Insulin-oligomer conjugates, formulations and uses thereof

1. An insulin compound coupled to a modifying moiety having a formula:

—X—R 1 —Y-PAG-Z—R 2   (Formula VI)

where,

X, Y and Z are independently selected linking groups and Y and Z are each optionally present and if present is —O—, and X is —C(O)—, and wherein the linking group X is coupled to the insulin compound by a covalent bond;

R 1 and R 2 are present and are a lower alkyl of C 1 to C 5 ;

PAG is a linear or branched carbon chain incorporating one or more alkylene glycol moiety wherein the alkylene glycol moiety is a substantially monodispersed PEG molecule having a formula (CH 2 CH 2 O) n , wherein n is 2-7,

wherein the insulin is mammalian or an insulin analog thereof and wherein the modifying moiety is coupled to a lysine residue at position B28, B29 or B30 of insulin, wherein the modifying moiety has the following formula:

where n is 2 to 7, and m is 2 to 5 thereby providing a monoconjugate.

2. The insulin compound conjugate of claim 1 , wherein the modifying moiety is selected to render the insulin compound conjugate equally as soluble or more soluble than a corresponding unconjugated insulin compound.

3. The insulin compound conjugate of claim 1 wherein the water solubility of the insulin compound conjugate is decreased by addition of the zinc.

4. A method of treating an insulin deficiency in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an insulin compound of claim 1 .

5. The method of claim 4 wherein the insulin deficiency has a cause comprising:

diabetes;

pre-diabetes; or

metabolic syndrome.

6. The method of claim 4 wherein the insulin compound is administered to effect post-prandial glucose control.

7. The method of claim 4 wherein the insulin compound is administered within one hour prior to a meal.

8. The method of claim 4 wherein the insulin compound is administered to effect overnight glucose control.