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 .
Claim Status
Claims 1-2, 4-11, and 13-15 are pending and under examination.
Claims 3 and 12 are canceled.
Claims 1-2, 4-11, and 13-15 are rejected.
Claims 5, 6, and 15 are objected to.
Claims 1 and 11 are independent.
No claims are allowed, new, or withdrawn.
Office Action Outline
Rejections applied
Abbreviations
x
112/b Indefiniteness
PHOSITA
"a Person Having Ordinary Skill In The Art before the effective filing date of the claimed invention"
112/b "Means for"
BRI
Broadest Reasonable Interpretation
112/a Enablement,
Written description
CRM
"Computer-Readable Media" and equivalent language
112 Other
IDS
Information Disclosure Statement
x
102, 103
JE
Judicial Exception
x
101 JE(s)
112/a
35 USC 112(a) and similarly for 112/b, etc.
101 Other
N:N
page:line
Double Patenting
MM/DD/YYYY
date format
Priority
As detailed in the 07/19/2022 filing receipt, this application claims priority to as early as 09/12/2019, the filing date of EP19382790.4. Additionally, this application is a 371 of PCT PCT/EP2020/073886, filed 08/26/2020. At this point in examination, all claims have been interpreted as being accorded the priority date 09/12/2019.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. See paper entered 03/11/2022.
Overview of Withdrawal/Revision of Objections/Rejections
In view of the amendment and remarks received 02/02/2026:
• The claim objections are withdrawn.
• The 112(b) rejections are withdrawn.
• The 112(d) rejection is withdrawn.
• The 101 rejection is maintained with revision.
• The 103 rejection is maintained with revision.
Rejections and/or objections not maintained from previous office actions are withdrawn. The following rejections and/or objections are either maintained or newly applied. They constitute the complete set applied to the instant application.
Claim Objections
Claims 5, 6, and 15 are objected to because of the following informalities:
Claims 5 and 6 each recite "the previous general anesthesia procedure" which recites a singular procedure that should be amended to the plural "the previous general anesthesia procedures."
Claim 15 recites "obtaining, during a training phase separate from an actual use of a model during the actual anesthesia procedure" which is missing the term "general" and should be amended to "obtaining, during a training phase separate from an actual use of a model during the actual general anesthesia procedure."
Appropriate correction is required.
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.
Claim 1-2 and 4-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims depending from rejected claims are rejected similarly, unless otherwise noted, and any amendments in response to the following rejections should be applied throughout the claims, as appropriate.
The "wherein the reference data..." element of claim 1 includes the recitation "...in a patient during an anesthesia procedure..." (emphasis added). It is not clear if "an anesthesia procedure" is meant to be the same procedure first instantiated in the preamble of "a general anesthesia procedure," or the same procedure as one of the "previous general anesthesia procedures," or the same procedure as "...during the general anesthesia procedure based on the index of nociception." For examination purposes, the anesthesia procedure in the recitation "...in a patient during an anesthesia procedure..." will be interpreted as one of the previous general anesthesia procedures (of the clinical data).
The last element of claim 1 recites "wherein the trained model is used to control administration of the drug during the general anesthesia procedure based on the index of nociception," however, no index of nociception has been computed in claim 1. For examination purposes, "wherein the trained model is used to control administration of the drug during the general anesthesia procedure based on the index of nociception" will be interpreted as "wherein the trained model is used to control administration of the drug during the general anesthesia procedure." (Emphasis added by examiner.)
Claim 4 is dependent on claim 3, which is now canceled. It is not clear from which claim that claim 4 should now depend. For compact examination, it is assumed that claim 4 should be dependent on claim 1.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 4-11, and 13-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
MPEP 2106 details the following framework to analyze Subject Matter Eligibility:
• Step 1: Are the claims directed to a category of statutory subject matter (a process, machine, manufacture, or composition of matter)? (See MPEP § 2106.03.)
• Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. an abstract idea, a law of nature, or a natural phenomenon? (See MPEP § 2106.04(a), 2106.04(a)(2), and 2106.04(b).)
• Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application? (See MPEP § 2106.04(d).)
• Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept? (See MPEP § 2106.05.)
Step 1:
Claims 1-2 and 4-10 are directed to a 101 process, here a method. Claims 11 and 13-15 are directed to a 101 machine or manufacture, here a device. As such, claims 1-2, 4-11, and 13-15 are directed to a related method and device which fall under categories of statutory subject matter. (See MPEP § 2106.03). (Step 1: Yes.)
Step 2A, Prong One:
Claims 1-2, 4-11, and 13-15 recite abstract ideas as follows:
Independent claim 1 and dependent claim 15 recite mathematical concepts and mental processes of:
• deriving training data (TD) from the clinical data;
• deriving reference data (RD) from the clinical data;
• training and adjusting the model (M2) using the training data (TD) as input data and the reference data (RD) as output data;
• deriving the reference data (RD) from the clinical data using an equation including a mathematical term whose value is non-linearly variable as a function of a concentration value relating to a drug concentration in a patient during an anesthesia procedure;
• the function of the concentration value is an exponential function.
• the mathematical term is defined as a·f1 (CeRemi) wherein a is a coefficient, and f1 defines the function, and CeRemi is the concentration value (claim 1 only)
Independent claim 11 recites mathematical concepts and mental processes of:
• to compute the index of nociception (qNOX) using a model and input data to obtain a value for the qNOX (note: there is no active step of computing during an actual anesthesia procedure)
• to modify the value of the qNOX using information derived from the EEG to obtain a corrected value of the qNOX (note: there is no active step of modifying the value)
Claims 5, 6, 8, 9 further limit the mathematical concepts and mental processes of claim 1 by reciting:
• the concentration value is time-variable within the anesthesia procedure (claim 5);
• for deriving the reference data (RD) time-variable reference curves for the anesthesia procedure are computed (claim 6);
• the model mathematical (M2) includes a set of coefficients for computing said index of nociception (qNOX) from input data derived from an encephalography signal (EEG), wherein during said training the coefficients are adjusted to define the model (claim 8);
• the model is a fuzzy logic model or a quadratic equation model (claim 9).
Claim 4 further limits the mathematical concepts and mental processes of claim 3 by reciting: the equation is defined RD = a·f1(CeRemi) + b qCON + f3(Resp); wherein b is a coefficient, qCON is an index of consciousness, f3 is a function and Resp is a patient response parameter
Claim 7 further limits the mathematical concepts and mental processes of claim 6 by reciting: the reference curves are at least one of scaled to a range between 0 and 100 and smoothed by applying a moving average technique.
Claims 13-14 further limit the mathematical concepts and mental processes of claim 11 by reciting:
• to modify said value for the index of nociception (qNOX) obtained from the model (M2) by using information related to at least one of an electrooculogram derived from the EEG, a burst suppression ratio derived from the EEG (EEG) and a near-burst
suppression index derived from said encephalography signal (EEG) (claim 13)
• to modify the value for the qNOX obtained from the model (M2) by applying a scaling operation and/or a smoothing operation (claim 14)
Step 2A Prong One Summary: The claims recite abstract ideas, characterized as mental processes and mathematical concepts. Considering the broadest reasonable interpretation (BRI) of the claims, the mental processes recited in independent claim 1 and 11 [e.g., deriving training data, deriving reference data, training the model, using an equation (claim 1); compute the value (claim 11); etc.] are directed to processes that may be performed in the human mind, or with pen and paper, as there are no details recited in the claims which would prevent mental performance (and as such, the mathematical concepts are also considered to be mental processes). Additionally, the mathematical concepts recited in the limitations [e.g., for reference data derived from an equation including a mathematical term (claim 1); the exponential function (claim 2); the mathematical term defined (claim 1); the equation defined (claim 4); to compute the value (claim 11); etc.] either explicitly recite mathematical concepts (claim 4) or inherently recite mathematical concepts such as those disclosed in Specification 17:28 through 20:30. Such analysis performed mentally, or with paper and pencil, may take considerable time and effort, and although a general-purpose computer can perform these calculations at a rate and accuracy that can far exceed the mental performance of a skilled artisan, the nature of the activity is essentially the same, and therefore constitutes an abstract idea. See MPEP§2106.04(a)(2)(I) and (III); and MPEP§2106.04(a)(2)(III)(C).
Therefore, the claims recite elements that constitute a judicial exception in the form of an abstract idea. (Step 2A, Prong One: Yes.)
Step 2A, Prong Two:
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs). Here at Step 2A, Prong Two, any remaining steps and/or elements not identified as JEs are therefore in addition to the identified JE(s), and are considered additional elements. Because the claims have been interpreted as being directed to judicial exceptions (abstract ideas in this instance) then Step 2A, Prong Two provides that the claims be examined further to determine whether the judicial exception is integrated into a practical application [see MPEP § 2106.04(d)]. A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception.
MPEP § 2106.04(d)(I) lists the following five example considerations for evaluating whether a judicial exception is integrated into a practical application:
(1) An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a).
(2) Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2).
(3) Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b).
(4) Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c).
(5) Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
The claims recite additional elements as follows:
Additional elements of data gathering in claims 1 and 11: Obtaining data (claim 1); and an encephalography signal (EEG) (claim 11). Data gathering steps are additional elements which perform functions of inputting, collecting, and outputting the data needed to carry out the abstract idea. These steps are considered insignificant extra-solution activity, and are not sufficient to integrate an abstract idea into a practical application as they do not impose any meaningful limitation on the abstract idea or how it is performed, nor do they provide an improvement to technology [see MPEP § 2106.04(d)(I)].
Additional element of controlling administration of the drug during general anesthesia in claim 1: The trained model is used to control administration of the drug during the general anesthesia procedure based on the index of nociception (claim 1). Because the step does not provide a nexus between the judicial exception and a practical application (in that the connection between the index of nociception and the trained model is vague), then it is not yet clear that the claim provides a transformation needed in the 101 sense. See further discussion in "Response to Applicant Arguments - 35 USC § 101" section below.
Additional elements of computer components in claims 10 and 11: A processing system and a software code (claim 10); a monitor, processor, data storage, and display device (claim 11). The monitor device is comprises only the generically claimed processor device (see claim 11; Specification 17:7-8; and Fig.9 together with Specification 21:17-19). The claims require only generic computer components, which do not improve computer technology, and do not integrate the recited judicial exception into a practical application (see MPEP § 2106.04(d)(1) and MPEP § 2106.05(f)).
Step 2A Prong Two summary: Claims 1-2, 4-11, and 13-15 have been further analyzed with respect to Step 2A, Prong Two, and no additional elements have been found, alone or in combination, that would integrate the judicial exception into a practical application. At this point in examination, it is not yet the case that any of the Step 2A Prong Two considerations enumerated above clearly demonstrates integration of the identified JE(s) into a practical application. Referring to the considerations above, none of: (1) an improvement, (2) a treatment, (3) a particular machine, or (4) a transformation is clear in the record. For example, regarding the first consideration for improvement at MPEP 2106.04(d)(1), the record, including the Specification, does not yet clearly disclose an explanation of improvement over the previous state of the technology field, and the claims do not yet clearly result in such an improvement. (Step 2A, Prong Two: No).
Step 2B:
Because the additional claim elements do not integrate the abstract ideas into a practical application, the claims are further examined under Step 2B, which evaluates whether the additional elements, individually and in combination, amount to significantly more than the judicial exception itself by providing an inventive concept. An inventive concept is furnished by an element or combination of elements that is recited in the claim in addition to the judicial exception, and is sufficient to ensure that the claim, as a whole, amounts to significantly more than the judicial exception itself (see MPEP § 2106.05).
Claims 1-2, 4-11, and 13-15 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are well-understood, routine, and conventional as follows:
Additional elements of data gathering: The additional elements of obtaining data (claim 1); and an encephalography signal (EEG) (claim 11) do not cause the claims to rise to the level of significantly more than the judicial exception. The courts have recognized receiving or transmitting data over a network; and storing and retrieving information in memory [see MPEP§2106.05(d)(II)], as well-understood, routine, conventional activity when they are claimed in a merely generic manner (e.g., at a high level of generality) or as extra-solution activity.
Additionally, the following reference shows the data gathering of EEG signals during anesthesia monitoring to be well-understood, routine, and conventional:
Al-Kadi et al., (Evolution of electroencephalogram signal analysis techniques during anesthesia. Sensors, vol. 13(5), pages 6605-6635 (2013); cited on the attached form PTO-892). Al-Kadi presents a review on EEG signal analysis during anesthesia monitoring (entire document), and discusses acquiring of EEG signal especially at pages 6608, 6610, 6614, 6615, 6617, 6626, and 6627.
Therefore, the data gathering steps are shown to be routine, well-understood, and conventional in the art, and as a result, do not provide an inventive concept by amounting to significantly more than the judicial exception.
Additional element of controlling administration of a drug during anesthesia: Regarding "wherein the trained model is used to control administration of the drug during the general anesthesia procedure based on the index of nociception ' of claim 1, the claim does not yet recite significantly more at Step 2B as the connection between the index of nociception and the trained model is vague, (See further discussion in "Response to Applicant Arguments - 35 USC § 101" section below.) Additionally, the following reference shows trained models used to control drug administration during anesthesia to be well-understood, routine, and conventional:
Nunes (In 2014 IEEE International Symposium on Medical Measurements and Applications (MeMeA), pages 1-6, IEEE (2014); cited on the attached form PTO-892), discusses automation in anesthesia (entire document); qNOX in anesthesia (p.2, col.2, ¶ 6); and trained models (p.3, col.2, ¶ 1).
Additional elements of computer components: A processing system and a software code (claim 10); a monitor, processor, data storage, and display device (claim 11). The monitor device comprises only the generically claimed processor device (see claim 11; Specification 17:7-8; and Fig.9 together with Specification 21:17-19). The claims require only conventional computer components, which do not improve computer technology, and do not integrate the recited judicial exception into a practical application (see MPEP § 2106.04(d)(1) and MPEP § 2106.05(f)).
Further regarding the conventionality of additional elements, the MPEP at 2106.05(b) and 2106.05(d) presents several points relevant to conventional computers and data gathering steps in regard to Step 2A Prong 2 and Step 2B, including:
• A general purpose computer that applies a judicial exception, such as an abstract idea, by use of conventional computer functions, does not qualify as a particular machine (see 2106.05(b)(I)), as in the case of claim 11, which applies the abstract ideas on conventional computer components.
• Integral use of a machine to achieve performance of a method may integrate the recited judicial exception into a practical application or provide significantly more, in contrast to where the machine is merely an object on which the method operates, which does not integrate the exception into a practical application or provide significantly more (see 2106.05(b)(II). In the instant claims, the recited processing system (claim 10) and processor device (claim 11), used in deriving data or computing the index, act only as tools to perform the steps of data analysis, and do not integrate the judicial exception into a practical application or provide significantly more.
• Use of a machine that contributes only nominally or insignificantly to the execution of the claimed method (e.g., in a data gathering step or in a field-of-use limitation) would not integrate a judicial exception or provide significantly more (see 2106.05(b)(III). The processing system/processor device of claims 10 and 11, used in the EEG signal data analysis do not impose meaningful limitations on the claims.
• The courts have recognized "receiving or transmitting data over a network", "performing repetitive calculations", and "storing and retrieving information in memory", as well-understood, routine, and conventional functions when they are claimed in a merely generic manner (e.g., at a high level of generality) or as insignificant extra-solution activity (see MPEP 2106.05(d)(II)). The obtaining of data in claims 1 and 11 is recited in a generic manner.
All limitations of claims 1-2, 4-11, and 13-15 have been analyzed with respect to Step 2B, and none provides a specific inventive concept, as they all fail to rise to the level of significantly more than the identified judicial exception, and thus do not transform the judicial exception into a patent eligible application of the exceptions. (Step2B: NO.)
Therefore, the claims, when the limitations are considered individually and as a whole, are rejected under 35 U.S.C. § 101 as being directed to non patent-eligible subject matter.
Response to Applicant Arguments - 35 USC § 101
Applicant's arguments filed 02/02/2026 have been fully considered but they are not yet persuasive.
Applicant asserts (considered to pertain to Step 2A Prong Two):
• "The claims, as amended, integrate an abstract idea into a practical application by
reciting a specific technological improvement in anesthesia monitoring." (p.7, ¶ 2)
• The method of training the model ...and the monitor device that modifies the index of nociception...provide a concrete technical solution for improving patient safety during general anesthesia by more accurately predicting nociception responses...is not merely applying mathematical concepts on a computer but rather solving a specific problem in the medical device field." (p.7, ¶ 2)
The arguments are not yet persuasive because regarding an improvement to technology or a technical field (see MPEP §§ 2106.04(d)(1) and 2106.05(a)), the record, including Applicant's remarks and the Specification, does not yet clearly disclose an explanation of improvement over the previous state of the technology field, and the claims do not yet clearly result in such an improvement. Please provide evidence or detailed explanation of the improvement, as a detailed explanation of a technical improvement may help to overcome a 101 rejection, (see MPEP 2106.04(d) and (d)(1), as well as MPEP 2106.05(a)). The explanation might include a concise statement of the improvement, including improvement over the previous state of the technology field; identification of the technology field; explanation of how the claims deliver the improvement and that reasonably all embodiments within the claim scope also will result in the asserted improvement, and extension of the explanation to persuasively demonstrate the nexus of integration of the judicial exceptions into a practical application. As further examples, arguments may clearly and adequately explain cause and effect leading to improvement or, for example when such cause and effect explanation is not possible, then may include evidence (e.g. experimental data) comparing a claimed result to conventional results. Also, arguments and evidence may be extrinsic to the original disclosure, including references available after the priority date, as long as it is clear that an argument applies to all embodiments of a properly supported claim. In the present invention, the 02/02/2026 arguments do not persuasively explain the improvement.
Further, a nexus is lacking between the judicial exceptions (JEs) and integration into a practical application, when considering the claim as a whole. Claim 1 recites "...to compute an index of nociception..." and "...wherein the trained model is used to control administration of the drug during the general anesthesia procedure based on the index of nociception," however, no index of nociception has been computed as there is no active step of computing the index of nociception, therefore the nexus between JEs and integration into a practical application is absent.
Applicant might consider trying to show a transformation or particular therapy in addition, or in place of, an improvement to technology. Claim 1 appears to have the beginnings of a scaffold for reciting a transformation, which may be an easier path to overcoming 101 than showing improvement. However, whichever consideration is used to show a practical application at Step 2a Prong Two, a nexus must be evident between the JE (or output of the JE) and the practical application; in this case, there must be a nexus between controlling the administration of anesthesia and the output of the J.E. In claim 1, the connection between the index of nociception and the trained model is vague; it is suggested to strengthen this connection.
Applicant is encouraged to request an interview to discuss this and other issues.
Claim Rejections - 35 USC § 103
Note: the mathematical term of claim 1 (previously recited in now canceled claim 3, and previously considered to appear to be free of the prior art) has been reconsidered and is now considered to be taught by Melia (Journal of clinical monitoring and computing, vol. 31(6), pages 1273-1281 (2017); cited on the attached form PTO-892; also cited on the 03/13/2026 IDS).
Note: Claim 4 appears to be free of the prior art, for the mathematical term for the equation "RD= a·f1(CeRemi) + b qCON = f3(Resp)." The closest prior art references are Jensen, (2014; Acta Anaesthesiologica Scandinavica, vol. 58(8), pages 1-9; cited on the 03/11/2022 IDS) in view of Melia, (Journal of clinical monitoring and computing, vol. 31(6), pages 1273-1281 (2017); cited on the attached form PTO-892; also cited on the 03/13/2026 IDS).
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 5-11, and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Jensen, (2014; Acta Anaesthesiologica Scandinavica, vol. 58(8), pages 933-941; cited on the 03/11/2022 IDS) in view of Melia, (Journal of clinical monitoring and computing, vol. 31(6), pages 1273-1281 (2017); cited on the attached form PTO-892).
Regarding claim 1, 2, 8-11, and 15, Jensen teaches the following limitations:
• Obtaining, during a training phase separate from an actual use of the model (M2) during an anesthesia procedure, clinical data relating to a multiplicity of previous anesthesia procedures (recited in claims 1 and 15)
• Deriving training data (TD) from the clinical data; deriving reference data (RD) from the clinical data (recited in claims 1 and 15)
• Training the model (M2) using the training data (TD) as input data to the model (M2) and the reference data (RD) as output data to the model (M2), wherein the training includes adjusting the model (M2) according to the training data (TD) and the reference data (RD); the reference data (RD) is derived from the clinical data (recited in claims 1 and 15)
• an exponential function (recited in claim 2)
• mathematical (M2) includes a set of coefficients for computing said index of nociception (qNOX) from input data derived from an encephalography signal (EEG), wherein during said training the coefficients are adjusted to define the model (recited in claim 8)
• a fuzzy logic model (recited in claim 9)
• a processing system configured to execute a software code (recited in claim 10)
• a processor device configured to compute said index of nociception (qNOX) during an actual anesthesia procedure using a model (M2) and input data which is derived from an encephalography signal (EEG) obtained during said general anesthesia procedure, wherein a value for the index of nociception (qNOX) is obtained as output from the model (M2) (recited in claim 11)
• to modify said value for the index of nociception (qNOX) obtained from the model (M2) using additional information derived from said encephalography signal (EEG) to obtain a corrected value for the index of nociception (qNOX) (recited in claim 11)
• to compute the value for the index of nociception (qNOX) in real-time during the actual anesthesia procedure (recited in claim 11)
Jensen teaches data was recorded from 60 surgical patients scheduled for general anesthesia with a combination of propofol and remifentanil (p.2, col.1). Jensen teaches the qCON and qNOX indices were continuously recorded (p.2, col.2 ). Jensen teaches the qNOX algorithm was developed using a database of 450 patients undergoing endoscopy sedated with propofol and remifentanil, 80 patients in general anesthesia with sevoflurane, 10 patients anaesthetized with desflurane, and 50 awake volunteers, a total of 590 patients (bridging p.7-8). Jensen teaches the mathematical model used for the development of both qCON and qNOX is the Adaptive Neuro Fuzzy Inference System (ANFIS), a hybrid of an artificial neural network and a Sugeno-type fuzzy system, having a special five-layer feed-forward network architecture where the inputs are not counted as a layer (p.8, col.1). Jensen teaches an epoch in the learning procedure uses an iterative least mean squares (LMS) procedure in the forward pass while the antecedent parameters are fixed for the current cycle through the training set (p.8, col.1). Jensen teaches the electroencephalogram (EEG) spectral ratios were fed into an ANFIS. A reference scale was developed based on the Observer Assessment of Alertness and Sedation (OAAS) scale and the Ramsay scale (p.8, bridging col.1-2). Jensen teaches the model was trained using the spectral ratios as input while the reference clinical scale was the output (p.8, col.2). Jensen teaches logistic regression analysis to show that a qNOX less than 40 means approximately 20% probability of response (defined as movement) to noxious stimuli (p.6, col.1). Jensen teaches the data from the qCON and the qNOX indices were stored in a personal computer with proprietary software, qCON display (Quantium Medical) (p.2, col.2).
Regarding claim 5 and 6, Jensen teaches the following limitations:
• the concentration value is time-variable within the anesthesia procedure (recited in claim 5)
• time-variable reference curves for the anesthesia procedure are computed (recited in claim 6)
Jensen teaches the three electroencephalogram indices (Bis, qCON and qNOX) and the effect-site concentrations of propofol (Ce prop) and remifentanil (Ce remi) (p.3, fig.3). Jensen teaches data was recorded from 60 surgical patients scheduled for general anesthesia with a combination of propofol and remifentanil (p.2, col.1). Jensen teaches the qCON and qNOX indices were continuously recorded (p.2, col.2 ).
.
Regarding claim 7, 13, and 14, Jensen teaches the following limitations:
• the reference curves are at least one of scaled to a range between O and 100 and smoothed by applying a moving average technique (recited in claim 7)
• to modify said value for the index of nociception (qNOX) obtained from the model (M2) by using information related to at least one of an electrooculogram derived from said encephalography signal (EEG), a burst suppression ratio derived from said encephalography signal (EEG) and a near-burst suppression index derived from said encephalography signal (EEG) (recited in claim 13)
• to modify said value for the index of nociception (qNOX) obtained from the model (M2) by in addition applying at least one of a scaling operation and a smoothing operation (recited in claim 14)
Jensen teaches the qCON and qNOX indices are based on the combination of different frequency bands that are fed into an Adaptive Neuro Fuzzy Inference System (ANFIS) which generates the output on a 0–99 scale (p.2, col.1). Jensen teaches the ANFIS model was trained using the spectral ratios as input while the reference clinical scale was the output. The final step was adding the burst suppression (BS) as the major parameter to indicate deep anesthesia. When BS occurs, the clinical signs of responsiveness have already been suppressed. The qCON scale from a range below 25 relies solely on the BS ratio (BSR). The BSR is the percentage of near isoelectric EEG in a window of 30 s. Both suppression and bursts should have a duration of more than 1 s in order to add up to the final BS count, detected by a maximum-likelihood algorithm. The frequency ratios are calculated every second, thus the qCON is updated every second. An exponential moving average has been applied in order to smoothen rapid transitions, therefore the 50% update time of the qCON is 5 s, assuming no artefacts in the EEG (p.8, col.2).
Jensen does not specifically show the claim 1 and 15 limitation for using an equation including a mathematical term whose value is non-linearly variable as a function of a concentration value relating to a drug concentration in a patient during an anesthesia procedure (taught by Melia).
While Jensen shows a trained model of claim 1, Jensen does not show wherein the claim 1 element to control administration of the drug during the general anesthesia procedure based on the index of nociception (taught by Melia).
Jensen does not show the mathematical term of claim 1 (taught by Melia).
Regarding the claim 1 and 15 limitation, using an equation including a mathematical term whose value is non-linearly variable as a function of a concentration value relating to a drug concentration in a patient during an anesthesia procedure; Melia teaches to analyze the qCON and qNOX kinetics in relation with the speed of loss of consciousness and loss of response to nociceptive stimuli, the fall and rise times of the two indices were defined at the beginning and at the end of the surgery. The fall times were defined as the difference between the times when the effect site concentration of propofol or remifentanil was above zero (T0) and the time when qCON and qNOX reached a value below x (T<x) (p.1275, col.1).
Regarding the mathematical term of claim 1, Melia shows a series of equations calculating the fall and rise times of both qCON and qNOX (p.1275, col.1), including the equations:
Fall time qCON = T<x – T0
Fall time qNOX = T<x – T0
Where T<x = min {t|qCON(t) < x ∨ qNOX(t) < x} and T0 = min {t|Ce prop(t) > 0 ∨ Ce remi(t) > 0} and t includes all the time instants of the recorded qCON and qNOX of each patient. The equations (p.1275, col.1) of Melia shows the mathematical term T0 which relates to the effect site drug concentrations of propofol and remifentanil (showing a mathematical term of claim 1).
Regarding the claim 1 element to control administration of the drug during the general anesthesia procedure based on the index of nociception, Melia shows their findings can also give guidance to clinicians as how to control anesthetic effect by looking at qCON and qNOX as indicators of hypnosis and analgesia (p.1280, col.1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the method for training and use of a nociception model of Jensen, with the nociception model using concentrations of propofol or remifentanil in analyzing qCON and qNOX during anesthesia of Melia, to come to a trained model for computing an index of nociception (qNOX), because Melia confirms that the use of a nociception index in addition to a consciousness index improves the detection of the effect of the analgesic that are induced in the EEG, and thus it permits to monitor the responsiveness of the patients in a more accurate way (p.1280, col.1). One of ordinary skill would have had a reasonable expectation of success in doing so because Jensen and Melia are drawn to related teaching of nociception models, and one of ordinary skill in the art would have understood how to and would have been motivated to modify the model of Jensen with the teachings of Melia, and as such, the combination would have been obvious.
Response to Applicant Arguments - 35 USC § 103
Applicant's arguments filed 02/02/2026 have been fully considered but they are not yet persuasive. Applicant asserts:
• "independent claim 1 is amended herein to incorporate the limitations of dependent claim 3, canceled herein, which is acknowledged to appear to be free of the prior art. (p.6, ¶ 4)
• "Claim 1 also has been amended to further recite "wherein the trained model is used to control administration of the drug during the general anesthesia procedure based on the index of nociception." (p.6, ¶ 4)
The mathematical term of claim 1 (previously recited in now canceled claim 3, and previously considered to appear to be free of the prior art) has been reconsidered and is now considered to be taught by Melia, in that the equations (p.1275, col.1) of Melia shows the mathematical term T0 which relates to the effect site drug concentrations of propofol and remifentanil (showing a mathematical term of claim 1).
Regarding "...control administration of the drug during the general anesthesia procedure based on the index of nociception" of claim 1, Melia shows their findings can also give guidance to clinicians as how to control anesthetic effect by looking at qCON and qNOX as indicators of hypnosis and analgesia (p.1280, col.1).
Claim 4 still appears free of the prior art, despite reconsideration, and has not been rejected under 35 U.S.C. 103. Amending claim 1 to recite claim 4 would very likely result in the withdrawal of the 103 rejection for claims 1-2 and 5-10.
Also of note, if no other amendments were made to claim 11, the 103 rejection of claims 11 and 13-15 would likely be maintained.
Applicant is encouraged to request an interview to discuss this and other issues. As noted below in the conclusion section, an interview may be conveniently requested at http://www.uspto.gov/interviewpractice.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/M.A.V./Examiner, Art Unit 1687
/G. STEVEN VANNI/Primary patents examiner, Art Unit 1686
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