Polymeric reagents comprising a terminal vinylic group and conjugates formed therefrom
View Patent ↗The present invention provides conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates. Methods of making polymeric reagents and conjugates, as well as methods for administering conjugates and compositions, are also provided.
1. A pharmaceutical composition comprising a purified conjugate in solid form and a pharmaceutically acceptable excipient, wherein the conjugate has the structure:
wherein:
POLY 1 is a poly(alkylene oxide);
POLY 2 is a poly(alkylene oxide);
X 1 is a first spacer moiety of atoms;
X 2 is a second spacer moiety of atoms;
R 1 is H or an organic radical;
R 2 is H or an organic radical;
Nu is an amine nitrogen or a sulfur atom; and
Nu-D is a residue of a biologically active polypeptide.
2. The pharmaceutical composition of claim 1 , wherein each of R 1 and R 2 is hydrogen.
3. The pharmaceutical composition of claim 1 , wherein POLY 1 and POLY 2 are the same.
4. The pharmaceutical composition of claim 1 , wherein each poly(alkylene oxide) is terminally capped with an end-capping moiety selected from the group consisting hydroxy, alkoxy, substituted alkoxy, alkenoxy, substituted alkenoxy, alkynoxy, substituted alkynoxy, aryloxy and substituted aryloxy.
5. The pharmaceutical composition of claim 4 , wherein each poly(alkylene oxide) is terminally capped with methoxy.
6. The pharmaceutical composition of claim 1 , wherein each poly(alkylene oxide) has a weight-average molecular weight in the range of from about 120 Daltons to about 6,000 Daltons.
7. The pharmaceutical composition of claim 1 , wherein each poly(alkylene oxide) has a weight-average molecular weight in the range of from about 6,000 Daltons to about 100,000 Daltons.
8. The pharmaceutical composition of claim 1 , wherein each poly(alkylene oxide) has a weight-average molecular weight in the range of from about 10,000 Daltons to about 85,000 Daltons.
9. The pharmaceutical composition of claim 1 , wherein each poly(alkylene oxide) has a weight-average molecular weight in the range of from about 20,000 Daltons to about 85,000 Daltons.
10. The pharmaceutical composition of claim 1 , wherein each poly(alkylene oxide) is linear.
11. The pharmaceutical composition of claim 1 , wherein each of the first spacer moiety and second spacer moiety is selected from the group consisting of —NH—C(O)—CH 2 —, —NH—C(O)—CH 2 —O—, —CH 2 —C(O)—NH—, and O—CH 2 —C(O)—NH—.
12. The pharmaceutical composition of claim 1 , wherein the polypeptide does not include glutathione.
13. The pharmaceutical composition of claim 1 , in lyophilized form.
14. The pharmaceutical composition of claim 1 , in unit dosage form.
15. The pharmaceutical composition of claim 1 , housed in a glass vial.