US 12,187,773 B2
Modified GIP peptide analogues
Alexander Hovard Sparre-Ulrich, Copenhagen N (DK); Bjørn Behrens Sivertsen, Copenhagen S (DK); Ditte Riber, Brønshøj (DK); and Mette Marie Rosenkilde, Hellerup (DK)
Assigned to Antag Therapeutics ApS, Copenhagen N (DK)
Appl. No. 17/298,444
Filed by Antag Therapeutics ApS, Copenhagen N (DK)
PCT Filed Dec. 3, 2019, PCT No. PCT/EP2019/083509
§ 371(c)(1), (2) Date May 28, 2021,
PCT Pub. No. WO2020/115049, PCT Pub. Date Jun. 11, 2020.
Claims priority of application No. 18209896 (EP), filed on Dec. 3, 2018; and application No. 19176739 (EP), filed on May 27, 2019.
Prior Publication US 2022/0025010 A1, Jan. 27, 2022
Int. Cl. C07K 14/605 (2006.01); A61K 38/00 (2006.01); C07K 14/645 (2006.01)
CPC C07K 14/605 (2013.01) [C07K 14/645 (2013.01); A61K 38/00 (2013.01)] 16 Claims
 
1. A glucose-dependent insulinotropic peptide (GIP) analogue selected from the group consisting of:
(a) a GIP analogue consisting of the amino acid sequence of SEQ ID NO: 1:
3   4   5   6   7   8   9  10  11  12  13  14  
X1 - G - T - F - I - S - D - Y - S - I - A - M -
 
15  16  17  
  D - R - I  
 
18  19  20  21  22  23  24  25  26  27  28  29  30  
X2 - Q - Q - D - F - V - N - W - L - L - A - Q - X3  
wherein said amino acid residue X1 is P, G, A, S, or pyroE (pyroglutamic acid),
wherein said amino acid X2 is K or Orn, and
wherein said amino acid X3 is R or E,
or a functional variant thereof, wherein said functional variant has 1 to 4 individual amino acid substitutions at any one of the amino acid residues at positions 4 to 15, 17 and 19 to 29 of SEQ ID NO: 1,
wherein said amino acid sequence is modified by attaching a fatty acid molecule at the amino acid at position 18 of SEQ ID NO: 1 or said functional variant thereof, and wherein said GIP analogue is an antagonist of GIP receptor (GIPR); and
(b) a GIP analogue consisting of the amino acid sequence of SEQ ID NO: 11:
3   4   5   6   7   8   9  10  11  12  13  14  
X1 - G - T - F - I - S - D - Y - S - I - A - M -
 
15  16  17  
  D - R - I  
 
18  19  20  21  22  23  24  25  26  27  28  29  30  
X2 - Q - Q - D - F - V - N - W - L - L - A - Q - X3  
wherein said amino acid X2 is K or Orn, and
wherein said amino acid X3 is R or E,
or a functional variant thereof having 1 to 4 individual amino acid substitutions at any one of the amino acid residues at positions 4 to 17 and 19 to 29 of SEQ ID NO: 11,
wherein said peptide amino acid sequence is modified by attaching a fatty acid molecule at the amino acid at position 18 of SEQ ID NO: 11, or a functional variant thereof, and wherein said GIP analogue is an antagonist of GIPR; and
(c) a GIP analogue consisting of the amino acid sequence of SEQ ID NO: 12:
3   4   5   6   7   8   9  10  11  12  13  14  
E - G - T - F - I - S - E - Y - S - I - A - M -
 
15  16  17  
 E - K - I  
 
18  19  20  21  22  23  24  25  26  27  28  29  30  
X2 - Q - Q - E - F - V - Q - W - L - L - A - Q - K  
wherein said amino acid X2 is K or Orn,
or a functional variant thereof having 1 to 4 individual amino acid substitutions at any one of positions 3 to 30 of SEQ ID NO: 12,
wherein said amino acid sequence is modified by attaching a fatty acid molecule at the amino acid at position 18 of SEQ ID NO: 12, or said functional variant thereof, and wherein said GIP analogue is an antagonist of GIPR.