FLOW-THROUGH PROCESSES AND DEVICES FOR PURIFYING A TARGET MOLECULE

1 . A flow-through process for purifying a target molecule from a biological solution in a sample that includes the target molecule, the process comprising:

optionally, contacting the sample with an anion exchange adsorptive depth filter;

optionally, conducting a buffer exchange with the sample before and/or after contacting the sample with an anion exchange adsorptive depth filter;

contacting the sample with a salt-tolerant anion exchange nonfibrous porous filter element; and

immediately thereafter, contacting the sample with a cation exchange nonfibrous porous filter element;

wherein the flow-through process comprises one or two buffer exchanges, with no buffer exchange between the sample contacting the salt-tolerant anion exchange nonfibrous porous filter element and the cation exchange nonfibrous porous filter element.

2 . A flow-through process for purifying a target molecule from a biological solution in a sample that includes the target molecule, the process comprising:

contacting the sample with an anion exchange adsorptive depth filter;

immediately thereafter, contacting the sample with a salt-tolerant anion exchange nonfibrous porous filter element; and

immediately thereafter, contacting the sample with a cation exchange nonfibrous porous filter element;

wherein the flow-through process comprises no buffer exchanges.

3 . A flow-through process for purifying a target molecule from a biological solution in a sample that includes the target molecule, the process comprising:

contacting the sample with an anion exchange adsorptive depth filter;

conducting a buffer exchange with the sample after contacting the sample with an anion exchange adsorptive depth filter;

contacting the sample with a salt-tolerant anion exchange nonfibrous porous filter element; and

immediately thereafter, contacting the sample with a cation exchange nonfibrous porous filter element.

4 . A flow-through process for purifying a target molecule from a biological solution in a sample that includes the target molecule, the process comprising:

conducting a buffer exchange with the sample;

contacting the sample with a salt-tolerant anion exchange nonfibrous porous filter element; and

immediately thereafter, contacting the sample with a cation exchange nonfibrous porous filter element.

5 . The flow-through process of claim 1 wherein the target molecule comprises a monoclonal antibody.

6 . The flow-through process of claim 1 wherein the biological solution comprises a neutralized viral inactivation pool.

7 . The flow-through process of claim 1 wherein the anion exchange adsorptive depth filter comprises a porous substrate comprising immobilized anion exchange ligands.

8 . The flow-through process of claim 7 wherein the anion exchange ligands of the anion exchange adsorptive depth filter comprise cationic nitrogen-containing ligands.

9 . The flow-through process of claim 8 wherein the cationic nitrogen-containing ligands of the anion exchange adsorptive depth filter comprise a primary amine, a secondary amine, a tertiary amine, or combinations thereof.

10 . The flow-through process of claim 9 wherein the cationic nitrogen-containing ligands of the anion exchange adsorptive depth filter comprise a quaternary ammonium-containing ligand, a guanidinyl-containing ligand, or a combination thereof.

11 . The flow-through process of claim 7 wherein the anion exchange adsorptive depth filter comprises a porous substrate and a ligand-functional polymer grafted thereto, wherein the grafted ligand-functional polymer is of the formula:

-(M PI ) w -(M b ) x -(M c ) y -(M d ) z ,

wherein:

-(M PI ) w represent the residue of grafted photoinitiator monomers, where w is zero or at least one;

-(M b ) x represents polymerized ligand monomers, having “x” polymerized monomer units, where x is at least one, and the ligand monomer is of the formula (X):

wherein:

R 1 is H or CH 3 ;

R 2 is a (hetero)hydrocarbylene;

each R 3 is independently H or (hetero)hydrocarbyl;

R 14 is H, (hetero)hydrocarbyl, or —N(R 3 ) 2 , where each R 3 is independently H or (hetero)hydrocarbyl;

X 1 is —O— or —NR 3 —, where R 3 is H or (hetero)hydrocarbyl, and

n is 1 or 2;

-(M c ) y represents polymerized crosslinking monomers, having y polymerized monomer units, where y may be zero or at least one; and

-(M d ) z represents polymerized hydrophilic monomers, having z polymerized monomer units, where z may be zero or at least one.

12 . The flow-through process of claim 1 wherein the salt-tolerant anion exchange nonfibrous porous filter element comprises a porous membrane comprising immobilized anion exchange ligands.

13 . The flow-through process of claim 12 wherein the anion exchange ligands of the salt-tolerant anion exchange nonfibrous porous filter element comprise cationic nitrogen-containing ligands.

14 . The flow-through process of claim 13 wherein the cationic nitrogen-containing ligands of the salt-tolerant anion exchange nonfibrous porous filter element comprise guanidinyl-containing ligands.

15 . The flow-through process of claim 14 wherein the grafted copolymer of the salt-tolerant anion exchange nonfibrous porous filter element comprises interpolymerized monomer units comprising:

a guanidinyl-containing ligand monomer;

an amide monomer;

an oxy monomer selected from the group of epoxy functional monomer units, alkyl ether functional monomer units, and combinations thereof; and

a poly(alkylene oxide) monomer.

16 . The flow-through process of claim 12 wherein the salt-tolerant anion exchange nonfibrous porous filter element comprises a nonfibrous porous filter element and a ligand-functional polymer grafted thereto, wherein the grafted ligand-functional polymer is of the formula:

-(M PI ) w -(M b ) x -(M c ) y -(M d ) z ,

wherein:

-(M PI ) w - represent the residue of grafted photoinitiator monomers, where w is zero or at least one;

-(M b ) x represents polymerized ligand monomers, having “x” polymerized monomer units, where x is at least one, and the ligand monomer is of the formula (X):

wherein:

R 1 is H or CH 3 ;

R 2 is a (hetero)hydrocarbylene;

each R 3 is independently H or (hetero)hydrocarbyl;

R 14 is H, (hetero)hydrocarbyl, or —N(R 3 ) 2 , where each R 3 is independently H or (hetero)hydrocarbyl;

X 1 is —O— or —NR 3 —, where R 3 is H or (hetero)hydrocarbyl, and

n is 1 or 2;

-(M c ) y represents polymerized crosslinking monomers, having y polymerized monomer units, where y may be zero or at least one; and

-(M d ) z represents polymerized hydrophilic monomers, having z polymerized monomer units, where z may be zero or at least one.

17 . The flow-through process of claim 1 wherein the cation exchange nonfibrous porous filter element comprises:

a nonfibrous porous substrate; and

disposed on the porous nonfibrous membrane, a polymer comprising:

a hydrocarbon backbone and a plurality of pendant groups attached to the hydrocarbon backbone, wherein each of a first plurality of pendant groups comprises:

at least one acidic group or salt thereof; and

a spacer group that directly links the at least one acidic group or salt thereof to the hydrocarbon backbone by a chain of at least 6 catenated atoms.

18 . The flow-through process of claim 17 wherein the polymer that is covalently attached to the nonfibrous porous filter element is a copolymer covalently attached to the nonfibrous porous filter element comprises a reaction product of a monomer composition comprising:

a first monomer comprising:

at least one ethylenically unsaturated group;

at least one acidic group or salt thereof; and

a spacer group that directly links the at least one ethylenically unsaturated group and the at least one acidic group or salt thereof by a chain of at least 6 catenated atoms; and

a second monomer comprising:

at least one ethylenically unsaturated group;

at least one acidic group or salt thereof; and

a spacer group that directly links the at least one ethylenically unsaturated group and the at least one acidic group by a chain of at least 6 catenated atoms;

wherein the second monomer is different than the first monomer; and

wherein a mole ratio of the first monomer to the second monomer is in a range of 95:5 to 5:95.

19 . A filter cartridge comprising salt-tolerant anion exchange nonfibrous porous filter element and a cation exchange nonfibrous porous filter element;

wherein the salt-tolerant anion exchange nonfibrous porous filter element comprises:

a nonfibrous porous filter element comprising immobilized cationic nitrogen-containing ligands, or

a nonfibrous porous filter element and a ligand-functional polymer grafted thereto, wherein the grafted ligand-functional polymer is of the formula:

-(M PI ) w -(M b ) x -(M c ) y -(M d ) z ,

wherein:

-(M PI ) w - represent the residue of grafted photoinitiator monomers, where w is zero or at least one;

-(M b ) x represents polymerized ligand monomers, having “x” polymerized monomer units, where x is at least one, and the ligand monomer is of the formula (X):

wherein:

R 1 is H or CH 3 ;

R 2 is a (hetero)hydrocarbylene;

each R 3 is independently H or (hetero)hydrocarbyl;

R 14 is H, (hetero)hydrocarbyl, or —N(R 3 ) 2 , where each R 3 is independently H or (hetero)hydrocarbyl;

X 1 is —O— or —NR 3 —, where R 3 is H or (hetero)hydrocarbyl, and

n is 1 or 2;

-(M c ) y represents polymerized crosslinking monomers, having y polymerized monomer units, where y may be zero or at least one; and

-(M d ) z represents polymerized hydrophilic monomers, having z polymerized monomer units, where z may be zero or at least one; and

wherein the cation exchange nonfibrous porous filter element comprises:

a nonfibrous porous filter element; and

disposed on the nonfibrous porous filter element, a polymer comprising:

a hydrocarbon backbone and a plurality of pendant groups attached to the hydrocarbon backbone, wherein each of a first plurality of pendant groups comprises:

at least one acidic group or salt thereof; and

a spacer group that directly links the at least one acidic group or salt thereof to the hydrocarbon backbone by a chain of at least 6 catenated atoms.

20 . The filter cartridge of claim 19 wherein the cation exchange nonfibrous porous filter element is positioned downstream from the salt-tolerant anion exchange nonfibrous porous filter element.