US 12,077,561 B2
CNP compounds
Jakob Ewald, Koebenhavn N (DK); Anne Louise Bank Kodal, Frederiksberg (DK); Jonas Alfred Karl Wilbs, Ballerup (DK); Christian Poulsen, Ballerup (DK); Peter Madsen, Bagsvaerd (DK); Kilian Waldemar Conde Frieboes, Maaloev (DK); and Christian Wenzel Tornoee, Lyngby (DK)
Assigned to Novo Nordisk A/S, Bagsvaerd (DK)
Filed by Novo Nordisk A/S, Bagsvaerd (DK)
Filed on Nov. 1, 2023, as Appl. No. 18/385,946.
Claims priority of application No. 22205128 (EP), filed on Nov. 2, 2022.
Prior Publication US 2024/0209028 A1, Jun. 27, 2024
Int. Cl. C07K 14/00 (2006.01)
CPC C07K 14/001 (2013.01) 13 Claims
 
1. A C-type natriuretic (CNP) compound comprising a CNP peptide and a modifying group;
wherein the net charge of the compound at physiological pH is 0 or negative;
wherein the amino acid sequence of the CNP peptide is:
AA01-AA02-AA03-AA04-AA05-AA06-AA07-AA08-AA09-AA10-AA11-AA12-AA13-AA14-AA15-AA16-AA17-AA18-AA19-AA20-AA21-AA22-AA23-AA24-AA25-AA26-AA27-AA28-AA29-AA30-AA31-AA32-AA33-AA34-AA35-AA36-AA37;
wherein:
AA01 is Gln or absent,
AA02 is Glu or absent,
AA03 is His or absent,
AA04 is Pro or absent,
AA05 is Asn or Gln or Glu or absent,
AA06 is Ala or absent,
AA07 is Arg or His or Ala or absent,
AA08 is Lys or Ser or His or absent,
AA09 is Tyr or Glu or absent,
AA10 is Lys or Glu or Gln or His or absent,
AA11 is Gly,
AA12 is Ala,
AA13 is Gln,
AA14 is Lys or His or Glu,
AA15 is Lys or Ser or Glu or Thr or His,
AA16 is Gly,
AA17 is Leu or Gly or Ser or Val,
AA18 is Ser or His
AA19 is Gln or Ser,
AA20 is Gly,
AA21 is Cys,
AA22 is Phe,
AA23 is Gly,
AA24 is Leu,
AA25 is Pro,
AA26 is Leu,
AA27 is Asp or Glu,
AA28 is Arg,
AA29 is Ile,
AA30 is Gly,
AA31 is Ser,
AA32 is Leu,
AA33 is Ser,
AA34 is Gly,
AA35 is Leu,
AA36 is Gly, and
AA37 is Cys;
wherein the modifying group comprises Chem A, Chem B, and Chem C;
wherein Chem A is

OG Complex Work Unit Chemistry
wherein p is an integer in the range of 14-20, and
wherein * denotes an amide bond connecting Chem A and Chem B;
wherein Chem B is

OG Complex Work Unit Chemistry
wherein q is an integer in the range of 1-8,
wherein * denotes an amide bond connecting Chem A- and Chem B-, and
wherein ** denotes an amide bond connecting Chem B- and Chem C-; and
wherein Chem C is selected from the group consisting of:

OG Complex Work Unit Chemistry
wherein r is an integer in the range of 0-4,
wherein s is an integer in the range of 0-3,
wherein t is an integer in the range of 0-1,
wherein u is an integer in the range of 0-3,
wherein ** denotes an amide bond connecting Chem B- and Chem C-, and
wherein *** denotes an amide bond connecting Chem C- and the N-terminal alpha-amine on the CNP peptide.