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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/5/2026 has been entered.
Status of Claims
Claim 3-6, 9-10, 12, 14, 20, 22 are cancelled.
Claims 1-2, 7-8, 11, 13, 15-19, 21 and 23-29 are pending and examined on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Priority of US application REPUBLIC OF KOREA 10-2023-0109872 filed 08/22/2023 is acknowledged.
Withdrawn Rejections/Objections
The rejections to claims 20 and 22 under 35 USC § 112(a) in the Office Action mailed 10 October 2025 are withdrawn in view of claim amendment filed 1/5/2026.
The rejection to claim 20 under 35 USC § 112(b) in the Office Action mailed 10 October 2025 is withdrawn in view of claim amendment filed 1/5/2026.
Claim Interpretation
In claims 1, 25 and 28, the “input” in recitation “input corresponding to the minimal residual disease” has never being defined. It is interpreted as the parameter acquired inside the 4th step (every single sub-step before the last sub-step of the 4th step). More specifically, all the following elements are used by the machine learning model as input:
identifying a number of tumor tissue mutations of the patient by comparing the first sequencing data and the second sequencing data;
calculating, based on the number of tumor tissue mutations of the patient and based on an average sequencing depth of the third sequencing data, a limit of detection for the patient;
detecting tumor tissue mutation information of the patient by comparing the first sequencing data and the second sequencing data;
performing, using genetic data associated with a plurality of sample patients who are distinct from the patient, background error filtering on the detected tumor tissue mutation information;
calculating, based on the filtered tumor tissue mutation information, a tumor cell fraction for the patient;
correcting, using the genetic data, the tumor cell fraction; and
determining, based on the limit of detection and the corrected tumor cell fraction, whether the patient has tumor recurrence;
This interpretation is supported by the disclosure at page 4, 3rd para:
“The performing the detection of minimal residual disease may include calculating a limit of detection for the patient based on the first sequencing data, the second sequencing data, and the third sequencing data, calculating a tumor cell fraction (TCF) for the patient based on the third sequencing data, correcting the tumor cell fraction using genetic data associated with a plurality of sample patients distinguished from the patient, and determining whether the patient has tumor recurrence based on the corrected tumor cell fraction and the limit of detection.”
Claim Rejections - 35 USC § 112 -- First Paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 7-8, 11, 13, 15-19, 21 and 23-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 4th step recites “detecting, by the one or more processors …” However, the last sub-step of the 4th step recites “performing, within an interval of time corresponding to the minimal residual disease, the recommendation”. The specification does not describe how “the one or more processors” can “performing, within an interval of time corresponding to the minimal residual disease, the recommendation” wherein the recommendation comprising initialing a therapy or additional surgery.
Claim 1 can be amended by moving the “performing, within an interval of time corresponding to the minimal residual disease, the recommendation” sub-step out of the 4th step and making it the 5th step of claim 1. The claim is interpreted this way in the current examination.
Claim Rejections - 35 USC § 112 -- Second Paragraph
The instant rejection is newly installed..
The following is a quotation of 35 U.S.C. 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 7-8, 11, 13, 15-19, 21 and 23-29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 25 and 28 at their first and their third elements inside their fourth step, recite the following two similar elements:
Identifying a number of tumor tissue mutations of the patient by comparing the first sequencing data and the second sequencing data (claims 1, 25 and 28);
Detecting tumor tissue mutation information of the patient by comparing the first sequencing data and the second sequencing data (claims 1, 25 and 28);
It is not clear the difference regarding the “mete--and-bound” of these two elements. It is the logical consequence to have the specific tumor tissue mutations of the patient as well as the number of mutations of the patient, after comparing the first sequencing data and the second sequencing data. It is not clear what other “tumor tissue mutation information of the patient” can be acquired by comparing the first sequencing data and the second sequencing data.
Applicant can amend the claims by consolidating the two elements into one, or delete one element. Claims are examined as if these two elements are consolidated.
Claim 1 (4th step) recites “detecting, by the one or more processors …” However, the last sub-step of the 4th step recites “performing, within an interval of time corresponding to the minimal residual disease, the recommendation”. The specification does not describe how “the one or more processors” can “performing, within an interval of time corresponding to the minimal residual disease, the recommendation” wherein the recommendation comprising initialing a therapy or additional surgery.
Claim 1 can be amended by moving the “performing, within an interval of time corresponding to the minimal residual disease, the recommendation” sub-step out of the 4th step and making it the 5th step of claim 1. The claim is interpreted this way in the current examination.
In claims 1, 25 and 28, it is not clear how these two neighboring steps relate to each other:
Determining, based on the limit of detection and the corrected tumor cell fraction, whether the patient has tumor recurrence (claims 1, 25 and 28); and
Receiving, from a trained machine learning model implemented using an artificial neural network and in response to input corresponding to the minimal residual disease, output indicating a recommendation associated with one or more of (claims 1, 25 and 28).
There is a disconnection between the “tumor recurrence” and “a trained machine learning model”. Applicant can amend the claims with the recitations provided in the disclosure at page 4, 3rd para:
“The performing the detection of minimal residual disease may include calculating a limit of detection for the patient based on the first sequencing data, the second sequencing data, and the third sequencing data, calculating a tumor cell fraction (TCF) for the patient based on the third sequencing data, correcting the tumor cell fraction using genetic data associated with a plurality of sample patients distinguished from the patient, and determining whether the patient has tumor recurrence based on the corrected tumor cell fraction and the limit of detection.”
Claim Rejections - 35 USC § 101
The instant rejection is maintained from the previous Office action.
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 1-2, 7-8, 11, 13, 15-19, 21 and 23-29 are rejected under 35 USC 101 because the claimed invention is directed to non-statutory subject matter.
Step 1: Process, Machine, Manufacture or Composition
Claims 1-2, 7-8, 11, 13, 15-19, 21 and 23-24 are directed to a process, here a "method," for detecting minimal residual disease and adapting treatment in response to that minimum residual disease.
Claims 25-27 are directed to another process, here another "method," for detecting minimal residual disease and adapting treatment in response to that minimum residual disease.
Claims 28-29 are directed to a third process, here a third "method," for detecting minimal residual disease and adapting treatment in response to that minimum residual disease.
Step 2A Prong One: Identification of an Abstract Idea
The claims recite:
Detecting, by the one or more processors and based on the first sequencing data, the second sequencing data, and the third sequencing data, a minimal residual disease for the patient by (claims 1, 25 and 28):
This step recites detecting disease based on first, second and third sequencing data, which is interpreted as a series of judgements and decision-making with respect to the data sets, that can be achieved in human mind. Therefore this step equates to an abstract idea of a mental processes;
Identifying a number of tumor tissue mutations of the patient by comparing the first sequencing data and the second sequencing data (claims 1, 25 and 28);
This step recites identifying a number of tumor tissue mutations of the patient, which is interpreted as a series of judgement and decision-making with respect to the data comparison of the two sequencing data sets, that can be achieved in human mind. Therefore this step equates to an abstract idea of a mental processes;
Calculating, based on the number of tumor tissue mutations of the patient and based on an average sequencing depth of the third sequencing data, a limit of detection for the patient (claims 1, 25 and 28);
This step recites a calculation operation with inputs and an output, which equates to an abstract idea of mathematical concepts.
Detecting tumor tissue mutation information of the patient by comparing the first sequencing data and the second sequencing data (claims 1, 25 and 28);
This step recites detecting tumor tissue mutation information of the patient, which is interpreted as a series of judgement and decision-making with respect to the data comparison of the two sequencing data sets, that can be achieved in human mind. Therefore this step equates to an abstract idea of a mental processes;
Performing, using genetic data associated with a plurality of sample patients who are distinct from the patient, background error filtering on the detected tumor tissue mutation information (claims 1, 25 and 28);
This step recites comparing detected mutation information against background information and filtering background information, which can be achieved in human mind. Therefore this step equates to an abstract idea of mental processes.
Calculating, based on the filtered tumor tissue mutation information, a tumor cell fraction for the patient (claims 1, 25 and 28);
This step recites calculating, which is a mathematical operation. Therefore this step equates to an abstract idea of mathematical concepts.
Correcting, using the genetic data, the tumor cell fraction (claims 1, 25 and 28);
This step recites correcting on the cell fraction (by another data), which is a mathematical operation. Therefore this step equates to an abstract idea of mathematical concepts.
Determining, based on the limit of detection and the corrected tumor cell fraction, whether the patient has tumor recurrence (claims 1, 25 and 28);
This step recites a series of judgement and decision-making with respect to the data comparison of data sets, that can be achieved in human mind. Therefore this step equates to an abstract idea of a mental processes;
Determining, based on the minimal residual disease, to shift from the first treatment to second treatment, wherein the second treatment comprises one or more of: chemotherapy, or surgery (claim 28); and
This step recites a series of judgement and decision-making with respect to the data comparison and data observation, that can be achieved in human mind. Therefore this step equates to an abstract idea of a mental processes;
Dependent claims further describe data, data analytical details, and therapy choices.
Step 2A Prong Two: Consideration of Practical Application
Claim 1 results in a process of computerized “performing” of additional treatment and/or surgery. Claim 1 does recite an additional element (“performing, within an interval of time corresponding to the minimum residual disease, the recommendation”) but in a general way. The recitation of performing actions based on the model output is particular in claim 1. However, the determined “tumor recurrence” is not integrated into the next step “receiving, from a trained machine learning model implemented using an artificial neural network and in response to input corresponding to the minimal residual disease, output indicating a recommendation associated with one or more of” in all the three independent claims 1, 25 and 28. In another words, the treatment or therapy pertains to the MRD but the MRD is disconnected to the “tumor recurrence”.
Claims 25 and 28 result in alternative embodiments of predicted “therapy” of additional treatment and/or surgery. The “additional surgery” or “surgery” recited in the recommendation list of these two claims are not particular. The recommended “additional surgery” (claim 25) and “surgery” (claim 28) are too broad. “Surgery” is not a particular surgery related to the determination of a minimum residual disease. Hence in claims 25 and 28, there is no particular treatment to integrate the judicial exceptions into a practical applications.
Reciting a particular type of surgery related to tumor tissue or tumor removal (see spec page 15, line 23; page 16, line 1; page 29, line 5) is suggested.
This judicial exceptions are not integrated into a practical application because the claims do not meet any of the following criteria:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses 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.
Step 2B: Consideration of Additional Elements and Significantly More
The claimed method also recites "additional elements" that are not limitations drawn to an abstract idea:
Acquiring, by one more processors of an information processing system, first sequencing data associated with a tumor tissue biopsy sample, of a patient, acquired prior to surgery of the patient (claims 1, 25 and 28);
Acquiring, by the one or more processors, second sequencing data associated with a normal blood sample, of the patient, acquired prior to the surgery of the patient (claims 1, 25 and 28);
Acquiring, by the one or more processors, after the surgery of the patient, and via whole genome sequencing, third sequencing data associated with a plasma sample of the patient, wherein the plasma sample of the patient was acquired after the surgery of the patient, and wherein the plasma sample includes cell free Deoxyribonucleic Acid (cfDNA) and circulating tumor Deoxyribo Nucleic Acid (ctDNA) (claims 1, 25 and 28);
Receiving, from a trained machine learning model implemented using an artificial neural network and in response to input corresponding to the minimal residual disease, output indicating a recommendation associated with one or more of: initiating a therapy selected from the group consisting of chemotherapy-based therapy, antibody-based therapy, and small molecule kinase inhibitor-based therapy, switching from a first therapy to a second therapy, the first therapy and the second therapy being selected from the group consisting of chemotherapy-based therapy, antibody-based therapy, and small molecule kinase inhibitor-based therapy; or perform an additional surgery on the tumor tissue (claim 1);
Receiving, from a trained machine learning model implemented using an artificial neural network and in response to input corresponding to the minimal residual disease, output indicating a recommendation associated with one or more of: chemotherapy-based therapy, antibody-based therapy, small molecule kinase inhibitor-based therapy, or additional surgery (claim 25);
Performing, within an interval of time corresponding to the minimal residual disease, the recommendation (claims 1, 25 and 28);
Causing one or more user terminals to display an indication of recommendation (claim 21); and
Receiving, from a trained machine learning model implemented using an artificial neural network and in response to input corresponding to the minimal residual disease, output indicating the second treatment (claim 29).
The above additional elements can be divided into three groups: 1) elements of sample and data acquiring (first 3 elements); 2) elements of model output results (4th-5th, and 8th elements) at the terminals (the 7th element); and 3) treatment and/or surgery choices (6th element). Group 1 and group 2 additional elements are insignificant extra-solution activities as they are required for data inputting and outputting. Group 3 additional elements are generic therapy choices. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions because the additional elements are insignificant extra-solution activity or generic choice of therapies.
The claims do not include additional elements that are sufficient to amount of significantly more than the judicial exception because it is routine and conventional to perform the acts of acquiring necessary data for analysis. Other elements of the method include an artificial neural network modeling that serve to perform generic data model functions that are well-understood, routine, and conventional activities previously known to the pertinent industry. Therapy is common in the clinical industry. Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself. Therefore, the claim(s) are rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Response to Applicant’s Arguments
In the Remarks (pages 11-14) filed 01/05/2026, Applicant argues that claims are not directed to an abstract ideas (pages 11, last para through page 12, 1st para). Applicant’s argument refers to Step 2A/Prong One in the 35 USC 101 analysis.
In response, Applicant’s argument is not persuasive. Applicant argued that human mind is not equipped to perform the claim limitations. However, as discussed in the 35 USC 101 analysis above (Section “Step 2A Prong One: Identification of an Abstract Idea”), claims do recite abstract ideas in the mathematical concept grouping. Claim element like “identifying a number of tumor tissue mutations of the patient by comparing the first sequencing data and the second sequencing data” (claims 1, 25 and 28), under a BRI and at its simplest embodiment, encompass the practice of comparing two sequence reads and identifying mutations. Such an activity can be accomplished in human mind, with the aid of a pen and paper.
Therefore, claims do recite elements directed to abstract ideas.
In the Remarks, Applicant argues (pages 12, 2nd para through page 14, 1st para) that claims are integrated into a practical application. Applicant particularly argued that claims like example 43, effect a particular treatment (page 12, last para). Applicant’s argument refers to Step 2A/Prong two in the 35 USC 101 analysis.
In response, Applicant’s argument is not persuasive. In example 43, the treatment for patient diagnosed with NAS-3 using rapamycin is particular, regarding the disease and the medicine. However, for the instant case, claim 1 results in a process of computerized “performing” of additional treatment and/or surgery. Claim 1 does recite an additional element (“performing, within an interval of time corresponding to the minimum residual disease, the recommendation”) but in a general way. The recitation of performing actions based on the model output is particular in claim 1. However, the determined “tumor recurrence” is not integrated into the next step “receiving, from a trained machine learning model implemented using an artificial neural network and in response to input corresponding to the minimal residual disease, output indicating a recommendation associated with one or more of” in all the three independent claims 1, 25 and 28. In another words, the treatment or therapy pertains to the MRD but the MRD is disconnected to the “tumor recurrence”.
In the instant case, claims 25 and 28 result in alternative embodiments of predicted “therapy” of additional treatment and/or surgery. The “additional surgery” or “surgery” recited in the recommendation list of these two claims are not particular. The recommended “additional surgery” (claim 25) and “surgery” (claim 28) are too broad. “Surgery” is not a particular surgery related to the determination of a minimum residual disease. Hence in claims 25 and 28, there is no particular treatment to integrate the judicial exceptions into a practical applications.
Applicant particularly argued that claims like McRO, improve the functioning of a computer (page 13, last two paras and page 14, 1st para).
In response, Applicant’s argument is not persuasive. Contrary to appellant argument, the case of McRO is not analogous to the instant claims because the instant claims only involve a generic computer in the generation of an in silico resonation of a biological sequence. Unlike McRO, there is no improvement to the generic computer of the instant claims beyond the conventional use as a computational workhorse running algorithmic based programming.
Appellant did not provide evidence the claimed “computer system” is anything more than a generic computer that implements the pseudo-ordering of molecules, machine learning algorithm, etc., in the conventional and well- known way that computers ordinary function. To qualify as “a patent- eligible improvement,” the invention must be directed to a specific improvement in the computer’s functionality, not simply to use of the computer “as a tool” to implement an abstract idea. Customedia Techs., LLC v. Dish Network Corp., 951 F.3d 1359, 1363-1364 (Fed. Cir. 2020). Here, the invention falls into the latter category. It focuses on using a general purpose computer to carry out the abstract idea. Consequently, we do not discern an inventive concept in how the computer system operates.
In the Remarks, Applicant argues (pages 14, paras 3-4) that claims add significantly more than any alleged abstract idea. Applicant’s argument refers to Step 2B in the 35 USC 101 analysis.
In response, as discussed in the 35 USC 101 analysis, it is routine and conventional to perform the acts of acquiring necessary data for analysis. Other elements of the method include an artificial neural network model that serve to perform generic data modeling functions that are well-understood, routine, and conventional activities previously known to the pertinent industry. Therapies listed (“initiating a therapy selected from the group consisting of chemotherapy-based therapy, antibody-based therapy, and small molecule kinase inhibitor-based therapy, switching from a first therapy to a second therapy, the first therapy and the second therapy being selected from the group consisting of chemotherapy-based therapy, antibody-based therapy, and small molecule kinase inhibitor-based therapy; or perform an additional surgery on the tumor tissue”) are common and well-known in the clinical industry. Viewed as a whole, these additional claim element(s) do not provide meaningful limitation(s) to transform the abstract idea recited in the instantly presented claims into a patent eligible application of the abstract idea such that the claim(s) amounts to significantly more than the abstract idea itself.
Therefore, the 35 U.S.C. 101 rejection is maintained.
Conclusion
No claims are allowed.
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/GL/
Patent Examiner
Art Unit 1686
/Anna Skibinsky/
Primary Examiner, AU 1635
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