MULTIFUNCTIONAL ZWITTERIONIC POLYMER CONJUGATES

1 . A random copolymer of Formula I:

wherein

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

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

each R 2 is independently selected from the group consisting of H, C 1-20 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, aryl, heteroaryl, A 2 , L 2 -A 2 , LG 2 , L 2 -LG 2 , I 2 and L 2 -I 2 ;

ZW is a zwitterionic moiety;

I is an initiator fragment and I′ is a radical scavenger, such that the combination of I-I′ is an initiator, I 1 , for the polymerization of the random copolymer of Formula I;

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

I 2 is an initiator;

each of L 1 and L 2 is a linker;

each of A 1 and A 2 is a functional agent;

each of LG 1 and LG 2 is a linking group;

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

subscript z is an integer of from 1 to 10;

subscript s is an integer of from 1 to 100; and

subscript n is an integer of from 1 to 20,

wherein either R 1 is L 1 -A 1 or one of R 2 is L 2 -A 2 .

2 . The random copolymer of claim 1 , wherein the random copolymer has the formula:

3 . The random copolymer of claim 1 , wherein the random copolymer has the formula:

4 . The random copolymer of claim 1 , having the formula:

5 . The random copolymer of claim 1 , having the formula:

6 . The random copolymer of claim 1 , having the formula:

7 . The random copolymer of claim 1 , wherein at least one R 2 is selected from the group consisting of H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 3-8 cycloalkyl, C 3-8 heterocycloalkyl, aryl, and heteroaryl.

8 . The random copolymer of claim 1 , wherein the random copolymer has the formula:

9 . The random copolymer of claim 8 , wherein the random copolymer has the formula:

10 . The random copolymer of claim 8 , wherein the random copolymer has the formula:

11 . The random copolymer of claim 10 , having the following formula:

12 . The random copolymer of claim 1 , wherein each of L 1 and L 2 is a cleavable linker independently selected from the group consisting of hydrolyzable linkers, enzymatically cleavable linkers, pH sensitive linkers, disulfide linkers, photolabile linkers, and self-immolative or double prodrug linkers.

13 . The random copolymer of claim 1 , wherein at least one of L 1 and L 2 is a cleavable linker independently selected from the group consisting of hydrolyzable linkers, enzymatically cleavable linkers, pH sensitive linkers, disulfide linkers, photolabile linkers, and self-immolative or double prodrug linkers.

14 . The random copolymer of claim 1 , wherein the functional agent is a bioactive agent selected from the group consisting of a drug, a therapeutic protein and a targeting agent.

15 . The random copolymer of claim 1 , wherein the radical scavenger I′ is a halogen.

16 . The random copolymer of claim 1 , wherein the initiator I 1 is selected from the group consisting of:

17 . The random copolymer of claim 1 , wherein the random copolymer is selected from the group consisting of:

18 . The random copolymer of claim 1 , wherein the random copolymer has the formula:

wherein

PC is phosphorylcholine;

HEMA is hydroxyethyl methacrylate;

GMA is glycidyl methacrylate; and

Glu is glutamic acid.

19 . The random copolymer of claim 1 , wherein the random copolymer has the formula:

wherein the block copolymer has the formula:

20 . The random copolymer of claim 1 , wherein the random copolymer has the formula:

wherein

subscripts x and y 1 are such that the Mn of the polymer portion is about 95,000 g/mol;

A 1 is an antibody; and

L-CTP has the formula:

21 . The random copolymer of claim 1 , wherein the random copolymer has the formula:

wherein

subscripts x, y 1a and y 1b are such that the Mn of the polymer portion is about 107,100 g/mol;

A 1 is an antibody; and

L-CTP has the formula:

22 . The random copolymer of claim 1 , wherein the random copolymer has the formula:

wherein subscripts x and y 1 are such that the Mn of the polymer portion is about 95,000 g/mol;

A 1 is an IgG; and

L-CTP has the formula:

23 . The random copolymer of claim 1 , wherein each of A 1 and A 2 is independently selected from the group consisting of an antibody, an antibody fragment, a Fab, IgG, a peptide, a protein, an enzyme, an oligonucleotide, a polynucleotide, nucleic acids, and an antibody drug conjugate (ADC).

24 . The random copolymer of claim 1 , wherein A 1 is independently selected from an antibody, an antibody fragment, a Fab, a scFv, an immunoglobulin domain, an IgG, and A 2 is independently selected from an anti-cancer agent, a toxin, a small molecule drug, a chemotherapy agent, a kinase inhibitor, an anti-inflammatory agent, and an antifibrotic agent.

25 . The random copolymer of claim 1 , wherein R 1 is LG 1 , and L 2 -A 2 is independently selected from an anti-cancer agent, a toxin, a small molecule drug, a chemotherapy agent, a kinase inhibitor, an anti-inflammatory agent, and an antifibrotic agent.

26 . A process for preparing a random copolymer, the process comprising: contacting a mixture of a first monomer and a second monomer with an initiator, I I , under conditions sufficient to prepare a random copolymer via free radical polymerization, wherein the first monomer comprises a phosphorylcholine, and each of the second monomer and initiator independently comprise at least one of a functional agent or a linking group for linking to the functional agent.

27 . The process of claim 26 , wherein the mixture further comprises a catalyst and a ligand.

28 . A random copolymer comprising a first monomer comprising phosphorylcholine; a second monomer comprising a functional agent or a linking group; and an initiator moiety comprising a functional agent or a linking group, wherein the functional agent is linked to the second monomer or the initiator moiety via a linker.