US 11,773,150 B2
Antibody peptide conjugates that have agonist activity at both the glucagon and glucagon-like peptide 1 receptors
Paul E. Carrington, San Mateo, CA (US); Grigori Ermakov, Santa Clara, CA (US); Robert M. Garbaccio, Lansdale, PA (US); Wolfgang Seghezzi, Mountain View, CA (US); Elisabetta Bianchi, Pomezia (IT); Federica Orvieto, Pomezia (IT); Dennis Gately, San Diego, CA (US); Nick Knudsen, Escondido, CA (US); and Anthony Manibusan, San Diego, CA (US)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US); and Ambrx, Inc., La Jolla, CA (US)
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US); and Ambrx, Inc., La Jolla, CA (US)
Filed on Aug. 27, 2020, as Appl. No. 17/4,395.
Application 17/004,395 is a division of application No. 15/765,505, granted, now 10,800,826, previously published as PCT/US2016/055265, filed on Oct. 4, 2016.
Claims priority of provisional application 62/237,009, filed on Oct. 5, 2015.
Prior Publication US 2020/0392197 A1, Dec. 17, 2020
Int. Cl. C07K 14/605 (2006.01); C07K 16/26 (2006.01); C07K 16/28 (2006.01); A61K 47/68 (2017.01); A61P 3/10 (2006.01); A61K 39/00 (2006.01)
CPC C07K 14/605 (2013.01) [A61K 47/6811 (2017.08); A61K 47/6843 (2017.08); A61P 3/10 (2018.01); C07K 16/26 (2013.01); C07K 16/2869 (2013.01); A61K 2039/505 (2013.01); C07K 2317/75 (2013.01); C07K 2319/00 (2013.01)] 7 Claims
 
1. An antibody peptide conjugate comprising an antibody having a light chain having the amino acid sequence of SEQ ID NO:64 and a heavy chain having the amino acid sequence of SEQ ID NO:65 conjugated to a peptide having the amino acid sequence
 
 (SEQ ID NO: 63)
 
 His-Xaa2-Gln-Gly-Thr-Phe-Thr-Ser-Asp-
 
 
 
 Xaa10-Ser-Xaa12-Tyr-Leu-Asp-Xaa16-Arg-
 
 
 
 Ala-Ala-Xaa20-Asp-Phe-Val-Xaa24-Xaa25-
 
 
 
 Xaa26-Xaa27-Xaa28-Xaa29-Lys-Xaa31 
wherein
Xaa2 is α-aminoisobutyric acid (aib) or D-Ser;
Xaa 16 is aib;
Xaa31 is Lys;
Xaa10 is Tyr;
X12 is Lys;
Xaa20 is Gln;
Xaa24 is Gln;
Xaa25 is Trp;
Xaa26 is Leu;
Xaa27 is Met;
Xaa28 is Asp;
Xaa29 is Thr;
wherein Lys31 is covalently linked at its epsilon amino group to an aminooxy acid residue;
wherein either the light chain includes a substitution of the amino acid at position 125 or 142 with a para-acetylphenylalanine (pAcF) or the heavy chain includes a substitution of the amino acid a position 16, 32, 33, 56, 114, 179, 198, or 211 with a AcF; and
wherein the aminooxy acid residue of the peptide is covelantly linked to the pAcF residue of the antibody.