US 11,993,637 B2
Modified FGF-21 polypeptides with non-naturally encoded amino acids
Thomas P. Cujec, San Diego, CA (US); Roberto Mariani, San Diego, CA (US); Anna-Maria A. Hays Putnam, San Diego, CA (US); William M. Keefe, Los Angeles, CA (US); Nick Knudsen, Escondido, CA (US); Lillian Skidmore, San Diego, CA (US); Jason Pinkstaff, Carlsbad, CA (US); and Vadim Kraynov, San Diego, CA (US)
Assigned to AMBRX, INC.
Filed by AMBRX, INC., La Jolla, CA (US)
Filed on Feb. 2, 2021, as Appl. No. 17/165,351.
Application 17/165,351 is a division of application No. 16/443,226, filed on Jun. 17, 2019, granted, now 10,961,291.
Application 16/443,226 is a division of application No. 15/953,091, filed on Apr. 13, 2018, granted, now 10,377,805, issued on Aug. 13, 2019.
Application 15/953,091 is a division of application No. 15/292,700, filed on Oct. 13, 2016, granted, now 9,975,936, issued on May 22, 2018.
Application 15/292,700 is a division of application No. 14/680,543, filed on Apr. 7, 2015, granted, now 9,517,273, issued on Dec. 13, 2016.
Application 14/680,543 is a division of application No. 13/732,522, filed on Jan. 2, 2013, granted, now 9,079,971, issued on Jul. 14, 2015.
Application 13/732,522 is a division of application No. 13/051,953, filed on Mar. 18, 2011, granted, now 8,383,365, issued on Feb. 26, 2013.
Application 13/051,953 is a division of application No. 12/051,830, filed on Mar. 19, 2008, granted, now 8,012,931, issued on Sep. 16, 2011.
Claims priority of provisional application 60/988,060, filed on Nov. 14, 2007.
Claims priority of provisional application 60/921,297, filed on Mar. 30, 2007.
Prior Publication US 2021/0261637 A1, Aug. 26, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 14/50 (2006.01); A61K 38/00 (2006.01); A61K 38/18 (2006.01); A61K 45/06 (2006.01); A61K 47/60 (2017.01); C12N 15/70 (2006.01)
CPC C07K 14/50 (2013.01) [A61K 38/1825 (2013.01); A61K 45/06 (2013.01); A61K 47/60 (2017.08); C12N 15/70 (2013.01); A61K 38/00 (2013.01); Y02A 50/30 (2018.01)] 20 Claims
 
1. A modified FGF-21 polypeptide comprising a non-naturally encoded amino acid,
wherein said modified FGF-21 polypeptide maintains the biological activity of human FGF-21 and comprises a non-naturally encoded amino acid, and:
(a) the modified FGF-21 polypeptide comprises a sequence at least 95% identical to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, or SEQ ID NO: 7;
(b) the non-naturally encoded amino acid has the structure:

OG Complex Work Unit Chemistry
wherein the R group is any substituent other than the side chain found in alanine, arginine, asparagine, aspartic acid, cysteine, glutamine, glutamic acid, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine, pyrrolysine, or selenocysteine;
(c) the modified FGF-21 polypeptide contains a substitution of an amino acid with the non-naturally encoded amino acid at a position in said modified FGF-21 polypeptide corresponding to residue 72, 77, 86, 108, 110, 131, or 146 of SEQ ID NO: 1;
(d) the non-naturally encoded amino acid is linked to a linker or a polymer; and
(e) the FGF-21 polypeptide has an in vivo half-life which is at least two-fold greater than the human FGF-21 polypeptide in SEQ ID NO: 1.