DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
The amendment filed on 04/06/26 has been entered in the case. Claims 1-20 are pending for examination.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 4, 11 & 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Nowhere in the original specification has described the limitation that: wherein adjusting the first amount or rate of the basal dosage comprises subtracting the amount of unmetabolized therapeutic substance from the output of the integral term, as recited in claims 4, 11 & 18. Oppositely, in the step 504 (in Fig. 4), it states that adjust basal dosage based on amount of unmetallized therapeutic substance.
Claim Rejections - 35 USC § 102/103
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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 1-20 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Roy et al. (US 2011/0313390, or equivalent to US 10,561,785)
Regarding claim 1, Roy discloses a processor-implemented method for closed-loop control in steady-state conditions, the method comprising:
determining an amount of unmetabolized therapeutic substance, i.e., insulin on board -IOB, a meal bolus at mealtime in a patient, para [0045], or glucagon 23 and/or glucose 25, see Fig. 1, paras [0099-0102]) in a patient that excludes unmetabolized basal deliveries of insulin;
Note: the equation 10 in para [0110]: If (IOB BOLUS > Minimum IOB BOLUS), Extra IOB BOLUS = ՇIOB x IOBBOLUS - UBASAL. In other words, the IOB in equation 10 above, excludes unmetabolized basal deliveries of insulin).
determining, based on a recent measurement of a physiological condition of the patient (e.g., the insulin to be infused to that patient at a predetermined basal rate while the patient’s glucose level is within the predetermined range, para [0041]) and a target value for the physiological condition (blood glucose concentration of between 80-130 mg/dl, or target or set point glucose level at 120mg/dl, para [0040]), a first amount or rate of a basal dosage for delivery to the patient, para [0041];
adjusting, based on the amount of unmetabolized therapeutic substance, (i.e., meal bolus, or glucose and/or glucagon), the first amount or rate of the basal dosage (para [0056], using feedback control mechanism using various approaches, e.g., PID, treat-to-target range, model-predictive to determine the second amount or rate of the basal dosage; or para [0099-0100], If a patient’s blood glucose is below a targeted set point, then glucose and/or glucagon is delivered to increase the glucose level of the patient; para [0102], if a present estimate of blood glucose level is lower than a desired blood glucose level, then controller 12 reduces or stops insulin), also see paras [0110-0118], Figs. 9a-9b;
For example: the amount of unmetabolized therapeutic substance, i.e., meal bolus at the meal time, and because the amount of the basal dosage is delivering all day long (unless the blood glucose value is below the target value 80mg/dl), with broadest interpretation, the first amount or first rate of the basal dosage being delivered at same time with the meal bolus time, and will give the result of another blood glucose value, then a second amount or rate of the basal dosage will be determined that based on the recently value of the blood glucose value (or based on the amount of mean bolus, and the first amount or rate of the basal dosage);
causing delivery of the second amount or rate of the basal dosage, see Figs. 9a-9b, paras [0041, 0056, 0099-0102, 0110-0118].
Regarding claim 2, wherein the amount of unmetabolized therapeutic substance is corresponds to unmetabolized bolus deliveries (e.g. the amount of insulin on board – IOB).
Regarding claim 3, wherein determining the amount of unmetabolized therapeutic substance comprises:
obtaining historical insulin delivery data that includes historical basal deliveries of insulin and historical bolus deliveries of insulin, see Fig. 9b;
filtering the historical insulin delivery data to exclude the historical basal deliveries of insulin, wherein the amount of unmetabolized therapeutic substance (IOB) is determined based on the filtered historical insulin delivery data, see equation 10 in para [0110], paras [0072-0080, 0110-0117], Figs. 9a-9b.
For example: the insulin is delivered based on blood glucose levels in the four zones as shown in Fig. 9a. From the Fig. 9b, a constant basal insulin infusion rate is applied while the patient’s blood glucose level is in safe level at zone 2. While the patient’s blood glucose level exceeds upper bound UB (160mg/dl), as shown in zone 1, an insulin infusion rate is applied according to a controller command PID. Or while the patient’s blood glucose level is lower bound in zone 3-4, the infusion rate is reduced or suspended and/or provide a glucagon (if needed) for controlling blood-glucose levels of a patient (e.g., in a hypoglycemic context).
Regarding claim 4, as best as understood, wherein determining the first amount or rate of the basal dosage comprises using a proportional-integral-derivative (PID) closed-loop control process, para [0056]; wherein in the steady-state conditions (for example: the blood glucose in zone 2, in Fig. 9a), the first amount or rate of the basal dosage corresponds to an output of an integral term of the PID closed-loop control process, and wherein adjusting the first amount or rate of the basal dosage comprises subtracting the amount of unmetallized therapeutic substance from the output of the integral term.
Note: as seen in Figs. 9a-9b, when the blood glucose level in steady-state condition, (in zone 2 in Fig. 9a), there is no unmetallized therapeutic substance (bolus dosage) introduced, only basal dosage rate introduced in zone 2).
Regarding claim 5, wherein an integral path of the PID closed-loop control process comprises an upper limit (of upper bound, see Fig. 9a) equal to a maximum amount or rate for the basal dosage at PID (see Fig. 9b).
Regarding claim 6, wherein the maximum amount or rate for the basal dosage is patient-specific.
Regarding claim 7, wherein the first amount or rate of the basal dosage is less than the amount of unmetabolized therapeutic substance, (For example: when the blood glucose concentration is in between period of before eat that is under 80 mg/ml, see Figs. 9a-9b) and wherein causing delivery of the second amount or rate of the basal dosage (at below 80 mg/ml) comprises causing suspended delivery of any basal dosages, see Figs 9a-9b.
Regarding claims 8-15 & 17-20, these claims are being rejected using same analysis with regard to the claims 1-7 above.
Regarding claim 16, wherein the amount of unmetabolized therapeutic substance is determined based on one or more pharmacokinetic models, see Fig. 10.
Claims 1-20 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Mazlish et al. (US 10,275,573).
Regarding claim 1, Mazlish discloses a processor-implemented method for closed-loop control in steady-state conditions, the method comprising:
determining an amount of unmetabolized therapeutic substance, i.e., insulin 472 with bolus 2.2 unit, in Fig. 3A, in a patient that excludes unmetabolized basal deliveries of insulin (i.e., basal insulin 462);
determining, based on a recent measurement of a physiological condition of the patient and a target value for the physiological condition (it is well-known in the art that the target value of blood glucose in between 70-130mg/dl or 80-130 mg/dl depend on the medical condition of the patient), a first amount or rate of a basal dosage for delivery to the patient (the basal insulin amount at line 462 that corresponding to the bolus insulin unit 472, as shown in Fig. 3A; the basal dosage chart 460 indicates the basal delivery rates, which DMS 10 automatically adjusted based on data from a continuous glucose monitor, blood glucose meter, and/or recent insulin deliveries... chart 460 depicts the basal delivery as a step graph 462 showing a continuous insulin delivery as a rate over time, col. 11, lines 12-24);
adjusting, based on the amount of unmetabolized therapeutic substance, the first amount or rate of the basal dosage to determine a second amount or rate of the basal dosage (by using prediction model to estimate or predict the next blood glucose value, and then the system can determine a second amount or rate of the basal dosage, col. 7, lines 50-65, col. 11, lines 12-15).
Note: the basal insulin amount at line 462 in Fig. 3A changes that based on the changing values of the blood glucose concentration, col. 11, lines 12-24.
and, causing delivery of the second amount or rate of the basal dosage, see Fig. 3A.
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Regarding claim 2, wherein the amount of unmetabolized therapeutic substance corresponds to unmetabolized bolus deliveries.
Regarding claim 3, wherein determining the amount of unmetabolized therapeutic substance comprises:
obtaining historical insulin delivery data that includes historical basal deliveries of insulin (#460/462 in Fig. 3A); and filtering the historical insulin delivery data to exclude the historical basal deliveries of insulin (#472/474 in Fig. 3A; #484/485 in Fig. 3B); wherein the amount of unmetabolized therapeutic substance is determined based on the filtered historical insulin delivery data.
Regarding claim 4, wherein determining the first amount or rate of the basal dosage comprises using a proportional-integral-derivative (PID) closed-loop control process; wherein in the steady-state conditions, the first amount or rate of the basal dosage corresponds to an output of an integral term of the PID closed loop control process, and wherein adjusting the first amount or rate of the basal dosage comprises subtracting (excluding) the amount of unmetabolized therapeutic substance from the output of the integral term (e.g., as seen in Fig. 3A, at steady state condition around 12:45pm, i.e., when the blood glucose value does not fluctuate, the rate of the basal dosage 462 (excluding bolus insulin unit 470) deliveries to a patient.
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Regarding claim 5, wherein an integral path of the PID closed-loop control process comprises an upper limit (upper limit value of the target blood glucose, for example: 180 mg/dl) equal to a maximum amount or rate for the basal dosage (when the blood glucose rising at 180 mg/dl or above, the basal dosage also increases along with the blood glucose value).
Regarding claim 6, wherein the maximum amount or rate for the basal dosage is patient-specific.
Regarding claim 7, as shown in Fig. 3A, wherein the first amount or rate of the basal dosage (about 0.2 unit) is less than the amount of unmetabolized therapeutic substance (2.2 units), and wherein causing delivery of the second amount or rate of the basal dosage comprises causing suspended delivery of any basal dosages (if the blood glucose value starts decrease below 70 or 80 mg/dl).
Regarding claims 8, 10-20, these claims are being rejected using same analysis with regard to the claims 1-7 above.
Regarding claim 9, wherein the amount of unmetabolized therapeutic substance is determined based on one or more pharmacokinetic models.
Response to Arguments
Applicant's arguments filed 04/06/26 have been fully considered but they are not persuasive.
1) Applicant argues that Roy does not disclose the limitation of determining an amount of unmetabolized basal deliveries of insulin. Applicant further states that the cited portion of Roy is not related to “steady-state conditions”, as recited in the independent claims.
In response, the term “amount of unmetabolized therapeutic substance” is equivalent to an insulin on board (IOB), or meal bolus at mealtime that includes glucagon and/or glucose. In other words, the amount of unmetabolized therapeutic substance does not include the number of basal deliveries of insulin.
In this case, Roy discloses the method comprising: determining an amount of unmetabolized therapeutic substance (Insulin on board, i.e., initiating insulin bolus injections for meal, para [0045]. Specially, the equation 10 in para [0110]: If (IOB BOLUS > Minimum IOB BOLUS), Extra IOB BOLUS = ՇIOB x IOBBOLUS - UBASAL. In other words, the IOB in equation 10 above, excludes unmetabolized basal deliveries of insulin). In addition, the Figs. 9a-9b shows that when the blood glucose at steady-state condition (in zone 2 in Fig. 9a), the amount of basal rate is continuing delivering but excluding the bolus insulin during this time at zone 2).
2) Applicant argues that nothing in Mazlish discloses or states that insulin 472 as shown in Fig. 3A is an amount of unmetabolized therapeutic substance. Applicant further states that Mazlish simply states that insulin 427 is a larger dosage of insulin and is entirely silent on whether insulin 472 has been metabolized or not. Mazlish cannot and does not disclose or suggest “determining an unmetabolized amount of therapeutic substance in a patient that excludes unmetabolized basal deliveries of insulin.”
In response, the term “amount of unmetabolized therapeutic substance” is equivalent to an insulin on board (IOB), or meal bolus at mealtime that includes glucagon and/or glucose. In other words, the amount of unmetabolized therapeutic substance does not include the number of basal deliveries of insulin.
In this case, Mazlish shows in Fig. 3A that chart 460 depicts the basal delivery as a step graph 462 showing a continuous insulin delivery as a rate over time. Bolus dosage chart 470 depicts a history of larger dosages of insulin 472 along the time x-axis 473 as bars 472 on a graph with units of insulin along the y-axis 475. Each bar can include a numerical display 474 of units delivered. In other words, the bolus dosage 470 and the basal dosage 462 are separate; wherein the bolus dosage 470 is a meal bolus or called as an insulin on board. Therefore, Mazlish clearly discloses a method of determining an unmetabolized amount of therapeutic substance in a patient that excludes unmetabolized basal deliveries of insulin.
3) Applicant argues that col. 11, lines 12-15 state “basal dosage chart 460 indicates the basal delivery rates, which DMS 10 automatically adjusts based on data from a continuous glucose monitor, blood glucose meter, and/or recent insulin deliveries.” Applicant also states that Mazlish makes no mention of unmetabolized therapeutic substance.
In response, the statement in col. 11,lines 12-15 above is being used to apply the equivalent of the claimed limitation, i.e., adjusting, based on the amount of unmetabolized therapeutic substance (#472, i.e. 2.2 unit), the basal dosage 460 (in line #462) to determine a rate of the basal dosage
It does not rely on nor use to apply to reject the claimed invention “determining an amount of unmetabolized therapeutic substance.
4) Applicant argues that nowhere does Mazlish disclose or suggested “adjusting, based on the amount of unmetallized therapeutic substance, the first amount or rate of the basal dosage to determine a second amount or rate of the basal dosage”
In response, as mentioned in part #3 of Response to Arguments above, the col. 11, lines 12-15 states “basal dosage chart 460 indicates the basal delivery rates, which DMS 10 automatically adjusts based on data from a continuous glucose monitor, blood glucose meter, and/or recent insulin deliveries.” By using prediction model to estimate or predict the next blood glucose value, and then the system can determine a second amount or rate of the basal dosage, col. 7, lines 50-65, col. 11, lines 12-15).
The basal insulin amount at line 462 in Fig. 3A changes that based on the changing values of the blood glucose concentration. The basal insulin amount at line 462 that corresponding to the bolus insulin unit 472, as shown in Fig. 3A; the basal dosage chart 460 indicates the basal delivery rates, which DMS 10 automatically adjusted based on data from a continuous glucose monitor, blood glucose meter, and/or recent insulin deliveries... chart 460 depicts the basal delivery as a step graph 462 showing a continuous insulin delivery as a rate over time, col. 11, lines 12-24.
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 QUYNH-NHU HOANG VU whose telephone number is (571)272-3228. The examiner can normally be reached M-F 7:30 am-4:00 pm.
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/QUYNH-NHU H. VU/ Primary Examiner, Art Unit 3783
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