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 .
Applicant's arguments, filed 3/18/2026, have been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Applicants have amended their claims, filed 3/18/2026.
Claims 1, 3-11, and 13-22 are the currently pending claims hereby under examination. Claim 2 has been canceled.
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 3-6, 9-11, 13-15, and 21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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 3 depends from canceled claim 2. A claim that depends from a canceled claim is indefinite since the metes and bounds of the claim cannot be determined. For the purposes of examination, claim 3 will be interpreted to depend from claim 1.
Claims 4-6 are rejected by virtue of their dependence from claim 3.
Concerning claims 4 and 9. Claim 4 recites "between successive comparison "Δ_ss" on the line-graph remains constant but the rate of change "ΔP" is not equal to the rate of change in "ΔF"" (claim 4, lines 2-3). Claim 9 recites "between successive quantified comparisons "Δ_ss" is constant but the rate of change "ΔP" is not equal to the rate of change in "ΔF"" (claim 9, lines 19-20). The specification describes that the maximum amplitudes "P_max" and "F_max" occur at different times during a heart muscle cycle and that their respective rates of change "ΔP_max" and "ΔF_max" from pulse to pulse may be different (see, e.g., paragraphs [0010]-[0015]). The specification further explains, with reference to Figures 3 and 4, that comparisons "Δ_ss" are used to construct a line graph 34 as a sequence of distinct calibration points (see, e.g., paragraphs [0027]-[0028], [0037]-[0038], Figs. 3-4), but does not identify any parameter that "remains constant" or "is constant" between successive comparisons, such as a fixed spacing, interval, or graphical separation. As a result, the claims fail to identify what quantity "remains constant" or "is constant" between successive comparisons, and multiple reasonable interpretations exist as to how the line graph is constructed and interpreted. One of ordinary skill in the art therefore cannot determine the metes and bounds of the claimed subject matter with reasonable certainty. For purposes of examination, the Examiner interprets the limitations “between successive comparison/quantified comparisons Δ_ss … remains constant” as requiring that a parameter associated with the construction or acquisition of successive Δ_ss points (for example, spacing along an axis, a sampling interval, or an increment in a controlled test condition) is maintained constant between those successive comparisons, while the underlying pressure and flow values change at unequal rates.
Claims 5-6 are rejected by virtue of their dependence from claim 4.
Claims 10-11, 13-15, and 21 are rejected by virtue of their dependence from claim 9.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3-6 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3 depends from canceled claim 2, which is improper. For the purposes of examination, claim 3 will be interpreted to depend from claim 1.
Claims 4-6 are rejected by virtue of their dependence from claim 3.
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.
Claims 1, 3-11, and 13-22 are rejected under 35 U.S.C. 103 as being unpatentable over Curtis (US-20150051463-A1), hereto referred as Curtis’463, and further in view of Spencer et al. (US-20220249055-A1), hereto referred as Spencer, and further in view of Martin et al. (Martin SL, Carek AM, Kim CS, Ashouri H, Inan OT, Hahn JO, Mukkamala R. Weighing Scale-Based Pulse Transit Time is a Superior Marker of Blood Pressure than Conventional Pulse Arrival Time. Sci Rep. 2016 Dec 15; 6:39273. doi: 10.1038/srep39273.), hereto referred as Martin.
Regarding claim 1, Curtis’463 teaches that a system for continuously using blood flow measurements "F" from a patient as indications of the patient's blood pressure "P", comprises: (Curtis’463, ¶[0002]: "the present invention pertains to systems and methods for continuously monitoring the blood pressure of a patient over an extended period of time. More particularly, the present invention pertains to systems and methods wherein a patient’s blood flow, as measured by an oximeter, is evaluated in terms of blood pressure readings"; Curtis’463 teaches a system that continuously monitors blood pressure by evaluating oximeter-measured blood flow in terms of blood pressure readings, i.e., using blood flow measurements F from the patient as indications of blood pressure P) a sphygmomanometer configured to measure blood pressure variations in a patient’s vasculature including a maximum blood pressure measurement "P_systolic" near the beginning of each heart muscle cycle and a pressure measurement "P_diastolic" near the end of each heart muscle cycle (Curtis’463, FIG.4; ¶[0003]: "a sphygmomanometer will provide blood pressure pulse measurements during its duty cycle that include a systolic measurement and a diastolic measurement. In detail, the systolic measurement provides a blood pressure reading for the phase of the patient’s heartbeat when the heart muscle contracts and pumps blood from the chambers into the arteries. On the other hand, the diastolic measurement provides a blood pressure reading for the phase of the heartbeat when the heart muscle relaxes and allows the chambers of the heart to fill with blood"; Curtis’463 discloses that a sphygmomanometer provides systolic and diastolic pressure measurements corresponding to different phases of the heartbeat, ¶[0025]: "the measurement at point 34 on graph 28 which is taken at time t7, corresponds to the diastolic pressure, ps(diastolic), of the patient 16. Further, for reasons more clearly established below, the systolic pressure, ps(systolic), of the patient 16 (point 32) is correlated with a simultaneous measurement taken by the oximeter 14"; Curtis’463 further illustrates that sequential measurements taken during the sphygmomanometer duty cycle include specific systolic and diastolic values that bracket each heart cycle); a collator coupled to the sphygmomanometer and with the oximeter to establish a steady state quantified comparison "Δ_ss" between "P_systolic" and "P_diastolic" (Curtis’463, ¶[0011]-[0012]: "a calibration of the oximeter begins by first connecting both the oximeter and the sphygmomanometer to the patient… the sphygmomanometer is used for measuring a blood pressure pulse magnitude p for each pulse of the patients heart. Simultaneously, the oximeter is used for measuring a blood flow pulse amplitude p. Both measurements are taken contemporaneously during a sphygmomanometer duty cycle which extends between a systolic pressure p_s(systolic) and a diastolic pressure p_s(diastolic) of the patient… the respective magnitude and amplitude measurements for p_s (sphygmomanometer) and p_o (oximeter) are received as input at a computer. After completion of the duty cycle, these measurements are used by the computer to establish an operational ratio, Δp_o/Δp_s, that is based on contemporary measurements of p and p"; Curtis’463 discloses a computer that receives both sphygmomanometer and oximeter measurements taken over a duty cycle extending between systolic and diastolic pressures, and processes them into a quantitative relationship (operational ratio) between pressure and pulse amplitude using contemporaneous, patient-specific data; ¶[0006]: "a patient’s diastolic pressure will remain substantially constant during a stabilized condition. On the other hand, the systolic pressure will vary most significantly"; Curtis’463 explains that under stabilized conditions diastolic pressure is substantially constant while systolic pressure varies, which provides the basis for defining a steady-state relationship between P_systolic and P_diastolic for a given patient); the collator collects a value for "P" relative to a value of "F" during a same heart muscle cycle to establish a data set for use in providing quantified comparison "Δ_ss" (Curtis’463, Abstract: "Calibration of the oximeter for this purpose requires use of a sphygmomanometer to determine a sequence of blood pressure readings taken for a patient over a sphygmomanometer duty cycle. During the duty cycle, readings for both blood pressure (sphygmomanometer) and blood flow amplitude (oximeter) are taken simultaneously at predetermined time intervals (e.g. patient pulse rate)"; Curtis’463 teaches that the calibration computer receives contemporaneous blood pressure and blood flow amplitude readings at predetermined time intervals tied to the patient’s pulse rate during a sphygmomanometer duty cycle, i.e., the collator is configured to acquire P and F data points once per heart pulse over the duty cycle for building the comparison data set; ¶[0023]: "FIG. 2 shows a calibration graph 28 which illustrates an exemplary correspondence between blood pressure pulse magnitudes p and simultaneous blood flow pulse amplitudes p. For a set-up of the system 10, measurements of both p and p are respectively taken by the sphygmomanometer 12 and the oximeter 14 during a same sphygmomanometer duty cycle 30"; Curtis’463 discloses that the collator (computer 24) collects paired blood pressure and blood flow values during the same sphygmomanometer duty cycle to generate a set of contemporaneous P and F data points for each heart muscle cycle; ¶[0024]–[0025]: "As indicated by the graph 28, exemplary blood pressure measurements (i.e. ps) are sequentially taken for each heartbeat during the duty cycle 30 (e.g. at times t0 through t7)…", ¶[0012]: "After completion of the duty cycle, these measurements are used by the computer to establish an operational ratio, po/ps, that is based on contemporary measurements of ps and po during the duty cycle"; Curtis’463 teaches that for each heartbeat during the duty cycle the computer stores a blood pressure value together with a corresponding oximeter pulse amplitude and then uses the resulting set of paired values to compute a patient-specific comparison ratio, i.e., a quantified comparison derived from a data set of P–F pairs collected on a per-cycle basis). The claim requires only a value for "P" within the same heart muscle cycle and does not require that both systolic and diastolic pressure measurements be obtained within that same cycle.
Also regarding claim 1, Curtis’463 does not fully teach an oximeter configured to measure blood flow variations commensurate with the blood flow variations "F" including a maximum amplitude "F_max" near the end of each heart muscle cycle. Rather, Curtis’463 teaches acquiring a single oximeter-derived amplitude value for every cardiac cycle during the sphygmomanometer duty cycle and using those amplitudes together with contemporaneous blood pressure measurements to form a calibration curve and subsequent monitoring relationship (Curtis’463, ¶[0011]–[0012], [0025]–[0028]). However, Curtis’463 does not explicitly teach that the amplitude value acquired in each cycle corresponds to the maximum amplitude F_max near the end of the cardiac cycle as claimed.
Spencer teaches that waveform peaks may be intentionally selected as the measured feature of a cardiovascular signal, stating that "details such as the peak can be used as a marker for the pulse wave arrival" (Spencer, ¶[0133]: features of the waveform can also be measured, and in such cases details such as the peak can be used as a marker for the pulse wave arrival"). Thus, Spencer expressly discloses identifying and using the maximum amplitude of each cardiac waveform as the characteristic measurement.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Curtis’463 in view of Spencer so that the oximeter measurement used for calibration and monitoring is taken at the peak of each pulse waveform, corresponding to the maximum amplitude F_max near the end of the heart muscle cycle. The combination is feasible because Curtis’463 already acquires one amplitude value per beat and uses that value for calibration, and Spencer merely clarifies that the peak (maximum amplitude) is a known, preferred, and physiologically meaningful choice for that per-beat measurement. Spencer teaches selecting waveform features such as peaks, and a peak inherently represents the maximum amplitude of the waveform within each cardiac cycle. The benefit of the combination would be to improve consistency and physiological relevance by anchoring the oximeter measurement to a readily identifiable maximal point in the waveform, thereby enhancing calibration accuracy without altering Curtis’463’s system architecture.
Also regarding claim 1, the modified Curtis’463 does not fully teach a line-graph is created by a plurality of quantified comparisons "Δ_ss" for calibrating the use of measured "F" from the oximeter as an indicator of blood pressure "P" for the patient. The modified Curtis’463 teaches generating a patient-specific line graph 40 by collecting multiple paired blood pressure and pulse-amplitude values during a sphygmomanometer duty cycle and computing a slope or operational ratio that allows subsequent determination of blood pressure based solely on oximeter-derived pulse amplitudes (Curtis’463, FIG. 3; ¶[0025]–[0028]). However, Curtis’463 does not describe the line graph as being created from a plurality of steady-state quantified comparisons Δ_ss, nor does it teach that each point on the calibration line corresponds to a physiologically steady calibration condition of pressure and a flow-related measurement as recited in claim 1.
Martin teaches forming a calibration curve from multiple pairs of blood pressure values and corresponding hemodynamic timing measurements, stating that reference systolic and diastolic BP are detected each beat and a line is fitted to the pairs of timing parameters and BP levels so that new measurements can be mapped through the line to predict BP (Martin, FIG. 3; p. 3–4, ‘Data Analysis’: "We also detected the minimum and maximum of the cuff BP waveform between successive ECG R waves to establish reference diastolic and systolic BP for each beat”; "We also calibrated a time delay to each reference BP level by finding the line that best fitted the pairs of the time delays and BP levels for a subject and then mapping the time delays… through the line so as to predict the BP levels"). Although Martin’s surrogate is a waveform-derived timing parameter rather than a pulse-amplitude value, in both Martin and Curtis’463 the noninvasive measurement is a hemodynamic quantity derived from cardiovascular waveforms that varies with arterial conditions and must be calibrated against cuff-based blood pressure using a subject-specific line. Thus, Martin explicitly teaches constructing a line graph formed from multiple calibration points between a waveform-derived surrogate and blood pressure and using that graph to convert subsequent surrogate measurements into blood pressure predictions.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Martin to construct the calibration line from a plurality of steady-state quantified comparisons Δ_ss between cuff-based blood pressure and a waveform-derived flow surrogate measured by the oximeter, and to use that calibration line to map oximeter-derived flow measurements to blood pressure values. The combination is feasible because both Curtis’463 and Martin acquire paired blood pressure and waveform-derived surrogate measurements over multiple cycles and both rely on standard line-fitting techniques to derive a subject-specific calibration relationship; incorporating Martin’s explicit multi-point calibration procedure into Curtis’463 would merely refine the selection and conceptualization of the calibration pairs (as steady-state Δ_ss points) while retaining the same basic system architecture. The benefit of the combination would be increased calibration accuracy and robustness through explicit use of multiple steady-state calibration points between blood pressure and a waveform-derived flow surrogate, thereby producing the claimed line-graph created by a plurality of quantified comparisons Δ_ss for calibrating F to indicate P.
Also regarding claim 1, the modified Curtis’463 does not fully teach that the collator is preprogrammed with input information, including a heart pulse rate from the patient for identifying a duration for a heart muscle cycle Rather, the modified Curtis’463 teaches a calibration and monitoring system in which computer 24 receives simultaneous blood pressure and blood flow amplitude readings from the sphygmomanometer and oximeter during a sphygmomanometer duty cycle, with measurements taken at predetermined time intervals corresponding to the patient’s pulse rate (Curtis’463, Abstract; ¶[0023]–[0025], [0012]). These disclosures show that the collator is configured to collect values of P and F once per heartbeat and to use the resulting set of paired values across heart muscle cycles to establish an operational comparison ratio po/ps from that data set. However, Curtis’463 does not expressly state that the computer is preprogrammed with input information including the patient’s heart pulse rate as an explicit parameter used to identify the duration of each heart muscle cycle.
Spencer teaches a cardiovascular monitoring system in which a processor identifies peak timings of a pulse-pressure wave, calculates the time differences between successive peaks, and determines a heart rate associated with each time difference (Spencer, ¶[0035]: "The system comprises: an ambulatory blood pressure monitoring system and recording device; a processor and memory within which code for execution by the processor is stored. The processor comprises: an identification module configured to identify a plurality of P-P timing of a pulse-pressure wave (PPW); a calculation module configured to calculate a difference between recording times of successive pairs of the P-wave peaks and to determine a heart rate associated with each time difference"). Thus, Spencer explicitly discloses using beat-to-beat timing information to derive heart rate and to associate each heart cycle duration with a corresponding heart rate value within a programmed processor.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the modified Curtis’463 in view of Spencer by configuring the collator (computer 24) to be preprogrammed or supplied with input information representing the patient’s heart pulse rate and corresponding heart cycle duration, so that the acquisition of contemporaneous P and F values during the sphygmomanometer duty cycle is explicitly tied to the identified duration of each heart muscle cycle. The combination is feasible because both Curtis’463 and Spencer employ digital processors that operate on beat-to-beat cardiovascular waveform data, and Spencer’s use of derived heart rate and cycle timing as programmable inputs would represent a routine refinement of Curtis’463’s predetermined sampling intervals to parameterize them directly in terms of patient heart pulse rate and heart cycle duration. The benefit of this combination would be to ensure that the collator’s sampling and data-set construction for Δ_ss are explicitly synchronized with the patient’s heart rate information, improving the accuracy and robustness of the per-cycle P–F data set used to establish the steady-state quantified comparison Δ_ss.
Regarding claim 3, the modified Curtis’463 teaches that a line-graph is created from multiple paired measurements of "P" and "F" and wherein locations along the line-graph are used to correlate a measured "F_max" with a corresponding "P" to be indicated by a display as an indication of blood pressure (Curtis’463, ¶[0023]–[0025]: "FIG. 2 shows a calibration graph 28 which illustrates an exemplary correspondence between blood pressure pulse magnitudes p and simultaneous blood flow pulse amplitudes p... A series of an in number of such measurements taken over a duty cycle 30 can then be represented by the line graph 40 in FIG. 3 using well known curve fitting techniques"; Curtis’463 discloses that the computer uses multiple contemporaneous pairs of blood pressure and pulse amplitude measurements collected over the sphygmomanometer duty cycle to generate a fitted line graph 40 that expresses the relationship between changes in pulse amplitude and blood pressure for the patient, which the system then employs for subsequent blood pressure indication based on measured pulse amplitudes; ¶[0014]: "during a calibration of the oximeter, blood pressure pulse magnitudes ps and blood flow pulse amplitudes po are taken during the sphygmomanometer duty cycle at a same selected point in each pulse of the patient’s heart... the operational ratio Δpo/Δps for calibrating the oximeter is preferably recalculated at least every hour"; Curtis’463 teaches that the system establishes a patient-specific operational ratio Δp_o/Δp_s derived from multiple paired measurements taken at the same selected point in each pulse, and that this calibration ratio is periodically updated so that later measured pulse amplitudes can be converted into indicated blood pressure values on the monitor).
Also regarding claim 3, the modified Curtis’463 does not fully teach that each reference point is identified by a separate quantified comparison "Δ_ss", wherein each quantified comparison "Δ_ss" is established when the patient is respectively posed in different positions, wherein the plurality of quantified comparison "Δ_ss" collectively establish the line-graph, and wherein each location along the line graph between quantified comparison "Δ_ss" provides a unique "Δ_ss" to correlate a measured "F_max" along the line graph, with a corresponding "P" to be indicated by a display as an indication of blood pressure. Rather, the modified Curtis’463 teaches a calibration system in which contemporaneous blood pressure and blood flow pulse amplitude measurements are collected during a sphygmomanometer duty cycle and used to generate a fitted line graph 40 and an operational ratio Δp_o/Δp_s that relate changes in pulse amplitude to changes in blood pressure for the patient (Curtis’463, ¶[0023]–[0025], [0014]). These disclosures show that multiple paired measurements are used to establish a calibration relationship which the computer and monitor subsequently use to indicate blood pressure values based on measured pulse amplitudes. However, Curtis’463 does not disclose that the calibration line graph is constructed from at least two distinct steady state quantified comparisons taken while the patient is in different positions, nor that each such quantified comparison serves as a separate reference point on a positional calibration line graph that spans different postural conditions.
Spencer teaches that, for accurate blood pressure estimation from pulse wave data, calibration may employ multiple baseline measurements obtained while the subject is in several positions and that each position specific baseline is formed from multiple recordings. In particular, Spencer describes a calibration step using a standard digital brachial pressure cuff, where "a mathematical transformation function may be determined" so that "a correlation [is] identified between the PPW and parameters associated with blood pressure" and further states that "baseline measurements may be taken whilst the subject is sitting, standing and supine, with 3 recordings being used at each position and the average (mean) of each being used" (Spencer, ¶[0135]–[0137]). Thus, Spencer explicitly teaches establishing multiple calibration baselines, each derived from a plurality of blood pressure and waveform measurement pairs acquired in different patient positions, so that the overall calibration encompasses several distinct reference conditions for the same subject.
Martin teaches constructing a subject specific calibration line from multiple pairs of a waveform based timing metric and reference blood pressure levels and then using that line to map each waveform measurement to a predicted blood pressure value. Martin explains that, for each subject, a time delay is calibrated to each reference BP level "by finding the line that best fitted the pairs of the time delays and BP levels for a subject and then mapping the time delays of that subject through the line so as to predict the BP levels" (Martin, p. 3-4, 'Data Analysis'). Martin therefore provides an explicit example of using a line graph created from a plurality of calibration pairs such that every point along the line corresponds to a unique combination of waveform derived metric and blood pressure level for that subject.
It would have been prima facie obvious before the effective filing date of the claimed invention to modify the modified Curtis’463 in view of Spencer and Martin by configuring the calibration procedure so that the system acquires steady state paired blood pressure and blood flow measurements while the patient is in different postural positions, computes a quantified comparison Δ_ss for each such position, and uses the resulting plurality of Δ_ss values as separate reference points when fitting a calibration line graph that relates Δ_ss (and thus F_max) to blood pressure P for that patient. The combination is feasible because Curtis’463, Spencer, and Martin all employ digital processing of paired cardiovascular measurements to derive subject specific calibration relationships, and substituting Spencer’s multi position calibration baselines and Martin’s line fitting procedure into Curtis’463’s duty cycle calibration merely implements known calibration refinements within the same technical framework of non-invasive blood pressure estimation from pulsatile signals. The benefit of this combination would be to provide a calibration line graph defined by multiple reference points representing different postural steady states, so that each location along the line between those quantified comparisons yields a unique Δ_ss that can be used to correlate a measured F_max with a corresponding blood pressure P for the patient across a wider range of physiologic positions while still allowing the computer and monitor of Curtis’463 to indicate blood pressure continuously based on the calibrated relationship.
Regarding claim 4, the modified Curtis’463 teaches aspects of, but does not fully teach, that “P_max” and “F_max” have an inverse relationship, and further wherein between successive comparison “Δ_ss” on the line-graph remains constant but the rate of change “ΔP” is not equal to the rate of change in “ΔF”, with a new steady state comparison “Δ_ss” for the subsequent data set having a new value wherewith “Δ_ss”=(P±ΔP) and (F±ΔF). The modified Curtis’463 teaches generating a calibration line by collecting paired changes in blood pressure pulse magnitude ps and blood flow pulse amplitude po during a sphygmomanometer duty cycle and determining a patient-specific operational ratio based on those paired changes (Curtis’463, ¶[0014], ¶[0025]–[0026]). These disclosures show that Curtis’463 establishes a calibration relationship represented by a line graph and uses that relationship to determine blood pressure from changes in the oximeter-derived signal, but Curtis’463 does not explicitly teach that a maximum pressure value P_max and a maximum flow-derived value F_max have an inverse relationship, and Curtis’463 also does not explicitly teach that, between successive comparisons on the line graph, a parameter “remains constant” under the Examiner’s interpretation requiring that a constant between-point mapping rule is maintained for intermediate locations between successive calibration points while ΔP and ΔF are not required to be equal in magnitude.
Spencer teaches obtaining baseline measurements in multiple distinct steady states associated with different postures, including “sitting, standing and supine”, with multiple recordings per posture and use of an average (mean) for each posture (Spencer, ¶[0137], ¶[0138]–[0148]). Spencer therefore teaches establishing multiple posture-dependent calibration conditions that yield distinct calibration reference values for the same subject and that naturally produce different magnitudes of blood pressure change between states.
Martin teaches that a waveform-derived surrogate can exhibit a “tight, inverse relationship” with blood pressure in individual subjects (Martin, p. 1) and teaches calibrating a surrogate to blood pressure levels “by finding the line that best fitted the pairs” of surrogate and BP values and then “mapping” surrogate values “through the line so as to predict the BP levels” (Martin, p. 4, “Data Analysis”). Martin further teaches that surrogate changes can differ in magnitude, stating that “the magnitudes of the changes in the two time delays were different” (Martin, p. 4, “Results”). Thus, Martin supports the Examiner’s interpretation that the calibration mapping between successive calibration points is constant in form as the fitted line relationship used to map intermediate locations, while ΔP and ΔF may differ in magnitude.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Spencer and Martin to obtain multiple steady state calibration points under different posture-defined physiological conditions and to represent those points on a single patient-specific fitted line relationship such that intermediate locations between successive points are determined by the constant fitted line mapping rule, while recognizing that the magnitude of ΔP and the magnitude of ΔF are not required to be equal and therefore are handled and applied separately as updated mapped values (P±ΔP) and (F±ΔF). The combination is feasible because Curtis’463 already represents the calibration relationship as a curve-fit line graph based on paired changes in ps and po, Spencer supplies an established protocol for obtaining multiple steady state posture-dependent baseline conditions for the same subject, and Martin teaches fitting a line to multiple calibration pairs, applying that fitted line as the mapping rule between calibration points, and accounting for unequal magnitudes of surrogate change relative to BP change while still mapping through the same fitted relationship. The benefit of the combination would be improved robustness and accuracy of the patient-specific calibration relationship across posture-dependent steady states while maintaining a consistent line-based mapping rule for converting oximeter-derived measurements into corresponding blood pressure indications between successive calibration points.
Regarding claim 5, the modified Curtis’463 teaches aspects of, but does not fully teach, that a “P_systolic”, a “P_diastolic” and an “F_max” are periodically re-measured for each quantified comparison “Δ_ss”, and wherein a re-measurement is accomplished at least every thirty minutes to reconfigure the line-graph. The modified Curtis’463 teaches that blood pressure pulse magnitudes and blood flow pulse amplitudes are measured for each pulse during a sphygmomanometer duty cycle to establish a patient-specific operational ratio and that this operational ratio used for calibration is preferably recalculated at least every hour, thereby implying periodic re-measurement of systolic/diastolic pressure and corresponding flow amplitudes for recalibration of the line-based comparison relationship (Curtis’463, ¶[0014], ¶[0027]). However, Curtis’463 does not specify that P_systolic, P_diastolic, and F_max are explicitly re-measured for each quantified comparison Δ_ss, nor does it disclose a particular recalibration period of at least every thirty minutes.
Spencer teaches that calibration estimates are more accurate when more pairs of blood pressure and pulse wave measurements are collected and expressly encourages increasing the number and frequency of blood pressure measurements over a 24 hour recording compared to the current gold standard, up to and including beat-to-beat blood pressure assessment, to obtain more accurate and individualized blood pressure profiles (Spencer, ¶[0149], ¶[0151]). Spencer therefore provides a clear motivation to perform more frequent recalibration measurements than conventional sparse schedules in order to improve the accuracy and clinical utility of noninvasive blood pressure monitoring systems.
It would have been prima facie obvious before the effective filing date of the claimed invention to further modify the modified Curtis’463 in view of Spencer by configuring the system so that P_systolic, P_diastolic, and F_max are periodically re-measured for each quantified comparison Δ_ss and by shortening the recalibration interval from “at least every hour” to a more frequent interval such as at least every thirty minutes in order to reconfigure the line-graph. The combination is feasible because Curtis’463 already establishes a periodic recalibration scheme based on repeated paired pressure and flow measurements and Spencer teaches that increasing the number and frequency of blood pressure measurements improves calibration accuracy and individualized risk profiling. The benefit of this combination would be a modified Curtis’463 system that maintains a more tightly updated patient-specific line-graph calibration by re-measuring P_systolic, P_diastolic, and F_max at least every thirty minutes, thereby improving the accuracy and responsiveness of noninvasive blood pressure estimation across a patient’s daily activities while remaining consistent with established motivations in the art for more frequent measurement-based calibration.
Regarding claim 6, the modified Curtis’463 teaches aspects of, but does not fully teach, that data sets are created with the patient posed standing, sitting, and lying down to respectively create the quantified comparisons "Δ_ss" needed for a 3-point line graph. The modified Curtis’463 teaches generating a patient specific calibration line graph 40 from multiple paired changes in blood pressure and flow pulse amplitude collected during a sphygmomanometer duty cycle and using this line to determine blood pressure values from measured pulse amplitudes (Curtis’463, ¶[0025]–[0026]). However, the modified Curtis’463 as combined with Spencer for claim 4 already teaches creating separate calibration data sets with the patient posed standing, sitting, and lying down, but does not teach that exactly three such postural steady states must be used to form quantified comparisons “Δ_ss” that define a 3-point line graph.
Spencer teaches that calibration may be performed while the subject is in multiple distinct postural conditions, specifically sitting, standing, and supine, and that three blood pressure recordings may be taken at each position and averaged to obtain a baseline value for that posture (Spencer, ¶[0137]-[0148]). These posture-dependent baselines provide three distinct steady-state calibration points for the same subject under different physiological conditions and thereby offer multiple reference values for characterizing how the subject’s blood pressure behaves across positions.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Spencer to configure the calibration procedure so that separate data sets are acquired with the patient posed standing, sitting, and lying down, each data set providing a steady-state comparison between blood pressure and pulse-derived measurements that can be treated as a quantified comparison "Δ_ss" for that posture and used as one of three reference points on a 3-point line graph. The combination is feasible because Curtis’463 already establishes a line-graph calibration framework based on paired pressure and flow measurements for a single steady-state condition, while Spencer supplies the established clinical practice of acquiring multiple posture-dependent baseline measurements as separate calibration points. The benefit of this combination would be to provide a calibrated system in which the 3-point line graph reflects how the relationship between blood pressure and pulse-derived measurements varies across common postural states, improving robustness and accuracy of noninvasive blood pressure estimation for patients who routinely transition between standing, sitting, and lying positions.
Regarding claim 7, Curtis’463 teaches that the duration of a heart muscle cycle is determined using blood pressure variations measured by the sphygmomanometer (Curtis’463, ¶[0011]: "the sphygmomanometer is used for measuring a blood pressure pulse magnitude ps for each pulse of the patient's heart"; ¶[0012]: "During the sphygmomanometer duty cycle that is used for calibrating the oximeter, the respective magnitude and amplitude measurements for ps0 (sphygmomanometer) and po (oximeter) are received as input at a computer"; ¶[0019]: "Both measurements are taken contemporaneously during a sphygmomanometer duty cycle which extends between a systolic pressure ps(systolic) and a diastolic pressure ps(diastolic) of the patient"; FIG. 2, ¶[0024]: "As indicated by the graph 28, exemplary blood pressure measurements (i.e. ps) are sequentially taken for each heart beat during the duty cycle 30 (e.g. at times t0 through t7)"; Curtis’463 explains that the sphygmomanometer acquires blood pressure pulse readings for each heartbeat over a duty cycle that extends from systolic to diastolic pressure, thereby defining the duration of each heart pulse cycle from the sequence of pressure measurements over time).
Regarding claim 8, the modified Curtis’463 does not fully teach that the line graph is created using the "P" and "F_max" values taken for successive quantified comparisons "Δ_ss", and wherein to account for "P" and "F_max" having an inverse relationship, a horizontal axis for the graph will show a decreasing value for "F_max" while a vertical axis for the graph will show an increasing value for "P", with each location on the resulting line graph between any two quantified comparisons "Δ_ss" representing a specific comparison "Δ_ss" having unique values for "P" relative to "F_max". The modified Curtis’463 teaches generating a line graph 40 from successive paired changes in blood pressure pulse magnitudes and blood flow pulse amplitudes during a sphygmomanometer duty cycle and using the slope Δps/Δpo of this line as a patient specific calibration factor to determine blood pressure values from measured pulse amplitudes (Curtis’463, ¶[0023], ¶[0025]–¶[0026]). In this context, the blood flow pulse amplitudes po correspond to the pulse waveform amplitude that is used as the F_max-type surrogate in the present claims. However, even as modified in claim 1 in view of Martin to interpret the calibration relationship as being applied to steady-state quantified comparisons "Δ_ss" between pressure and pulse-derived measurements, Curtis’463 does not explicitly require that the line graph be described as using "P" and "F_max" values taken for successive quantified comparisons "Δ_ss", nor does it expressly specify that the graph’s horizontal axis should show decreasing "F_max" while its vertical axis shows increasing "P", or that each location between quantified comparisons "Δ_ss" must be characterized as a specific comparison "Δ_ss" having unique values for "P" relative to "F_max".
Martin teaches that arterial stiffness increases with BP and that PTT often shows a tight inverse relationship with BP in individual subjects, and further teaches calibrating a time-delay marker to reference BP levels by finding the line that best fits the pairs of time delays and BP levels for a subject and then mapping measured time delays through that line to predict BP levels (Martin, p. 1; p. 4, 'Data Analysis'). Thus, Martin explicitly discloses an inverse calibration relationship between a physiological marker and BP and describes using a fitted line whose axes respectively represent the marker and BP, with points along the line defining specific mappings between the marker values and corresponding BP values.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Martin to formulate the calibration line graph so that successive steady-state quantified comparisons "Δ_ss" between "P" and "F_max" are plotted as points on a line in which the horizontal axis is understood to represent the surrogate pulse-derived measurement ("F_max") and the vertical axis represents blood pressure ("P"), and to interpret the calibration such that decreases in "F_max" correspond to increases in "P" along the line, with each location between calibration points representing a specific comparison "Δ_ss" having unique values of "P" relative to "F_max". The combination is feasible because Curtis’463 already provides a framework for constructing a patient specific calibration line from successive pairs of pressure and pulse amplitude measurements, while Martin provides explicit guidance that physiological markers used in such calibrations may be inversely related to BP and that a fitted line can be used to map marker values to BP levels. A person of ordinary skill in the art would have been motivated to adopt the explicit inverse-orientation interpretation and axis convention from Martin when implementing Curtis’463’s calibration line with "F_max" as the surrogate metric, so that the graph clearly reflects the empirically observed inverse relationship between the surrogate and BP and allows any point along the calibration line between measured comparisons "Δ_ss" to be used to infer a unique blood pressure value for a given "F_max". The benefit of this combination would be to provide an intuitively interpretable calibration graph in which the axes and line orientation transparently encode the inverse relationship between pulse-derived measurements and blood pressure, thereby improving the clarity, robustness, and continuous usability of the calibration for noninvasive blood pressure estimation.
Regarding claim 9, Curtis’463 teaches a method for using blood flow measurements from a patient as indications of blood pressure, which comprises the operations of: (Curtis’463, ¶[0002]: "the present invention pertains to systems and methods for continuously monitoring the blood pressure of a patient over an extended period of time. More particularly, the present invention pertains to systems and methods wherein a patient’s blood flow, as measured by an oximeter, is evaluated in terms of blood pressure readings"; Curtis’463 teaches a method that continuously monitors blood pressure by evaluating oximeter-measured blood flow in terms of blood pressure readings, i.e., using blood flow measurements F from the patient as indications of blood pressure P) positioning a sphygmomanometer on a patient to measure blood pressure "P" of the patient, wherein "P" comprises a "P_systolic" and a "P_diastolic" (Curtis’463, FIG.1; ¶[0011]: "a calibration of the oximeter begins by first connecting both the oximeter and the sphygmomanometer to the patient", Curtis’463 explains that the sphygmomanometer is positioned on the patient for measuring blood pressure during calibration; ¶[0011]: "the sphygmomanometer is used for measuring a blood pressure pulse magnitude ps for each pulse of the patients heart", Curtis’463 shows measuring the patient’s blood pressure pulses comprises a systolic and diastolic blood pressure within each duty cycle; ¶[0011]: "Both measurements are taken contemporaneously during a sphygmomanometer duty cycle which extends between a systolic pressure ps(systolic) and a diastolic pressure ps(diastolic) of the patient", Curtis’463 explicitly identifies systolic and diastolic pressures measured by the sphygmomanometer for the patient); obtaining a pulse rate measurement from the sphygmomanometer (Curtis’463, ¶[0011]: "the sphygmomanometer is used for measuring a blood pressure pulse magnitude ps for each pulse of the patients heart", Curtis’463 shows that the sphygmomanometer obtains per pulse measurements that identify the patient’s pulses and thereby provide the basis for determining a pulse rate; see also Abstract);
Also regarding claim 9, Curtis’463 does not fully teach positioning an oximeter on a patient to measure blood flow "F" of the patient comprises an "F_max" and taking "P" and "F_max" from the measuring operation for use as components in a data set wherein "P" and "F_max" have concurrence in the same heart muscle cycle. Curtis’463 teaches positioning an oximeter on the patient and contemporaneously measuring a blood pressure pulse magnitude ps and a blood flow pulse amplitude po for each pulse of the patient’s heart, stating that the method includes “measuring a blood pressure pulse magnitude ps, with a sphygmomanometer, for each pulse of the patient's heart during a sphygmomanometer duty cycle” and “measuring a blood flow pulse amplitude po, with an oximeter, for each pulse of the patient's heart during the sphygmomanometer duty cycle, wherein ps and po are measured simultaneously for each pulse” (Curtis’463, Claim 10). Curtis’463 further teaches that “Both measurements are taken contemporaneously during a sphygmomanometer duty cycle” (Curtis’463, ¶[0011]-[0014]). As used herein, the Curtis’463 blood pressure pulse magnitude ps corresponds to the claimed blood pressure “P”, and the Curtis’463 blood flow pulse amplitude po corresponds to a claimed blood flow measurement “F” derived from the oximeter signal. However, it does not state that the calibration measurement point is the maximum of each cycle, even if it is implied.
Spencer teaches that waveform features may be selected and that “details such as the peak can be used as a marker for the pulse wave arrival” (Spencer, ¶[0133]: "features of the waveform can also be measured, and in such cases details such as the peak can be used as a marker for the pulse wave arrival").
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Curtis’463 in view of Spencer to select and use the peak of each measured oximeter pulse waveform as the per cycle blood flow value (F_max) while maintaining Curtis’463’s contemporaneous per pulse pairing of the pressure measurement P with the oximeter measurement, such that P and F_max have concurrence in the same heart muscle cycle. The combination is feasible because Curtis’463 already measures and uses one oximeter pulse amplitude value for each pulse while measuring the corresponding blood pressure value at the same time, and Spencer teaches selecting the peak as a known per cycle waveform feature. The benefit of the combination would be improved repeatability of the per cycle blood flow feature used in the paired data set and improved robustness of the blood flow based indication of blood pressure.
Also regarding claim 9, the modified Curtis’463 implies but does not fully teach using the pulse rate to determine a time duration for a heart muscle cycle. Specifically, Curtis’463 teaches taking measurement samples on a timing schedule tied to cardiac pulsation during the sphygmomanometer duty cycle, stating: “During the duty cycle, readings for both blood pressure (sphygmomanometer) and blood flow amplitude (oximeter) are taken simultaneously at predetermined time intervals (e.g. patient pulse rate)” (Curtis’463, Abstract: “During the duty cycle, readings for both blood pressure (sphygmomanometer) and blood flow amplitude (oximeter) are taken simultaneously at predetermined time intervals (e.g. patient pulse rate)”). Curtis’463 further teaches that measurements are taken for each heartbeat during the duty cycle and are indexed in time, stating: “exemplary blood pressure measurements (i.e. ps) are sequentially taken for each heartbeat during the duty cycle 30 (e.g. at times t0 through t7)” (Curtis’463, ¶[0024]-¶[0025]: “exemplary blood pressure measurements (i.e. ps) are sequentially taken for each heartbeat during the duty cycle 30 (e.g. at times t0 through t7)”). However, Curtis’463 does not explicitly teach the operation of using a pulse rate as an input to determine a time duration for a heart muscle cycle, as Curtis’463 describes sampling at time intervals associated with the patient’s pulse rate but does not expressly state calculating or determining a heart cycle duration from that pulse rate.
Spencer teaches using cardiac peak timing to determine heart rate, and expressly links heart rate and the time duration between adjacent peaks, stating: “determining a time between adjacent peaks of the pressure wave, the time between peaks being indicative of a heart rate of the subject” (Spencer, ¶[0032]: “determining a time between adjacent peaks of the pressure wave, the time between peaks being indicative of a heart rate of the subject”). Spencer further teaches the inverse relationship between heart rate and elapsed time between peaks, stating: “the time elapsed between peaks is used to give an inverse of the heart rate” (Spencer, ¶[0167]: “the time elapsed between peaks is used to give an inverse of the heart rate”).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Spencer to use the pulse rate associated with the patient’s pulses to determine a time duration for a heart muscle cycle. The combination is feasible because Curtis’463 already schedules and records paired sphygmomanometer and oximeter measurements at predetermined time intervals associated with the patient’s pulse rate over successive heartbeats, and Spencer teaches a direct relationship between heart rate and the time between adjacent peaks, including that the time between peaks corresponds to the inverse of heart rate. The benefit of the combination would be improved consistency in defining and applying a per cycle timing window for associating and collecting pressure and blood flow measurements within a heart muscle cycle, thereby supporting accurate cycle-by-cycle construction and use of the claimed data sets.
Also regarding claim 9, the modified Curtis’463 does not teach establishing different data sets, wherein each data set is specific with the patient posed in different positions for each data set and quantifying each data set as an individually specific steady state quantified comparison "Δ_ss", wherein "P" and "F_max" are taken with the patient posed in different positions during the establishing operation, and wherein "P" and "F_max" have an inverse relationship. Rather, the modified Curtis’463 teaches obtaining paired blood pressure and oximeter pulse amplitude measurements during a calibration duty cycle to establish an operational ratio for subsequent blood pressure estimation, but it does not teach repeating that calibration to establish separate data sets specific to different patient positions or quantifying each position-specific data set as an individually specific steady state quantified comparison "Δ_ss" (Curtis’463, ¶[0011]–[0012]).
Spencer teaches acquiring baseline measurements in multiple distinct patient positions, including "sitting, standing and supine", with repeated recordings at each position and use of an average (mean) for each position (Spencer, ¶[0137]-[0148]: "baseline measurements may be taken whilst the subject is sitting, standing and supine, with 3 recordings being used at each position and the average (mean) of each being used").
Martin teaches that a physiologic surrogate measurement can show a "tight, inverse relationship" with blood pressure in individual subjects (Martin, p. 1: "PTT often shows a tight, inverse relationship with BP in individual subjects"). Martin thus illustrates that an inverse calibration relationship between a surrogate physiological marker and blood pressure can be embodied in a line-graph representation, and that the direction (direct or inverse) of the relationship is empirically determined from calibration data and then encoded in the fitted function rather than being fixed by any universal physical law of the circulation. In view of Martin, one of ordinary skill in the art would have understood that for other surrogate metrics such as a maximum flow related signal Fmax, it is routine to determine from calibration measurements whether the relationship to blood pressure is direct or inverse and to encode that empirically observed relationship in a line-based calibration function.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Spencer to repeat the calibration measurements as multiple separate data sets corresponding to different patient positions and to quantify each resulting position-specific data set as an individually specific steady state quantified comparison "Δ_ss", and to have further modified the modified Curtis’463 in view of Martin to account for an inverse relationship between blood pressure "P" and a per-cycle surrogate value "F_max".
The combination is feasible because the modified Curtis’463 already performs calibration based on paired cuff and waveform-derived measurements, Spencer provides a known protocol for repeating baseline measurements across postures to improve accuracy, and Martin teaches how to embody an empirically determined inverse relationship between a surrogate marker and blood pressure in a fitted line that remains valid across calibration states with different marker changes. The benefit of the combination would be improved robustness and accuracy of the calibration relationship across common changes in patient posture allowing for more diverse calibrations that are applicable to a patient as they use different positioning.
Also regarding claim 9, the modified Curtis’463 does not teach creating a line graph with a plurality of steady state quantified comparisons "Δ_ss", wherein each location on the line graph between quantified "Δ_ss" is a unique comparison "Δ_ss". Rather, the modified Curtis’463 teaches representing a series of paired blood pressure and waveform derived measurements as a line graph using curve fitting techniques to enable subsequent determination of blood pressure from measured waveform amplitudes, but it does not describe using multiple steady state comparisons Δ_ss derived from distinct postural data sets as the plurality of reference points that collectively establish the calibration line (Curtis’463, ¶[0025]–[0028]).
Martin teaches fitting a calibration line to multiple paired values of a surrogate measurement and blood pressure, stating that "the line that best fitted the pairs of the time delays and BP levels" is used so that subsequent surrogate values are mapped through that line to predict blood pressure levels (Martin, p. 4, 'Data Analysis': "we also calibrated a time delay to each reference BP level by finding the line that best fitted the pairs of the time delays and BP levels for a subject and then mapping the time delays of that subject through the line so as to predict the BP levels").
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Martin to structure the calibration as a plurality of reference comparisons (Δ_ss points) that collectively establish a fitted line relationship between the blood pressure values and the waveform derived surrogate values, with intermediate locations on the line corresponding to unique mapped comparisons. The combination is feasible because both references acquire paired blood pressure and surrogate waveform based measurements and apply conventional line fitting to generate a subject specific calibration relationship. The benefit of the combination would be improved calibration accuracy and improved ability to map new measurements through the fitted line to obtain consistent blood pressure indications.
Also regarding claim 9, the modified Curtis’463 does not fully teach that between successive quantified comparisons "Δ_ss" is constant but the rate of change "ΔP" is not equal to the rate of change in "ΔF" with a new value for each unique comparison "Δ_ss"=(P±ΔP) and (F±ΔF), calibrating a measured "F" with a corresponding "P" in a comparison "Δ_ss" for every location along the line graph, and displaying "P" as an indication of blood pressure based on the graph line location for "Δ_ss" fixed by the measured "F_max". Rather, the modified Curtis’463 teaches generating a calibration relationship represented as a line graph, stating that a series of successive paired changes (Δps and Δpo) over the duty cycle "can then be represented by the line graph 40" using curve fitting techniques (Curtis’463, ¶[0025]: "A series of an n number of such measurements taken over a duty cycle 30 can then be represented by the line graph 40 in FIG. 3 using well known curve fitting techniques"). The modified Curtis’463 further teaches that the line graph has a slope/operational ratio (Δps/Δpo) that "can be used for determining a blood pressure value ps based on changes in pulse amplitude po" (Curtis’463, ¶[0026]: "The result here is the ability to mathematically determine an operational ratio Δps/Δpo (e.g. the slope of the line graph 40) that is patient specific, and that can be used for determining a blood pressure value ps based on changes in pulse amplitude po") and teaches that this operational ratio is used in real time (Curtis’463, ¶[0012]: "the operational ratio ps/po is then used to determine a blood pressure value ps that is based on pulse amplitudes po that are measured in real time"). The modified Curtis’463 also teaches indicating/displaying blood pressure based on real-time oximeter measurements via a monitor (Curtis’463, ¶[0013]: "a monitor, which is connected to the computer, is used to continuously compare pulse amplitude signals po from the oximeter with the base amplitude po(base). Specifically, this comparison is done in real time, to detect variations of po from the base amplitude po(base) as an indicator of changes in blood flow and, hence, changes in blood pressure").
However, the modified Curtis’463 does not teach that successive steady state quantified comparisons are defined as quantified comparisons “Δ_ss” and that, between successive quantified comparisons “Δ_ss”, a parameter of the calibration relationship is constant as interpreted for prosecution to require a constant between-point mapping rule for intermediate locations on the line graph. The modified Curtis’463 further does not expressly teach the claimed handling of each successive comparison as a new value for each unique comparison “Δ_ss”=(P±ΔP) and (F±ΔF), nor does the modified Curtis’463 expressly teach that every location on the line graph corresponds to a unique comparison “Δ_ss” fixed by a measured maximum flow value “F_max”, even though Curtis’463 teaches using a line graph relationship to determine and indicate blood pressure from real-time oximeter pulse amplitude measurements.
Martin teaches treating a fitted calibration line itself as the constant mapping rule between calibration points, explaining that a surrogate timing value is calibrated to reference blood pressure levels “by finding the line that best fitted the pairs of the time delays and BP levels for a subject” and then “mapping the time delays of that subject through the line so as to predict the BP levels” (Martin, p. 4, “Data Analysis”). In this framework, the fitted line defines a constant relationship that is applied between successive calibration points, such that intermediate surrogate values are converted to predicted blood pressure values by reference to the same fitted line. Martin further teaches that the magnitude of surrogate change need not equal the magnitude of blood pressure change, stating that “the magnitudes of the changes in the two time delays were different” (Martin, p. 4, “Results”). Thus, Martin explicitly supports an interpretation in which the calibration mapping between successive quantified comparisons remains constant in form (i.e., the fitted line), while ΔP and ΔF may differ in magnitude and are applied as new mapped values at each location along that line.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Martin so that the calibration relationship between blood pressure and the oximeter-derived flow surrogate is explicitly treated as a fitted line that is applied between successive calibration points, such that intermediate locations between successive points are determined by the constant fitted line relationship, while recognizing that the magnitude of ΔP and the magnitude of ΔF need not be equal and therefore must be handled and applied separately for each successive comparison point as updated mapped values (P±ΔP) and (F±ΔF). The combination is feasible because Curtis’463 already teaches a curve-fit line graph and a slope/operational ratio used to determine and indicate blood pressure values from real-time pulse amplitude measurements, and Martin expressly teaches mapping measured surrogate values through the fitted line to predict BP levels and further teaches that surrogate-change magnitudes can differ even when mapped against BP. The benefit of the combination would be a more explicit, line-based interpolation framework for correlating continuously measured flow-derived values with corresponding blood pressure values at every location along the calibration line and for indicating blood pressure based on the measured flow-derived value.
Regarding claim 10, the modified Curtis’463 does not fully teach that the data sets are periodically remeasured with updated “P_max” measurements taken by the sphygmomanometer and updated “F_max” measurements taken by the oximeter. Rather, the modified Curtis’463 teaches periodically repeating the contemporaneous sphygmomanometer and oximeter measurements by recalibrating the oximeter as necessary, including expressly indicating recalculating the patient-specific operational ratio at least every hour (Curtis’463, ¶[0028], ¶[0035]). However, Curtis’463 does not expressly describe this periodic remeasurement using updated maximum values “P_max” from the sphygmomanometer and updated maximum values “F_max” from the oximeter as now recited.
Spencer teaches that increasing the number and frequency of measurements improves accuracy and yields more detailed, individualized blood pressure profiles, stating that increasing measurements will “greatly improve the accuracy of blood pressure measurements” and provide “more detailed, individual blood pressure profiles” (Spencer, ¶[0151]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Spencer to periodically remeasure the claim 9 data sets by repeating the contemporaneous sphygmomanometer and oximeter measurements at an increased frequency, including using updated maximum pressure-related values (P_max-type values) taken by the sphygmomanometer and updated maximum flow-related values (F_max-type values) taken by the oximeter. The combination is feasible because the modified Curtis’463 already teaches periodic recalibration using repeated contemporaneous pressure and flow amplitude measurements, and Spencer expressly motivates increasing measurement frequency to improve accuracy and individualized profiling. The benefit of the combination would be improved stability and accuracy of the patient-specific calibration relationship over time by refreshing the paired pressure/flow calibration data more frequently to reflect physiologic drift and changing conditions.
Regarding claim 11, the modified Curtis’463 does not fully teach that “P” is measured during the heart muscle cycle, and “F_max” is measured near the end of the heart muscle cycle. The modified Curtis’463 teaches measuring blood pressure ps during the heart muscle cycle, including identifying systolic and diastolic measurement points within that cycle (Curtis’463, ¶[0024]), but it selects an oximeter pulse amplitude measurement correlated with systolic and uses it as a base amplitude po(base), rather than expressly teaching measurement of a maximum flow-related value F_max near the end of the heart muscle cycle.
Spencer teaches identifying waveform features such as the peak as a marker for pulse wave arrival (Spencer, ¶[0133]) and further explains that the pulse pressure wave is created by the heart’s contraction and propagates outwardly along the vessel walls (Spencer, ¶[0073]). Under the broadest reasonable interpretation, a person of ordinary skill in the art would have understood that, at a peripheral measurement location, the pulse wave “arrival” (and its associated peak) occurs later in time within the same cardiac cycle after propagation, i.e., closer to the end of that heart muscle cycle than the initial systolic onset.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Spencer to measure, for each cardiac cycle, the maximum oximeter pulse waveform feature (F_max) at a timing corresponding to the pulse wave arrival (as identified by the peak marker), while continuing to measure blood pressure during the heart muscle cycle as taught by Curtis’463 (Curtis’463, ¶[0024]; Spencer, ¶[0073], ¶[0133]). The combination is feasible because Curtis’463 already performs contemporaneous pressure and oximeter measurements within each heart cycle, and Spencer provides a known per-cycle feature selection (peak at pulse wave arrival) for timing and defining the maximum measurement within that cycle. The benefit of the combination would be improved consistency of the flow-derived maximum used in the data sets by anchoring F_max to a repeatable, physiologically meaningful waveform feature associated with pulse wave arrival for each heart muscle cycle.
Regarding claim 13, the modified Curtis’463 does not fully teach that different data sets are established with the patient respectively sitting, standing, and lying down. The modified Curtis’463 taught measuring blood pressure pulse magnitudes ps with a sphygmomanometer and measuring blood flow pulse amplitudes po with an oximeter during a sphygmomanometer duty cycle, with ps and po measured simultaneously for each pulse (Curtis’463, Claim 10). However, the modified Curtis’463 did not expressly teach establishing different data sets with the patient respectively sitting, standing, and lying down.
Spencer teaches that for calibration and improved accuracy, “baseline measurements may be taken whilst the subject is sitting, standing and supine, with 3 recordings being used at each position and the average (mean) of each being used” (Spencer, ¶[0137]-[0148]).
It would have been prima facie obvious before the effective filing date of the claimed invention to modify the modified Curtis’463 in view of Spencer to establish different data sets by taking the Curtis’463 contemporaneous pressure-and-flow measurements for the patient in different positions, specifically sitting, standing, and lying down (supine), because Spencer taught that multiple posture-specific baseline measurement sets improved calibration accuracy and because the modified Curtis’463 already relied on paired contemporaneous measurements suitable for use as calibration data in each posture (Curtis’463, Claim 10; Spencer, ¶[0137]). The combination would have improved the robustness of the calibrated relationship across typical postural conditions encountered during monitoring.
Regarding claim 14, the modified Curtis’463 does not fully teach that the different data sets establish a 3-point line graph. Rather, the modified Curtis’463 teaches that a plurality of contemporaneous blood pressure pulse magnitudes ps and blood flow pulse amplitudes po measured during a sphygmomanometer duty cycle can be represented by a line graph using curve fitting techniques (Curtis’463, ¶[0023]–[0025]). However, the modified Curtis’463 does not expressly teach that the “different data sets” (as recited in claim 13) specifically establish a 3-point line graph.
Spencer teaches obtaining separate baseline measurement sets with the subject in three distinct positions (“sitting, standing and supine”) with multiple recordings at each position to form an averaged baseline for that position (Spencer, ¶[0137]). These three posture-specific baselines provide three distinct calibration data sets for a single subject under different physiological steady states.
It would have been prima facie obvious before the effective filing date of the claimed invention to modify the modified Curtis’463 in view of Spencer so that the three posture-specific data sets (sitting, standing, and supine) are used as three reference points to establish a 3-point line graph for calibration, because Curtis’463 already teaches representing calibration measurement pairs on a line graph, and Spencer teaches the established practice of taking calibration baselines in three distinct positions for improved accuracy (Curtis’463, ¶[0023]–[0025]; Spencer, ¶[0137]). The combination is feasible because the same type of contemporaneous pressure-and-flow measurement pairs taught by Curtis’463 can be collected in each of Spencer’s postural conditions, and the resulting three posture-specific calibration points can be plotted as a 3-point line graph. The benefit of the combination would be to provide a posture-robust calibration framework that spans common patient positions using a simple three-point representation, improving blood pressure indication accuracy across typical postural changes.
Regarding claim 15, the modified Curtis’463 does not fully teach that the line graph is created using the “P” and “F_max” values taken for successive quantified comparison “Δ_ss”, and wherein to account for “P” and “F” having an inverse relationship, a horizontal axis for the line graph will show a decreasing value for “F” while a vertical axis for the graph will show an increasing value for “P”, with each location on the line graph representing a comparison “Δ_ss” having unique values for “P” and “F” between any two quantified comparisons “Δ_ss”. Rather, the modified Curtis’463 teaches creating a line graph calibration in which an operational ratio (slope) is determined from a series of paired blood pressure pulse magnitudes ps and blood flow pulse amplitudes po, and then used for determining a blood pressure value ps based on measured pulse amplitudes po (Curtis’463, ¶[0025]–[0026]). However, the modified Curtis’463 does not expressly teach configuring the line graph to account for an inverse relationship between the pressure variable and the flow-related variable by plotting a decreasing flow-related value along a horizontal axis while plotting an increasing pressure value along a vertical axis.
Martin teaches that a physiological surrogate can exhibit an inverse relationship with blood pressure for an individual subject, stating that PTT "often shows a tight, inverse relationship with BP in individual subjects" (Martin, p. 1: "Pulse transit time (PTT) is the time elapsed for the pressure wave to travel between two arterial sites… Since arterial stiffness increases with blood pressure (BP) via the mechanical properties of the arterial wall, PTT often shows a tight, inverse relationship with BP in individual subjects"). Martin’s disclosure explains in context that inverse behavior is expected for certain waveform-derived measures and therefore the calibration relationship may be represented as decreasing surrogate values corresponding to increasing BP values.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Martin to configure the line graph so that it accounts for an inverse relationship by plotting decreasing flow-derived values along one axis while plotting increasing blood pressure values along the other axis, with intermediate locations between successive quantified comparisons being represented by the fitted line relationship. The combination is feasible because Curtis’463 already fits a line graph (slope) to paired pressure and flow-derived measurements and uses that relationship for mapping, and Martin teaches that inverse relationships between a waveform-derived surrogate and blood pressure are expected and can be captured by the calibration representation. The benefit of the combination would be to correctly represent and use an empirically inverse calibration relationship so that measured changes in the flow-derived surrogate map to appropriate blood pressure indications across the line graph.
Regarding claim 16, the modified Curtis’463 teaches that a method for using blood flow measurements "F" from a patient as indications of blood pressure "P" for the patient which comprises the operations of: (Curtis’463, [0002]: "the present invention pertains to systems and methods for continuously monitoring the blood pressure of a patient over an extended period of time. More particularly, the present invention pertains to systems and methods wherein a patient's blood flow, as measured by an oximeter, is evaluated in terms of blood pressure readings"; Curtis’463 teaches a method that continuously monitors blood pressure by evaluating oximeter-measured blood flow in terms of blood pressure readings, i.e., using blood flow measurements F from the patient as indications of blood pressure P).
Also regarding claim 16, Curtis’463 partially teaches measuring a blood pressure "P1", wherein "P1" comprises "P_systolic1" and "P_diastolic1", and a maximum blood flow value "F_max1" during the same heart muscle cycle to establish a data set therewith, wherein the data set comprises a first steady state quantified comparison "Δ_ss1"="P_max1" and "F_max1". Specifically, Curtis’463 teaches acquiring a per pulse blood flow pulse amplitude po contemporaneously with a blood pressure pulse magnitude ps during a sphygmomanometer duty cycle, and further teaches that "each blood pressure pulse magnitude ps and each blood flow pulse amplitude po is taken at a selected point in each heart pulse of the patient 16" (Curtis’463, [0027]). However, Curtis’463 does not expressly teach that the selected point corresponds to the maximum blood flow value "F max" of the pulse waveform as recited.
Spencer teaches that waveform features may be measured and that "details such as the peak can be used as a marker for the pulse wave arrival" (Spencer, 1[0133]: "features of the waveform can also be measured, and in such cases details such as the peak can be used as a marker for the pulse wave arrival").
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Curtis’463 in view of Spencer to select and use the peak of each measured oximeter pulse waveform as the per cycle maximum blood flow value "F_max1" while maintaining Curtis’463's contemporaneous pairing of the blood pressure measurement "P1" with the oximeter measurement. The combination is feasible because Curtis’463 already measures and uses one oximeter pulse amplitude value for each pulse while measuring the corresponding blood pressure value at the same time, and Spencer teaches selecting the peak as a known per cycle waveform feature that may be used as the measured detail. The benefit of the combination would be improved repeatability and physiological relevance of the per cycle blood flow feature used in the paired data set for indicating blood pressure.
Also regarding claim 16, Curtis’463 partially teaches measuring a blood pressure "P2", wherein "P2" comprises"P_systolic2" and "P_diastolic2", and a maximum blood flow value "F_max2" during the second heart muscle cycle to establish a data set therewith, wherein the data set comprises a second steady state quantified comparison "Δ_ss2"="P_max2" and "F_max2". Specifically, Curtis'463 teaches acquiring a per pulse blood flow pulse amplitude po contemporaneously with a blood pressure pulse magnitude ps during a sphygmomanometer duty cycle, and further teaches that "each blood pressure pulse magnitude ps and each blood flow pulse amplitude po is taken at a selected point in each heart pulse of the patient 16" (Curtis’463, [0027]). However, Curtis’463 does not expressly teach that the selected point corresponds to the maximum blood flow value "F_max2" of the pulse waveform as recited.
Spencer teaches that waveform features may be measured and that "details such as the peak can be used as a marker for the pulse wave arrival" (Spencer, 1[0133): "features of the waveform can also be measured, and in such cases details such as the peak can be used as a marker for the pulse wave arrival").
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Curtis’463 in view of Spencer to select and use the peak of each measured oximeter pulse waveform as the per cycle maximum blood flow value "F_max2" while maintaining Curtis’463's contemporaneous pairing of the blood pressure measurement "P2" with the oximeter measurement. The combination is feasible because Curtis’463 already measures and uses one oximeter pulse amplitude value for each pulse while measuring the corresponding blood pressure value at the same time, and Spencer teaches selecting the peak as a known per cycle waveform feature that may be used as the measured detail. The benefit of the combination would be improved repeatability and physiological relevance of the per cycle blood flow feature used in the paired data set for indicating blood pressure.
Also regarding claim 16, Curtis’463 does not fully teach creating a line graph using "Δ_ss1" and "Δ_ss2" as separate reference points, wherein each location on the line graph between these reference points is representative of an independent unique comparison "Δ_ss". Rather, Curtis’463 teaches obtaining multiple paired measurements of blood pressure pulse magnitude and oximeter pulse amplitude during a measurement cycle and representing a series of these paired measurements by a line graph using curve fitting techniques (Curtis’463, [0023]; [0025]). However, Curtis’463 does not expressly teach creating the line graph using a first steady state quantified comparison "Δ_ss1" and a second steady state quantified comparison "Δ_ss2" as separate reference points or that each location between those reference points represents an independent unique comparison “Δ_ss".
Martin teaches calibrating paired reference blood pressure values to a fitted line and mapping observed surrogate measurements through that line to predict blood pressure levels (Martin, p. 4, 'Data Analysis': "we also calibrated a time delay to each reference BP level by finding the line that best fitted the pairs of the time delays and BP levels for a subject and then mapping the time delays of that subject through the line so as to predict the BP levels").
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Curtis’463 in view of Martin to create the calibration line graph using at least two paired reference measurements as separate reference points and to treat each location between those reference points as a unique mapping along the fitted line between the paired measurements. The combination is feasible because both Curtis’463 and Martin acquire paired reference blood pressure values and a waveform-derived surrogate and then apply line fitting to establish a subject-specific calibration relationship, such that incorporating Martin's explicit use of paired reference points for line fitting into Curtis’463 would use the same types of paired inputs and the same curve-fitting approach already taught by Curtis’463. The benefit of the combination would be an explicit two-point calibration framework that supports mapping intermediate surrogate values between the reference points to corresponding blood pressure indications using the fitted line.
Also regarding claim 16, Curtis’463 does not fully teach referencing an observed blood flow measurement "F" to a location on the line graph with a "P diastolic" to identify a "P" as an indication of the patient's blood pressure. The modified Curtis’463 teaches determining a blood pressure value based on observed oximeter pulse amplitude by using a subject-specific operational ratio derived from a line graph relationship between pressure change and pulse amplitude change (Curtis’463, [0026]). However, Curtis’463 does not expressly teach identifying the indicated "P" using the diastolic pressure term "P diastolic" when referencing an observed blood flow measurement to a location on the line graph.
Martin teaches establishing reference diastolic and systolic blood pressure values and calibrating paired surrogate measurements to a fitted line in order to map observed waveform-derived values to predicted blood pressure levels (Martin, p. 4, 'Data Analysis': "We also detected the minimum and maximum of the cuff BP waveform between successive ECG R waves to establish reference diastolic and systolic BP for each beat... we also calibrated a time delay to each reference BP level by finding the line that best fitted the pairs of the time delays and BP levels for a subject and then mapping the time delays of that subject through the line so as to predict the BP levels").
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Martin to reference an observed waveform-derived surrogate measurement to a location on the calibration line to identify a corresponding indicated blood pressure level including a diastolic blood pressure level. The combination is feasible because Curtis’463 already teaches using an observed oximeter pulse amplitude measurement with a calibration line relationship to determine a blood pressure value, and Martin teaches using reference diastolic blood pressure values as calibration levels and mapping observed surrogate values through a fitted line to predict blood pressure levels, such that the indicated blood pressure output in Curtis’463 would include the diastolic level as taught by Martin. The benefit of the combination would be improved clinical interpretability of the indicated blood pressure by explicitly providing diastolic-level indications derived from the same calibration line mapping.
Regarding claim 17, the modified Curtis’463 partially teaches that the method of claim 16 wherein there is a unique “Δ_ss” at each location on the line graph between the different quantified “Δ_ss”, and further wherein between successive “Δ_ss” on the line graph the rate of change “ΔP” is not equal to the rate of change in “ΔF” with a new value for each unique “Δ_ss”=(P±ΔP) and (F±ΔF). Specifically, the modified Curtis’463 teaches generating a calibration relationship represented as a line graph based on successive paired changes in blood pressure pulse magnitude and pulse amplitude, stating that a correlation “is based on changes Δps and Δpo” between successive measurements and that “a series of an n number of such measurements… can then be represented by the line graph 40… using well known curve fitting techniques” (Curtis’463, ¶[0025]). The modified Curtis’463 further teaches that this line graph has an operational ratio or slope “Δps/Δpo (e.g. the slope of the line graph 40)” that “can be used for determining a blood pressure value ps based on changes in pulse amplitude po” (Curtis’463, ¶[0026]). However, Curtis’463 does not expressly teach that each location between quantified comparisons corresponds to a unique “Δ_ss”, does not expressly teach that between successive “Δ_ss” a parameter of the calibration relationship “remains constant” as required by the claim interpretation, and does not expressly teach the claimed expression of each unique “Δ_ss” as “Δ_ss”=(P±ΔP) and (F±ΔF).
Martin teaches treating a fitted calibration line as the mapping rule between calibration points, explaining that the surrogate timing values are calibrated to reference blood pressure levels “by finding the line that best fitted the pairs” and then “mapping the time delays… through the line so as to predict the BP levels” (Martin, p. 4). Martin further teaches that the magnitude of surrogate change may differ, stating that “the magnitudes of the changes in the two time delays were different” (Martin, p. 4).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Curtis’463 in view of Martin to treat the fitted line relationship as the constant between-point mapping rule for intermediate locations between successive quantified comparisons “Δ_ss”, and to apply that mapping even where the magnitude of the surrogate change differs from the magnitude of the blood pressure change, such that “ΔP” is not equal to “ΔF”. The combination is feasible because Curtis’463 already forms a curve-fit line graph and uses its slope or operational ratio to map changes in pulse amplitude to corresponding blood pressure values, and Martin teaches the explicit practice of mapping intermediate surrogate values through the fitted line while recognizing that change magnitudes can differ, which can be implemented in Curtis’463 by applying the same fitted-line mapping process to successive paired measurements. The benefit of the combination would be improved robustness and consistency of the calibration mapping across intermediate locations on the fitted line even when the surrogate change magnitude and blood pressure change magnitude differ.
Regarding claim 18, the modified Curtis’463 teaches that “P1” and “P2” are measured using a sphygmomanometer, and “F_max1” and “F_max2” are measured using an oximeter (Curtis’463, ¶[0020]: “the system 10 includes both a sphygmomanometer 12 and an oximeter 14… the sphygmomanometer 12 is used for the purpose of taking blood pressure pulse measurements… the oximeter 14 is used for the purpose of taking blood flow pulse amplitude measurements”, Curtis’463 explains that blood pressure measurements are taken using the sphygmomanometer and blood flow pulse amplitude measurements are taken using the oximeter; Claim 13: “for an n number of pulses during a sphygmomanometer duty cycle, successively different blood pressure measurements ps are taken by the sphygmomanometer and corresponding blood flow measurements po are taken by the oximeter”, Curtis’463 further teaches taking multiple blood pressure measurements using the sphygmomanometer and corresponding multiple blood flow measurements using the oximeter, which corresponds to measuring P1 and P2 using a sphygmomanometer and measuring F_max1 and F_max2 using an oximeter).
Regarding claim 19, the modified Curtis’463 teaches that "P" and "F_max" have concurrence within the same heart muscle cycle (Curtis’463, Claim 10: "measuring a blood flow pulse amplitude po, with an oximeter, for each pulse of the patient's heart during the sphygmomanometer duty cycle, wherein ps and po are measured simultaneously for each pulse", Curtis’463 teaches that the blood pressure pulse magnitude ps and the blood flow pulse amplitude po are measured simultaneously for each pulse, which corresponds to concurrence within the same heart muscle cycle; ¶[0011]: "Both measurements are taken contemporaneously during a sphygmomanometer duty cycle", Curtis’463 further teaches contemporaneous measurement of pressure and oximeter pulse amplitude during the duty cycle).
Also regarding claim 19, the modified Curtis’463 does not fully teach that "P_systolic" is measured near the beginning of the heart muscle cycle, while "P_diastolic" and "F_max" are measured near the end of the heart muscle cycle. Rather, the modified Curtis’463 teaches systolic and diastolic blood pressure measurements during a sphygmomanometer duty cycle and explains that systolic corresponds to the phase when the heart muscle contracts and diastolic corresponds to the phase when the heart muscle relaxes (Curtis’463, ¶[0003]). However, Curtis’463 does not expressly teach that the systolic measurement is taken near the beginning of the heart muscle cycle or that the diastolic measurement is taken near the end of the heart muscle cycle, and Curtis’463 does not expressly identify its oximeter per pulse amplitude measurement po as being taken at the maximum value F_max of the pulse waveform near the end of the heart muscle cycle.
Spencer explains that "During contraction of the heart, a longitudinal pressure wave is created that propagates outwardly along the vessel walls of the vasculature" and further teaches that waveform features may be measured such that "details such as the peak can be used as a marker for the pulse wave arrival" (Spencer, ¶[0003]; ¶[0133]). Thus, Spencer teaches that a pulse wave feature at a peripheral measurement location is associated with pulse wave arrival after the contraction event within the same cardiac cycle, and that the waveform peak may be selected as that arrival marker.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Curtis’463 in view of Spencer to time the selection of the per cycle oximeter waveform maximum F_max at the pulse wave arrival peak, and to treat the systolic pressure measurement as taken near the beginning of the heart muscle cycle and the diastolic pressure measurement as taken near the end of the heart muscle cycle, consistent with Curtis’463’s description of systolic during contraction and diastolic during relaxation. The combination is feasible because Curtis’463 already contemporaneously acquires blood pressure measurements and oximeter pulse amplitude measurements during a duty cycle spanning systolic to diastolic (Curtis’463, ¶[0011]), and Spencer provides a known per cycle waveform feature selection and timing reference (peak at pulse wave arrival) that can be applied to the same measured waveform data without changing Curtis’463’s measurement hardware or data pairing approach. The benefit of the combination would be improved temporal consistency of selecting F_max as a physiologically meaningful per cycle waveform feature and improved alignment of the measured blood pressure values with defined phases of the heart muscle cycle for calibration and indication.
Also regarding claim 19, the modified Curtis’463 does not fully teach that different data sets are established with the patient respectively sitting, standing, and lying down. The modified Curtis’463 teaches acquiring paired blood pressure and oximeter measurements contemporaneously during a sphygmomanometer duty cycle for calibration and subsequent blood pressure indication (Curtis’463, ¶[0002]; ¶[0011]). However, it does not expressly teach establishing different calibration data sets with the patient in different positions such as sitting, standing, and lying down.
Spencer teaches that, for calibration and improved accuracy, "baseline measurements may be taken whilst the subject is sitting, standing and supine, with 3 recordings being used at each position and the average (mean) of each being used" (Spencer, ¶[0137]-[0148]). Spencer further explains that measuring the subject in several positions may be prudent to gain better accuracy across activities (Spencer, ¶[0137]). Thus, Spencer teaches collecting multiple sets of paired measurements in different body positions and treating each position as its own baseline data set.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Curtis’463 in view of Spencer to establish different calibration data sets by acquiring the paired blood pressure and oximeter measurements taught by Curtis’463 while the patient is respectively sitting, standing, and lying down. The combination is feasible because Curtis’463’s calibration process already uses paired blood pressure and oximeter measurements during a duty cycle, and Spencer teaches that the same types of baseline measurements may be repeated across multiple body positions to form distinct position-specific data sets without requiring changes to the measurement devices. The benefit of the combination would be improved calibration robustness and accuracy across different patient postures by accounting for position-dependent physiological differences in the relationship between the waveform-derived surrogate measurement and blood pressure.
Regarding claim 20, the modified Curtis’463 does not fully teach that the line graph is created using the "P" and "F_max" values taken for successive quantified comparisons "Δ_ss", and wherein to account for "P" and "F_max" having an inverse relationship, a horizontal axis for the graph will show a decreasing value for "F_max" while a vertical axis for the graph will show an increasing value for "P", with each location on the resulting line graph between any two quantified comparisons "Δ_ss" representing a specific comparison "Δ_ss" having unique values for "P" relative to "F_max". Rather, the modified Curtis’463 teaches generating a line graph 40 from successive paired changes in blood pressure pulse magnitudes and blood flow pulse amplitudes during a sphygmomanometer duty cycle and using the slope/operational ratio Δps/Δpo of this line as a patient specific calibration factor to determine blood pressure values from measured pulse amplitudes (Curtis’463, ¶[0023]; ¶[0025]–¶[0026]). However, the modified Curtis’463 does not expressly teach creating the line graph using "P" and "F_max" values for successive quantified comparisons "Δ_ss" that are described as having an inverse relationship, with the horizontal axis showing decreasing "F_max" and the vertical axis showing increasing "P", or that each location on the resulting line graph between any two quantified comparisons "Δ_ss" represents a specific comparison "Δ_ss" having unique values for "P" relative to "F_max".
Martin teaches that a physiological surrogate can exhibit an inverse relationship with blood pressure for an individual subject, stating that PTT "often shows a tight, inverse relationship with BP in individual subjects" (Martin, p. 1). Martin further teaches calibrating a surrogate marker to reference blood pressure levels by finding the line that best fits pairs of marker values and BP levels and mapping measured marker values through the fitted line to predict BP levels (Martin, p. 4, 'Data Analysis').
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the modified Curtis’463 in view of Martin to explicitly treat the fitted calibration line as representing an inverse mapping between the waveform-derived flow surrogate and blood pressure by plotting decreasing "F_max" values along one axis while plotting increasing "P" values along the other axis, and to interpret each location between calibration points along the fitted line as representing a specific unique mapping between a particular "F_max" value and a corresponding "P" value. The combination is feasible because Curtis’463 already fits a line relationship (and determines its slope/operational ratio) from paired pressure and flow-derived measurements for calibration and subsequent blood pressure determination, and Martin teaches that inverse relationships between a waveform-derived surrogate and blood pressure are expected and are captured by fitting and using a line to map measured surrogate values to predicted BP levels. The benefit of the combination would be a more explicit inverse-axis calibration representation that improves clarity and correctness when using the line graph to map intermediate surrogate values between the quantified comparisons to corresponding blood pressure indications.
Regarding claim 21, the modified Curtis'463 partially teaches periodically remeasuring a “P_systolic”, a “P_diastolic” and an “F_max” for each quantified comparison “Δ_ss”, wherein a re-measurement is accomplished at least every thirty minutes to reconfigure the line-graph. The modified Curtis’463 teaches periodic recalibration of the relationship between oximeter-derived pulse amplitude and blood pressure, stating that “the operational ratio Δpo/Δps for calibrating the oximeter is preferably recalculated at least every hour” (Curtis’463, ¶[0014]) and further that “the operational ratio Δpo/Δps will, preferably, be recalculated to recalibrate the oximeter at least every hour” (Curtis’463, ¶[0029]). It therefore teaches periodically remeasuring pressure-related values and corresponding flow-related values in order to update the calibration relationship used to determine blood pressure from oximeter measurements. However, it does not explicitly teach that the recalibration occurs at least every thirty minutes.
The selection of a particular recalibration interval constitutes a result-effective variable. The frequency of recalibration directly affects the accuracy and stability of the calibration relationship, as more frequent recalibration may better account for physiological drift, sensor variation, or environmental changes, while less frequent recalibration reduces measurement burden.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further modified the modified Curtis’463 to perform recalibration at a selected interval, including an interval of at least every thirty minutes, as a matter of routine optimization of a result-effective variable based on known system performance considerations. The modification is feasible because the modified Curtis’463 already performs periodic recalibration using the same types of measurements (blood pressure and oximeter-derived flow amplitude), and changing the recalibration interval does not alter the underlying measurement or calibration process. The benefit of the modification would be improved responsiveness of the calibration relationship to changing physiological conditions while maintaining an appropriate balance between accuracy and measurement burden.
Regarding claim 22, the modified Curtis'463 partially teaches periodically remeasuring a “P_systolic”, a “P_diastolic” and an “F_max” for each quantified comparison “Δ_ss”, wherein a re-measurement is accomplished at least every thirty minutes to reconfigure the line-graph. The modified Curtis’463 teaches periodic recalibration of the relationship between oximeter-derived pulse amplitude and blood pressure, stating that “the operational ratio Δpo/Δps for calibrating the oximeter is preferably recalculated at least every hour” (Curtis’463, ¶[0014]) and further that “the operational ratio Δpo/Δps will, preferably, be recalculated to recalibrate the oximeter at least every hour” (Curtis’463, ¶[0029]). It therefore teaches periodically remeasuring pressure-related values and corresponding flow-related values in order to update the calibration relationship used to determine blood pressure from oximeter measurements. However, it does not explicitly teach that the recalibration occurs at least every thirty minutes.
The selection of a particular recalibration interval constitutes a result-effective variable. The frequency of recalibration directly affects the accuracy and stability of the calibration relationship, as more frequent recalibration may better account for physiological drift, sensor variation, or environmental changes, while less frequent recalibration reduces measurement burden.
It would have been prima facie obvious before the effective filing date of the claimed invention to have further modified the modified Curtis’463 to perform recalibration at a selected interval, including an interval of at least every thirty minutes, as a matter of routine optimization of a result-effective variable based on known system performance considerations. The modification is feasible because the modified Curtis’463 already performs periodic recalibration using the same types of measurements (blood pressure and oximeter-derived flow amplitude), and changing the recalibration interval does not alter the underlying measurement or calibration process. The benefit of the modification would be improved responsiveness of the calibration relationship to changing physiological conditions while maintaining an appropriate balance between accuracy and measurement burden.
Response to Arguments
Objections
Applicant's arguments filed 3/18/2026, page 7, regarding the previous Objections of claims 1-2, 9, 12, 16, and 19-20 have been fully considered and are persuasive. The previous Objections have been withdrawn.
35 U.S.C. §112(b)
Applicant's arguments filed 3/18/2026, page 7, regarding the previous 112(b) Rejections of claims 4-6 and 9-15 have been fully considered but are not persuasive. The amendment to claims 4 and 9 clarifies the grammatical structure of the clause but does not resolve the underlying ambiguity. Specifically, although the claims now state that Δ_ss is constant between successive comparisons, the claims do not identify what aspect of Δ_ss constant or with respect to what parameter the constancy is defined. The specification describes Δ_ss values as distinct calibration points that vary based on measured pressure and flow values and does not disclose any parameter that remains constant between successive Δ_ss values. Accordingly, one of ordinary skill in the art would not be able to determine the metes and bounds of the claimed subject matter with reasonable certainty. See the original 112 rejections above.
35 U.S.C. §103
Applicant's arguments filed 3/18/2026, pages 7-10, regarding the previous 103 Rejections of claims 1-20 have been fully considered but are not persuasive for at least the reasons outlined below.
Argument: Applicant contends that Curtis fails to disclose collecting blood pressure (P) and blood flow (F) measurements within the same heart muscle cycle because Curtis performs measurements over a sphygmomanometer duty cycle that is significantly longer than a heart muscle cycle. Applicant further argues that Spencer does not remedy this deficiency because Spencer allegedly does not disclose performing the claimed comparisons within the same heart muscle cycle.
Response: The argument is not persuasive. The prior Office Action already relied on Curtis’ disclosure that pressure and flow measurements are taken simultaneously for each pulse of the patient’s heart (Curtis, Claim 10). The present response clarifies that each such pulse corresponds to a heart muscle cycle. Applicant conflates the sphygmomanometer duty cycle, which is the window across which calibration measurements are gathered, with the timing of each individual measurement taken during that window. These are distinct concepts. Applicant’s argument that Curtis must explicitly determine a heart muscle cycle in order to perform measurements within that cycle is not persuasive, as Curtis inherently performs per-pulse measurements, and each pulse corresponds to a heart muscle cycle regardless of whether the duration of that cycle is explicitly calculated. The relative duration of the sphygmomanometer duty cycle as compared to a heart muscle cycle, even if differing by orders of magnitude, does not preclude that individual measurements taken within that duty cycle are acquired on a per-pulse basis and therefore occur within individual heart muscle cycles. Curtis expressly teaches that for each pulse of the patient’s heart during the duty cycle, both a blood pressure pulse magnitude and a blood flow pulse amplitude are measured simultaneously: "measuring a blood pressure pulse magnitude ps, with a sphygmomanometer, for each pulse of the patient's heart during a sphygmomanometer duty cycle" and "measuring a blood flow pulse amplitude po, with an oximeter, for each pulse of the patient's heart during the sphygmomanometer duty cycle, wherein ps and po are measured simultaneously for each pulse" (Curtis, Claim 10). Each pulse of the patient’s heart corresponds to a heart muscle cycle. The simultaneity of these measurements within each pulse teaches that the blood pressure and blood flow values are obtained in the same heart muscle cycle. The duty cycle spans multiple heart muscle cycles, but within each such cycle Curtis collects the paired data set required by the claims. Curtis further teaches that measurements are taken "at predetermined time intervals (e.g. patient pulse rate)" (Curtis, Abstract), reinforcing that sampling is aligned with individual cardiac cycles. Spencer teaches that "determining a time between adjacent peaks of the pressure wave, the time between peaks being indicative of a heart rate of the subject" and that "the time elapsed between peaks is used to give an inverse of the heart rate" (Spencer, ¶[0032]; ¶[0167]). The inverse of heart rate corresponds to the duration of a heart muscle cycle. Accordingly, it would have been prima facie obvious before the effective filing date of the claimed invention to have modified Curtis in view of Spencer to use the pulse rate associated with each heartbeat to explicitly determine the duration of the corresponding heart muscle cycle, in order to provide improved consistency in defining and applying a per-cycle timing window for associating and collecting pressure and blood flow measurements within each heart muscle cycle. Therefore, when Curtis is modified in view of Spencer, the combined teachings render obvious the claimed limitation of collecting blood pressure and blood flow measurements during the same heart muscle cycle and establishing a corresponding data set.
Argument: Applicant contends that Curtis cannot disclose same-cycle comparisons because Curtis operates over a sphygmomanometer duty cycle that is much longer than a heart muscle cycle.
Response: The argument is not persuasive because it improperly focuses on the duration of the overall measurement process rather than the timing of the individual data acquisitions. Curtis expressly ties its simultaneous blood pressure and blood flow measurements to each pulse of the patient’s heart (Curtis, Claim 10) and to pulse-rate-based sampling (Curtis, Abstract). Thus, although Curtis performs calibration during a broader sphygmomanometer duty cycle, the individual paired measurements are acquired within individual heart muscle cycles. The heart muscle cycle is the unit of measurement, whereas the duty cycle is the aggregate window across which multiple such units are sampled. Spencer further teaches determining and utilizing heart cycle timing (Spencer, ¶[0032]; ¶[0167]), and the combination yields the claimed functionality.
Argument: Applicant asserts that Spencer and Martin do not remedy the alleged deficiencies of Curtis.
Response: The argument is not persuasive. The rejection does not require Spencer to supply the within-cycle pairing of measurements, which is taught by Curtis as discussed above. Spencer is relied upon for the separate limitation of determining heart muscle cycle duration from pulse rate, for which Spencer expressly teaches that the time between waveform peaks gives the inverse of heart rate and therefore the cycle duration (Spencer, ¶[0032]; ¶[0167]). Spencer is further relied upon for additional limitations as set forth in the prior Office Action. Martin is relied upon for establishing the general principle that inverse relationships between waveform-derived physiological surrogate measurements and blood pressure are known and empirically determined. Martin teaches that "PTT often shows a tight, inverse relationship with BP in individual subjects" (Martin, p. 1). This teaching demonstrates that a waveform-derived physiological surrogate can exhibit an inverse relationship with blood pressure in individual subjects, supporting the examiner’s position that such relationships are known in the art and can be applied to other surrogates when supported by calibration data. The combination of Curtis, Spencer, and Martin teaches all claimed limitations as set forth in the prior Office Action. Applicant does not specifically rebut the cited teachings and reasoning for these elements.
Accordingly, the rejection of claim 1 and its dependents under 35 U.S.C. §103 is maintained.
Argument: Applicant contends that claim 9 requires that systolic pressure and diastolic pressure both be obtained within the same heart muscle cycle, and that Curtis’463 does not teach this because systolic and diastolic pressures are measured at different times during a sphygmomanometer duty cycle.
Response: The argument is not persuasive. Claim 9 recites that the blood pressure “P” comprises a “P_systolic” and a “P_diastolic”, and further recites taking “P” and “F_max” such that “P” and “F_max” have concurrence in the same heart muscle cycle. However, the claim does not require that both “P_systolic” and “P_diastolic” be obtained within the same heart muscle cycle. Rather, the claim requires only that a value for “P” and a value for “F_max” be taken with concurrence in the same heart muscle cycle. The term “comprises” as used in the claim is open-ended and does not require that “P_systolic” and “P_diastolic” each be individually collected within the same heart muscle cycle as “F_max”. Rather, “P” encompasses pressure information that may include systolic and diastolic values obtained over the measurement process, while the claim requires only that a pressure value “P” and a flow value “F_max” be taken with concurrence in the same heart muscle cycle.
Curtis’463 teaches measuring a blood pressure pulse magnitude ps and a blood flow pulse amplitude po simultaneously for each pulse of the patient’s heart (Curtis’463, Claim 10), such that a pressure value and a corresponding flow value are obtained contemporaneously for each pulse. Each pulse corresponds to a heart muscle cycle, and thus Curtis’463 teaches taking a pressure value “P” and a flow value “F” during the same heart muscle cycle. As set forth in the rejection, Spencer teaches identifying peaks of a waveform on a per-cycle basis, which correspond to maximum values within each cardiac cycle, thereby teaching the claimed “Fmax”. Accordingly, the combination of Curtis’463 and Spencer teaches taking “P” and “F_max” with concurrence in the same heart muscle cycle.
The recitation that “P” comprises systolic and diastolic pressure describes the types of pressure values that may be obtained from the pressure measurement process and does not impose a requirement that both values be obtained within the same cycle. Curtis’463 expressly teaches that systolic and diastolic pressures are identified at different times during the duty cycle, which is consistent with the claim language and does not preclude the contemporaneous per-pulse pairing of a pressure value with a flow value as required by the claim.
Accordingly, Curtis’463, in view of Spencer, teaches or renders obvious the disputed limitation and the rejection of claim 9 and its dependents under 35 U.S.C. §103 are maintained. Applicant does not specifically rebut the cited teachings and reasoning for the position-based calibration limitations supported by Spencer (¶[0137]–[0148]) or the inverse relationship between a waveform-derived surrogate and blood pressure supported by Martin (p. 1), and these limitations remain properly taught and applied.
Argument: Applicant contends that claim 16 requires that both systolic and diastolic pressure values be measured within the same heart muscle cycle together with F_max, and that Curtis 463 does not teach such simultaneous acquisition because systolic and diastolic pressures occur at different times within the sphygmomanometer duty cycle.
Response: The argument is not persuasive. Claim 16 recites that the measured blood pressure “P1” comprises “P_systolic1” and “P_diastolic1”, but the operative limitation requires only that a pressure value “P1” and a maximum blood flow value “F_max1” be measured during the same heart muscle cycle. The claim does not require that both “P_systolic1” and “P_diastolic1” be obtained within that same cycle. Rather, the “comprises” language describes the types of pressure values that may be included in the pressure measurement process. The term “comprises” is open-ended and does not require that “P_systolic1” and “P_diastolic1” each be individually collected within the same heart muscle cycle as “F_max1”. Rather, “P1” encompasses pressure information that may include systolic and diastolic values obtained over time, while the claim requires only that a pressure value derived from that measurement and a corresponding flow value be taken during the same heart muscle cycle.
Curtis 463 teaches measuring a blood pressure pulse magnitude ps and a corresponding blood flow pulse amplitude po simultaneously for each pulse of the patient’s heart (Curtis 463, [0027]; Claim 10), such that a pressure value and a flow value are obtained contemporaneously for each pulse. Each pulse corresponds to a heart muscle cycle, and thus Curtis 463 teaches measuring a pressure value “P1” and a corresponding flow value within the same heart muscle cycle as required. While “P1” comprises systolic and diastolic pressure values over time, the claimed step requires only that a pressure value derived from that measurement and a corresponding flow value be taken during the same heart muscle cycle. As set forth in the rejection, Spencer teaches selecting the peak of the waveform as a per-cycle feature corresponding to “F_max1”. Accordingly, the combination of Curtis 463 and Spencer teaches measuring “P1” and “F_max1” during the same heart muscle cycle.
Furthermore, Curtis 463 explicitly teaches that systolic and diastolic pressures are identified at different times during the duty cycle, which confirms that these values are features of a time-varying pressure waveform rather than values that must be obtained simultaneously within a single cycle. Therefore, the recitation that “P1” comprises systolic and diastolic pressure does not impose a requirement that both be measured within the same cycle and does not distinguish over the teachings of Curtis 463 in view of Spencer.
Accordingly, Curtis 463, in view of Spencer and further in view of Martin where applied, teaches or renders obvious the disputed limitation of claim 16.
Argument: Applicant has presented claims 21 and 22.
Response: Claims 21 and 22 have been considered. The added limitation of periodically remeasuring values at a specified interval to update or reconfigure a calibration relationship constitutes a routine calibration parameter. Curtis expressly teaches periodic recalibration: "the operational ratio Δpo/Δps for calibrating the oximeter is preferably recalculated at least every hour" and "the operational ratio Δpo/Δps will, preferably, be recalculated to recalibrate the oximeter at least every hour" (Curtis, ¶[0014]; ¶[0029]). The selection of a particular recalibration interval, including a more frequent interval such as every thirty minutes, would have been a matter of routine optimization of a result-effective variable, namely calibration frequency, to balance accuracy and measurement burden. It would have been prima facie obvious before the effective filing date of the claimed invention to have selected an appropriate recalibration interval, including the claimed interval, based on known system performance considerations. Accordingly, claims 21 and 22 are unpatentable under 35 U.S.C. §103 over Curtis in view of Spencer and Martin for the reasons set forth above.
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.
Any inquiry concerning this communication or earlier communications from the
examiner should be directed to AARON MERRIAM whose telephone number is (703) 756-
5938. The examiner can normally be reached M-F 8:00 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing
using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is
encouraged to use the USPTO Automated Interview Request (AIR) at
http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
supervisor, Jason Sims can be reached on (571)272-4867. The fax phone number for the
organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained
from Patent Center. Unpublished application information in Patent Center is available to
registered users. To file and manage patent submissions in Patent Center, visit:
https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for
more information about Patent Center and https://www.uspto.gov/patents/docx for
information about filing in DOCX format. For additional questions, contact the Electronic
Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO
Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AARON MERRIAM/Examiner, Art Unit 3791
/MATTHEW KREMER/Primary Examiner, Art Unit 3791
Prosecution Insights