US 12,214,018 B2
Glucose responsive insulins
Alborz Mahdavi, Pasadena, CA (US)
Assigned to PROTOMER TECHNOLOGIES, INC., Indianapolis, IN (US)
Filed by PROTOMER TECHNOLOGIES, INC., Pasadena, CA (US)
Filed on May 21, 2021, as Appl. No. 17/327,498.
Application 17/327,498 is a division of application No. 15/571,496, granted, now 11,052,133, previously published as PCT/US2016/031361, filed on May 6, 2016.
Claims priority of provisional application 62/157,897, filed on May 6, 2015.
Prior Publication US 2021/0369815 A1, Dec. 2, 2021
Int. Cl. A61K 38/28 (2006.01); A61K 31/70 (2006.01); A61K 38/26 (2006.01); A61K 47/64 (2017.01); A61P 3/10 (2006.01); C07K 14/62 (2006.01); C12N 9/12 (2006.01); A61K 38/00 (2006.01)
CPC A61K 38/28 (2013.01) [A61K 31/70 (2013.01); A61K 38/26 (2013.01); A61K 47/643 (2017.08); A61P 3/10 (2018.01); C07K 14/62 (2013.01); C12N 9/1205 (2013.01); A61K 38/00 (2013.01); C07K 2319/00 (2013.01); C07K 2319/30 (2013.01); C07K 2319/31 (2013.01); C12Y 207/01001 (2013.01)] 15 Claims
 
1. An insulin molecule comprising insulin, an insulin analogue, glucagon, GLP-1, GLP-2, or a GLP-1 agonist, the insulin molecule containing one or more artificial amino acids independently selected from F26-F41:

OG Complex Work Unit Chemistry

OG Complex Work Unit Chemistry
wherein:
each R1 is independently selected from —H, —NH2, —NO2, —Cl, —CF3, —I, —COCH3, —CN, —C═CH, —N3, or —Br,
each R2 is independently selected from —CF3, —H, or —CH3;
each R3 is independently selected from —C═CH, —H, —N3, or vinyl group;
each R4 is independently selected from R2 or R3,
each R5 is independently selected from —S— or —NH—; and
wherein if R1 or R3 is —N3 the one or more artificial amino acids is independently covalently conjugated using click chemistry to an alkyne functional group, and if R1 or R3 is —C═CH the one or more artificial amino acids is independently covalently conjugated using click chemistry to a terminal azide functional group, or alternatively R1, R2, R3, R4, or R5 is independently covalently conjugated using native chemical ligation, biorthogonal reactions, click chemistry, cycloaddition reactions, strain-promoted Alkyne-Nitrone Cycloadditions, Strained Alkenes, Alkene and Tetrazine inverse-demand Diels-Alder, Copper (I)-Catalyzed Azide-Alkyne Cycloaddition (CuAAC), Strain-promoted Azide-Alkyne Cycloaddition, Staudinger ligation, nucleophilic ring-opening reaction or additions to carbon-carbon multiple bonds.