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 .
Response to Amendment
The amendments filed 05 JUNE 2026 have been entered. Claims 1 – 9 and 13 - 17 are pending. Applicant’s amendments have overcome each and every objection to the specification, drawings, and claims previously applied in the office action dated 11 MARCH 2026. Applicant’s amendments have overcome each and every rejection under 35 U.S.C. 112 previously applied in the office action dated 11 MARCH 2026.
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 2 and 17 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 2 (line 4) recites the term “determining at least one fluctuation of the signal from a baseline of the signal”. The currently-recited signal in Claim 1 “comprises at least one of a blood composition, a urine composition, hemodynamic waveform data, comorbidity data, a central venous pressure, or a frailty score. Broadly, a blood composition could be comprised of categorical data in a field on a medical record, with the result being that the “urine contains blood”, blood composition could also be categorical data, as could comorbidity data (fields that say the name of a disease that a person may have), and a frailty score (a single numeric value). These categorical data are not obviously a “signal”, such that it is unclear how “fluctuation” in this data occurs, not how the “baseline of the signal” is determined. It is further unclear how the pieces of clinical data including both categorical (or discrete) and continuous data are combined to form a unified “signal”. Looking to [0050] and [0051], these descriptions of “baseline” and “fluctuation” appear to refer to determining the baseline or variation of values of a series of the same data type or continuous data waveforms. As such, it becomes further unclear how a fluctuation is determined. With the combination of data types, a fluctuation could be merely the addition of another type of data to the record, or broad “signal”, since that would induce a “change” for the overall “signal” composition. For the purposes of examination, the term “determining at least one fluctuation of the signal from a baseline of the signal” is deemed to claim “determining at least one fluctuation of the at least one clinical data related to the patient from a baseline of the at least one clinical data related to the patient.”
Claim 17 (line 2 – 3) recites the limitation “pre-emtively administering at least one of fluids or pressors to the patient in response to the prediction of the subsequent AHE event”. The term “pre-emtively” a relative term which renders the claim indefinite. The term “pre-emtively” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear if the fluids or pressors are intended to be administered either pre-emtively relative to when they are traditionally recommended to be administered, or pre-emtively administering pressors before fluids relative to common guidance of treatment timing, or pre-emtively relative to prior to obtaining the prediction of the subsequent AHE. For the purposes of examination, the term “pre-emtively administering at least one of fluids or pressors to the patient in response to the prediction of the subsequent AHE event” is deemed to claim “administering at least one of fluids or pressors to the patient in response to the prediction of the subsequent AHE event”.
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 – 17 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.
Regarding Claim 1, the claim recites "an act or step, or series of acts or steps" and is therefore a process, which is a statutory category of invention (Step 1). The claims are then analyzed to determine whether it is directed to any judicial exception (Step 2A, Prong 1).
Each of Claims 1 – 17 has been analyzed to determine whether it is directed to any judicial exceptions.
Step 2A, Prong 1
Each of Claims 1 – 17 recites at least one step or instruction for observations, evaluations, judgments, and opinions, which are grouped as a mental process under the 2019 PEG. The claimed invention involves making observations, evaluations, judgments, and opinions, which are concepts performed in the human mind under the 2019 PEG.
Accordingly, each of Claims 1 – 17 recites an abstract idea.
Specifically, Independent Claim 1 recite (underlined are observations, judgements, evaluations, or opinions, which are grouped as a mental process under the 2019 PEG) (additional elements bolded, see Step 2A, prong 2);
Claim
A method for adaptively detecting an Acute Hypotension Episode (AHE) event of a patient, comprising:
receiving at least one clinical data related to the patient, wherein the at least one clinical data comprises at least one of a blood composition, a urine composition, hemodynamic waveform data, comorbidity data, a central venous pressure, or a frailty score;
processing, by a processor, a signal comprising the at least one clinical data relating to the patient to determine at least one mean arterial pressure (MAP) threshold value for the patient;
detecting, by the processor, one or more AHE event of the patient based on the at least one MAP threshold value
receiving an input relating to a time frame;
determining, by the processor, a prediction of a subsequent AHE event of the patient during the time frame based on the at least one MAP threshold value and the signal;
outputting the prediction to a user interface.
(observation, judgment or evaluation, which is grouped as a mental process under the 2019 PEG);
These underlined limitations describe a mathematical calculation and/or a mental process, as a skilled practitioner is capable of performing the recited limitations and making a mental assessment thereafter. Examiner notes that nothing from the claims suggests that the limitations cannot be practically performed by a human with the aid of a pen and paper, or by using a generic computer as a tool to perform mathematical calculations and/or mental process steps in real time. Examiner additionally notes that nothing from the claims suggests and undue level of complexity that the mathematical calculations and/or the mental process steps cannot be practically performed by a human with the aid of a pen and paper, or using a generic computer as a tool to perform mathematical calculations and/or mental process steps. For example, in Independent Claim 1, these limitations include:
Observation and judgment of at least one clinical data related to the patient, wherein the at least one clinical data comprises at least one of a blood composition, a urine composition, hemodynamic waveform data, comorbidity data, a central venous pressure, or a frailty score
Observation and judgment of a signal comprising the at least one clinical data relating to the patient to observe and judge at least one mean arterial pressure (MAP) threshold value for the patient;
Observation and judgment of one or more AHE event of the patient based on the at least one MAP threshold value
Observation and judgment of a prediction of a subsequent AHE event of the patient during the time frame based on the at least one MAP threshold value and the signal;
Similarly, Dependent Claims 2 – 17 include the following abstract limitations, in addition to the aforementioned limitations in Independent Claim 1 (underlined observation, judgment or evaluation, which is grouped as a mental process under the 2019 PEG):
determining at least one fluctuation of the signal from a baseline of the signal.
Observation and judgment of at least one fluctuation of the signal from a baseline of the signal.
comparing one or more MAP values of the signal against the at least one MAP threshold value.
Observation and judgment to compare one or more MAP values of the signal against the at least one MAP threshold value.
determining if a duration relating to the one or more MAP values is longer than a pre-configured threshold duration.
Observation and judgment if a duration relating to the one or more MAP values is longer than a pre-configured threshold duration.
determining if the at least one MAP threshold value is lower than a first pre- configured MAP threshold value.
Observation and judgment if the at least one MAP threshold value is lower than a first pre- configured MAP threshold value.
determining if a mean MAP value of a baseline of the signal is lower than a second pre-configured MAP threshold value.
Observation and judgment if a mean MAP value of a baseline of the signal is lower than a second pre-configured MAP threshold value.
detecting an onset and a duration of the AHE event of the patient based on the at least one MAP threshold value and the signal.
Observation and judgment of an onset and a duration of the AHE event of the patient based on the at least one MAP threshold value and the signal.
storing the onset and the duration of the AHE event of the patient, and one or more MAP values associated with the AHE event in a database.
Observation and judgment to store the onset and the duration of the AHE event of the patient, and one or more MAP values associated with the AHE event in a database.
receiving a MAP waveform,
Observation and judgment of a MAP waveform,
determining, by the processor, a prediction of a subsequent AHE event of the patient based on the at least one MAP threshold value and the signal.
Observation and judgment of a prediction of a subsequent AHE event of the patient based on the at least one MAP threshold value and the signal.
determining a MAP value of the subsequent AHE event of the patient, the MAP value relating to a severity level of the subsequent AHE event.
Observation and judgment of a MAP value of the subsequent AHE event of the patient, the MAP value relating to a severity level of the subsequent AHE event.
extracting at least one feature in the signal, wherein the determination of the prediction of the subsequent AHE event of the patient is based on the at least one feature of the signal.
Observation and judgment of at least one feature in the signal, wherein the determination of the prediction of the subsequent AHE event of the patient is based on the at least one feature of the signal.
determining two or more predictions based on the at least one feature extracted from a plurality of signals relating to a plurality of patients;
Observation and judgment of two or more predictions based on the at least one feature extracted from a plurality of signals relating to a plurality of patients;
comparing the two or more predictions
Observation and judgment of the two or more predictions
determine an optimal prediction of subsequent AHE events of the plurality of patients based on the at least one feature extracted from the plurality of signals,
Observation and judgment of an optimal prediction of subsequent AHE events of the plurality of patients based on the at least one feature extracted from the plurality of signals,
Certain methods of organizing human activity:
Pre-emptively administering at least one of fluids or pressors to the patient in response to the prediction of the subsequent AHE event
all of which are grouped as mental processes or mathematical algorithms or certain methods of organizing human activity under the 2019 PEG.
Accordingly, as indicated above, each of the above-identified claims recite an abstract idea.
Step 2A, Prong 2
The above-identified abstract ideas in each of Independent Claim 1 (and their respective Dependent Claims) are not integrated into a practical application under 2019 PEG because the additional elements (identified in Claims 1 – 17), either alone or in combination, generally link the use of the above-identified abstract ideas to a particular technological environment or field of use. More specifically, the additional elements of:
“processor”, “at least one processor”
“at least one memory”
“user interface”
Additional elements recited include “processor”, “at least one processor”, “at least one memory”, and “user interface” in Independent Claim 1 (and their respective Dependent Claims). These components are recited at a high level of generality, , i.e., as a processor performing a generic function of processing data (the detecting, determining, and comparing); These generic hardware component limitations “processor”, “at least one processor”, and “at least one memory”, are no more than mere instructions to apply the exception using generic computer and hardware components. As such, these additional elements do not impose any meaningful limits on practicing the abstract idea.
Further additional elements from Claims 1 - 17 includes pre-solution activity limitations, such as:
receiving an input relating to a time frame;
outputting the prediction to a user interface.
the prediction comprises a prediction of an occurrence of the subsequent AHE event of the patient within the time frame.
at least one memory including computer program code
the optimal prediction being either one of or a combination of the two or more predictions, wherein the prediction of the subsequent AHE of the patient is based on the optimal prediction of the subsequent AHE events of the plurality of patients.
the at least one memory and the computer program code configured to, with at least one processor, cause the apparatus at least to perform the method according claim 1.
These pre-solution measurement elements are insignificant extra-solution activity, setting up the parameters of the system, and serve as data-gathering for the subsequent steps.
The “processor”, “at least one processor”, “at least one memory”, and “user interface” recited in Independent Claim 1 (and their respective Dependent Claims) are generically recited computer and hardware elements which do not improve the functioning of a computer, or any other technology or technical field. Nor do these above-identified additional elements serve to apply the above-identified abstract idea with, or by use of, a particular machine, effect a transformation or apply or use the above-identified abstract idea in some other meaningful way beyond generally linking the use thereof to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. Furthermore, the above-identified additional elements do not add a meaningful limitation to the abstract idea because they amount to simply implementing the abstract idea on a computer. For at least these reasons, the abstract ideas identified above in Independent Claim 1 (and their dependent claims) is not integrated into a practical application under 2019 PEG.
Moreover, the above-identified abstract idea is not integrated into a practical application under 2019 PEG because the claimed method and system merely implements the above-identified abstract idea (e.g., mental process and certain method of organizing human activity) using rules (e.g., computer instructions) executed by a computer processor as claimed. In other words, these claims are merely directed to an abstract idea with additional generic computer elements which do not add a meaningful limitation to the abstract idea because they amount to simply implementing the abstract idea on a computer. Additionally, Applicant’s specification does not include any discussion of how the claimed invention provides a technical improvement realized by these claims over the prior art or any explanation of a technical problem having an unconventional technical solution that is expressed in these claims. That is, like Affinity Labs of Tex. v. DirecTV, LLC, the specification fails to provide sufficient details regarding the manner in which the claimed invention accomplishes any technical improvement or solution. Thus, for these additional reasons, the abstract idea identified above in Independent Claim 1 (and their dependent claims) is not integrated into a practical application under the 2019 PEG.
Accordingly, Independent Claim 1 (and their dependent claims) are each directed to an abstract idea under 2019 PEG.
Step 2B –
None of Claims 1 – 17 include additional elements that are sufficient to amount to significantly more than the abstract idea for at least the following reasons.
These claims require the additional elements of: “processor”, “at least one processor”, “at least one memory”, and “user interface” as recited in Independent Claim 1 (and their dependent claims).
The additional elements of the “processor”, “at least one processor”, “at least one memory”, and “user interface” in Independent Claim 1 (and their dependent claims), as discussed with respect to Step 2A Prong Two, amounts to no more than mere instructions to apply the exception using generic computer and hardware components. The same analysis applies here in 2B, i.e., mere instructions to apply an exception using a generic computer component cannot integrate a judicial exception into a practical application at Step 2A or provide an inventive concept in Step 2B.
The above-identified additional elements are generically claimed computer components which enable the above-identified abstract idea(s) to be conducted by performing the basic functions of automating mental tasks. The courts have recognized such computer functions as well understood, routine, and conventional functions when claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity. See, Versata Dev. Group, Inc. v. SAP Am., Inc. , 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93.
Per Applicant’s specification, the “processor” and “at least one processor” is described generically at [0010] and [0011] as part of the apparatus that processes a signal and detects an AHE event based on the signal processing; [0081] as “a physical device comprising at least one processor and at least one memory including computer program code.”; and [0143] as “processor 2204 for executing software routines…may include a multi-processor system”. The “processor” and “at least one processor” are shown as generic box element “Processor 2204” in Figure 22.
Per Applicant’s specification, the “at least one memory”, is described generically in [0058] with “The computer readable medium may include storage devices such as magnetic or optical disks, memory chips, or other storage devices suitable for interfacing with a computer” and [0144] as “main memory 2208” with examples given for generic types of storage. The “at least one memory” is shown as generic box element “Main memory 2208” in Figure 22.
Per Applicant’s specification, the “user interface” is described generically in [0122] with “the user interface 1411 is configured to be displayed on a monitoring module (not shown) integrated into or separated from the hypotension prediction module 1404… connection may be wired, wireless (e.g., via NFC communication, Bluetooth, etc.), over a network (e.g., the Internet) or another device to which both modules are in communication with.” The “user interface” is shown as generic block element “user interface 1411” in Fig. 14.
Accordingly, in light of Applicant’s specification, the claimed terms “processor”, “at least one processor”, “at least one memory”, and “user interface” are reasonably construed as a generic computing and hardware devices. Like SAP America vs Investpic, LLC (Federal Circuit 2018), it is clear, from the claims themselves and the specification, that these limitations require no improved computer resources, just already available computers, with their already available basic functions, to use as tools in executing the claimed process.
Furthermore, Applicant’s specification does not describe any special programming or algorithms required for “processor”, “at least one processor”, “at least one memory”, and “user interface”. This lack of disclosure is acceptable under 35 U.S.C. §112(a) since this hardware performs non-specialized functions known by those of ordinary skill in the computer arts. By omitting any specialized programming or algorithms, Applicant's specification essentially admits that this hardware is conventional and performs well understood, routine and conventional activities in the computer industry or arts. In other words, Applicant’s specification demonstrates the well-understood, routine, conventional nature of the above-identified additional elements because it describes these additional elements in a manner that indicates that the additional elements are sufficiently well-known that the specification does not need to describe the particulars of such additional elements to satisfy 35 U.S.C. § 112(a) (see Berkheimer memo from April 19, 2018, (III)(A)(1) on page 3). Adding hardware that performs “‘well understood, routine, conventional activit[ies]’ previously known to the industry” will not make claims patent-eligible (TLI Communications).
The recitation of the above-identified additional limitations in Independent Claim 1 (and their dependent claims) amounts to mere instructions to implement the abstract idea on a computer. Simply using 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 provide significantly more. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); and TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). Moreover, implementing an abstract idea on a generic computer does not add significantly more, similar to how the recitation of the computer in the claim in Alice amounted to mere instructions to apply the abstract idea of intermediated settlement on a generic computer.
A claim that purports to improve computer capabilities or to improve an existing technology may provide significantly more. McRO, Inc. v. Bandai Namco Games Am. Inc., 837 F.3d 1299, 1314-15, 120 USPQ2d 1091, 1101-02 (Fed. Cir. 2016); and Enfish, LLC v. Microsoft Corp., 822 F.3d 1327, 1335-36, 118 USPQ2d 1684, 1688-89 (Fed. Cir. 2016). However, a technical explanation as to how to implement the invention should be present in the specification for any assertion that the invention improves upon conventional functioning of a computer, or upon conventional technology or technological processes. That is, the disclosure must provide sufficient details such that one of ordinary skill in the art would recognize the claimed invention as providing an improvement. Here, Applicant’s specification does not include any discussion of how the claimed invention provides a technical improvement realized by these claims over the prior art or any explanation of a technical problem having an unconventional technical solution that is expressed in these claims. Instead, as in Affinity Labs of Tex. v. DirecTV, LLC 838 F.3d 1253, 1263-64, 120 USPQ2d 1201, 1207-08 (Fed. Cir. 2016), the specification fails to provide sufficient details regarding the manner in which the claimed invention accomplishes any technical improvement or solution.
For at least the above reasons, the methods and apparatus of Claims 1 – 17 are directed to applying an abstract idea as identified above on a general-purpose computer without (i) improving the performance of the computer itself, or (ii) providing a technical solution to a problem in a technical field. None of Claims 1 – 17 provides meaningful limitations to transform the abstract idea into a patent eligible application of the abstract idea such that these claims amount to significantly more than the abstract idea itself.
Taking the additional elements individually and in combination, the additional elements do not provide significantly more. Specifically, when viewed individually, the above-identified additional elements for Step 2A Prong 2 in Independent Claim 1 (and their dependent claims) do not add significantly more because they are simply an attempt to limit the abstract idea to a particular technological environment. That is, neither the general computer elements nor any other additional element adds meaningful limitations to the abstract idea because these additional elements represent insignificant extra-solution activity. When viewed as a combination, these above-identified additional elements simply instruct the practitioner to implement the claimed functions with well-understood, routine and conventional activity specified at a high level of generality in a particular technological environment. As such, there is no inventive concept sufficient to transform the claimed subject matter into a patent-eligible application. When viewed as whole, the above-identified additional elements do not provide meaningful limitations to transform the abstract idea into a patent eligible application of the abstract idea such that the claims amount to significantly more than the abstract idea itself. Thus, Claims 1 – 17 apply an abstract idea to a computer and do not (i) improve the performance of the computer itself (as in Bascom and Enfish), or (ii) provide a technical solution to a problem in a technical field (as in DDR).
Therefore, none of the Claims 1 – 17 amounts to significantly more than the abstract idea itself. Accordingly, Claims 1 – 17 are not patent eligible and rejected under 35 U.S.C. 101.
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.
Claims 1 – 3, 9 , 14, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Genc in view of Corrêa et. al., (“Arterial blood pressure targets in septic shock: is it time to move to an individualized approach?”).
Regarding Claim 1, Genc discloses A method for adaptively detecting an Acute Hypotension Episode (AHE) event of a patient ([Abstract]), comprising:
receiving at least one clinical data related to the patient ([0005] “…mean arterial pressure data from the patent over the given time period“),
processing, by a processor ([0008] “execution with a processor…“), a signal comprising the at least one clinical data ([0005] “…mean arterial pressure data from the patent over the given time period“ [0002] “Mean Arterial Pressure (MAP) measurements”; [0005] “reading heart rate data…mean arterial pressure data from the patent over the given time period“) to determine at least one mean arterial pressure (MAP) threshold value for the patient ([0032] “P is the AHE prediction threshold…If a positive AHE detection is found for P out of R repetitions, an AHE is declared and its onset time is known, at 60”; Fig 4; [0002] “AHE may be defined as…at least ninety percent…of Mean Arterial Pressure (MAP) measurements are at or below 60 mmHg.”)(Examiner notes that the initial threshold is based on the signals that indicate that the patient is a human being monitored for AHE, so a standard level is applied.);
detecting, by the processor, one or more AHE event of the patient ([0005] “reporting the acute hypotensive episode and its onset time when detected.”; [0008]) based on the at least one MAP threshold value ([0032] “P is the AHE prediction threshold…If a positive AHE detection is found for P out of R repetitions, an AHE is declared and its onset time is known, at 60”; Fig 4; [0002] “AHE may be defined as…at least ninety percent…of Mean Arterial Pressure (MAP) measurements are at or below 60 mmHg.”)
receiving an input ([0037] “The period could be longer, where it may be defined by data that is available.”)(Examiner notes that the input is “data that is available”, which is received by the model as an input.) relating to a time frame ([0037] “estimate model 25 is provided a defined size of data collected over at least a thirty-minute period. “; [0026] “pre-specified prediction window.”);
determining, by the processor, a prediction of a subsequent AHE event of the patient ([0026] “probabilistic measure on occurrence of AHE in a prediction window is generated. If the probability is above a pre-specified value then the occurrence of the AHE is predicted and the onset time is output.”) during the time frame (Fig 5, [0037] “the simulate model 35 has a prediction window size of more than thirty minutes.”; [0031] including “discrete prediction time…”; Fig 3 and Fig 4; [0032] “…AHE is within the prediction window…onset is recorded”) based on the at least one MAP threshold value and the signal ([0002] “AHE may be defined as…at least ninety percent…of Mean Arterial Pressure (MAP) measurements are at or below 60 mmHg.”; Fig 5, information from “Sensor/Probes” fed into “Estimate model”, “Simulated Model”, and eventually to “Prediction Model”; [0036]
outputting the prediction to a user interface ([0009] “The computer software module further comprises a computer software module for determining whether an acute hypotensive episode is occurring within the prediction window…a computer software module for reporting the acute hypotensive episode and its onset time when detected, operable with the processor…”; Fig. 2 - 4)(Examiner notes that a computer routinely outputs or “reports” information from computer software on a user interface such as a monitor or screen.)
Genc does not specifically disclose the at least one clinical data comprising at least one of a blood composition, a urine composition, hemodynamic waveform data, comorbidity data, a central venous pressure, or a frailty score.
Corrêa teaches the at least one clinical data comprising at least one of a blood composition, a urine composition, hemodynamic waveform data, comorbidity data ([Page 2, Left Column, Top] “…the subgroup of patients with chronic hypertension was analyzed, targeting a higher MAP decreased the need for renal replacement therapy…”) a central venous pressure, or a frailty score; processing, a signal comprising the at least one clinical data to determine at least one mean arterial pressure (MAP) threshold value for the patient ([Page 1, Right Column, Bottom] “…high MAP targets (80 to 85 mmHg) in comparison with conventional targets (65 to 70 mmHg)…when the subgroup of patients with chronic hypertension was analyzed, targeting a higher MAP decreased the need for renal replacement therapy.”)
Genc is open to combine with additional information to inform the AHE calculation with [0008] “The computer software code…configured for execution with a processor designated for collecting and controlling sharing of data associated with a patient's medical condition.” and [0036] “plurality of sensors 32, collectors, and/or probes, are provided to measure heart rate, MAP, stroke volume, or total peripheral resistance, age, etc., of a patient. Some of the information may be actually measured, but may be calculated and/or approximated...” In order to collect the age of a patient, this suggests categorical or discrete data information is obtained through interview with a patient or medical record that is then used to inform Genc’s calculations at [0036] and [0031] for stroke compliance calculations (that ultimately affect AHE determination). Corrêa provides a motivation to combine at [Page 2, Left Column, 2nd Full Paragraph] with “It is well known that patients admitted to the intensive care unit vary widely in terms of age, number and type of comorbidities, and functional status”, “when the subgroup of patients with chronic hypertension was analyzed, targeting a higher MAP decreased the need for renal replacement therapy,” and “the individualized approach may allow us to identify non-hypertensive patients who may tolerate lower mean arterial and perfusion pressure levels to maintain their organs’ function...decreased exposure to vasopressors may limit their side effects and improve outcomes” A person having ordinary skill in the art before the effective filing date of the claimed invention would recognize that obtaining comorbidity information about a patient regarding chronic hypertension would inform setting a higher threshold for MAP, which would be useful for obtaining more individualized MAP threshold and beneficial AHE prediction and care for the patient.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the AHE prediction device that collects multiple aspects of data to inform the AHE prediction with the chronic hypertension comorbidity information to attain a more individualized MAP threshold for prediction and care of AHE for the patient.
Regarding Claim 2, Genc in view of Corrêa discloses as described above, The method according to claim 1. For the remainder of Claim 2, Genc discloses wherein the step of processing, by the processor, the signal to determine the at least one MAP threshold value for the patient (See citation in Claim 1 above) comprises:
determining at least one fluctuation ([0025] “…disturbance”) of the signal from a baseline of the signal ([0025] “disturbance may be added to MAP specifically d is added to the MAP prior to Neural 16.”);
Regarding Claim 3, Genc in view of Corrêa discloses as described above, The method according to claim 1. For the remainder of Claim 3, Genc discloses wherein the detecting, by the processor, the AHE event of the patient (See citation in Claim 1 above) comprises:
comparing one or more MAP values of the signal against the at least one MAP threshold value ([0028] “determination, at 32, is made whether the MAP is already below a certain level, such as 60 mmHg.. This level is selected because AHE has already started and is still the same AHE.”)
Regarding Claim 9, Genc in view of Corrêa discloses as described above, The method according to claim 1. For the remainder of Claim 9, Genc discloses further comprising:
receiving a MAP waveform (Fig 1, “MAP (mmHg)” the x axis for the drawn wave; [0024] “when MAP increases SNA decreases, as illustrated in graph 11.”; Fig 4 Block 40: “Read HR and MAP N-point time series data…”; [0025] “The input 14…eventual output of the effector portion 10 is the MAP, which is also an input 16 to the neural portion 12…”) wherein the signal comprises the MAP waveform ([0002] “Mean Arterial Pressure (MAP) measurements”; [0005] “reading heart rate data…mean arterial pressure data from the patent over the given time period“; Fig 1 “graph 11”)
Regarding Claim 14, Genc in view of Corrêa discloses as described above, The method according to claim 1. For the remainder of Claim 14, Genc discloses further comprising:
extracting at least one feature (Fig 4; [0031] “Conditioning…the MAP data for…determining an onset of an acute hypotensive episode”, “A mean and standard deviation of random coefficients of the nth (<N) order linear neural portion with a maximum likelihood estimator is calculated, at 44.”) in the signal ([0005] “…mean arterial pressure data from the patent over the given time period“) wherein the determination of the prediction of the subsequent AHE event of the patient is based on the at least one feature of the signal (Fig 5, Fig 3 and 4; [0031] – [0033] including “determination…whether an AHE is within the prediction window…onset it recorded, at 54” (of Figure 4)).
Regarding Claim 16, Genc in view of Corrêa discloses An apparatus for adaptively detecting an Acute Hypotension Episode (AHE) event of a patient ([Abstract]), comprising:
at least one processor ([0008] “execution with a processor…“); and
at least one memory including computer program code ([0018] “memory…appropriate program means for executing the method of the invention.”; [0021] “…program modules…memory storage devices”; [0022])
the at least one memory and the computer program code configured to, with at least one processor, cause the apparatus at least to perform the method ([0018] “memory…appropriate program means for executing the method of the invention.”; according claim 1 (See citations above in Claim 1).
Claims 4, 6 – 8, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Genc in view of Corrêa, further in view of Stapelfeldt et. al., (United States Patent Application Publication US 2014/0107504 A1).
Regarding Claim 4, Genc in view of Corrêa discloses as described above, The method according to claim 3. For the remainder of Claim 4, Genc discloses wherein the detecting, by the processor, the AHE event of the patient (See citation in Claim 1 above) comprises:
Genc does not specifically disclose determining if a duration relating to the one or more MAP values is longer than a pre-configured threshold duration.
Stapelfeldt teaches systems and methods for monitoring a patient during a procedure to record severity and duration of hypotension events based on MAP thresholds, determining a calculated risk metric for predicted adverse outcomes related to the procedure. Specifically for Claim 4, Stapelfeldt teaches determining if a duration relating to the one or more MAP values is longer than a pre-configured threshold duration ([0040] “duration of hypotensive periods of time spent below a range of mean arterial blood pressure (MAP) thresholds.”; [0019] “the risk metric can comprise a number of mean arterial blood pressure thresholds that were met for cumulative times exceeding certain predetermined values, Such as one minute or a certain number of minutes”; [0042])
Stapelfeldt provides a motivation to combine at [0023] with “system 30 can also be used to identify and stratify patients after the procedure for more intensive post procedure follow-up care due to risk portended by the severity and duration of aberrant levels of physiological parameters that were experienced during the procedure.” A person having ordinary skill in the art before the effective filing date of the claimed invention would recognize that documenting the duration of the hypotension events would be useful for determining patients that could require additional follow-up care due to risk predicted by the severity and duration of hypotension during a procedure.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the system for detecting and predicting the onset of an acute hypotensive episode from evaluating MAP readings against a threshold disclosed in Genc with the determination of the duration of hypotensive periods of time spent below MAP threshold taught by Stapelfeldt, creating a single hypotension detection and prediction device that can correlate duration of a hypotensive episode with a need for follow-up care to counteract the higher risk of post-procedural adverse events.
Regarding Claim 6, Genc in view of Corrêa discloses as described above, The method according to claim 1. For the remainder of Claim 6, Genc discloses wherein the detecting, by the processor, the AHE event of the patient (See citation in Claim 1 above) comprises:
determining if a mean MAP value of a baseline of the signal is lower than a second MAP threshold value ([0056] “changes in MAP with respect to time can be derived by subtracting the average of the MAP over the past five minutes, ten minutes, or other time durations, from the current value of the MAP.”; [0028] “…whether the MAP is already below a certain level, such as 60 mmHg”)(Examiner notes that the past value can be considered second MAP threshold in regard to determining a change in MAP (with the to the first MAP threshold set at 60 mmHg.)
Genc does not particularly disclose is lower than a second pre-configured MAP threshold value. Genc does broadly disclose that the MAP can be set at an exemplar level [0028] “such as 60 mmHg”, but is not limited to that level. Further, it broadly discloses evaluating MAP levels dynamically to other average MAP levels at [0056] with the “changes in MAP with respect to time…”
Stapelfeldt teaches determining if a mean MAP value of a baseline of the signal is lower than a second pre-configured MAP threshold value ([0034] “Intraoperative hypotension was common, with MAP dropping (for at least one minute) below 75 mm Hg in 92% of cases and below 45 mm Hg in 10% of cases
(FIG. 6).”)
Stapelfeldt provides a motivation to combine at [0034] with “Worsening hypotension (any amount of time spent below progressively lower MAP thresholds) was reflected by a progressive increase in the average cumulative amounts of time spent below each of the other thresholds across the entire array of MAP thresholds and, associated with this, a progressive increase in 30-day mortality.” A person having ordinary skill in the art before the effective filing date of the claimed invention would recognize that evaluating the MAP against progressively lower MAP thresholds would be useful to determine the severity of the hypotension event, which is useful for determining the risk of 30-day mortality after the hypotensive episode.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the system for detecting and predicting the onset of an acute hypotensive episode from evaluating MAP readings against a threshold disclosed in Genc with the comparing a patient’s MAP values against multiple, increasingly low pre-configured MAP threshold values taught by Stapelfeldt, creating a single hypotension detection and prediction device that can evaluate severity of the AHE by comparing against multiple, increasingly low pre-configured MAP threshold values in order to determine the risk of 30-day mortality after the hypotensive episode.
Regarding Claim 7, Genc in view of Corrêa discloses as described above, The method according to claim 1. For the remainder of Claim 7, Genc discloses wherein the detecting, by the processor, the one or more AHE events (Examiner notes the 112(b) interpretation above) of the patient comprises:
detecting an onset ([0032] “ a determination is made as to whether an AHE is within the prediction window and the onset is recorded, at 54.”) of the AHE event based on the at least one MAP threshold value and the signal ([0032] “P is the AHE prediction threshold…If a positive AHE detection is found for P out of R repetitions, an AHE is declared and its onset time is known, at 60”; Fig 4; [0002] “AHE may be defined as…at least ninety percent…of Mean Arterial Pressure (MAP) measurements are at or below 60 mmHg.”).
Genc does not specifically disclose and a duration of the AHE event of the patient based on the at least one MAP threshold value and the signal.
Stapelfeldt teaches and a duration of the AHE event of the patient based on the at least one MAP threshold value and the signal [0019] “…a number of mean arterial blood pressure thresholds that were met for cumulative times exceeding certain predetermined values, such as one minute or a certain number of minutes”; [0042] “…duration of hypotension below a wide range of commonly encountered MAP thresholds.” [0028] “blood pressure thresholds for monitoring hypotension…blood pressure values”).
The motivation for Claim 7 to combine Genc with Stapelfeldt is the same as that described in more detail in Claim 4. In summary, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the system for detecting and predicting the onset of an acute hypotensive episode from evaluating MAP readings against a threshold disclosed in Genc with the determination of the duration of hypotensive periods of time spent below MAP threshold taught by Stapelfeldt, creating a single hypotension detection and prediction device that can correlate duration of a hypotensive episode with a need for follow-up care to counteract the higher risk of post-procedural adverse events.
Regarding Claim 8, Genc in view of Corrêa, further in view of Stapelfeldt discloses as described above, The method according to claim 7. For the remainder of Claim 8, Genc discloses storing the onset of the AHE event of the patient ([0032] “ a determination is made as to whether an AHE is within the prediction window and the onset is recorded, at 54.”), and one or more MAP values associated with the AHE event in a database ([0021] “program modules may be located in both local and remote computer storage media including memory storage devices.”; [0035] “the records, or data collected…”; [0019])
Genc does not specifically disclose and the duration of the AHE event of the patient in a database.
Stapelfeldt teaches store… a duration of the AHE event of the patient ([0040] “duration of hypotensive periods of time spent below a range of mean arterial blood pressure (MAP) thresholds.”; …in a database ([0052] “…arterial blood pressure…The encounter server 122 can store information from such devices 130 data as part of a patient encounter in memory”)
The motivation for Claim 8 to combine Genc with Stapelfeldt is the same as that described in more detail in Claims 4 and 7. In summary, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the system for detecting and predicting the onset of an acute hypotensive episode from evaluating MAP readings against a threshold disclosed in Genc with the determination of the duration of hypotensive periods of time spent below MAP threshold taught by Stapelfeldt, creating a single hypotension detection and prediction device that can correlate duration of a hypotensive episode with a need for follow-up care to counteract the higher risk of post-procedural adverse events.
Regarding Claim 13, Genc in view of Corrêa discloses as described above, The method according to claim 1. For the remainder of Claim 13, Genc discloses wherein the determining, by the processor, the prediction of the subsequent AHE event of the patient (See citation in Claim 11) comprises:
determining a MAP value of the subsequent AHE event of the patient ([0026] “predict the MAP in simulate model 35…”)
Genc does not disclose the MAP value relating to a severity level of the subsequent AHE event.
Stapelfeldt teaches the MAP value relating to a severity level of the AHE event ([0035] “the severity of hypotension (the hypotensive MAP threshold exceeded)”; [0034] “MAP dropping (for at least one minute) below 75 mm Hg in 92% of cases and below 45 mm Hg in 10% of cases (FIG. 6)”, “…Worsening hypotension (any amount of time spent below progressively lower MAP thresholds)…”)
The motivation for Claim 13 to combine Genc with Stapelfeldt is the same as that described in more detail in Claim 6. In summary, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the system for detecting and predicting the onset of an acute hypotensive episode from evaluating MAP readings against a threshold disclosed in Genc with the comparing a patient’s MAP values against multiple, increasingly low pre-configured MAP threshold values taught by Stapelfeldt, creating a single hypotension detection and prediction device that can evaluate severity of the AHE by comparing against multiple, increasingly low pre-configured MAP threshold values in order to determine the risk of 30-day mortality after the hypotensive episode.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Genc in view of Corrêa, further in view of Schneider et. al., (United States Patent Application Publication US 2022/0400965 A1), further in view of Mathis et. al., “Preoperative Risk and the Association between Hypotension and Postoperative Acute Kidney Injury”.
Regarding Claim 5, Genc in view of Corrêa discloses as described above, The method according to claim 1. For the remainder of Claim 5, Genc discloses wherein the detecting, by the processor, the AHE event of the patient (See citation in Claim 1 above) comprises:
determining at least one MAP threshold, a first pre- configured MAP threshold value ([0028] “determination, at 32, is made whether the MAP is already below a certain level, such as 60 mmHg.. This level is selected because AHE has already started and is still the same AHE.”)
Genc does not disclose at least one MAP threshold is lower than a first pre-configured MAP threshold value. Genc does broadly disclose that the MAP can be set at an exemplar level [0028] “such as 60 mmHg”, but is not limited to that level. Further, it broadly discloses evaluating MAP levels dynamically to other average MAP levels at [0056] with the “changes in MAP with respect to time…”
Schneider teaches implementing a configurable MAP threshold to which the AHE prediction algorithm can adapt. Specifically for Claim 5, Schneider teaches at least one MAP threshold value different than a first pre- configured MAP threshold value ([0043] “an adjusted MAP threshold.”; [0042] “define the occurrence of hypotension with respect to a standard ( e.g., defined) MAP threshold, such as 65 mmHg or other pressure thresholds.”)(Examiner notes that the MAP threshold can be “adjusted´ to something other than the first pre-set value, 65 mmHg as taught by Schneider, or it would be 60 mmHg as disclosed by Genc.)
Schneider provides a motivation to combine at [0024] with “enabling dynamic adaptation of the model to an adjusted MAP threshold that may be based on training and expertise of medical personnel.“ A person having ordinary skill in the art before the effective filing date of the claimed invention would recognize that being able to adjust the MAP threshold for a patient would be useful for applying medical expertise and experience to set an effective MAP threshold for actually detecting hypotensive events, in cases where the standard value of 60 mmHg (disclosed in Genc) is less effective for the patient.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the system for detecting and predicting the onset of an acute hypotensive episode from evaluating MAP readings against a threshold broadly “such as 60 mmHg” disclosed in Genc with the particular accommodation to adjust the MAP threshold in a predictive AHE model taught by Schneider, creating a single hypotension detection and prediction device that can evaluate severity of the AHE by comparing against different settings of MAP threshold values in order to more accurately evaluate hypotensive events for patients.
Schneider does not specifically disclose how to determine an appropriate adjusted MAP threshold. Schneider is open to obtaining the adjusted MAP threshold through other means than direct user input at [0017] “accommodate the adjustable (e.g., user defined or otherwise adjusted) MAP threshold”, and it defers to medical
Mathis teaches determining different MAP thresholds on a patient-by-patient basis that are indicative of potential acute kidney injury based on the determined pre-operative risk level. Specifically for Claim 5, Mathis teaches determining if the at least one MAP threshold value is lower than a first pre- configured MAP threshold value (Figure 3 with MAP 60 – 64 mmHg, 50 – 59 mmHg, 50 – 54 mmHg, and <50 mmHg; [Page 2, “Results:” Section] “Patients with medium risk…associations between severe-range intraoperative hypotension (mean arterial pressure less than 50 mmHg) and acute kidney injury… patients with the highest risk, mild hypotension ranges (mean arterial pressure 55 to 59 mmHg) were associated with acute kidney injury”; [Page 12, “Conclusions” Section] “high-risk patients are sensitive to hypotension as mild as MAP of less than 65 mmHg, levels routinely tolerated in perioperative or critical care settings.“)(Examiner notes that the pre-configured MAP threshold can be the standard MAP threshold of a mean arterial pressure (MAP) of less than 65 mmHg.)
Mathis provides a motivation to combine at [Page 9, Bottom] with “The data presented establish the intuitive concept that the relationship between hypotension and AKI varies by underlying patient and procedural risk,” and [Page 8, Bottom] that describes differing levels of acute kidney injury risk based on the MAP range of less than 50 mmHg for persons with medium preoperative risk and 60 – 65 mmHg for persons with highest preoperative risk. A person having ordinary skill in the art before the effective filing date of the claimed invention would recognize that setting the MAP threshold based on the preoperative risk for the patient would be useful for having an appropriate level to minimize the risk of acute kidney injury for the particular patient. Genc in view of Schneider already includes the ability for a medical professional (or other means) to dynamically set the threshold. Mathis provides teaching of logic that could be used to determine what a threshold should be for a given patient.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the system for detecting and predicting the onset of an acute hypotensive episode from evaluating MAP readings against an adjustable MAP threshold disclosed in Genc in view of Schneider with the different MAP thresholds, lower and higher, depending on the overall preoperative risk levels taught by Mathis, creating a single hypotension detection and prediction device that can evaluate severity of the AHE by comparing against appropriate settings of MAP threshold values to minimize the risk of acute kidney injury for the particular patients of differing preoperative risk levels.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Genc in view of Corrêa, further in view of Rocha et. al., “Prediction of acute hypotensive episodes by means of neural network multi-models”.
Regarding Claim 15, Genc in view of Corrêa discloses as described above, The method according to claim 14. For the remainder of Claim 15, Genc discloses wherein the step of determining, by the processor, the prediction of the subsequent AHE of the patient (See citation in Claim 14 above) comprises:
determining two or more predictions based on the at least one feature extracted from a plurality of signals ([0005] “predicting (or determining) one or more occurrences of acute hypotensive episodes (AHE) prior to their onset.”)
Genc does not disclose relating to a plurality of patients; comparing the two or more predictions to determine an optimal prediction of subsequent AHE events of the plurality of patients based on the at least one feature extracted from the plurality of signals, the optimal prediction being either one of or a combination of the two or more predictions, wherein the prediction of the subsequent AHE of the patient is based on the optimal prediction of the subsequent AHE events of the plurality of patients.
Rocha teaches application of neural network multi-models to the prediction of adverse acute hypotensive episodes (AHE) occurring in intensive care units using data from multiple patients. Specifically for Claim 15, Rocha teaches determining two or more predictions based on the at least one feature extracted from a plurality of signals relating to a plurality of patients ([Page 882, Right Column, “2.1. Challenge Goal Section”, Paragraph 1 - 2])…” predict which patients in the available dataset (MIMIC-II) would experience an acute hypotensive episode…”; “challenge dataset…a time series of mean arterial blood pressure (MAP) at one-minute intervals…”; [Page 882, right column – Page 883, Left Column, “2.2. Mimic-II project” Section] – [Page 882, “2.3. Training and test datasets” Section] “…data from about 30,000 ICU patients to date, including recorded physiologic signals and time series,”, “…patient records from the MIMIC-II database…”);
determining two or more predictions based on the at least one feature extracted from a plurality of signals [Page 882, Right Column, “2.1. Challenge Goal Section”, Paragraph 1 - 2])…” predict which patients in the available dataset (MIMIC-II) would experience an acute hypotensive episode…”; “challenge dataset…a time series of mean arterial blood pressure (MAP) at one-minute intervals…”; [Page 882, right column – Page 883, Left Column “2.2. Mimic-II project” Section] – [Page 882, “2.3. Training and test datasets” Section] “…data from about 30,000 ICU patients to date, including recorded physiologic signals and time series,”, “…patient records from the MIMIC-II database…”));
comparing the two or more predictions to determine an optimal prediction of subsequent AHE events of the plurality of patients [Page 886, Left Column, “3.3.3. Prediction of MAP signals” Section, Paragraph 1 – Paragraph 5], “Given a new MAP testing signal, truncated at time instant To, the MAP forecast is done based on previous trained GRNN multi-models…“, “…a weighted average of the predictions performed by the M multi-models is computed…”; [Page 888, Left Column, 4th Full Paragraph] “The final MAP predicted signal is computed as the weighted average of all four estimated predictions, Eq. (14)“) based on the at least one feature extracted from the plurality of signal [Page 886, “3.3.3. Prediction of MAP signals” Section, Paragraph 1 – Paragraph 5]…“…stored MAP templates…”, [Page 888, Left Column, 4th Full Paragraph] “The final MAP predicted signal...weighted average of all fours estimated predictions…”), the optimal prediction being either one of or a combination of the two or more predictions [Page 886, Left Column “3.3.3. Prediction of MAP signals” Section, Paragraph 1 – Paragraph 5]…“…a weighted average of the predictions performed by the M multi-models is computed…”; [Page 888, Left Column, 4th Full Paragraph] “The final MAP predicted signal...weighted average of all fours estimated predictions…”), wherein the prediction of the subsequent AHE of the patient is based on the optimal prediction of the subsequent AHE events of the plurality of patients ([Page 882, Right Column, “2.1. Challenge Goal Section”, Paragraph 1 - 2])…” predict which patients in the available dataset (MIMIC-II) would experience an acute hypotensive episode…”; “challenge dataset…a time series of mean arterial blood pressure (MAP) at one-minute intervals…”; [Page 886, Left Column, “3.3.3. Prediction of MAP signals” Section, Paragraph 1 – Paragraph 5], “Given a new MAP testing signal, truncated at time instant To, the MAP forecast is done based on previous trained GRNN multi-models…“, “…a weighted average of the predictions performed by the M multi-models is computed…”; [Page 888, Left Column, 4th Full Paragraph] “The final MAP predicted signal...weighted average of all fours estimated predictions…”)
Rocha provides a motivation to combine at [Page 881, Left Column] with “early detection of AHE will give professionals enough time to select a more effective treatment, without exposing the patient to additional risks of delaying therapy” and [Page 881, Right Column, 1st Full Paragraph] “It is clinically accepted that if there exists enough patient’s clinical information, then a prediction system for hypotensive episodes, over a specific time period, can be developed.” A person having ordinary skill in the art before the effective filing date of the claimed invention would recognize that using neural network multi-models would be useful to analyze data from many patients to increase the accuracy of the prediction, as well as allow for predictions to be made for more than one patient, overall enabling early detection to select an effective treatment of the hypotension episode.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the system for make one or more predictions of the onset of an acute hypotensive episode from evaluating patient MAP data disclosed in Genc with Rocha’s taught neural network multi-models for predicting AHE using data from multiple patients and weighted optimization of the prediction, creating a single hypotension detection and prediction device that can predict AHE by incorporating data and predictions from many patients to increase the accuracy of the predictions and enabling early detection to select an effective treatment of the hypotension episode.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Genc in view of Corrêa, further in view of Bhattacharya et. al., (“A dual boundary classifier for predicting acute hypotensive episodes in critical care”, Ref U on PTO-892)
Regarding Claim 17, Genc in view of Corrêa discloses The method according to claim 1. For the remainder of Claim 17, Genc does not particularly disclose further comprising: pre-emptively administering at least one of fluids or pressors to the patient in response to the prediction of the subsequent AHE event. Genc does broadly disclose at [0003] “AHE requires effective, prompt intervention. When detected in time, an appropriate intervention can significantly lower the risks for a patient.”
Bhattacharya teaches a dual boundary classifier for predicting acute hypotensive episodes in critical care, for the purpose of enabling prompt intervention such as administration of vasopressors and fluid resuscitation ([Title, Abstract]. [Page 3 and 4]). Specifically for Claim 17, Bhattacharya teaches disclose further comprising: pre-emptively administering at least one of fluids or pressors to the patient in response to the prediction of the subsequent AHE event ([Page 3, “2.2. Related Work” Section] “Existing intervention approaches to AHE…interventions include administration of vasopressors, fluid resuscitation and other treatments depending on the case. Instead, if patients at risk for AHE are identified in advance, the intervention most appropriate to the patient can be determined and administered.”)
Genc provides a motivation to combine at [0003] with “AHE requires effective, prompt intervention. When detected in time, an appropriate intervention can significantly lower the risks for a patient. Determining what intervention is appropriate in any given case depend on diagnosing the cause
of the episode…”. Bhattacharya provides an option for an “appropriate intervention” at ([Page 3, “2.2. Related Work” Section] with “Hypotension is a precursor to septic shock, the second most common cause of death in ICU patients in the United States, and a study shows that mortality in such cases depends critically on the duration of hypotension before treatment.” and “…interventions include administration of vasopressors, fluid resuscitation and other treatments…if patients at risk for AHE are identified in advance, the intervention most appropriate to the patient can be determined and administered.” A person having ordinary skill in the art before the effective filing date of the claimed invention would recognize that it would be useful to administer treatments, such as the existing hypotension intervention techniques of fluids or pressors, when a prediction of AHE is made in order to reduce mortality risk for the affected patient.
Therefore, it would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the AHE prediction system and method taught by Genc with the application to use information from an AHE predictor to inform administering a treatment for the patient (such as fluids or pressors), lowering the mortality risk for the patient due to delayed treatment.
Response to Arguments
Applicant's arguments filed 05 JUNE 2026 have been fully considered but they are not persuasive.
Regarding 35 U.S.C. 102 Rejections:
Applicant argues at [Page 9, “Rejections under 35 U.S.C. 101” Section, Paragraphs 1 – 2] that the data types recited in claim 1 cannot be practically obtained through mental processes because they require specialized medical equipment, laboratory testing, and patient monitoring systems that are located in an ICU, ED, PMU, or patient data from the perioperative departments. As recited, the data types are merely received, which would include a medical professional communicating verbally a patient’s current comorbidity condition or numeric central venous pressure. The information can be broadly received by a human using medical equipment, laboratory testing, and patient monitoring in its usual way as a data-gathering tool, by observing reports, outputs, or a patient’s paper or electronic medical record. The argument is not persuasive.
Applicant argues at [Page 9, Bottom] – [Page 10, top] that claim 1 as amended provides a technical improvement to AHE prediction accuracy because it does not use a single, hard blood pressure threshold values but adaptively determines a personalized MAP threshold value for a prediction of a subsequent AHE event. The limitation of “determining…a prediction of a subsequent AHE event of the patient during the time frame base on the at least one MAP threshold value and the signal” is an abstract idea, and it can broadly be performed by a medical professional as described. Given the information of a current central venous pressure, a clinician can broadly give a broad prediction, or opinion, of whether they think an AHE will occur during a particular broad time frame based on MAP threshold, based on their background, education, and experience, such as with threating patients with sepsis. From MPEP 2106.05(a): It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements. See the discussion of Diamond v. Diehr, 450 U.S. 175, 187 and 191-92, 209 USPQ 1, 10 (1981)) in subsection II, below. In addition, the improvement can be provided by the additional element(s) in combination with the recited judicial exception. See MPEP § 2106.04(d) (discussing Finjan, Inc. v. Blue Coat Sys., Inc., 879 F.3d 1299, 1303-04, 125 USPQ2d 1282, 1285-87 (Fed. Cir. 2018)). The argument is not persuasive.
Applicant argues at [Page 10, 1st full paragraph] that the time frame is a clinically meaningful time frame that enables the prediction to be tailored to the specific care setting, differentiating between long- or short-term time frames depending on whether the setting is intraoperative care or post-operative monitoring. This distinction of the time scales is not positively recited in the claims. As recited, it is “an input relating to a time frame”, which also does not positively recite an actual time. An input “relating to a time frame” could broadly just be an input that occurs within some period of time (such as a blood pressure entered during the afternoon), or an input about a time frame (that something is “early”). As phrased, there is no time-scale specificity present. Overall, regarding the time aspect, receiving an input of a time frame is pre-solution data-gathering activity that gathers the time for which the subsequently-recited abstract idea activity applies. Further, the broad recitation of ”receiving an input relating to a time frame” is routinely performed by humans when they are either told what time it is currently, or when a doctor is consulted for prognosis questions of timelines for disease or condition progression. The argument is not persuasive.
Applicant argues at [Page 10, 2nd full paragraph] that outputting a prediction to a user interface is a concrete, actionable output that enables clinical action and transforms the claimed method from abstract data processing into a practical medical monitoring tool. As recited in Claim 1, there is no concrete action output that is provided by the method itself. No particular action is required to be taken by providing information. This limitation represents extra-solution activity because it is a mere nominal or tangential addition to the claim. See MPEP 2106.05(g), discussing limitations that the Federal Circuit has considered to be insignificant extra-solution activity, for instance the step of printing a menu that was generated through an abstract process in Apple, Inc. v. Ameranth, Inc., 842 F.3d 1229, 1241-42 (Fed. Cir. 2016) and the mere generic presentation of collected and analyzed data in Electric Power Group, LLC v. Alstom S.A., 830 F.3d 1350, 1354 (Fed. Cir. 2016). The argument is not persuasive.
Applicant argues at [Page 10, 2nd full paragraph] that total peripheral resistance was previously mischaracterized as comorbidity data in the office action dated 11 March 2026, and comorbidity data refers to data about co-existing medical conditions a patient may have. As such, Applicant argues that the claimed clinical data types are specific technical inputs that cannot be reduced to mere mental observations. As recited, the invention does not appear to be diagnosing a comorbidity using particular specialized hardware. Rather, it is recited that it is “receiving at least one clinical data”. The claimed clinical data types are data that are routinely “received” or observed by medical professional in a clinical setting, or by patients in appointment summary sheets, including recordings of blood composition or urine composition in paper reports, or listed conditions that the patient may currently have. The argument is not persuasive.
Applicant summarily argues at [Page 11, 1st – 2nd – 3rd Full Paragraph] that Claim 1 is directed to patent eligible subject matter, as are Claims 2 – 9 and 13 – 16 due to their dependence on Claim 1. Based on the 35 U.S.C 101 analysis herein and the discussion of arguments above, Claims 1 – 9 and 13 - 17 do not qualify as eligible subject matter under 35 U.S.C. 101. The argument is not persuasive.
Regarding 35 U.S.C. 102 Rejections:
Based on the amendments to Claim 1, the rejection under 35 U.S.C. 102 is withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Genc in view of Corrêa.
Regarding 35 U.S.C. 103 Rejections:
Applicant argues at [Page 12, Paragraphs 1 – 2] that Genc does not explicitly or inherently disclose receiving at least one clinical data including blood composition, urine composition, comorbidity data, a central venous pressure, or a frailty score. In light of the amendments, Genc has been combined with Corrêa for a particular teaching of comorbidity data and how it affects the MAP threshold. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The argument is not persuasive.
Applicant argues at [Page 12, Paragraph 3] that Genc does not disclose “processing by a processor a signal comprising the at least one clinical data to determine at least one mean arterial pressure (MAP) threshold value for the patient.” There is no particular algorithmic method by which the processor is processing to obtain a particular MAP threshold. As such, retrieving data that there are signals being obtained from a human, and processing a default threshold value is broadly “processing by the processor a signal…to determine at least one mean arterial pressure (MAP) threshold value for the patient”. The argument is not persuasive.
Applicant argues at [Page 12, Paragraph 3] that Genc does not explicitly or inherently disclose outputting the prediction to a user interface, rather it includes reporting the AHE and onset time. Looking to the 35 U.S.C. 103 rejection above, at [0009] Genc discloses that “The computer software module further comprises a computer software module for determining whether an acute hypotensive episode is occurring within the prediction window…a computer software module for reporting the acute hypotensive episode and its onset time when detected, operable with the processor…” A computer routinely outputs or “reports” information from a computer software interface on a physical user interface such as a monitor or screen. The argument is not persuasive.
Applicant argues at [Page 13, “Rejections under 35 U.S.C. 103” section, Paragraphs 1 - 5] that for Claims 4, 6 – 8, and 13, the office failed to apply Stapelfeldt in a manner sufficient to cure the deficiencies of Genc, because the office failed to properly determine the scope and content of the cited references. Applicant argues that assuming the combination of Stapelfeldt and Genc is proper, the Office failed to apply Stapelfeldt in a manner sufficient to cure the deficiencies of Genc. Looking to the 35 U.S.C. 103 rejection above, Genc in view of Corrêa discloses the elements of Claim 1, and the limitations of Claims 4, 6 – 8, and 13 are disclosed by Genc in view of Corrêa, further in view of Stapelfeldt. The argument is not persuasive.
Applicant argues at [Page 13, “Rejections under 35 U.S.C. 103” section, Paragraph 6] – [Page 14, Top] that for Claim 5, the office failed to apply Schneider and Mathis in a manner sufficient to cure the deficiencies of Genc, because the office failed to properly determine the scope and content of the cited references. Applicant argues that assuming the combination of Genc and Schneider and Mathis is proper, the Office failed to apply Schneider and Mathis in a manner sufficient to cure the deficiencies of Genc. Looking to the 35 U.S.C. 103 rejection above, Genc in view of Corrêa discloses the elements of Claim 1, and the limitations of Claim 5 are disclosed by Genc in view of Corrêa, further in view of Schneider and Mathis. The argument is not persuasive.
Applicant argues at [Page 13, “Rejections under 35 U.S.C. 103” section, Paragraph 6] – [Page 14, Top] that the office failed to apply Rocha in a manner sufficient to cure the deficiencies of Genc, because the office failed to properly determine the scope and content of the cited references. Applicant argues that assuming the combination of Genc and Rocha is proper, the Office failed to apply Rocha in a manner sufficient to cure the deficiencies of Genc. Looking to the 35 U.S.C. 103 rejection above, Genc in view of Corrêa discloses the elements of Claim 1, and the limitations of Claim 5 are disclosed by Genc in view of Corrêa, further in view of Rocha. The argument is not persuasive.
Applicant argues at [Page 14, Bottom] that Claim 17 recites additional features and distinguishes over the applied references for at least the reasons set forth for Claim 1. Looking to the 35 U.S.C. rejection and the discussion above, the limitations of Claim 17 are disclosed by Genc in view of Corrêa, further in view of Bhattacharya. The argument is not persuasive.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/MELISSA JO MONTGOMERY/Examiner, Art Unit 3791 /ALEX M VALVIS/Supervisory Patent Examiner, Art Unit 3791
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