IP Library › Granted Patent US 12,466,883
Granted Patent B1
US 12,466,883 · App. 19/207,094 · Granted Nov 11, 2025

Leptin compositions and methods of making and using the same to support weight loss and/or maintenance

Inventors: James Michael Roberts (Seattle, WA); Mesfin Mulugeta Gewe (Bothell, WA); Uland Lau (Redmond, WA); Mark Heinnickel (Seattle, WA); Michael Dodds (Normandy Park, WA); David Bolick (Whitewater, CO); Nhi Yen Khuong (Kenmore, WA); Hannah Tabakh (Seattle, WA); Brian Finrow (Seattle, WA); Jennifer Lynn Wierman (Ithaca, NY)
Assignee: LUMEN BIOSCIENCE, INC.
C07K16/26A61K9/0053A61P3/04A61K38/00
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Quick Facts
Patent No.
US 12,466,883
App. No.
19/207,094
Granted
Nov 11, 2025
Kind
B1
Abstract

Provided are compositions comprising leptin and methods of using the same to support weight loss. Also provided are modified leptins, including recombinant leptins, and methods of making and using the same.

Claims (29)

1 . A recombinant leptin receptor agonist comprising an amino acid sequence having at least about 80% sequence identity with SEQ ID NO: 56.

2 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist having at least about 80% sequence identity with SEQ ID NO: 56 comprises an activity improving amino acid selected from the group consisting of 4E, 5Q, 6I, 10L, 17V, 18I, 22D, 25P, 27V, 32P, 40E, 49I, 51Y, 53D, 54A, 66S, 67L, 70E, 71P, 74Q, 77A, 78L, 83I, 88R, 97P, 106D, 116E, 121V, 124T, 125T, 130K, 132F, 139E, and combinations thereof, wherein the positions are determined by alignment with SEQ ID NO: 56.

3 . The recombinant leptin receptor agonist of claim 2 , wherein the recombinant leptin receptor agonist comprises at least 5 of the recited activity improving amino acids.

4 . The recombinant leptin receptor agonist of claim 2 , wherein the recombinant leptin receptor agonist comprises at least 10 of the recited activity improving amino acids.

5 . The recombinant leptin receptor agonist of claim 2 , wherein the recombinant leptin receptor agonist comprises at least 15 of the recited activity improving amino acids.

6 . The recombinant leptin receptor agonist of claim 2 , wherein the recombinant leptin receptor agonist comprises all of the recited activity improving amino acids.

7 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist does not comprise an activity-reducing amino acid substitution selected from the group consisting of D9E, L13Q, T16N, T16K, R20N, R20K, K33D, K33E, K33N, Q34L, Q34K, Q34I, K35V, V36I, T37E, Q75E, Q75T, S117R, S117Q, Y119E, Y119K, Y119D, S120E, S120K, and S120D.

8 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist does not comprise any activity-reducing amino acid substitutions selected from the group consisting of D9E, L13Q, T16N, T16K, R20N, R20K, K33D, K33E, K33N, Q34L, Q34K, Q34I, K35V, V36I, T37E, Q75E, Q75T, S117R, S117Q, Y119E, Y119K, Y119D, S120E, S120K, and S120D.

9 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist having at least about 80% sequence identity with SEQ ID NO: 56 comprises an amino acid selected from the group consisting of D9, L13, T16, R20, K33, Q34, K35, V36, T37, Q75, D85, L86, S117, Y119, and $120.

10 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist having at least about 80% sequence identity with SEQ ID NO: 56 comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 of the amino acids selected from the group consisting of D9, L13, T16, R20, K33, Q34, K35, V36, T37, Q75, D85, L86, S117, Y119, S120, and combination thereof.

11 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist having at least about 80% sequence identity with SEQ ID NO: 56 comprises D9, L13, T16, R20, K33, Q34, K35, V36, T37, Q75, D85, L86, S117, Y119, and S120.

12 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist is comprised within a chimeric protein, said chimeric protein comprising a protein fusion partner.

13 . The recombinant leptin receptor agonist of claim 12 , wherein the protein fusion partner is N-terminally translationally fused to the recombinant leptin receptor agonist.

14 . The recombinant leptin receptor agonist of claim 12 , wherein the protein fusion partner is C-terminally translationally fused to the recombinant leptin receptor agonist.

15 . The recombinant leptin receptor agonist of claim 12 , wherein the protein fusion partner is a protein purification tag or solubility enhancer.

16 . The recombinant leptin receptor agonist of claim 15 , wherein the protein purification tag or solubility enhancer is selected from the group consisting of a maltose binding protein (MBP), thioredoxin (TRX), a histidine tag, a green fluorescent protein (GFP), a glutathione S-transferase (GST), a FLAG tag, a tag comprising the amino acid peptide sequence of SEQ ID NO: 91 (WSHPQFEK), and a HA tag.

17 . The recombinant leptin receptor agonist of claim 15 , wherein the solubility enhancer is MBP.

18 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist having at least about 80% sequence identity with SEQ ID NO: 56 induces higher weight loss when administered to an overweight animal compared to SEQ ID NO: 63.

19 . The recombinant leptin receptor agonist of claim 18 , wherein at least 80% of the weight loss is body fat mass.

20 . The recombinant leptin receptor agonist of claim 18 , wherein less than 20% of the weight loss is lean mass.

21 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist having at least about 80% sequence identity with SEQ ID NO: 56 results in a lower food intake by an overweight animal receiving the recombinant leptin receptor agonist compared to SEQ ID NO: 63.

22 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist having at least about 80% sequence identity with SEQ ID NO: 56 exhibits higher thermostability compared to SEQ ID NO: 63.

23 . The recombinant leptin receptor agonist of claim 18 , wherein the animal is a mouse.

24 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist is comprised within a biological cell.

25 . The recombinant leptin receptor agonist of claim 24 , wherein the biological cell is an Escherichia coli cell.

26 . The recombinant leptin receptor agonist of claim 24 , wherein the biological cell is Spirulina.

27 . The recombinant leptin receptor agonist of claim 1 , wherein the recombinant leptin receptor agonist is comprised within a composition comprising a protease inhibitor and/or proteinase inhibitor.

28 . A method comprising orally administering a therapeutically effective dose of the recombinant leptin receptor agonist of claim 1 to an individual in need thereof.

29 . A recombinant leptin receptor agonist comprising an amino acid sequence having at least 95% sequence identity with a sequence selected from the group consisting of SEQ ID NO: 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, and 64.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 24, 2025
From: ROBERTS, JAMES MICHAEL; GEWE, MESFIN MULUGETA; LAU, ULAND; HEINNICKEL, MARK; DODDS, MICHAEL; BOLICK, DAVID; KHUONG, NHI YEN; TABAKH, HANNAH; FINROW, BRIAN; WIERMAN, JENNIFER LYNN
To: LUMEN BIOSCIENCE, INC.
Reel/Frame 072362/0983 →
Continuity (1)
Provisional Application 63646354 · May 13, 2024
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