US2022226425A1PendingUtilityA1
Method of treating melanocortin-4 receptor pathway-associated disorders
Est. expirySep 30, 2035(~9.2 yrs left)· nominal 20-yr term from priority
C07K 7/54C07K 14/685C07K 7/06A61P 3/04A61K 9/0019A61K 38/12A61P 3/10C07K 14/723A61K 38/00
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Claims
Abstract
The disclosure is related to a method of treating a disorder, such as obesity or a condition associated with obesity, such as hyperphagia, in a subject using a melanocortin-4 receptor (MC4R) agonist.
Claims
exact text as granted — not AI-modified1 . A compound of formula I:
where Xxx is Asn, Gln, Ser, or Thr,
where A 1 is H or Ac,
where A 2 is OH or NH 2 , and
where Yyy is Lys, Arg, D-Lys, or D-Arg, or
a pharmaceutically acceptable salt, single stereoisomer, mixture of stereoisomers, ester, tautomer or prodrug thereof.
2 . The compound of claim 1 wherein the compound is a compound of Formula II.
where Xxx is Asn, Gln, Ser, or Thr,
where A 1 is H or Ac,
where A 2 is OH or NH 2 , and
where Yyy is Lys, Arg, D-Lys, or D-Arg.
3 . The compound of formula 1 wherein the compound comprises the sequence of any of SEQ ID NOs:1-64.
4 . A pharmaceutical composition comprising a compound of any of claims 1 - 3 and a pharmaceutically acceptable carrier.
5 . A unit dosage any of the compounds of claims 1 - 3 , wherein the unit dosage contains 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 100 mg of the compound.
6 . The unit dosage of claim 5 , which contains 0.5 mg, 1.0 mg, or 1.5 mg of the compound.
7 . The unit dosage of any of claims 5 - 6 , suitable for injection, e.g., subcutaneous injection.
8 . The unit dosage of any of claims 5 - 7 , disposed in a delivery device suitable for injection, e.g., subcutaneous injection.
9 . A method of treating a condition or disorder in a subject in need thereof, comprising administering a therapeutically effective amount of an MC4R agonist of any of claims 1 - 3 .
10 . The method of claim 9 , comprising eliciting an agonist effect from a melanocortin receptor in the subject.
11 . The method of claim 9 , wherein administering the MC4R agonist elicits an agonist effect from the melanocortin receptor in the subject.
12 . The method of claim 9 , wherein the disorder is a metabolic disease or medical condition accompanied by weight gain such as obesity, feeding disorders or Prader-Willi Syndrome.
13 . The method of claim 9 , wherein the MC4R agonist is administered in an amount sufficient to decrease food intake, decrease body weight, or both, in the subject.
14 . The method of claim 9 , wherein the MC4R agonist is administered in an amount sufficient to decrease appetite in the subject without compromising body weight.
15 . The method of claim 9 , wherein the MC4R agonist is administered in amount sufficient to ameliorate or improve a clinical symptom of obesity, type-II diabetes, a pre-diabetic condition, a blood level of hemoglobin A1C (Hb1Ac) above 6%, hyperinsulimenia, hyperlipidemia, insulin insensitivity, or glucose intolerance; aspects of metabolic syndrome, delaying, inhibiting or preventing the progression of obesity and/or obesity related indications; or partially or totally delaying, inhibiting or preventing the onset or development of obesity or a obesity related indication.
16 . The method of claim 9 , wherein the condition or disorder is obesity or a disorder associated with obesity, e.g., Prader-Willi Syndrome, decreasing food intake in a subject in need thereof, or decreasing body weight.
17 . The method of any of the preceding claims, comprising administering the agonist in a unit dosage suitable for injection, e.g., subcutaneous injection, to the subject.
18 . The method of claim 6 , wherein the unit dosage is disposed within a delivery device, e.g., a syringe (e.g., prefilled syringe),an implantable device, a needleless hypodermic injection device, an infusion pump (e.g., implantable infusion pump), or an osmotic delivery system.
19 . The method of any of the preceding claims, wherein the agonist is administered subcutaneously, e.g., by subcutaneous injection.
20 . The method of any of the preceding claims, wherein the agonist is administered daily over a period of at least 3 weeks, e.g., at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 weeks or more, or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 months or more, or at least 1, 2, 3, 4 years or more.
21 . The method of any of the preceding claims wherein administration of the compound decreases body weight in the subject.
22 . The method of any of the preceding claims, wherein the subject is obese, e.g., severely obese.
23 . The method of any of the preceding claims, wherein the subject has early onset severe obesity.
24 . The method of any of the preceding claims, wherein the subject is hyperphagic.
25 . The method of any of the preceding claims, wherein the subject has a body mass index (BMI) greater than 25 kg/m 2 (e.g., ≥25, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 kg/m 2 or greater) prior to administration of the agonist, e.g., at the time the agonist is prescribed, or at the time of the first administration.
26 . The method of any of the preceding claims, wherein the subject has failed one or more previous therapies, e.g., exercise, diet, bariatric surgery or vertical banded gastroplasty, or behavioral therapies, prior to administration of the agonist, e.g., at the time the agonist is prescribed, or at the time of the first administration.
27 . The method of any of the preceding claims, wherein administration of the agonist results in a reduction of food intake by the subject compared to a control (e.g., the food intake of the subject prior to treatment), e.g., wherein the food intake is daily food intake over a period of 24 hours, or one week.
28 . The method of any of the preceding claims, wherein the agonist comprises the sequence
001554C
(SEQ ID NO: 1)
Ac-Arg-(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH 2
001555C
(SEQ ID NO: 2)
Ac-Arg-(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH 2
001556C
(SEQ ID NO: 3)
Ac-Arg-(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH 2
001574C:
(SEQ ID NO: 4)
Ac-Arg-(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH 2
001576C:
(SEQ ID NO: 5)
Ac-Arg-(Glu-Gln-D-Phe-Arg-Trp-Apr)-NH 2
(SEQ ID NO: 6)
Ac-Arg-(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 7)
H-Arg-(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 8)
H-Arg-(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 9)
Ac-D-Arg-(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 10)
H-D-Arg-(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 11)
Ac-D-Arg-(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 12)
H-D-Arg-(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 13)
Ac-Lys-(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 14)
Ac-Lys-(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 15)
H-Lys-(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 16)
H-Lys-(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 17)
Ac-D-Lys-(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 18)
H-D-Lys-(hCys-Asn-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 19)
Ac-D-Lys-(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 20)
H-D-Lys-(hCys-Asn-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 21)
Ac-Arg-(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 22)
H-Arg-(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 23)
H-Arg-(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 24)
Ac-D-Arg-(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 25)
H-D-Arg-(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 26)
Ac-D-Arg-(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 27)
H-D-Arg-(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 28)
Ac-Lys-(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 29)
Ac-Lys-(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 30)
H-Lys-(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 31)
H-Lys-(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 32)
Ac-D-Lys-(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 33)
H-D-Lys-(hCys-Gln-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 34)
Ac-D-Lys-(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 35)
H-D-Lys-(hCys-Gln-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 36)
Ac-Arg-(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 37)
H-Arg-(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 38)
H-Arg-(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 39)
Ac-D-Arg-(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 40)
H-D-Arg-(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 41)
Ac-D-Arg-(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 42)
H-D-Arg-(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 43)
Ac-Lys-(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 44)
Ac-Lys-(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 45)
H-Lys-(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 46)
H-Lys-(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 47)
Ac-D-Lys-(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 48)
H-D-Lys-(hCys-Ser-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 49)
Ac-D-Lys-(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 50)
H-D-Lys-(hCys-Ser-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 51)
Ac-Arg-(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 52)
H-Arg-(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 53)
H-Arg-(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 54)
Ac-D-Arg-(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 55)
H-D-Arg-(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 56)
Ac-D-Arg-(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 57)
H-D-Arg-(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 58)
Ac-Lys-(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 59)
Ac-Lys-(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 60)
H-Lys-(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 61)
H-Lys-(hCys-Thr-D-Phe-Arg-Trp-Pen)-OH
(SEQ ID NO: 62)
Ac-D-Lys-(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 63)
H-D-Lys-(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH 2
(SEQ ID NO: 64)
Ac-D-Lys-(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH2
or
(SEQ ID NO: 65)
H-D-Lys-(hCys-Thr-D-Phe-Arg-Trp-Pen)-NH 2 .Join the waitlist — get patent alerts
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