HIGH MOLECULAR WEIGHT ZWITTERION-CONTAINING POLYMERS

1 . A polymer comprising

at least two polymer arms each comprising a plurality of monomers each independently selected from the group consisting of acrylate, methacrylate, acrylamide, methacrylamide, styrene, vinyl-pyridine, vinyl-pyrrolidone and vinyl-ester, wherein each monomer comprises a hydrophilic group;

an initiator fragment linked to a proximal end of the polymer arm, wherein the initator moiety is suitable for radical polymerization; and

an end group linked to a distal end of the polymer arm,

wherein at least one of the initiator fragment and the end group comprises a functional agent or a linking group.

2 . The polymer of claim 1 , wherein each hydrophilic group comprises a zwitterionic group.

3 . The polymer of claim 2 , wherein each zwitterionic group comprises phosphorylcholine.

4 . The polymer of claim 3 , wherein the monomer comprises 2-(acryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate.

5 . The polymer of claim 3 , wherein the monomer comprises 2-(methacryloyloxyethyl)-2′-(trimethylammoniumethyl) phosphate (HEMA-PC).

6 . The polymer of claim 1 , wherein the initiator fragment is linked to the proximal end of from 2 to about 100 polymer arms.

7 . The polymer of claim 6 , wherein the polymer has a polydispersity index of less than about 2.0.

8 . The polymer of claim 6 , wherein the initiator fragment is linked to the proximal end of 2, 3, 4, 5, 6, 8, 9 or 12 polymer arms.

9 . A conjugate comprising:

at least one polymer comprising:

at least two polymer arms each comprising a plurality of monomers each independently selected from the group consisting of acrylate, methacrylate, acrylamide, methacrylamide, styrene, vinyl-pyridine, vinyl-pyrrolidone and vinyl-ester, wherein each monomer comprises a hydrophilic group,

an initiator fragment linked to a proximal end of the polymer arm, wherein the initiator moiety is suitable for radical polymerization, and

an end group linked to a distal end of the polymer arm; and

at least one functional agent comprising a bioactive agent or a diagnostic agent, linked to the initiator fragment or the end group.

10 . The conjugate of claim 9 , wherein the bioactive agent is selected from the group consisting of a drug, an antibody, an antibody fragment, a single domain antibody, an avimer, an adnectin, diabodies, a vitamin, a cofactor, a polysaccharide, a carbohydrate, a steroid, a lipid, a fat, a protein, a peptide, a polypeptide, a nucleotide, an oligonucleotide, a polynucleotide, and a nucleic acid.

11 . The conjugate of claim 9 , wherein the diagnostic agent is selected from the group consisting of a radiolabel, a contrast agent, a fluorophorc and a dye.

12 . The conjugate of claim 9 , wherein at least two polymers are linked to the functional agent.

13 . The conjugate of claim 14 , wherein at least two polymers are linked to the functional agent via proximal reactive groups on the functional agent to create a pseudo-branched structure.

15 . The conjugate of claim 9 , wherein the conjugate comprises at least two functional agents attached to the polymer.

16 . A polymer of the formula:

wherein

R 1 is selected from the group consisting of H, L 3 -A 1 , LG 1 and L 3 -LG 1 ;

each M 1 and M 2 is independently selected from the group consisting of acrylate, methacrylate, acrylamide, methacrylamide, styrene, vinyl-pyridine, vinyl-pyrrolidone and vinyl-ester;

each of G 1 and G 2 is each independently a hydrophilic group;

each I and I′ is independently an initiator fragment, such that the combination of I-I′ is an initiator, I 1 , for the polymerization of the polymer of Formula I via radical polymerization;

alternatively, each I′ is independently selected from the group consisting of H, halogen and C 1-6 alkyl;

each of L 1 , L 2 and L 3 is independently a bond or a linker;

each A 1 is a functional agent;

each LG 1 is a linking group;

subscripts x and y 1 are each independently an integer of from 1 to 1000;

each subscript z is independently an integer of from 0 to 10; and

subscript s is an integer of from 2 to 100.

17 . The polymer of claim 16 , wherein the polymer has the formula:

wherein

R 1 is selected from the group consisting of H, L 3 -A 1 , LG 1 and L 3 -LG 1 ;

each M 1 and M 2 is independently selected from the group consisting of acrylate, methacrylate, acrylamide, methacrylamide, styrene, vinyl-pyridine, vinyl-pyrrolidone and vinyl-ester;

each of ZW and ZW 1 is independently a zwitterionic moiety;

each I and I′ is independently an initiator fragment, such that the combination of I-I′ is an initiator, I 1 , for the polymerization of the polymer of Formula I via radical polymerization;

alternatively, each I′ is independently selected from the group consisting of H, halogen and C 1-6 alkyl;

each of L 1 , L 2 and L 3 is a linker;

each A 1 is a functional agent;

each LG 1 is a linking group;

subscripts x and y 1 are each independently an integer of from 1 to 1000;

each subscript z is independently an integer of from 0 to 10; and

subscript s is an integer of from 2 to 100.

18 . The polymer of claim 16 , wherein each hydrophilic group comprises a zwitterionic group.

19 . The polymer of claim 16 , wherein each hydrophilic group comprises phosphorylcholine.

20 . The polymer of claim 16 , wherein subscripts is 2, 3, 4, 5, 6, 8, 9 or 12.

21 . The polymer of claim 16 , wherein the polymer has the formula:

22 . The polymer of claim 16 , wherein the polymer has the formula:

wherein

R 2 is selected from the group consisting of H and C 1-6 alkyl; and

PC is phosphorylcholine.

23 . The polymer of claim 16 , wherein the initiator I 1 has the formula:

LG 2 -L 5 -CL 4 -I′] p

wherein

each I′ is independently selected from the group consisting of halogen, —SCN, and —NCS;

L 4 and L 5 are each independently a bond or a linker, such that one of L 4 and L 5 is a linker;

C is a bond or a core group;

LG 2 is a linking group; and

subscript p is from 1 to 20, wherein when subscript p is 1, C is a bond, and when subscript p is from 2 to 20, C is a core group.

24 . The polymer of claim 23 , wherein each of the initiators I 1 is of the formula:

wherein each R 3 and R 4 is independently selected from the group consisting of H, CN and C 1-6 alkyl.

25 . The polymer of claim 23 , wherein each of the initiators I 1 is independently selected from the group consisting of:

26 . The polymer of claim 16 , having the formula selected from the group consisting of:

wherein PC is phosphorylcholine.

27 . The polymer of claim 26 , wherein

R 1 is selected from the group consisting of L 3 -A 1 , LG 1 and L 3 -LG 1 ;

A 1 is selected from the group consisting of a drug, an antibody, an antibody fragment, a single domain antibody, an avimer, an adnectin, diabodies, a vitamin, a cofactor, a polysaccharide, a carbohydrate, a steroid, a lipid, a fat, a protein, a peptide, a polypeptide, a nucleotide, an oligonucleotide, a polynucleotide, a nucleic acid. a radiolabel, a contrast agent, a fluorophore and a dye;

L 3 is —(CH 2 CH 2 O) 1-10 —; and

LG 1 is selected from the group consisting of maleimide, acetal, vinyl, allyl, aldehyde, —C(O)O—C 1-6 alkyl, hydroxy, diol, ketal, azide, alkyne, carboxylic acid, and succinimide.

28 . The polymer of claim 27 , wherein each LG 1 is independently selected from the group consisting of:

hydroxy, carboxy, vinyl, vinyloxy, allyl, allyloxy, aldehyde, azide, ethyne, propyne, propargyl, —C(O)O—C 1-6 alkyl,

29 . The polymer of claim 16 , having the formula selected from the group consisting of:

30 . A polymer comprising

a polymer arm independently comprising a plurality of monomers each independently selected from the group consisting of acrylate, methacrylate, acrylamide, methacrylamide, styrene, vinyl-pyridine, vinyl-pyrrolidone and vinyl-ester, wherein each monomer comprises a hydrophilic group;

an initiator fragment linked to a proximal end of the polymer anti, wherein the initiator moiety is suitable for radical polymerization; and

an end group linked to a distal end of the polymer arm,

wherein at least one of the initiator fragment and the end group comprises a functional agent or a linking group,

and wherein the polymer has a peak average molecular weight of from about 50 kD to about 1,500 kD, as measured by light scattering.