Claims for Patent: 10,335,464

Summary for Patent: 10,335,464

Title:	Device for titrating basal insulin
Abstract:	The invention relates to a novel administration regime useful in the treatment of diseases or conditions where administration of insulin will be of benefit. In particular, the invention relates to a long-acting or ultra-long acting insulin for use in treating a disease or condition where administration of insulin will be of benefit, wherein the administration of said insulin includes or consists of one or more of the following steps: (a) obtaining a first data set of the subject, (b) obtaining a second data set of the subject, (c) obtaining a first data structure of the subject, and (d) obtaining a second data structure of the subject. When a determination is made that the at least first data structure, second data structure, first data set, and second data set collectively do contain the set of evaluation information, the device further includes providing the long-acting or ultra-long-acting insulin dose guidance recommendation.
Inventor(s):	Michelich; Alan John (Seattle, WA), Miller; Thomas Dedenroth (Seattle, WA), Shvets; Oleksandr (Everett, WA), Imanbayev; Anuar (Seattle, WA), Van Orden; Brad (Seattle, WA)
Assignee:	Novo Nordisk A/S (Bagsvaerd, DK)
Application Number:	16/020,478
Patent Claims:	1. A device for providing a long-acting or ultra-long-acting insulin dose guidance recommendation for a subject to treat diabetes mellitus, wherein the device comprises one or more processors and a memory, the memory comprising: instructions that, when executed by the one or more processors, perform a method responsive to receiving a dose guidance request (DGR), said instructions comprising: obtaining a first data structure that comprises at least: (i) a body weight (BW) of the subject, (ii) an upper limit target glucose range (UTR) of the subject, (iii) a lower limit target glucose range (LTR) of the subject, and (iv) an overbasalisation limit (OBL) of the subject; obtaining a second data structure that comprises at least: (i) a most recent adjustment day dose recommendation (ADDR), and/or (ii) a starting basal dose (SBD); obtaining a first data set, comprising a plurality of glucose measurements of the subject taken over a time course and thereby establish a blood glucose history (BGH) and, for each respective glucose measurement in the plurality of glucose measurements, a corresponding glucose timestamp representing when in the time course the respective glucose measurement was made; obtaining a second data set, comprising: (i) a basal insulin injection history (IH) of the subject, wherein the injection history comprises a plurality of injections during all or a portion of the time course and, for each respective injection in the plurality of injections, (ii) a corresponding injection amount (IU), (iii) an injection timestamp (UTC) representing when in the time course the respective injection occurred, and (iv) a last injection data refresh (IDR) of the subject; evaluating at least the first data structure, the second data structure, the first data set, and the second data set and thereby determine whether they collectively contain a set of evaluation information comprising at least: (i) the body weight of the subject, (ii) the plurality of glucose measurements of the subject taken over the time course, (iii) the injection history of the subject, (iv) (1) the last adjustment day dose recommendation, and/or (2) the starting long-acting or starting ultra-long-acting insulin dose of the subject, (v) the overbasalisation limit of the subject, (vi) the last injection data refresh for the subject, (vii) the upper limit target glucose range of the subject, and (viii) the lower limit target glucose range of the subject; wherein when a determination is made that the at least first data structure, second data structure, first data set, and second data set fail to collectively contain the set of evaluation information, no update to the long-acting or ultra-long-acting insulin dose guidance recommendation is made, and when a determination is made that the at least first data structure, second data structure, first data set, and second data set collectively do contain the set of evaluation information, the method further comprises providing the long-acting or ultra-long-acting insulin dose guidance recommendation. 2. The device of claim 1, wherein the long-acting or ultra-long-acting insulin, has a side chain attached to the .alpha.-amino group of the N-terminal amino acid residue of the B chain or to the .epsilon.-amino group of the Lys residue present in the B chain of the parent insulin, the side chain being of the general formula: --W--X--Y--Z wherein W is: (i) an .alpha.-amino acid residue having a carboxylic acid group in the side chain which residue forms, with one of its carboxylic acid groups, an amide group together with the .alpha.-amino group of the N-terminal amino acid residue of the B chain or together with the .epsilon.-amino group of a Lys residue present in the B chain of the parent insulin; (ii) a chain composed of two, three or four a-amino acid residues linked together via amide bonds, which chain--via an amide bond--is linked to the a-amino group of the N-terminal amino acid residue of the B chain or to the .epsilon.-amino group of a Lys residue present in the B chain of the parent insulin, the amino acid residues of W being selected from the group of amino acid residues having a neutral side chain and amino acid residues having a carboxylic acid group in the side chain so that W has at least one amino acid residue which has a carboxylic acid group in the side chain; or (iii) a covalent bond from X to the a-amino group of the N-terminal amino acid residue of the B chain or to the .epsilon.-amino group of a Lys residue present in the B chain of the parent insulin; wherein X is: (i) --CO--; (ii) --COCH(COOH)CO--; (iii) --CON(CH.sub.2COOH)CH.sub.2CO--; (iv) --CON(CH.sub.2COOH)CH.sub.2CON(CH.sub.2COOH)CHCO--; (v) --CON(CH.sub.2CH.sub.2COOH)CH.sub.2CH.sub.2CO--; (vi) --CON(CH.sub.2CH.sub.2COOH)CH.sub.2CH.sub.2CON(CH.sub.2CH.sub.2COOH)CH.su- b.2CH.sub.2CO--; (vii) --CONHCH(COOH)(CH.sub.2).sub.4NHCO--; (viii) --CON(CH.sub.2CH.sub.2COOH)CH.sub.2CO--; or (ix) --CON(CH.sub.2COOH)CH.sub.2CH.sub.2CO; provided that: (a) when W is an amino acid residue or a chain of amino acid residues, via a bond from the underscored carbonyl carbon forms an amide bond with an amino group in W; or (b) when W is a covalent bond, via a bond from the underscored carbonyl carbon forms an amide bond with the N-terminal a-amino group in the B chain or with the .epsilon.-amino group of a Lys residue present in the B chain of the parent insulin; wherein Y is: (i) a --(CH.sub.2).sub.m-- where m is an integer in the range of 6 to 32; (ii) a divalent hydrocarbon chain comprising 1, 2 or 3 --CH.dbd.CH-- groups and a number of --CH.sub.2-- groups sufficient to give a total number of carbon atoms in the chain in the range of 10 to 32; or (iii) a divalent hydrocarbon chain of the formula --(CH.sub.2).sub.vC.sub.6H(CH.sub.2).sub.w-- wherein v and w are integers or one of them is zero so that the sum of v and w is in the range of 6 to 30; wherein Z is: (i) --COOH; (ii) --CO-Asp; (iii) --CO-Glu; (iv) --CO-Gly; (v) --CO-Sar; (vi) --CH(COOH)2; (vii) --N(CH2COOH)2; (viii) --SO.sub.3H; or (ix) --PO.sub.3H; and any Zn.sup.2+ complexes thereof, provided that when W is a covalent bond and X is --CO--, then Z is different from --COOH. 3. The device of claim 1, wherein the long-acting or ultra-long-acting insulin is LysB29(N.epsilon.-hexadecandioyl-.gamma.-Glu) des(B30) human insulin, which is insulin degludec. 4. The device of claim 1, wherein the long-acting insulin or ultra-long-acting insulin is selected from the group consisting of: a) neutral protamine hagedorn insulin which is NPH insulin; b) Lente Insulin; c) Ultralente Insulin; d) Glargine Insulin; e) Detemir Insulin; f) Hypurin Bovine Lente; and g) Hypurin Bovine PZI. 5. The device of claim 1, wherein the long-acting or ultra-long-acting insulin is insulin degludec, and the long-acting or ultra-long-acting insulin is administered, concurrently or consecutively, with liraglutide. 6. The device of claim 1, wherein the time course comprises a current day and the past four days. 7. The device of claim 1, wherein the time course comprises the current day and between one and ten of the immediately preceding past days. 8. The device of claim 1, wherein the method further comprises updating the last injection data refresh within the immediately preceding 30 seconds or less, the immediately preceding 1 minute or less, or the immediately preceding 5 minutes or less. 9. The device of claim 1, wherein the method further comprises updating the dose guidance recommendation for the subject, unless the injection history of the subject comprises one or more injections of the subject that have injection timestamps within the current day. 10. The device of claim 1, wherein the method further comprises updating the dose guidance recommendation for the subject when at least one injection occurred within the current day and no injections occurred in the immediately preceding one day in the injection history time course. 11. The device of claim 1, wherein the method further comprises combining any injections in the injection history that have timestamps within a five-minute period in the time course into one injection. 12. The device of claim 1, wherein the method further comprises calculating a reconstructed blood glucose history of the subject when the blood glucose history time course contains a gap, and wherein the reconstructed blood glucose history is calculated based on the blood glucose history of each calendar day. 13. The device of claim 12, wherein the method further comprises performing a quality check of the reconstructed blood glucose history data, and wherein when the data quality check fails, the dose guidance recommendation is not updated. 14. The device of claim 1, wherein the method further comprises providing a re-recommendation of the dose guidance recommendation until: (i) one or more injections with an injection amount equivalent to the dose guidance baseline have occurred, (ii) one or more injections have occurred since the dose guidance baseline and when one or more injections have occurred over the current day and the past two or three or four days, and (iii) one or more does events with an injection amount greater than or equal to the dose guidance baseline have occurred. 15. The device of claim 12, wherein the method further comprises selecting the dose guidance baseline from the set of parameters comprising at least the starting basal dose and the most recent adjustment day dose recommendation, and wherein the selected parameter has the timestamp closest to the current time. 16. The device of claim 15, wherein the method further comprises calculating a daily titration glucose level and an overall titration glucose level, wherein: (i) the daily titration glucose level for each calendar day is calculated by selecting the lowest average of reconstructed blood glucose history data for any predetermined first time period within the blood glucose history time course and excluding any reconstructed blood glucose history data with a timestamp older than the timestamp of the dose guidance baseline: when there are gaps larger than a predetermined second time period in the blood glucose history time course, no daily titration glucose level is calculated, when there are gaps in the blood glucose history time course and these gaps are at least the predetermined second time period in length and less than a predetermined third time period in length within any calendar day in the blood glucose history time course, the daily titration glucose level averaging omits any predetermined first time period containing gaps when averaging the reconstructed blood glucose history data, when any calendar day in the blood glucose history time course contains gaps longer than the predetermined third time period or when more than a predetermined number of blood glucose measurements are absent no daily titration glucose level is calculated; and (ii) the overall titration glucose level is calculated by taking the average of the daily titration glucose levels, and wherein when no overall titration glucose level can be determined the dose guidance recommendation is not updated. 17. The device of claim 16, wherein the predetermined first time period is between 15 minutes and 120 minutes. 18. The device of claim 16, wherein the predetermined second time period is between 10 minutes and 40 minutes. 19. The device of claim 16, wherein the predetermined third time period is between 1 hour and 15 hours. 20. The device of claim 16, wherein the predetermined number of blood glucose measurements is between 20 and 100. 21. The device of claim 16, wherein the method further comprises: responsive to receiving a request for an updated adjustment day dose recommendation performing a new recommendation procedure to determine the injection amount for the updated adjustment day dose recommendation wherein the updated adjustment day dose recommendation function is based upon at least a titration glucose level and a max basal limit. 22. The device of claim 21, wherein the titration glucose level comprises one of (i), (ii), or (iii): (i) the overall titration glucose level is greater than the upper limit target glucose range, (ii) the overall titration glucose level is greater than or equal to the lower target glucose range and the overall titration glucose level is less than or equal to the upper limit target glucose range, (iii) the daily titration glucose level is less than the lower target glucose range. 23. The device of claim 22, wherein the max basal limit consists of the overbasalisation limit multiplied by the body weight of the subject. 24. The device of claim 22, wherein when the overall titration glucose level is greater than the upper limit target glucose range of the subject and when the most recent adjustment day dose recommendation is less than the max basal limit of the subject, then the updated adjustment day dose recommendation is determined to be the determined dose guidance baseline plus a predetermined number of units of long-acting or ultra-long-acting insulin. 25. The device of claim 22, wherein when the overall titration glucose level is greater than the upper limit target glucose range of the subject and when the most recent adjustment day dose recommendation is greater than or equal to the max basal limit of the subject, then the updated adjustment day dose recommendation is determined to be the determined dose guidance baseline. 26. The device of claim 22, wherein when the overall titration glucose level is between the upper limit target glucose range of the subject and the lower target glucose range of the subject, then the updated adjustment day dose recommendation is determined to be the determined dose guidance baseline. 27. The device of claim 22, wherein when the daily titration glucose level is less than the lower target glucose range of the subject, then the updated adjustment day dose recommendation is determined to be the determined dose guidance baseline minus a predetermined number of units of long-acting or ultra-long-acting insulin. 28. The device according to claim 27, wherein the predetermined number of units of long-acting or ultra-long-acting insulin by which to alter the adjustment day dose recommendation is selected from the set of at least 1 unit, 2 units, 4 units, 6 units and 8 units. 29. The device of claim 1, wherein the method further comprises updating the dose guidance recommendation for the subject, unless the injection history of the subject comprises one or more injections of the subject that have injection timestamps within the immediately preceding 4 hours or less, the immediately preceding 8 hours or less, the immediately preceding 12 hours or less, or the immediately preceding 16 hours or less.

Details for Patent 10,335,464

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Novo Nordisk Inc.	TRESIBA	insulin degludec	Injection	203314	September 25, 2015		2038-06-27
Novo Nordisk Inc.	TRESIBA	insulin degludec	Injection	203314	November 21, 2018		2038-06-27