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 .
DETAILED ACTION
In the response filed on 04 August 2025, the following has occurred: Claims 1 and 13 have been amended; Claims 2 and 14 have been canceled.
Now claims 1, 3-4, 6-13, 15-16 and 18-20 are pending.
Claim Rejections - 35 USC § 112
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 10, 12 and 20 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.
Claim 10 recites the limitation "the radiology report" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claims 12 and 20 recite the limitation "the end-stage liver-related outcome" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claims 10, 12 and 20 depend on a canceled claim (claim 2 for claim 10; claim 5 for claim 12; and claim 17 for claim 20). There is insufficient dependency for these claims.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 3-4, 6-13, 15-16 and 18-20 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.
Claims 1 and 13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite system and method for diagnosing nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH). The limitations of:
Claim 1, which is representative of claim 13
select at least one patient with a risk indicator using an electronic health record (EHR) database, wherein the risk indicator is associated with NAFLD and/or NASH; determine that the at least one patient fails to meet exclusion criteria; verify hepatic steatosis of the at least one patient using at least detection associated with the presence of intrahepatic fat; and [… provide …] the at least one patient in response to the determination; calculate scores […] or combinations thereof of the at least one patient using a predetermined metric; and provide a risk for progressing to an end-stage liver disease based on the one or more scores.
, as drafted, is a system which under its broadest reasonable interpretation, covers a method of organizing human activity (i.e., managing personal behavior including following rules or instructions) via human interaction with generic computer components. That is, by a human user interacting with one or more processors and one or more computer-readable non-transitory storage media, the claimed invention amounts to managing personal behavior or interaction between people, the Examiner notes as stated in 2106.04(a)(2), “certain activity between a person and a computer… may fall within the “certain methods of organizing human activity” grouping”. For example, via human interaction with one or more processors and one or more computer-readable non-transitory storage media, claim encompasses selecting patients in a database with a risk indicator for NAFLD or NASH by calculating scores and making a determination about risk for verification of hepatic steatosis in a patient, and then determining if the selected patient meet exclusion criteria and providing the results of the determination for a user to use in their workflow. If a claim limitation, under its broadest reasonable interpretation, covers managing personal behavior or interactions between people but for the recitation of generic computer components, then it falls within the “method of organizing human activity” grouping of abstract ideas. Accordingly, the claim recites an abstract idea.
This judicial exception is not integrated into a practical application. In particular, the claim recites the additional elements of one or more processors and one or more computer-readable non-transitory storage media, which implements the abstract idea. The one or more processors and one or more computer-readable non-transitory storage media are recited at a high-level of generality (i.e., a general-purpose computers/ computer components implementing generic computer functions; see Applicant’s Specification Figure 1, paragraph [0019]) such that it amounts no more than mere instructions to apply the exception using generic computer components. Accordingly, these additional element does not integrate the abstract idea into a practical application because it does not impose any meaningful limits on practicing the abstract idea. The claim is directed to an abstract idea.
The claim recites the additional elements of “display…” and “Fibrosis-4 (FIB-4), AST to Platelet Ratio Index, NAFLD Fibrosis Score (NAFLD-FS), or combinations thereof”. The “display…” is recited at a high-level of generality (i.e., as a generic presentation of information to a user) and amounts to generally linking the abstract idea to a particular technological environment. The “Fibrosis-4 (FIB-4), AST to Platelet Ratio Index, NAFLD Fibrosis Score (NAFLD-FS), or combinations thereof” is recited at a high-level of generality (i.e., as an off-the-shelf score for a predetermined condition) and amounts to generally linking the abstract idea to a particular technological environment. Accordingly, even in combination, these additional elements do not integrate the abstract idea into a practical application. The claim is directed to an abstract idea.
The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception. As discussed above with respect to integration of the abstract idea into a practical application, the additional elements of one or more processors and one or more computer-readable non-transitory storage media, to perform the noted steps amounts to no more than mere instructions to apply the exception using generic hardware components. Mere instructions to apply an exception using a generic hardware component cannot provide an inventive concept (“significantly more”).
Also, as discussed above with respect to integration of the abstract idea into a practical application, the additional elements of “display…” and “Fibrosis-4 (FIB-4), AST to Platelet Ratio Index, NAFLD Fibrosis Score (NAFLD-FS), or combinations thereof” were considered generally linking the abstract idea to particular technological environment. The “display…” has been re-evaluated under the “significantly more” analysis and determined to amount to be well-understood, routine, and conventional elements/functions. As described in Amarasingham (2017/0061093): see below but at least Figure 8, paragraph [0043]); Wang (2021/0022697): Figure 3, paragraph [0096]; display of data to a user is well-understood, routine and conventional. The “Fibrosis-4 (FIB-4), AST to Platelet Ratio Index, NAFLD Fibrosis Score (NAFLD-FS), or combinations thereof” has been re-evaluated under the “significantly more” analysis and determined to amount to be well-understood, routine, and conventional elements/functions. As described in Wang (2021/0022697): see below but at least paragraphs [0036] and [0158]; Cales (20170032099): see below but at least paragraphs [0024] and [0099]; Boursier (20200011869): paragraph [0004] and Table 7; use of scores of Fibrosis-4 (FIB-4), AST to Platelet Ratio Index or NAFLD Fibrosis Score (NAFLD-FS) is well-understood, routine, and conventional. Well-understood, routine, and conventional elements/functions cannot provide “significantly more.” As such the claim is not patent eligible.
Claims 3-4, 6-12, 15-16 and 18-20 are similarly rejected because either further define the abstract idea and/or do not further limit the claim to a practical application or provide as inventive concept such that the claims are subject matter eligible.
Claims 3 and 15 recite performing a quality control, but does not recite any additional elements and therefore cannot provide a practical application and/or significantly more.
Claims 4, 11 and 16 recite determination of weight-loss surgery, but does not recite any additional elements and therefore cannot provide a practical application and/or significantly more.
Claims 6 and 18 further describe the risk indicator, but does not recite any additional elements and therefore cannot provide a practical application and/or significantly more.
Claim 7 further describes the diagnosis codes, but does not recite any additional elements and therefore cannot provide a practical application and/or significantly more.
Claims 8-9 and 19 further describe the exclusion criteria, but does not recite any additional elements and therefore cannot provide a practical application and/or significantly more.
Claim 10 further describes the radiology report used, but does not recite any additional elements and therefore cannot provide a practical application and/or significantly more.
Claims 12 and 20 recite determination of end-stage liver outcomes, but does not recite any additional elements and therefore cannot provide a practical application and/or significantly more.
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 6, 8-10, 12-13 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Pub. No. 2017/0061093 (hereafter “Amarasingham”), in view of U.S. Patent Pub. No. 2021/0022697 (hereafter “Wang”), further in view of U.S. Patent Pub. No. 20170032099 (hereafter “Cales”).
Regarding (Currently Amended) claim 1, Amarasingham teaches a system for diagnosing […] disease […] in patients (Amarasingham: Figure 1, paragraph [0002], “a clinical dashboard user interface system and method, and in particular in the field of disease identification and monitoring”, paragraph [0034], “a clinical predictive and monitoring system”) comprising:
--one or more processors; and one or more computer-readable non-transitory storage media coupled to one or more of the processors and comprising instructions operable (Amarasingham: Figure 1, paragraph [0045], “computer system 12 may comprise a number of computing devices, including servers”. The Examiner notes a server teaches a processer and memory, and teaches what is required under the broadest reasonable interpretation) when executed by one or more of the processors to cause the system to:
--select at least one patient with a risk indicator using an electronic health record (EHR) database (Amarasingham: Figures 1, 4-5, paragraphs [0034]-[0035], “The data received by the clinical predictive and monitoring system 10 may include electronic medical records (EMR) that include both clinical and non-clinical data”, paragraph [0070], “receives structured and unstructured clinical and non-clinical data related to specific patients from a variety of sources and in a number of different formats… In block 58, by analyzing the pre-processed data, one or more diseases or conditions of interest as related to each patient are identified. In block 60, the method 50 applies one or more predictive models to further analyze the data and calculate one or more risk scores for each patient as related to the identified diseases or conditions. In blocks 62 and 64, one or more lists showing those patients with the highest risks for each identified disease or condition are generated”, paragraph [0072], “The risk score computed for each patient for a disease of interest is compared to a disease risk threshold in block 80. Each disease is associated with its own risk threshold… If the risk score is greater than or equal to the risk threshold, then the identified patient having the high risk score is included in a patient list in block 82.”. The Examiner notes generation of a list of patients via a risk score and threshold is selection of at least one patient using a risk indicator under the broadest reasonable interpretation, and teaches what is required of the claim), […];
--determine that the at least one patient fails to meet exclusion criteria (Amarasingham: Figures 10-11, 14, paragraph [0096], “In FIG. 14, the user may set the display criteria, such as to exclude selected risk groups from the worklist. In this example, those patients with medium and low risks as determined preferably by the clinical predictive and monitoring system are excluded. In addition, the user may also choose to exclude from the patient worklist certain patients with certain selected conditions, such as AIDS, hemodialysis, transplant, active oncology, substance abuse, pregnancy, skilled nursing facility (SNF) transfer, homeless, and jail.”, Claims 11-11, “excluding patients with the received condition”. Also see, paragraphs [0089]-[0093]. The Examiner notes patients are excluded based on display criteria (i.e., exclusion criteria), and teaches what is required of the claim under the broadest reasonable interpretation); […];
--display the at least one patient in response to the determination (Amarasingham: Figures 4-5, 10-11, paragraph [0048], “The clinical predictive and monitoring system and method 10 are operable to display, transmit, and otherwise present the list of high risk patients”, paragraph [0065], “The results from the disease/risk logic module 30 are provided to the hospital personnel, such as the intervention coordination team, and other caretakers by a data presentation and system configuration logic module 42”, paragraph [0072], “In block 84, the patient list and other associated information may then be presented to the intervention coordination team in one or more possible ways, such as transmission to and display on a desktop or mobile device”. Also see, claims 11-12);
calculate scores […] of the at least one patient using a predetermined metric (Amarasingham: Figures 4-5, 10-11, paragraph [0034], “data are used to determine a disease risk score for selected patients”, paragraphs [0046]-[0048], “The clinical predictive and monitoring system and method 10 is adapted to accurately stratify risk for certain diseases and conditions… calculates a risk score… If this particular patient's risk score… is above a certain risk threshold, then the patient is identified on a list of high-risk patients”, paragraphs [0055]-[0056], “calculate a risk score associated with an identified disease or condition for each patient… The disease identification process 34 considers data such as lab orders, lab values, clinical text and narrative notes, and other clinical and historical information to determine the probability that a patient has a particular disease”, paragraph [0066], “frequently used medical formulas to assist in care provision including but not limited to: acid-base calculation, MELD score”); and
provide a risk [… of disease progression or …] an end-stage liver disease based on the one or more scores (Amarasingham: Figures 4-5, 10-11, paragraphs [0046]-[0048], “certain diseases and conditions… calculates a risk score… If this particular patient's risk score… is above a certain risk threshold, then the patient is identified on a list of high-risk patients… present the list of high risk patients”, paragraphs [0060]-[0061], “a predictive model process 36 that is adapted to predict the risk of particular diseases or condition of interest according to one or more predictive models. For example, if the hospital desires to determine the level of risk… predictive models may include HIV readmission, diabetes identification, risk for cardio-pulmonary arrest, kidney disease progression, acute coronary syndrome, pneumonia, cirrhosis, all-cause disease-independent readmission, colon cancer pathway adherence, and others… output from the disease/risk logic module 30 includes the risk scores of all the patients for particular disease or condition”, paragraph [0079], “Targeted conditions due to possible adverse event for surveillance may include… hypertension” The Examiner determination of a level of risk a risk of progressing and notes these are described as examples of end-stage liver related outcomes in Applicant’s specification paragraph [0026], and teach what is required of the claim under the broadest reasonable interpretation).
Amarasingham may not explicitly teach (underlined below for clarity):
--a system for diagnosing nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in patients comprising:
--wherein the risk indicator is associated with NAFLD and/or NASH;
verify hepatic steatosis of the at least one patient using at least detection associated with the presence of intrahepatic fat;
calculate scores of Fibrosis-4 (FIB-4), AST to Platelet Ratio Index, NAFLD Fibrosis Score (NAFLD-FS), or combinations thereof of the at least one patient using a predetermined metric; provide a risk for progressing to an end-stage liver disease based on the one or more scores.
Wang teaches a system for diagnosing nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in patients (Wang: Figure 2, paragraphs [0002]-[0004], “Nonalcoholic fatty liver disease (NAFLD)… Nonalcoholic steatohepatitis (NASH) is a more severe form of NAFLD… Identifying NASH, and differentiating NASH from NAFLD”, paragraph [0006], “methods and systems for evaluating liver inflammation and associated conditions”) comprising:
--wherein the risk indicator is associated with NAFLD and/or NASH (Wang: Figure 3, paragraph [0006], “generate hepatic scores, such as a liver inflammation score that characterizes NASH in patients, based on one or more of the kinetic parameters”, paragraph [0082], “methods and systems for determining one or more kinetic parameters associated with a kinetic model of an imaging agent in a liver. These kinetic parameters can be used to determine hepatic scores that can be used to evaluate NAFLD and NASH in patients”, paragraph [0150], “the image reconstruction device may generate an output characterizing liver inflammation in the liver based on the one or more kinetic parameters. For example the image reconstruction device may generate an output indicating the presence (or absence) of nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH) in the liver. The output may be generated in view of the hepatic scores determined”);
verify hepatic steatosis of the at least one patient using at least detection associated with the presence of intrahepatic fat (Wang: paragraph [0034], “A "hepatic steatosis score" is a score characterizing hepatic steatosis”, paragraphs [0102]-[0103], “The hepatic scoring module 218 comprises code enabling the processor 202 to determine one or more hepatic scores, including a hepatic inflammation score, a hepatic steatosis score, and a hepatic fibrosis score based on the kinetic parameters, liver SUV, and liver SUVR… the hepatic scoring module 218 comprises code enabling the processor 202 to compare hepatic scores to predetermined thresholds and issue an alert when one or more hepatic scores exceeds predetermined thresholds”, paragraph [0219], “Embodiments compare dynamic FDG PET findings with liver histologic findings… This correlation was also noted with the overall NAFLD activity score (NAS) for which a decrease in K1 was associated with increased NAS scores. A combination of insulin resistance, increased intrahepatic fat (presumably resulting in decreased liver blood flow), and disease progression with fibrous tissue deposition, collagen deposition, or both may lead to the decrease in K1 with worsening of the disease state”. The Examiner notes determination of a hepatic steatosis score that is at least associated with a detected presence of intrahepatic fat, that is than compared to a threshold reads on “verify” under the broadest reasonable interpretation and would be prima facie obvious to one of ordinary skill in the art before the effective filing date);
calculate scores of Fibrosis-4 (FIB-4), AST to Platelet Ratio Index, NAFLD Fibrosis Score (NAFLD-FS), or combinations thereof of the at least one patient using a predetermined metric; provide a risk for progressing to an end-stage liver disease based on the one or more scores (Wang: Abstract, “a cirrhosis score”, paragraph [0003], “liver cancer and liver failure”, paragraph [0036], “A “hepatic fibrosis score” is a score characterizing hepatic fibrosis… The hepatic fibrosis score may have a defined range (e.g., 0-4)”, paragraph [0058], “NAFLD activity score”, paragraph [0158], “elevated liver enzyme levels (e.g., alanine transaminase (ALT) or aspartate transaminase (AST))”, Table 4a, “NAFLD Fibrosis Score:”, paragraph [0199], “Three of the patients had diabetes mellitus, 8 had hypertension”).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention was made to combine the noted features of Wang within teaching of Amarasingham since the combination of the two references is merely simple substitution of one known element for another producing a predictable result (KSR rationale B). Since each individual element and its function are shown in the prior art, albeit shown in separate references, the difference between the claimed subject matter and the prior art rests not on any individual element or function but in the very combination itself—that is, in the substitution of the risk indicators for NAFLD and NASH using Fib-4, AST ratio and NAFLD-FS and verification of hepatic steatosis as taught by Wang for the determination of risk for diseases and exclusion criteria as taught by Amarasingham. Thus, the simple substitution of one known element for another producing a predictable result renders the claim obvious.
Amarasingham and Wang may not explicitly teach (underlined below for clarity):
provide a risk for progressing to an end-stage liver disease based on the one or more scores.
Cales teaches provide a risk for progressing to an end-stage liver disease based on the one or more scores (Cales: paragraph [0011], “an in vitro non-invasive prognostic method for assessing the risk of death and/or of liver-related event in a subject”, paragraph [0059], ““Prognosis” refers to the statistical prediction of the occurrence of death or of the occurrence of a liver-related event (or of the first liver-related event) over a specific time period for a subject”, paragraph [0040], “at least one blood test result, preferably selected from the group comprising FibroMeter, CirrhoMeter, ELF score, FibroSpect, APRI, FIB-4 and Hepascore”, paragraph [0085], “assessing the risk of death and/or of liver-related event, especially complication, in the subject according to the value of the prognostic score”).
One of ordinary skill in the art before the effective filing date would have of found it obvious to include using a risk for progressing to an end-stage liver disease as taught by Cales within the risk of progression as taught by Amarasingham and Wang with the motivation of “improve the liver-prognosis assessment” (Cales: paragraph [0263]).
Regarding (Original) claim 6, Amarasingham, Wang and Cales teach the limitations of claim 1, and further teach wherein the risk indicator is selected from the group consisting of demographic data, a diagnosis code, a procedure code, a laboratory measurement, a medication history, a pathology code, a radiology code, and combinations thereof (Amarasingham: Figure 11, paragraph [0017], “showing a patient worklist that displays a list of patients matching certain criteria… and key laboratory data that show the drivers why a particular selected patient meet those criteria”, paragraphs [0055]-[0056], “calculate a risk score associated with an identified disease or condition for each patient… The disease identification process 34 considers data such as lab orders, lab values, clinical text and narrative notes, and other clinical and historical information to determine the probability that a patient has a particular disease”, paragraph [0072], “Data related to the patient generated during the inpatient and outpatient care, such as prescribed medicines and further laboratory results, radiological images, etc. is continually monitored”, paragraph [0093], “The lab test results highlighted at the bottom of the screen are key lab result data that contributed to the working diagnosis for the selected patient”).
The motivation to combine is the same as in claim 1, incorporated herein.
Regarding (Original) claim 8, Amarasingham, Wang and Cales teach the limitations of claim 1, and further teach wherein the exclusion criteria are selected from the group consisting of demographic data, a diagnosis code, a procedure code, a laboratory measurement, a medication history, a pathology code, a radiology code, and combinations thereof (Amarasingham: Figures 10-11, 14, paragraph [0017], “showing a patient worklist that displays a list of patients matching certain criteria… and key laboratory data that show the drivers why a particular selected patient meet those criteria”, paragraphs [0055]-[0056], “calculate a risk score associated with an identified disease or condition for each patient… The disease identification process 34 considers data such as lab orders, lab values, clinical text and narrative notes, and other clinical and historical information to determine the probability that a patient has a particular disease”, paragraph [0072], “Data related to the patient generated during the inpatient and outpatient care, such as prescribed medicines and further laboratory results, radiological images, etc. is continually monitored”, paragraph [0093], “The lab test results highlighted at the bottom of the screen are key lab result data that contributed to the working diagnosis for the selected patient”, paragraph [0096], “In FIG. 14, the user may set the display criteria, such as to exclude selected risk groups from the worklist. In this example, those patients with medium and low risks as determined preferably by the clinical predictive and monitoring system are excluded. In addition, the user may also choose to exclude from the patient worklist certain patients with certain selected conditions, such as AIDS, hemodialysis, transplant, active oncology, substance abuse, pregnancy, skilled nursing facility (SNF) transfer, homeless, and jail.”, Claims 11-11, “excluding patients with the received condition”. Also see, paragraphs [0089]-[0093].).
The motivation to combine is the same as in claim 1, incorporated herein.
Regarding (Original) claim 9, Amarasingham, Wang and Cales teach the limitations of claim 8, and further teach wherein the exclusion criteria comprise alcohol abuse, type 1 diabetes, viral hepatitis infection, HIV infection, age, or combinations thereof (Amarasingham: Figures 10-11, 14, paragraph [0061], “diseases and conditions that may be identified using predictive modeling include, for example, HIV”, paragraph [0067], “flagging high substance abuse score for consultation of rehabilitation counselling for patients with substance abuse issues”, paragraph [0096], “In FIG. 14, the user may set the display criteria, such as to exclude selected risk groups from the worklist. In this example, those patients with medium and low risks as determined preferably by the clinical predictive and monitoring system are excluded. In addition, the user may also choose to exclude from the patient worklist certain patients with certain selected conditions, such as AIDS, hemodialysis, transplant, active oncology, substance abuse, pregnancy, skilled nursing facility (SNF) transfer, homeless, and jail.”, Claims 11-11, “excluding patients with the received condition”; Wang: paragraph [0169], “Patients with history of alcohol abuse, chronic hepatitis B or C, or other chronic liver disease other than NAFLD were excluded from the first patient study”. Also see, paragraphs [0089]-[0093]).
The motivation to combine is the same as in claim 1, incorporated herein.
Regarding (Original) claim 10, Amarasingham, Wang and Cales teach the limitations of claim 2, and further teach wherein the radiology report is selected from the group consisting of an ultrasound report, a CT scan report, a MRI report, and combinations thereof (Amarasingham: paragraph [0035], “radiological imaging exams”; Wang: paragraph [0082], “The kinetic parameters can be determined by an image reconstruction device based on a plurality of imaging agent activities, which can be collected, for example, as part of a tracer transport kinetic imaging technique including but not limited to a PET scan, a computerized tomography (CT) scan, a Magnetic resonance imaging (MRI), etc.”).
The motivation to combine is the same as in claim 1, incorporated herein.
Regarding (Original) claim 12, Amarasingham, Wang and Cales teach the limitations of claim 5, and further teach wherein the end-stage liver-related outcome is selected from the group consisting of Model for End Stage Liver Disease (MELD) score, portal hypertension, hepatorenal syndrome, primary bacterial peritonitis, ascites, complications of transplanted liver, hepatic encephalopathy, cirrhosis, hepatocellular carcinoma, hepatopulmonary syndrome, hepatic failure, esophageal varices, esophagogastroduodenoscopy and combinations thereof (Amarasingham: paragraph [0060], “predictive models may include HIV readmission, diabetes identification, risk for cardio-pulmonary arrest, kidney disease progression, acute coronary syndrome, pneumonia, cirrhosis, all-cause disease-independent readmission, colon cancer pathway adherence, and others”, paragraph [0066], “frequently used medical formulas to assist in care provision including but not limited to: acid-base calculation, MELD score”, paragraph [0079], “Targeted conditions due to possible adverse event for surveillance may include… hypertension”; Wang: Abstract, “a cirrhosis score”, paragraph [0003], “liver cancer and liver failure”, paragraph [0199], “Three of the patients had diabetes mellitus, 8 had hypertension”).
The motivation to combine is the same as in claim 1, incorporated herein.
REGARDING CLAIM(S) 13 and 19-20
Claim(s) 13 and 19-20 is/are analogous to Claim(s) 1, 9 and 12, thus Claim(s) 13 and 19-20 is/are similarly analyzed and rejected in a manner consistent with the rejection of Claim(s) 1, 9 and 12.
Regarding (Original) claim 18, Amarasingham, Wang and Cales teach the limitations of claim 13, and further teach wherein the risk indicator is selected from the group consisting of type 2 diabetes, obesity, abnormal liver enzymes, hyperlipidemia, hypertension, chronic nonalcoholic liver disease, nonalcoholic steatohepatitis, steatosis, cirrhosis, and combinations thereof (Amarasingham: paragraphs [0055]-[0056], “calculate a risk score associated with an identified disease or condition for each patient… The disease identification process 34 considers data such as lab orders, lab values, clinical text and narrative notes, and other clinical and historical information to determine the probability that a patient has a particular disease”, paragraphs [0058]-[0060], “Fifty-five-year-old male with history of diabetes mellitus… predictive models may include HIV readmission, diabetes identification, risk for cardio-pulmonary arrest, kidney disease progression, acute coronary syndrome, pneumonia, cirrhosis, all-cause disease-independent readmission, colon cancer pathway adherence, and others”, paragraph [0079], “Targeted conditions due to possible adverse event for surveillance may include… hypertension”; Wang: paragraph [0102], “determine one or more hepatic scores, including a hepatic inflammation score, a hepatic steatosis score, and a hepatic fibrosis score based on the kinetic parameters, liver SUV, and liver SUVR”, paragraph [0158], “liver disorder indicators can include, but are not limited to, having a liver biopsy, fatty liver detected by ultrasound, patient high BMI score, having one or more risk factors for diabetes, and/or elevated liver enzyme levels (e.g., alanine transaminase (ALT) or aspartate transaminase (AST))”, paragraph [0199], “Three of the patients had diabetes mellitus, 8 had hypertension and six patients had hyperlipidemia”).
The motivation to combine is the same as in claim 1, incorporated herein.
Claim(s) 3, 7 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Pub. No. 2017/0061093 (hereafter “Amarasingham”), U.S. Patent Pub. No. 2021/0022697 (hereafter “Wang”) and U.S. Patent Pub. No. 20170032099 (hereafter “Cales”) as applied to claim 1 and 13 above, and further in view of U.S. Patent Pub. No. 2017/0098032 (hereafter “Desai”).
Regarding (Original) claim 3, Amarasingham, Wang and Cales teach the limitations of claim 1, and further teach wherein the system is further configured to [… determine confidence …] by excluding a patient who has […] less than three occurrences of the risk indicator (Amarasingham: Figure 7, 10-11, paragraph [0058], “establish a higher confidence”, paragraph [0080], “Key terms such as "shortness of breath," "BNP was elevated," and "Lasix" help the user validate the disease identification”, paragraph [0092], “the fact that Ethel Price has had three readmissions in the past year, and two emergency room visits in the last year are primary contributing factors that resulted in the very high risk”; Wang: paragraph [0158], “having one or more risk factors”).
Amarasingham, Wang and Cales may not explicitly teach (underlined below for clarity):
--wherein the system is further configured to perform a quality control by excluding a patient who has less than two risk indicators or less than three occurrences of the risk indicator.
Desai teaches wherein the system is further configured to perform a quality control by excluding a patient who has less than two risk indicators or less than three occurrences of the risk indicator (Desai: Figure 3, paragraph [0101], “the reliability of biomarkers as indicators or reflectors of the mechanism sought to be measured may also be variable or in question in various different contexts. Furthermore, some biomarkers may be significant indicators only when in the presence of other biomarkers as part of a combination of biomarkers. Thus, correlations between biomarkers and clinical efficacy or toxicity are, in many cases, not perfectly accurate. Instead, the biomarkers can be useful indicators for recognition of patterns”, claims 5-8, “an indicator of data quantity… wherein the indicator of data quality is defined based on an assessment of a number of biomarkers associated with the disease for which a biomarker to disease mapping is indicated in the data sources”. The Examiner notes the combination of biomarkers for a data quality check teaches what is required of the broadest reasonable interpretation).
One of ordinary skill in the art before the effective filing date would have of found it obvious to include using a data quality check as taught by Desai within the exclusion criteria including a confidence as taught by Amarasingham, Wang and Cales with the motivation of “[improving] healthcare quality and effectiveness… and healthcare cost and quality in the aggregate may also improve” (Desai: paragraph [0004]).
Regarding (Original) claim 7, Amarasingham, Wang and Cales teach the limitations of claim 6, and further teach wherein the diagnosis […] are selected from the group consisting of type 2 diabetes, obesity, abnormal liver enzymes, hyperlipidemia, hypertension, chronic nonalcoholic liver disease, nonalcoholic steatohepatitis, steatosis, cirrhosis, and combinations thereof (Amarasingham: paragraphs [0058]-[0060], “Fifty-five-year-old male with history of diabetes mellitus… predictive models may include HIV readmission, diabetes identification, risk for cardio-pulmonary arrest, kidney disease progression, acute coronary syndrome, pneumonia, cirrhosis, all-cause disease-independent readmission, colon cancer pathway adherence, and others”, paragraph [0079], “Targeted conditions due to possible adverse event for surveillance may include… hypertension”; Wang: paragraph [0102], “determine one or more hepatic scores, including a hepatic inflammation score, a hepatic steatosis score, and a hepatic fibrosis score based on the kinetic parameters, liver SUV, and liver SUVR”, paragraph [0158], “liver disorder indicators can include, but are not limited to, having a liver biopsy, fatty liver detected by ultrasound, patient high BMI score, having one or more risk factors for diabetes, and/or elevated liver enzyme levels (e.g., alanine transaminase (ALT) or aspartate transaminase (AST))”, paragraph [0199], “Three of the patients had diabetes mellitus, 8 had hypertension and six patients had hyperlipidemia”).
Amarasingham, Wang and Cales may not explicitly teach (underlined below for clarity):
--wherein the diagnosis codes are selected from the group consisting of type 2 diabetes, obesity, abnormal liver enzymes, hyperlipidemia, hypertension, chronic nonalcoholic liver disease, nonalcoholic steatohepatitis, steatosis, cirrhosis, and combinations thereof.
Desai teaches wherein the diagnosis codes are selected from the group consisting of type 2 diabetes, obesity, abnormal liver enzymes, hyperlipidemia, hypertension, chronic nonalcoholic liver disease, nonalcoholic steatohepatitis, steatosis, cirrhosis, and combinations thereof (Desai: paragraph [0040], “A disorder ontology can be compiled from existing resources such as the International classification of Diseases (ICD), the Diagnostic and Statistical Manual of Mental Disorders (DSM), the Medical Dictionary for Regulator Activities (MedDRA), BioOntology, and the Open Biological and Biomedical Ontologies”).
The motivation to combine is the same as in claim 3, incorporated herein.
REGARDING CLAIM(S) 15
Claim(s) 15 is/are analogous to Claim(s) 3, thus Claim(s) 15 is/are similarly analyzed and rejected in a manner consistent with the rejection of Claim(s) 3.
Claim(s) 4, 11 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Pub. No. 2017/0061093 (hereafter “Amarasingham”), U.S. Patent Pub. No. 2021/0022697 (hereafter “Wang”) and Amarasingham, Wang and Cales as applied to claims 1 and 13 above, and further in view of U.S. Patent Pub. No. 2016/0030378 (hereafter “Harada”).
Regarding (Original) claim 4, Amarasingham, Wang and Cales teach the limitations of claim 1, but may not explicitly teach wherein the system is further configured to determine that the at least one patient receives a weight-loss surgery.
Harada teaches wherein the system is further configured to determine that the at least one patient receives a weight-loss surgery (Harada: paragraphs [0331]-[0335], “Exclusion criteria have been designed to exclude subjects from the study if they will not be evaluable for the primary endpoint, if they have disease states that would interfere with analysis of study endpoints, or would put subjects at risk of serious adverse events associated with their participation… Potential subjects will be excluded from participating in the study if they meet any of the following exclusion criteria… Previous bariatric surgery or biliary diversion (i.e. gastric bypass), esophageal banding and gastric banding”. The Examiner notes these are weight-loss surgeries and teach what is required of the claim under the broadest reasonable interpretation).
One of ordinary skill in the art before the effective filing date would have found it obvious to include determination of a weight-loss surgery as taught by Harada with the determination of medical history in selecting patients as taught by Amarasingham, Wang and Cales with the motivation of “improvements of biochemical markers related to NASH” (Harada” paragraph [0272]).
Regarding (Original) claim 11, Amarasingham, Wang, Cales and Harada teach the limitations of claim 4, and further teach wherein the weight-loss surgery is selected from the group consisting of a laparoscopy procedure, a gastric restrictive procedure, a bariatric procedure, a bariatric revision, and combinations thereof (Harada: paragraphs [0331]-[0335], “Exclusion criteria have been designed to exclude subjects from the study if they will not be evaluable for the primary endpoint, if they have disease states that would interfere with analysis of study endpoints, or would put subjects at risk of serious adverse events associated with their participation… Potential subjects will be excluded from participating in the study if they meet any of the following exclusion criteria… Previous bariatric surgery or biliary diversion (i.e. gastric bypass), esophageal banding and gastric banding”).
The motivation to combine is the same as in claim 4, incorporated herein.
REGARDING CLAIM(S) 16
Claim(s) 16 is/are analogous to Claim(s) 4, thus Claim(s) 16 is/are similarly analyzed and rejected in a manner consistent with the rejection of Claim(s) 4.
Response to Arguments
Applicant's arguments filed 04 August 2025 have been fully considered but they are not persuasive. Applicants’ arguments will be addressed herein below in the order in which they appear in the response filed on 04 August 2025.
Rejections under 35 U.S.C. § 101
Regarding the rejection of claims 1-2, 5-6, 8-10, 12-14, and 17-20, the Examiner has considered the Applicant’s arguments but does not find them persuasive. Any arguments inadvertently not addressed are unpersuasive for at least the following reasons:
Applicant argues:
For Prong 1 in Step 2A, unlike conventional human decision-making, the claimed invention performs automated patient selection, exclusion criteria evaluation, and fibrosis score calculation using predefined medical metrics (e.g., FIB-4, APRI, NAFLD-FS). Notably, the features "verify hepatic steatosis of the at least one patient using at least a pathology report, incorporating detection associated with the presence of intrahepatic fat" recited in clam 1 involve the technical nature and provide its specific application to the field of medical diagnostics, which cannot be practically performed merely by conventional human decision-making and mental behaviors… the use of specific, non-generic clinical scoring systems integrated within a computational framework to assess progression to liver disease, e.g., "verify hepatic steatosis of the at least one patient using at least detection associated with the presence of intrahepatic fat; display the at least one patient in response to the determination", constitutes more than a mere "method of organizing human activity" or a merely generic computing system. Thus, claim 1 recites a system to diagnose nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) and further calculate and provide a risk score for progressing to an end-stage liver disease through predetermined metrics and noninvasive scoring techniques… Regardless, the amended claim 1 recites "verify hepatic steatosis of the at least one patient using at least detection associated with the presence of intrahepatic fat" to achieve a diagnosis improvement, rendering the amended claim 1 nonobvious over the cited references, as detailed below. Accordingly, even if Step 2B were considered, claim 1 includes significantly more than a judicial exception and remains patent eligible.
The Examiner respectfully disagrees.
It is respectfully submitted, verification of hepatic steatosis under the broadest reasonable interpretation is not an additional element, merely making a verification by organizing data is not an additional element, it is activity performed by humans to make a determination and is at best merely being performed by the generic off the shelf computer components to apply the abstract idea, which is not sufficient to show a technical solution to a technical problem recited in Applicant’s specification. The currently drafted claimed additional elements must either improve the performance of the computer and/or provide a technical solution to a technical problem recited in Applicant specification, Applicant does not argue any technical problems in their specification, at best verification of a disease is a doctor prognosis problem which is a human activity problem, as the claim do not recite a technical solution to a technical problem recited in Applicant’s specification or an improvement in the functionality of the computer the argument is not persuasive.
Rejections under 35 U.S.C. § 103
Regarding the rejection of claim 1-2, 5-6, 8-10, 12-14, and 17-20, the Examiner has considered the Applicant's arguments but does not find them persuasive. The Examiner has attempted to address all of the arguments presented by the Applicant; however, any arguments inadvertently not addressed are not persuasive for at least the following reasons:
Applicant argues:
Among other features, amended claim 1 recites a system for diagnosing nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) in patients that includes the features… As an initial matter, the Examiner alleges that Wang discloses the features of While Wang describes a determination of hepatic steatosis scores, Wang does not disclose or suggest at least the feature of "detection associated with the presence of intrahepatic M" to verify the hepatic steatosis. In addition, Wang focuses on the "determination" of hepatic steatosis scores as an end outcome thereof, without utilizing or integrating detection tied to intrahepatic fat for verification purposes… Furthermore, there is no motivation for a combination between Amarasingham and Wang… Thus, as Wang addresses an image characterization via scanning, and Amarasingham addresses user interface displaying, there is no motivation to combine Amarasingham and Wang. A person of ordinary skill in the art would not have combined these disparate references.
The Examiner respectfully disagrees.
It is respectfully submitted, that the argued feature is taught by the combination of Wang within Amarasingham. First, the amended feature uses “associated” language for use of presence of intrahepatic fat, as such, at least the teachings of Wang (see above but at least paragraphs [0102]-[0104] and [0219]), in which determination of a hepatic steatosis score that is at least associated with a detected presence of intrahepatic fat, that is than compared to a threshold reads on “verify” under the broadest reasonable interpretation and would be prima facie obvious to one of ordinary skill in the art before the effective filing date. Second, the Examiner notes that Amarasingham is directed at various medical conditions, one of which includes cirrhosis (i.e., an end stage liver condition; see above but at least paragraph [0060]), therefore one of ordinary skill in the art would find it prima facie obvious to include the various teachings directed at NAFLD/NASH as taught by Wang within the various risk of conditions being determined as taught by Amarasingham as merely simple substitution of one known element for another producing a predictable result (KS