IP Library › Granted Patent US 9,856,306
Granted Patent B2
US 9,856,306 · App. 15/314,466 · Granted Jan 2, 2018

Peptide pharmaceuticals for insulin resistance

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Quick Facts
Patent No.
US 9,856,306
App. No.
15/314,466
Granted
Jan 2, 2018
Kind
B2
Abstract

Described herein are methods of syntheses and therapeutic uses of covalently modified peptides and/or proteins. The covalently modified peptides and/or proteins allow for improved pharmaceutical properties of peptide and protein-based therapeutics.

Claims (92)

1. A peptide product selected from the group consisting of:

1) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-tetradecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 819);

2) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-hexadecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 820);

3) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-octadecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 821);

4) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-dodecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-dodecyl beta-D-glucouronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1114);

5) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-tetradecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-tetradecyl beta-D-glucouronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1115);

6) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-hexadecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-hexadecyl beta-D-glucouronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1116);

7) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1117);

8) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1118);

9) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1119);

10) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 Ala 18 -Ala 19 -Lys* 20 Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1120);

11) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1121);

12) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(17-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1122);

13) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1102, EU-A1865);

14) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1103, EU-A1866);

15) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1104, EU-A1867);

16) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Gln 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1105, EU-A1868);

17) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Gln 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1106, EU-A1869);

and

18) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Gln 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1107, EU-A1870);

or a pharmaceutically acceptable salt thereof.

2. The peptide product of claim 1 , which is:

His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1119),

or a pharmaceutically acceptable salt thereof.

3. The peptide product of claim 1 , which is:

His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1121),

or a pharmaceutically acceptable salt thereof.

4. The peptide product of claim 1 , which is:

His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1122),

or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising a peptide product selected from the group consisting of:

1) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-tetradecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 819);

2) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-hexadecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 820);

3) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-octadecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 821);

4) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-dodecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-dodecyl beta-D-glucouronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1114);

5) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-tetradecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-tetradecyl beta-D-glucouronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1115);

6) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-hexadecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-hexadecyl beta-D-glucouronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1116);

7) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1117);

8) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1118);

9) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1119);

10) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 Ala 18 -Ala 19 -Lys* 20 Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1120);

11) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1121);

12) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(17-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1122);

13) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1102, EU-A1865);

14) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1103, EU-A1866);

15) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1104, EU-A1867);

16) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Gln 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1105, EU-A1868);

17) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Gln 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1106, EU-A1869);

and

18) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Gln 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1107, EU-A1870);

or a pharmaceutically acceptable salt thereof,

and at least one pharmaceutically acceptable carrier or excipient.

6. The pharmaceutical composition of claim 5 , wherein the peptide product is:

His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1119),

or a pharmaceutically acceptable salt thereof.

7. The pharmaceutical composition of claim 5 , wherein the peptide product is:

His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 3 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1121),

or a pharmaceutically acceptable salt thereof.

8. The pharmaceutical composition of claim 5 , wherein the peptide product is:

His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 3 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1122),

or a pharmaceutically acceptable salt thereof.

9. A method of treating a condition associated with insulin resistance, diabetes, metabolic syndrome or cardiovascular disease, comprising administering to a subject in need of treatment a therapeutically effective amount of a peptide product selected from the group consisting of:

1) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-tetradecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 819);

2) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-hexadecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 820);

3) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-octadecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 821);

4) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-dodecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-dodecyl beta-D-glucouronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1114);

5) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-tetradecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-tetradecyl beta-D-glucouronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1115);

6) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-hexadecyl alpha-D-melibiouronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-hexadecyl beta-D-glucouronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1116);

7) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1117);

8) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1118);

9) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1119);

10) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 Ala 18 -Ala 19 -Lys* 20 Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1120);

11) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1121);

12) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 13 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(17-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1122);

13) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1102, EU-A1865);

14) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1103, EU-A1866);

15) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1104, EU-A1867);

16) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Gln 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(13-carboxyl-tridecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1105, EU-A1868);

17) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Gln 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1106, EU-A1869);

and

18) His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Glu* 10 -Ser 11 -Lys 12 -Tyr 13 -Lys* 14 -Asp 15 -Ser 16 -Gln 17 -Ala 18 -Ala 19 -Gln 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1107, EU-A1870);

or a pharmaceutically acceptable salt thereof.

10. The method of claim 9 , wherein the peptide product is:

His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 3 -Leu 14 -Asp 15 -Glu* 16 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Gln 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1119),

or a pharmaceutically acceptable salt thereof.

11. The method of claim 10 , wherein the peptide product is:

His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 3 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 3 -Lys(N-omega(1-(15-carboxyl-pentadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1121),

or a pharmaceutically acceptable salt thereof.

12. The method of claim 10 , wherein the peptide product is:

His 1 -Aib 2 -Gln 3 -Gly 4 -Thr 5 -Phe 6 -Thr 7 -Ser 8 -Asp 9 -Tyr 10 -Ser 11 -Lys 12 -Tyr 3 -Leu 14 -Asp 15 -Glu* 16 -Gln 17 -Ala 18 -Ala 19 -Lys* 20 -Glu 21 -Phe 22 -Ile 23 -Lys(N-omega(1-(17-carboxyl-heptadecyloxy)beta-D-glucuronyl)) 24 -Trp 25 -Leu 26 -Leu 27 -Gln 28 -Thr 29 -NH 2   (SEQ. ID. NO. 1122),

or a pharmaceutically acceptable salt thereof.

13. The method of claim 10 , wherein the peptide product causes weight loss.

Assignments (5)
SECURITY INTEREST Recorded May 14, 2025
From: ALTIMMUNE, INC.; SPITFIRE PHARMA, LLC
To: HERCULES CAPITAL, INC., AS AGENT
Reel/Frame 071108/0692 →
AFFIDAVIT OF ADDRESS CHANGE Recorded Feb 19, 2025
From: MEDERIS DIABETES, LLC
To: MEDERIS DIABETES LLC
Reel/Frame 070266/0875 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 20, 2019
From: SPITFIRE PHARMA INC.
To: MEDERIS DIABETES INC.
Reel/Frame 049809/0931 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 20, 2017
From: NESTOR, JOHN J.
To: SPITFIRE PHARMA, INC.
Reel/Frame 044182/0962 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 20, 2017
From: NESTOR, JOHN J.
To: SPITFIRE PHARMA, INC.
Reel/Frame 044183/0041 →