the above JEs:
Elements of the following claims are additional elements but nonetheless are conventional elements of a laboratory or computing environment, conventional data gathering elements or conventional post-processing elements:
claim 1: the recited "(a) extracting and isolating fragments of DNA from the subject DNA sample;(b) constructing a sequencing library comprising the fragments of DNA from the subject DNA sample overlapping a set of chromosomes;(c) sequencing, via whole genome sequencing, the sequencing library to obtain sequencing reads; ...obtained from low pass whole genome sequencing...," and "inputting to a machine learning supervised training algorithm a coverage data signal array from labelled real samples and labelled data augmented samples with known positive homologous recombination deficiency status and a coverage data signal array from labelled real samples and labelled data augmented samples with known negative homologous recombination deficiency status..." step/element. Obtaining and inputting data are mere data gathering activities. Data gathering steps have been determined by the courts to add insignificant extra-solution activity to the JE and does not integrate a JE into a practical application. See MPEP 2106.05(g).
claim 3: the recited "output a single label binary classification..." step/element. Outputting data is a post-solution activity. Post-solution activity is an element that does not integrate a JE into a practical application. See MPEP 2106.05(g).
claim 4: the recited "using a data augmented set generated by sample data..." step/element. Selecting a particular data source or type of data to be have been determined by the courts to add insignificant extra-solution activity to the JE and does not integrate a JE into a practical application. See MPEP 2106.05(g).
claim 5: the recited "wherein the low pass whole genome sequencing obtains a genome sequencing coverage..." step/element. As noted above, obtaining data is a data gathering step (i.e., referring to the low pass whole genome sequencing of the subject DNA sample). Data gathering steps have been determined by the courts to add insignificant extra-solution activity to the JE and cannot integrate a JE into a practical application. See MPEP 2106.05(g). The newly recited limitations “wherein the low pass whole genome sequencing obtains a genome sequencing coverage from about 0.1x to about 5x” merely further limits the data which is gathered (places a further limit on the gathered data, however fails to add an element that more than routine, conventional or well-known such to amount to significantly more).
Claim 6 recites: (a) extracting and isolating fragments of DNA from the subject DNA sample;(b) constructing a sequencing library comprising the fragments of DNA from the subject DNA sample overlapping a set of chromosomes;(c) sequencing, via whole genome sequencing, the sequencing library to obtain sequencing reads; …creating a data augmented training sample by combining chromosomes from a portion of the plurality of real samples with the same homologous recombination deficiency status. Creating a data augmented training sample is a data gathering step for use in training the machine learning model.
The additional elements indicated above are data gathering activities and include extracting and isolating fragments of DNA, constructing a sequencing library, sequencing, inputting to a machine learning supervised training algorithm a coverage data signal array and outputting a single label binary classification. Overall, the additional elements include retrieving, inputting and outputting data. Data gathering steps are not an abstract idea, they are extra-solution activity, as they collect the data needed to carry out the abstract idea. Data gathering does not impose any meaningful limitation on the abstract idea, or how the abstract idea is performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application. (MPEP 2106.05(g)). Furthermore, limitations that equate to mere data gathering and outputting via generic computer components, such as receiving data at a computer or outputting data, amount to insignificant extra-solution activity as set forth by the courts in Mayo, 566 U.S. at 79, 101 USPQ2d at 1968 and OIP Techs., Inc, v, Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015). Also, the courts have recognized that detecting DNA or enzymes in a sample, analyzing DNA to provide sequence information or detecting allelic variants and amplifying and sequencing nucleic acid sequences as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity (See MPEP 2106.05(d)). Additionally, methods for extracting and isolating fragments of DNA, constructing a sequencing library and sequencing are well-known conventional methods as disclosed by Anson ("DNA extraction from primary liquid blood cultures for bloodstream infection diagnosis using whole genome sequencing." Journal of Medical Microbiology 67.3 (2018): 347-357.; as cited on the attached “Noticed of References cited” 892 form). Also, low-pass whole genome sequencing is commercially available as disclosed by BGI (Low-Pass Whole Genome Sequencing. BGI Americas. 2018; as cited on the 06/30/2025 “Noticed of References cited” 892 form). Therefore, methods for extracting and isolating fragments of DNA, constructing a sequencing library, sequencing and lp-WGS are well-understood, routine and conventional methods. The use of machine learning models to analyze genomic data is also a known method. Evidence that these steps, in combination, are well-understood, routine and conventional in the field can be found in Leung, Michael KK, et al. "Machine learning in genomic medicine: a review of computational problems and data sets." Proceedings of the IEEE 104.1 (2015): 176-197; as cited on the 07/21/2022 “Noticed of References cited” 892 form. In particular, see Leung pg 179-180 under Section III; pg. 183-184 Figure 6 and 1) Sequencing, 2) Microarrays and 3) Basic computational models and, pg. 185 Section IV. Therefore, the additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception.
[Step 2B: claims 1-6: NO]
Summary and conclusion regarding claims 1-6
Summing up the above 101 JE analysis of claims 1-6, 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 above-identified JE(s), into patent eligible subject matter.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional element in the claims has been addressed, alone and in combination, to determine whether the additional elements 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. Individually, the limitations of the claims and the claims as a whole have been found to be patent ineligible under 35 U.S.C. 101.
Response to 35 USC § 101 Remarks received 12/12/2025
Applicant amended claims 1 and 6.
It is noted that Applicant’s remarks are based on amended claims.
In Applicant's remarks for Claim Rejections under 35 U.S.C. §101, see pages 5-6, Applicant states that amended claims 1 and 6 recite the limitation "extracting and isolating fragments of DNA from a patient DNA sample." Applicant states that the limitation is a step that must be performed physically and cannot practically be performed in the human mind, nor with any kind of computer, generic or otherwise. Therefore, Applicant asserts that the instantly amended claims 1 and 6 are not directed to an abstract idea without significantly more.
In response, Applicants' remarks have been fully considered and are not persuasive. The process of extracting and isolating fragments of DNA from a patient DNA sample amounts are additional elements that amount to mere data gathering and is a field of use or insignificant extra solution activity. As indicated in MPEP 2106.05(g), data gathering is insignificant extra solution activity and a data gathering step that is limited to a particular data source or a particular type of data could be considered to be both insignificant extra-solution activity and a field of use limitation. Also, the courts have also recognized that techniques for detecting DNA or enzymes in a sample, analyzing DNA to provide sequence information or detecting allelic variants and amplifying and sequencing nucleic acid sequences as well-understood, routine, conventional activity in the life science arts when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. (See MPEP 2106.05(d)). Therefore, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to well-understood, routine and conventional activities, insignificant extra-solution activity or mere instructions to implement the abstract idea on a generic computer. As discussed in the 101 rejection section above, the additional elements equate to mere data gathering and outputting via generic computer components, such as receiving data at a computer or outputting data, amount to insignificant extra-solution activity as set forth by the courts in Mayo, 566 U.S. at 79, 101 USPQ2d at 1968 and OIP Techs., Inc, v, Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015). Also, the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application or provide significantly more as identified by the courts in Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). Overall, the additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception.
Regarding 35 USC 103 -- no prior art applied
No prior art is applied to claims 1-6. The claims overcome the closest prior art to Bell (as cited on 05/25/2023 "Notice of References Cited" form 892). Bell teaches determining a homologous recombination deficiency (HRD) status of a DNA sample using machine learning models. However, Bell does not teach "wherein the reference genome is divided into a first set of at most 100kbp bins and further comprising a step of collapsing the 100kbp bins into a second set of bins of at least 500kbp prior to arranging the coverage signals of the chromosome arm into the coverage signal array" in independent claims 1 and 6. It is not clear that any combinable art of record would have rendered the claims obvious.
Response to 35 USC § 103 Remarks received 12/12/2025
Applicant amended claims 1 and 6.
It is noted that Applicant’s remarks are based on amended claims.
Applicant’s remarks, see pages 6-10, filed 12/12/2025, with respect to the rejection(s) of claim(s) 1-6 under 35 USC § 103 have been fully considered and are persuasive. Therefore, the rejections have been withdrawn as indicated above.
Response to Double Patenting Remarks, Filed 12/12/2025
In Applicant's remarks for Double Patenting Rejections, see pages 10-11, Applicant states that claims 1-6 are drawn to the non-elected invention as a result of a restriction requirement in co-pending Application No. 17/386,255, which was issued on February 22, 2022. Applicant further states that in accordance with 35 U.S.C. § 121, if a divisional application arises from an Examiner-imposed restriction and the claims in the divisional are consonant with the restriction groupings, then the divisional application is protected from a nonstatutory double patenting rejection based on the parent application or any sibling applications. Applicant also states that the following limitations render the instantly amended claims distinct from co-pending Application No. 17/386,255 and co-pending Application No. 17/534,368: inputting, to a machine learning supervised training algorithm, a coverage data signal array from labelled real samples and labelled data augmented samples with known positive homologous recombination deficiency status and a coverage data signal array from labelled real samples and labelled data augmented samples with known negative homologous recombination deficiency status, to generate a trained machine learning model, wherein the labelled data augmented samples are generated by sampling chromosomes from a plurality of real samples sharing the same homologous recombination deficiency status, wherein the coverage data signal array from labelled real samples and labelled data augmented samples with known positive homologous recombination deficiency status and the coverage data signal array from labelled real samples and labelled data augmented samples with known negative homologous recombination deficiency status are arranged into a 1D coverage data signal vector or a 2D coverage data signal array, and wherein arranging the 2D coverage data signal array comprises aligning in rows a coverage data signal for each chromosome with respect to a centromeric bin of each chromosome arm, that is the bin adjacent to the centromere region of the chromosome arm.
In response, the arguments have been fully considered and are persuasive. Therefore, the rejection of claims 1-6 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-9, 13 and 22 of copending Application No. 17386255 (reference application, 04/01/2025 claims) in view of Bell (as cited on the 05/25/2023 "Notice of References Cited" form 892) is withdrawn in view of the remarks filed 12/22/2025. The rejection of 1, 2, 3 and 5-6 as being unpatentable over claims 1 and 20 of copending Application No. 17534368 (reference application, 07/25/2025 claims) in view of Bell (as cited on the 05/25/2023 "Notice of References Cited" form 892) is also withdrawn in view of the amendments and remarks filed 12/12/2025.
Conclusion
No claims are allowed.
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/K.K./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686