Composition comprising a polymeric reagent
AssigneeNektar Therapeutics
InventorsMichael D. Bentley, Sean M. Culbertson, Samuel P. McManus
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Abstract
The present invention provides conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates. The conjugates as well as the polymeric reagents used to form the conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods of making polymeric reagents and conjugates, as well as methods for administering conjugates and compositions, are also provided.
Claims70
A polymeric reagent of Formula I:
- wherein:
- POLY1 is a first water-soluble polymer;
- POLY2 is a second water-soluble polymer;
- X1 is a first spacer moiety;
- X2 is a second spacer moiety;
- is an aromatic-containing moiety bearing an ionizable hydrogen atom, Hα;
- R1 is H or an organic radical;
- R2 is H or an organic radical;
- (a) is either zero or one;
- (b) is either zero or one;
- Re1, when present, is a first electron altering group;
- Re2, when present, is a second electron altering group;
- and
- (FG) is a functional group capable of reacting with an amino group of an active agent to form a degradable linkage.
A polymeric reagent of Formula VI:
- wherein:
- POLY is a water-soluble polymer;
- X is a spacer moiety that does not include a
- moiety;
- is an aromatic moiety bearing an ionizable hydrogen atom, Hα;
- R1 is H or an organic radical;
- R2 is H or an organic radical;
- (a) is either zero or one;
- Re, when present, is an electron altering group;
- and
- (FG) is a functional group capable of reacting with an amino group of an active agent to form a degradable linkage.
A conjugate of Formula I-C:
- wherein:
- POLY1 is a first water-soluble polymer;
- POLY2 is a second water-soluble polymer;
- X1 is a first spacer moiety;
- X2 is a second spacer moiety;
- is an aromatic-containing moiety bearing an ionizable hydrogen atom, Hα;
- R1 is H or an organic radical;
- R2 is H or an organic radical;
- (a) is either zero or one;
- (b) is either zero or one;
- Re1, when present, is a first electron altering group;
- Re2, when present, is a second electron altering group;
- Y1 is O or S;
- Y2 is O or S;
- and
- D is a residue of a biologically active agent.
A conjugate of Formula VI-C:
- wherein:
- POLY is a water-soluble polymer;
- X is a spacer moiety that does not include a
- moiety;
- is an aromatic-containing moiety bearing an ionizable hydrogen atom, Hα;
- R1 is H or an organic radical;
- R2 is H or an organic radical;
- (a) is either zero or one;
- Re, when present, is an electron altering group;
- Y1 is O or S;
- Y2 is O or S;
- and
- D is a residue of a biologically active agent.
A method for preparing a polymeric reagent, comprising:
- (a) providing an aromatic moiety bearing a first attachment site, a second attachment site
- and a third attachment site;
- (b) reacting a functional group reagent with the first attachment site to result in the first attachment site bearing a functional group capable of reacting with an amino group of an active agent and resulting in a hydolyzable carbamate;
- (c) reacting a plurality of water-soluble polymers bearing a reactive group with the second attachment site and third attachment site to result in (i) the second attachment site bearing a water-soluble polymer through a spacer moiety, and (ii) the third attachment site bearing a second water-soluble polymer through a spacer moiety.
Dependencies are inferred from the claim text.