Compositions comprising a polymeric reagent and a pharmacologically active agent

1. A composition comprising

(i) a polymeric reagent of the following structure,

wherein:

POLY 1 is a poly(alkylene glycol);

POLY 2 is a poly(alkylene glycol);

(a) is 0, 1, 2 or 3;

(b) is 0, 1, 2 or 3;

(e) is 0, 1, 2 or 3;

(f′) is 0, 1, 2 or 3;

(g′) is 0, 1, 2 or 3;

(h) is 0, 1, 2 or 3;

(j) is 0 to 20;

each R 1 is independently H or an organic radical selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl;

X 1 , when present, is a first spacer moiety;

X 2 , when present, is a second spacer moiety;

X 5 , when present, is a fifth spacer moiety;

X 6 , when present, is a sixth spacer moiety;

X 7 , when present, is a seventh spacer moiety;

X 8 , when present, is an eighth spacer moiety;

R 5 is a branching moiety selected from the group consisting of

 wherein (p) is 1-10 and (q) is 1-10; and

Z is a reactive group suitable for reaction with an electrophile or nucleophile of a biologically active agent; and

(ii) a pharmacologically active agent,

wherein there is an excess of the polymeric reagent relative to the pharmacologically active agent in the composition.

2. The composition of claim 1 , wherein each R 1 is H.

3. The composition of claim 1 , wherein each poly(alkylene glycol) is a poly(ethylene glycol).

4. The composition of claim 3 , wherein each poly(ethylene glycol) is terminally capped with methoxy.

5. The composition of claim 4 , wherein each poly(ethylene glycol) has a molecular weight of from about 100 Daltons to about 100,000 Daltons.

6. The composition of claim 5 , wherein each poly(ethylene glycol) has a molecular weight of from about 1,000 Daltons to about 60,000 Daltons.

7. The composition of claim 6 , wherein each poly(ethylene glycol) has a molecular weight of from about 2,000 Daltons to about 50,000 Daltons.

8. The composition of claim 1 , wherein the polymeric reagent has the following structure:

when the branching moiety R 5 is

 and,

wherein:

(n) is 2 to 4000;

(g′) is 0, 1, 2 or 3;

(h) is 0, 1, 2 or 3;

(j) is 0 to 20

(p) is 1;

(q) is 1; and

Z is a reactive group suitable for reaction with an electrophile or nucleophile of a biologically active agent.

9. The composition of claim 1 , wherein the pharmacologically active agent is selected from the group consisting of erythropoietin, granulocyte-colony stimulating factor, interferon-α, human growth hormone, interferon-β, follicle stimulating hormone, Factor VIII, B-domain delated Factor VIII, desmopressin and amdoxivir.

10. The composition of claim 1 , wherein each R 1 is an organic radical and is selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl and substituted aryl.

11. The composition of claim 1 , wherein the polymeric reagent has as structure selected from the group consisting of

wherein each (m) is 2 to 4000.

12. The composition of claim 1 , wherein the polymeric reagent has a structure selected from the group consisting of

13. The composition of claim 1 , wherein the polymeric reagent has a structure selected from the group consisting of

wherein each (m) is 2 to 4000 and each (n) 0 to 20.

14. The composition of claim 1 , wherein the polymeric reagent has the following structure:

15. The composition of claim 1 , wherein the polymeric reagent has the following structure: