Polymer-factor IX moiety conjugates
View Patent ↗Conjugates of a Factor IX moiety and one or more water-soluble polymers are provided. Typically, the water-soluble polymer is poly(ethylene glycol) or a derivative thereof. Also provided (among other things) are compositions comprising the conjugates, methods of making the conjugates, and methods of administering to a patient compositions comprising the conjugates.
1. A conjugate having the structure,
where the conjugate is a mono-conjugate, mPEG is methyoxypolyethylene glycol, FIX is a Factor IX moiety that is either Factor IX or Factor IXa, and the ˜NH˜ in FIX-NH˜ is a Factor IX amino group, the conjugate having an in-vitro activity of at least about 15% relative to that of the same Factor IX moiety in unconjugated form, when evaluated under the same conditions and at an equivalent dosage amount as unconjugated Factor IX moiety using the same in-vitro model.
2. The conjugate of claim 1 , characterized by an in-vitro activity of at least about 25% relative to that of the same Factor IX moiety in unconjugated form.
3. The conjugate of claim 1 , characterized by an in-vitro activity of at least about 40% relative to that of the same Factor IX moiety in unconjugated form.
4. The conjugate of claim 1 , wherein the conjugate has a total weight average molecular weight in a range of from about greater than 5,000 Daltons to less than about 150,000 Daltons.
5. The conjugate of claim 1 , wherein the branched poly(ethylene glycol) polymer has a total weight average molecular weight in the range of from about 6,000 Daltons to about 100,000 Daltons.
6. The conjugate of claim 5 , wherein the branched poly(ethylene glycol) polymer has a total weight average molecular weight in the range of from about 10,000 Daltons to about 85,000 Daltons.
7. The conjugate of claim 6 , wherein the branched poly(ethylene glycol) polymer has a total weight average molecular weight in the range of from about 20,000 Daltons to about 85,000 Daltons.
8. The conjugate of claim 1 , wherein the branched poly(ethylene glycol) polymer has a total weight average molecular weight selected from the group consisting of about 6,000 Daltons, about 7,500 Daltons, about 10,000 Daltons, about 15,000 Daltons, about 20,000 Daltons, about 25,000 Daltons, about 30,000 Daltons, about 40,000 Daltons, about 50,000 Daltons, and about 60,000 Daltons.
9. The conjugate of claim 1 , wherein the branched poly(ethylene glycol) polymer has a polydispersity value of less than about 1.05.
10. The conjugate of claim 1 , wherein the Factor IX moiety is Factor IX.
11. The conjugate of claim 1 , wherein the Factor IX moiety is Factor IXa.
12. The conjugate of claim 1 , wherein the Factor IX moiety is recombinantly-derived.
13. The conjugate of claim 1 , wherein the Factor IX moiety is blood-derived.