Polymer conjugates of GLP-1
View Patent ↗Conjugates of a GLP-1 moiety may be covalently attached to one or more water-soluble polymers. For instance, a GLP-1 polymer conjugate may include a GLP-1 moiety releasably attached at its N-terminus to a water-soluble polymer. The GLP-1 polymer conjugate may include a GLP-1 moiety covalently attached to a water-soluble polymer, wherein the GLP-1 moiety possesses an N-methyl substituent.
1. A GLP-1 polymer conjugate comprising a GLP-1 moiety releasably attached at an amine to a water-soluble polymer, wherein the conjugate is formed by contacting the GLP-1 moiety with a polymeric reagent of the following structure:
where:
POLY 1 is a first water-soluble polymer;
POLY 2 is a second water-soluble polymer;
X 1 is a first spacer moiety;
X 2 is a second spacer moiety;
H α is an ionizable hydrogen atom;
R 1 is H or an organic radical;
R 2 is H or an organic radical; and
(FG) is a functional group capable of reacting with an amino group of the GLP-1 moiety.
2. The GLP-1 polymer conjugate of claim 1 , wherein each of the first water-soluble polymer and second water-soluble polymer is independently selected from poly(alkylene glycol), poly(oxyethylated polyol), poly(olefinic alcohol), poly(vinylpyrrolidone), poly(hydroxyalkylmethacrylamide), poly(hydroxyalkylmethacrylate), poly(saccharide), poly(α-hydroxy acid), poly(vinyl alcohol), polyphosphazene, polyoxazoline, poly(N-acryloylmorpholine), and copolymers and terpolymers thereof.
3. The GLP-1 polymer conjugate of claim 2 , wherein each of the first water-soluble polymer and second water-soluble polymer is a polyethylene glycol.
4. The GLP-1 polymer conjugate of claim 1 , wherein the releasably attached GLP-1 moiety is releasably attached via a linker selected from carbamate, carboxylate ester, phosphate ester, anhydride, acetal, ketal, acyloxyalkyl ether, imine, orthoester, thioester, thiolester, and carbonate.
5. The GLP-1 polymer conjugate of claim 1 , wherein the releasably attached GLP-1 moiety is releasably attached via a linker selected from carbamate, carboxylate ester, and carbonate.
6. The GLP-1 polymer conjugate of claim 1 , wherein each of the first water-soluble polymer and second water-soluble polymer has a molecular weight ranging from about 500 daltons to about 80,000 daltons.
7. The GLP-1 polymer conjugate of claim 6 , wherein each of the first water-soluble polymer and second water-soluble polymer has a molecular weight ranging from about 1000 daltons to about 40,000 daltons.
8. The GLP-1 polymer conjugate of claim 1 , wherein the GLP-1 moiety is glycosylated.
9. The GLP-1 polymer conjugate of claim 1 , wherein the GLP-1 moiety possesses an N-methyl substituent.