DETAILED ACTION Notice of Pre-AIA or AIA Status The present application is being examined under the pre-AIA first to invent provisions. 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 appl icant regards as his invention. Clai ms 25 and 38 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention . Claim 25 recites: "The medical device system of claim 23, wherein the at least one body index comprises a autonomic index." The indefinite article "a" is grammatically incorrect before a word beginning with a vowel sound. The claim should recite " comprises an autonomic index ." This grammatical error introduces ambiguity and should be corrected. Claim 38 recites in its final "wherein" clause: "wherein calculating the drug adverse index and modifying the pain treatment regimen are both performed automatically by the device." However, claim 38 introduces and calculates "a drug tolerance index" — not a "drug adverse index." There is no antecedent basis for the term "the drug adverse index" in claim 38 or in parent claim 37 . It appears that "the drug adverse index" should read "the drug tolerance index." The claim is indefinite because it is unclear what index the "wherein" clause refers to. Appropriate correction is required. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer . Claim 21 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 9,579,457 . Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of the cited patent discloses a medical device system, comprising at least one sensor configured to sense at least one body signal from a patient; and a medical device configured to: receive at least a first sensed body signal from said at least one sensor; determine a patient pain index, wherein said patient pain index is based at least in part on said first sensed body signal; determine whether said patient pain index is above at least a first pain index threshold; determine a safety index wherein said safety index is based at least in part on a second sensed body signal; select a pain treatment regimen based on at least one of said safety index or a determination that said pain index is above said first pain index threshold; and deliver said pain treatment regimen. Despite the fact that the claim language above is not identical to the claim language of claim 21 of this application, a person of ordinary skill in the art would have recognized that the step of delivering a pain treatment regimen would have required the activation or use of a medication dispenser. Therefore, such language modification would have been considered an obvious alternative in the design of the system. 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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action: (a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made. Claims 21 and 37 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hemmerling et al. (US2011/0137134A1; hereinafter “Hemmerling”) in view of Huiku (US 2005/0272984A1) . Independent c laim 21 recites a medical device system, comprising : (a) at least one sensor configured to sense at least one body signal from a patient; ( b ) receive at least a first sensed body signal from the at least one sensor; ( c ) determine a patient pain index, wherein the patient pain index is based at least in part on the first sensed body signal; ( d ) determine whether the patient pain index is above at least a first pain index threshold; ( e ) select a pain treatment regimen based on a determination that the patient pain index is above the first pain index threshold, the pain treatment regimen comprises a medication and a dose of the medication; and ( f ) deliver the pain treatment regimen by activating a medication dispenser communicatively coupled to the medical device in accordance with the selected pain tr eatment regimen. In relation to independent claim 2 1 , Hem merling discloses : (a) "at least one sensor configured to sense at least one body signal from a patient" : Hemmerling discloses a vital sign monitoring system 18 that senses body signals from a patient. Hemmerling at [0021] states: "The system comprises an operating table 12, on which the patient 14 is lying during the surgery procedure... the patient 14 is also monitored using a vital sign monitoring system 18. Measured parameters include Heart Rate (HR) and heart rhythm, blood pressure (BP), pulse oxymetry (amount of oxygen in the blood), respiratory rate, and temperature." Hemmerling further discloses a BIS monitoring system 20 at [0021]: "A Bispectral (BIS) monitoring system 20 is also used to measure the BIS index, which is representative of hypnosis i.e. the depth of anaesthesia." These monitoring systems constitute "at least one sensor configured to sense at least one body signal from a patient." (b) "receive at least a first sensed body signal from the at least one sensor": Hemmerling discloses that the anaesthesia control unit 26 receives body signals from the vital sign monitoring system 18. Hemmerling at [0022] states: "The control unit 26 receives information from the vital sign monitoring system 18, and more specifically the patient's blood pressure and heart rate, and uses this information to derive an indicator or index representative of the patient's pain level, i.e. the Analgoscore." ( c ) "determine a patient pain index, wherein the patient pain index is based at least in part on the first sensed body signal": Hemmerling discloses determining a patient pain index (the "Analgoscore") based on sensed body signals. Hemmerling at [0024] states: "The anaesthesia control unit 26 then computes a first Analgoscore value using MAP and HR measurements determined periodically (e.g. once every minute) and invokes a control algorithm, which identifies whether changes in the dosage of the infused analgesic are required, according to the computed index of patient intra-operative pain." Hemmerling at [0025] further describes the Analgoscore: "Referring now to FIG. 3 in addition to FIG. 2, the Analgoscore is obtained by comparing the offset percentage between target measured values of both MAP and HR, the target values being set by the anaesthesiologist... Using fuzzy logic, the Analgoscore is designed to range from a first level, illustratively −9, which represents excessive analgesia, to a second level, illustratively +9, which represents insufficient analgesia, in increments of 1." The Analgoscore is a "patient pain index" based on body signals (blood pressure and heart rate). ( d ) "determine whether the patient pain index is above at least a first pain index threshold": Hemmerling discloses comparing the Analgoscore to threshold values to determine the appropriate action. Hemmerling at [0027] states: "Once the anaesthesia control unit 26 computes the current Analgoscore from the patient's current MAP and HR (step 32), fuzzy logic rules are used at step 34 to determine the new analgesic infusion required to ease the patient's pain. Indeed, based on the current Analgoscore value, which determines whether the level of analgesia was insufficient, good or excellent, the analgesic infusion is either stopped (Analgoscore less than −2), remains the same (Analgoscore between −1 and 1) or is increased by a predetermined percentage to reach an adequate level of analgesia." The Analgoscore thresholds (e.g., values above +1 triggering increased infusion) constitute "a first pain index threshold." ( e ) "select a pain treatment regimen based on a determination that the patient pain index is above the first pain index threshold, the pain treatment regimen comprises a medication and a dose of the medication": Hemmerling discloses that when the Analgoscore indicates insufficient analgesia, the system determines a new analgesic infusion rate. Hemmerling at [0022] states: "From this index, the control unit 26 determines how the level of analgesic administered to the patient 14 should be adjusted." Hemmerling at [0027] further states: " the analgesic infusion is either stopped (Analgoscore less than −2), remains the same (Analgoscore between −1 and 1) or is increased by a pre-determined percentage to reach an adequate level of analgesia." The analgesic (medication) and the determined infusion rate (dose) constitute "a pain treatment regimen." Hemmerling does not explicitly disclose that the pain treatment regimen comprises selecting among different medications. Hemmerling’ s system adjusts the dose of the already-infusing analgesic rather than selecting from among multiple medications. However, Huiku teaches that the pain indicator can be supplied as input to a drug delivery system for automatic control. Huiku at [0090] states: "The microprocessor may display the results on the screen of a monitor 104 connected to the microprocessor, and it may further supply the calculated pain indicator, such as the index of analgesia, as input data to a device or system 106 delivering drugs to the patient, which enables automatic control of the pain state of the patient (cf. FIG. 7)." Huiku at [0053] further states: "The present invention provides a mechanism for measuring the sympathetical activity in the ANS of a patient in order to be able to assess the pain experienced by the patient and to deliver analgesic drugs based on the pain indicated by the measurement." Huiku's teaching of supplying a pain indicator to a drug delivery system for automatic pain control, combined with Hemmerling's closed-loop analgesic dose adjustment based on the Analgoscore, renders obvious the claimed "select a pain treatment regimen" limitation. The combination teaches automatically selecting an analgesic medication and dose based on the pain index. ( f ) "deliver the pain treatment regimen by activating a medication dispenser communicatively coupled to the medical device in accordance with the selected pain treatment regimen": Hemmerling discloses delivering the pain treatment regimen through an infusion pump 24 controlled by the anaesthesia control unit 26. Hemmerling at [0022] states: " liquid anaesthetic agents are administered intravenously from a delivery system, e.g. an infusion pump 24, to the patient 14 through a tube 22 such as a catheter. The infusion pump 24 is controlled by an anaesthesia control unit 26 to accurately monitor and regulate the dosage of analgesic administered to the patient 14 for pain management." Hemmerling at [0024] further states: "The information is then fed to the infusion pump 24, which will make necessary adjustments to the infusion." The infusion pump 24 is a "medication dispenser communicatively coupled to the medical device" (the anaesthesia control unit 26), and the control unit activates the pump in accordance with the determined treatment regimen. Based on the above comments , i t would have been obvious to one of ordinary skill in the art before the invention to combine the closed-loop analgesic delivery system of Hemmerling with the pain monitoring and automatic drug delivery teachings of Huiku because both references are directed to the same field of automated pain management during medical procedures, and Huiku's broader pain monitoring approach using multiple physiological signals would have enhance d the accuracy and reliability of Hemmerling's Analgoscore-based system for automatic pain control. Independent c laim 37 recites a method for providing pain medication, comprising : (a) receiving a first sensed body signal from a patient, the first sensed body signal provided by at least one sensor configured to sense at least one body signal from the patient; (b) determining a patient pain index based at least in part on the first sensed body signal; (c) determining whether the patient pain index is above a first pain index threshold; (d) selecting a pain treatment regimen based on a determination that the patient pain index is above the first pain index threshold, the pain treatment regimen comprising a medication and a dose of the medication; and (e) delivering the pain treatment regimen by activating a medication dispenser; (f) wherein both the selecting of the pain treatment regimen and the delivering of the pain treatment regimen by activating a medication dispenser are automated and performed by a device . In relation to independent claim 37 , this claim is a method claim that recites substantially the same steps as the functions performed by the medical device system of claim 21, with the additional explicit requirement that "both the selecting of the pain treatment regimen and the delivering of the pain treatment regimen by activating a medication dispenser are automated and performed by a device. " The analysis for claim 21 above applies to each corresponding element of claim 37. Regarding the additional "automated" requirement, Hemmerling explicitly discloses closed-loop automated control . Hemmerling at [0023] states: " infusion of an analgesic may be illustratively closed-loop controlled through a control algorithm invoked by the anaesthesia control unit 26." Huiku at [0090] similarly teaches automatic control: " it may further supply the calculated pain indicator, such as the index of analgesia, as input data to a device or system 106 delivering drugs to the patient, which enables automatic control of the pain state of the patient." The combination of Hemmerling and Huiku renders claim 37 obvious for the same reasons as claim 21. Accordingly, i t would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the closed-loop analgesic delivery system of Hemmerling with the pain monitoring and automatic drug delivery teachings of Huiku because both references are directed to the same field of automated pain management during medical procedures, and Huiku's broader pain monitoring approach using multiple physiological signals would enhance the accuracy and reliability of Hemmerling's Analgoscore-based system for automatic pain control. Claims 22, 27, and 28 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hemmerling et al. (US2011/0137134A1; hereinafter “Hemmerling”) in view of Huiku (US 2005/0272984A1), as applied to claim 21 , and in further view of Osorio (US 2011/0251468 A1) . In relation to claim 22 , t he combination of Hemmerling and Huiku, as applied to claim 21 above, discloses the medical device system of claim 21. However, Hemmerling and Huiku do not explicitly disclose determining a "drug tolerance index" relating to the pain treatment regimen. Osorio teaches the concept of assessing therapeutic efficacy over time and modifying therapy based on that assessment. Osorio at [0010] states: "Automated means for quantification of event frequency and severity would allow the stratification of patients by severity, estimation of risks injury and death, formulation of prognosis, tracking the progression of the disorder, and objective assessment of therapeutic efficacy." Osorio at [0107] further teaches: "Therapeutic efficacy of a therapy provided by a therapy unit 220 can be assessed by determining if there is a decrease in the severity or duration of the patient's loss of responsiveness over time... the therapy evaluation unit 290 may compare a measure of the patient's responsiveness when a therapy is administered by a therapy unit 220 compared to when therapy was not administered. Alternatively, the therapy may be administered by other than a therapy unit 220, e.g., by the patient's oral ingestion of a medication, or the like... Efficacy may also be quantified as the change in the latency time from medical event detection... to loss of function... over the course of a desired time interval such as weeks, months, or years." Osorio teaches assessing therapeutic efficacy by tracking changes in patient responsiveness over time, including quantifying efficacy as changes in latency and severity measures. While Osorio is directed to epilepsy rather than pain management, the concept of monitoring how a patient's response to therapy changes over time (i.e., a measure analogous to a "drug tolerance index") is directly applicable to pain treatment. A person of ordinary skill in the art would recognize that tracking changes in a patient's response to analgesic medication over multiple exposures — the essence of a drug tolerance index — is an obvious extension of Osorio's therapeutic efficacy assessment framework applied to the pain management context of Hemmerling and Huiku. Based on the above comments, i t would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate Osorio's therapeutic efficacy assessment into the pain management system of Hemmerling and Huiku in order to track whether the patient is developing tolerance to the administered analgesic over time, thereby enabling the system to proactively adjust treatment before the medication becomes ineffective. Monitoring therapeutic efficacy over time is a well-known concern in pharmacology, and Osorio provides a framework for automated assessment that could be applied to the pain treatment context. In relation to claim 27 , t he combination of Hemmerling, Huiku, and Osorio, as applied to claim 22 above, discloses the medical device system of claim 22 including a drug tolerance index. Hemmerling and Huiku do not explicitly disclose modifying the pain treatment regimen in response to a drug tolerance index. Osorio teaches modifying therapy based on efficacy assessment. Osorio at [0126] states: "a decision 670 is made to deliver and/or modify therapy. For example, the decision 670 may be to initiate delivery of electrical stimulation to a neural structure, such as a cranial nerve; change one or more parameters defining an electrical signal... deliver or change the dosage of a drug administered to the patient; etc." Osorio teaches that therapy parameters, including drug dosage, can be modified based on the assessment of therapeutic efficacy. Applied to the pain management context of Hemmerling and Huiku, this teaches modifying the pain treatment regimen in response to the drug tolerance index. Based on the above comments, i t would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate Osorio's therapeutic efficacy assessment into the pain management system of Hemmerling and Huiku in order to track whether the patient is developing tolerance to the administered analgesic over time, thereby enabling the system to proactively adjust treatment before the medication becomes ineffective. Monitoring therapeutic efficacy over time is a well-known concern in pharmacology, and Osorio provides a framework for automated assessment that could be applied to the pain treatment context. Additionally, it would have been obvious to modify the pain treatment regimen in response to a drug tolerance assessment because the purpose of monitoring therapeutic efficacy is to enable appropriate adjustments when the current therapy is no longer effective. In relation to claim 28 , t he combination of Hemmerling, Huiku, and Osorio, as applied to claim 27 above, discloses modifying the pain treatment regimen in response to the drug tolerance index. Hemmerling, Huiku, and Osorio do not explicitly disclose that the modification comprises "changing the medication" (i.e., switching to a different drug). However, Osorio [ paragraph 0126] teaches that therapy modification can include changing therapy parameters, including the type of therapy delivered. Osorio teaches that the decision to modify therapy can include "deliver or change the dosage of a drug administered to the patient." While this specifically mentions changing dosage, a person of ordinary skill in the art would have recognize d that when a patient develops tolerance to a particular medication (as indicated by the drug tolerance index), changing to a different medication is a well-known and obvious clinical response. Switching medications when tolerance develops is a fundamental principle of pharmacology and pain management. However, Osorio at [0126] teaches that therapy modification can include changing therapy parameters, including the type of therapy delivered. Osorio teaches that the decision to modify therapy can include "deliver or change the dosage of a drug administered to the patient." While this specifically mentions changing dosage, a person of ordinary skill in the art would recognize that when a patient develops tolerance to a particular medication (as indicated by the drug tolerance index), changing to a different medication is a well-known and obvious clinical response. Switching medications when tolerance develops is a fundamental principle of pharmacology and pain management. Based on the above comments, i t would have been obvious to one of ordinary skill in the art t hat when a drug tolerance index indicates that a patient has developed tolerance to a particular analgesic, one obvious response is to change to a different medication. This is a standard clinical practice in pain management, and incorporating this capability into the automated system of Hemmerling, Huiku, and Osorio would be a routine design choice. Claim s 34 and 40 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hemmerling et al. (US2011/0137134A1; hereinafter “Hemmerling”) in view of Huiku (US 2005/0272984A1), as applied to claim 21 , and in further view of Liu et al. (US 2009/0259113 A1; hereinafter “Liu”) . In relation to claim 34 , t he combination of Hemmerling and Huiku, as applied to claim 21 above, discloses the medical device system of claim 21. Regarding the electromyograph, Huiku discloses the use of electromyography (EMG), including facial EMG (fEMG), as a sensor for pain monitoring. Huiku at [0011] states: "Electromyography (EMG) is a method for recording electrical biopotentials of muscles. In an EMG measurement, the electrodes are attached on the surface of the skin at a muscle group. An EMG signal is often recorded from the skull of the patient, whereby the recorded signal indicates both the activity of the facial muscle (fEMG) and the brain (EEG)." Huiku at [0029] further states: "Pain-related responses may be detected as activity in the sympathetical branch of the ANS of the patient or as increased motoric activity, especially in facial mimic muscles." Huiku at [0054] lists the physiological signals that can be used: "The physiological signal may be, for example, an ECG, waveform or a photoplethysmographic, a blood pressure or a respiration waveform, or a signal representing a physiological trend parameter, such as heart rate, pulse rate, systolic, diastolic or mean blood pressure. The physiological signal may also be an (f)EMG signal or a skin conductivity signal." Huiku therefore discloses an electromyograph as a sensor and facial muscle activity as a body signal indicative of pain. Hemmerling and Huiku do not explicitly disclose a "video imager" or "infrared imager" as a sensor, nor do they explicitly disclose that the sensed body signal comprises a "facial expression" captured by such an imager (as opposed to EMG-detected facial muscle activity). Liu teaches the use of a video imager to monitor facial expressions for determining pain level. Liu at [0011] states: "One embodiment of the present invention provides a method for determining pain level in a clinical environment. The method includes monitoring continuously at least one of facial expressions and sound generated by a patient, analyzing the at least one of facial expressions and sound for determining the pain level, and translating the at least one of facial expressions and sound to a quantifiable parameter indicating the pain level." Liu at [0021] states: "In an embodiment, the system incorporates a video imager for recording the images along with the sound generated by the patient." Liu at [0031] further describes the system: "The patient-status monitoring system 350 includes a video imager 352, an analyzer 354, a recorder 356 and an Electronic Medical Record (EMR) 358. The video imager 352 is configured to monitor the patient 300 continuously for recording the gestures." Liu therefore teaches (1) a video imager as a sensor and (2) facial expressions as a sensed body signal used for determining pain level. The claim requires "at least one of a video imager, an infrared imager, and an electromyograph," and the combination of Huiku (electromyograph) and Liu (video imager) satisfies this limitation. Based on the above comments, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate Liu's video imager and facial expression monitoring into the pain management system of Hemmerling and Huiku because Liu teaches that facial expressions provide an objective, continuous, and non-invasive means of assessing pain level, which would complement and enhance the physiological signal-based pain monitoring already taught by Hemmerling and Huiku. Using multiple modalities for pain assessment improves accuracy and reliability. In relation to claim 40 , this claim is a method claim that depends from claim 37 and recites the same sensor and body signal limitations as claim 34 (which depends from claim 21). The analysis for claim 34 above applies equally to claim 40. The combination of Hemmerling, Huiku, and Liu renders claim 40 obvious for the same reasons as claim 34. Allowable Subject Matter Claim 23 [and dependent claims 24-25], claim 26 , claim 29 [and dependent claims 30-33] , claim 35 [and dependent claim 36], claim 38 , and claim 39 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. In relation to the patentability of claim 23 , this claim recites a specific formula for the drug tolerance index (DTI) : The prior art of record does not teach or suggest this specific formula for calculating a drug tolerance index based on magnitude changes, latency changes, body indices, and number of exposures. While the general concept of monitoring drug tolerance is known, this specific mathematical formulation for quantifying tolerance using body index changes normalized by the number of exposures is not found in the prior art. In relation to the patentability of claim 2 6 , this claim recites that the drug tolerance index is calculated by "determining a change in dose required to get a body index to match an observed value for the body index in response to an earlier delivery of the pain treatment regimen." The prior art of record does not teach or suggest this specific method of calculating a drug tolerance index by determining the dose change required to reproduce a previously observed body index response. This represents a novel approach to quantifying drug tolerance. In relation to the patentability of claim 29 , this claim recites the step of determining a drug adverse index relating to the pain treatment regimen selected by the medical device based, at least in part, on an observed change in at least one of the at least one body signals sensed by the at least one sensor. The prior art of record does not teach or suggest the concept of a "drug adverse index" as a quantified metric based on observed changes in body signals. In relation to the patentability of claim 35 , this claim recites that "the first pain index threshold is indicative of a level of pain below a pain perception threshold." The prior art of record does not teach or suggest setting the pain index threshold at a level below the patient's pain perception threshold such that treatment is delivered prophylactically before the patient perceives pain. While preemptive analgesia is a known concept in clinical practice, the specific implementation of using a pain index derived from body signals with a threshold set below the pain perception threshold for automated prophylactic delivery is not found in the prior art. In relation to the patentability of claim 38 , this claim recites the DTI formula in the context of the method of claim 37, along with modifying the pain treatment regimen in response to the calculated drug tolerance index. The prior art of record does not teach or suggest this specific formula for calculating a drug tolerance index based on magnitude changes, latency changes, body indices, and number of exposures. While the general concept of monitoring drug tolerance is known, this specific mathematical formulation for quantifying tolerance using body index changes normalized by the number of exposures is not found in the prior art. In relation to the patentability of claim 39 , this claim recites determining a drug adverse index based on observed changes in body signals and latency to maximal change, and issuing a warning based on standard deviation from an observed mean. Same as stated for claim 29 above, the specific drug adverse index concept with warning thresholds is not found in the prior art. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT MANUEL A MENDEZ whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-4962 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Mon-Fri 7:00 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, FILLIN "SPE Name?" \* MERGEFORMAT Bhisma Mehta can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-3383 . 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. Respectfully submitted, /MANUEL A MENDEZ/ Primary Examiner, Art Unit 3783