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WO2025179026A1 - Ligands de liaison à des cations multivalents et compositions les comprenant pour des séparations par affinité de chélates ioniques - Google Patents

Ligands de liaison à des cations multivalents et compositions les comprenant pour des séparations par affinité de chélates ioniques

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Publication number
WO2025179026A1
WO2025179026A1 PCT/US2025/016608 US2025016608W WO2025179026A1 WO 2025179026 A1 WO2025179026 A1 WO 2025179026A1 US 2025016608 W US2025016608 W US 2025016608W WO 2025179026 A1 WO2025179026 A1 WO 2025179026A1
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Prior art keywords
composition
group
substrate
multivalent cation
independently
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PCT/US2025/016608
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English (en)
Inventor
Timothy HANEY
Ying Chen
Anatoly ANDREYKO
Natalia Rodionova
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Life Technologies Corp
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Life Technologies Corp
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    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J43/00—Amphoteric ion-exchange, i.e. using ion-exchangers having cationic and anionic groups; Use of material as amphoteric ion-exchangers; Treatment of material for improving their amphoteric ion-exchange properties
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
    • B01D15/08—Selective adsorption, e.g. chromatography
    • B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
    • B01D15/36—Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/02—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material
    • B01J20/10—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate
    • B01J20/103—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising inorganic material comprising silica or silicate comprising silica
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
    • B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
    • B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
    • B01J20/288—Polar phases
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
    • B01J20/286—Phases chemically bonded to a substrate, e.g. to silica or to polymers
    • B01J20/289—Phases chemically bonded to a substrate, e.g. to silica or to polymers bonded via a spacer
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
    • B01J20/3204—Inorganic carriers, supports or substrates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
    • B01J20/3206—Organic carriers, supports or substrates
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3214—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the method for obtaining this coating or impregnating
    • B01J20/3217—Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond
    • B01J20/3219—Resulting in a chemical bond between the coating or impregnating layer and the carrier, support or substrate, e.g. a covalent bond involving a particular spacer or linking group, e.g. for attaching an active group
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3214—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the method for obtaining this coating or impregnating
    • B01J20/3225—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the method for obtaining this coating or impregnating involving a post-treatment of the coated or impregnated product
    • B01J20/3227—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the method for obtaining this coating or impregnating involving a post-treatment of the coated or impregnated product by end-capping, i.e. with or after the introduction of functional or ligand groups
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
    • B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
    • B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
    • B01J20/3244—Non-macromolecular compounds
    • B01J20/3246—Non-macromolecular compounds having a well defined chemical structure
    • B01J20/3248—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such
    • B01J20/3251—Non-macromolecular compounds having a well defined chemical structure the functional group or the linking, spacer or anchoring group as a whole comprising at least one type of heteroatom selected from a nitrogen, oxygen or sulfur, these atoms not being part of the carrier as such comprising at least two different types of heteroatoms selected from nitrogen, oxygen or sulphur
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/30—Processes for preparing, regenerating, or reactivating
    • B01J20/34—Regenerating or reactivating
    • B01J20/345—Regenerating or reactivating using a particular desorbing compound or mixture
    • B01J20/3475—Regenerating or reactivating using a particular desorbing compound or mixture in the liquid phase
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J39/00—Cation exchange; Use of material as cation exchangers; Treatment of material for improving the cation exchange properties
    • B01J39/26—Cation exchangers for chromatographic processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J41/00—Anion exchange; Use of material as anion exchangers; Treatment of material for improving the anion exchange properties
    • B01J41/20—Anion exchangers for chromatographic processes

Definitions

  • the present disclosure is directed to multivalent cation-binding ligands that can be bound to substrates to provide the ability to associate positively-charged species, along with methods of making and using the same.
  • compositions comprising: a substrate; and a multivalent cation-binding ligand covalently bound to a surface of the substrate, wherein the multivalent cation-binding ligand has a structure according to one of Formulas I or II
  • kits comprising: the composition as described herein; and a container configured to house the composition during use of the composition.
  • compositions comprising: a solid substrate; and an associating means for associating a positively-charged ion species with the solid substate.
  • FIG. 2 is a chromatogram showing protein separation and selectivity observed using a composition according to the present disclosure.
  • FIG. 3 is a chromatogram showing protein separation and selectivity observed using a composition according to the present disclosure.
  • Certain functional group terms used herein include a symbol which is used to show how the defined functional group attaches to, or within, the compound to which it is bound.
  • a dashed bond i.e. , “ — ” as used in certain formulas described herein indicates an “optional” bond to a substituent or atom of the formula other than hydrogen in the sense that the bond (and in some aspects, the substituent) may or may not be present.
  • the optional bond and/or any corresponding substituent is not present, then the valency requirements of any atom(s) bound thereto is completed by a bond to a hydrogen atom.
  • Alkoxy -O-aliphatic, such as -O-alkyl, -O-alkenyl, -O-alkynyl; with exemplary examples including, but not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, t-butoxy, sec-butoxy, n-pentoxy (wherein any of the aliphatic components of such groups can comprise no double or triple bonds, or can comprise one or more double and/or triple bonds).
  • Alkoxy groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.
  • an “antibody fragment” includes at least a portion of a full-length antibody and typically, an antigen binding or variable region thereof; for e.g., they include Fab, Fab', F(ab')2, and Fv fragments; single-chain antibody molecules like camelid antibodies; diabodies; linear antibodies; and multispecific antibodies formed from engineered antibody fragments.
  • the term "monoclonal" antibodies indicates the character of the antibody as being obtained from a substantially homogeneous population of antibodies, and is not to be construed as requiring production of the antibody by any particular method.
  • the monoclonal antibodies described herein include “chimeric” and “humanized” antibodies, and “human” antibodies, which can be isolated from various sources, including, e.g., from the blood of a human patient or recombinantly prepared using transgenic animals.
  • Aromatic A cyclic, conjugated group or moiety of, unless specified otherwise, from 5 to 15 ring atoms having a single ring (e.g., phenyl) or multiple condensed rings in which at least one ring is aromatic (e.g., naphthyl, indolyl, or pyrazolopyridinyl); that is, at least one ring, and optionally multiple condensed rings, have a continuous, delocalized Ti-electron system.
  • the number of out of plane n-electrons corresponds to the Huckel rule (4n + 2).
  • the point of attachment to the parent structure typically is through an aromatic portion of the condensed ring system. For example, z co u .
  • context or express disclosure may indicate that the point of attachment is through a non-aromatic portion of the condensed ring system.
  • An aromatic group or moiety may comprise only carbon atoms in the ring, such as in an aryl group or moiety, or it may comprise one or more ring carbon atoms and one or more ring heteroatoms comprising a lone pair of electrons (e.g. S, O, N, P, or Si), such as in a heteroaryl group or moiety.
  • Aromatic groups may be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.
  • Multivalent Cation-Binding Ligand A ligand group that facilitates indirect binding of a multivalent cationic species to a solid substrate, wherein the ligand group is bound to a surface of the solid substrate.
  • Multivalent cation-binding ligands include phosphorus-, sulfur-, boron-, nitrogen, and carboxyl-containing ligands disclosed herein.
  • Multivalent Cationic Species A representative a positively-charged species that includes a 2+ or higher positive charge.
  • Exemplary multivalent cationic species can include ions having a 2+, 3+, 4+ or higher positive charge.
  • Phosphate -O-P(O)(OR a )2, wherein each R a independently is hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group; or wherein one or more R a groups are not present and the phosphate group therefore has at least one negative charge.
  • the R a groups of the phosphate can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.
  • Phosphonate -P(O)(OR a )2, wherein each R a independently is hydrogen, aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group; or wherein one or more R a groups are not present and the phosphate group therefore has at least one negative charge.
  • the R a groups of the phosphonate group can be substituted with one or more groups other than hydrogen, such as aliphatic, heteroaliphatic, haloaliphatic, haloheteroaliphatic, aromatic, or an organic functional group.
  • Positively-Charged Species A chemical species (e.g., atom or molecule) that possesses a net positive charge. In particular aspects of the disclosure, the positively-charged species is a positively- charged ion.
  • Solid A physical form that is not a liquid or a fluid. Solids can include rigid solids as well as gels, hydrogels, and the like.
  • each Y independently for each occurrence, is a bond, an aliphatic group, an aromatic group, a heteroaliphatic group, or any combination thereof (e.g., aromatic- heteroaliphatic-aromatic or aromatic-aliphatic).
  • Z 1 or Z 2 groups are directly bound to the carbon to which Y is attached in Formulas I and II.
  • At least one Z 2 group of a repeating “n” unit is selected from any such groups disclosed above and the other Z 2 is an R 3 group that is hydrogen, an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, a heteroalkynyl group, an aryl group, or a heteroaryl group.
  • each of R 1 and R 2 independently, for each occurrence, is selected from hydrogen, an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, a heteroalkynyl group, an aryl group, or a heteroaryl group.
  • the TG group is hydrogen or hydroxyl.
  • one Z 2 is an R 3 group and R 3 is styrene group and the styrene group can be further coupled (e.g., via radical couplings/polymerization) to another styrene group, another Z 2 group that is selected from the groups listed above in the definition for Z 1 and/or Z 2 , or a combination thereof.
  • the external aliphatic portion of the R 3 styrene group is positioned para to the bond connecting the Z 2 /R 3 group to the rest of Formula II.
  • Y is a bond and Z 1 is -P(O)(OH)2; -P(O)(O’) 2 ; or - [P(O)(OH)O]2- 4 H or -[P(O)(O )O] 2 -4 (e.g., -P(O)(OH)O-P(O)(OH)OH, -P(O)(OH)O-P(O)(OH)O-P(O)(OH)OH, - P(O)(OH)O-P(O)(OH)O-P(O)(OH)O-P(O)(OH)OH, -P(O)(OjO-P(Oj 2 , -P(O)(OH)O-P(O)(OH)O-P(Oj 2 , or -P(O)(OH)O-P(O-P(O)(OH)O-P(O-P(O-P(O)(O-P(O)(Oj 2
  • one Y is a bond, alkyl (e.g., lower alkyl, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, or decyl), or -[NH2] + [CH 2 CH2] t -, or -[NH2] + [CH2CH 2 O]t-, wherein t is an integer ranging from 1 to 8, such as 1 to 6, or 1 to 4, or 1 , 2, 3, 4, 5, 6, 7 or 8, and the Z 2 attached to such Y is selected from -OP(O)(OH) 2 ; -P(O)(OH) 2 ; -OP(O)(O ) 2 ; -P(O)(O ) 2 ; or -O[P(O)(OH)O] 2 - P(O)(O)
  • Compounds of Formula I can also have structures according to Formula IA, wherein each of Z 1 and t can be as recited above for Formula I.
  • Compounds of Formula II can also have structures according to any of Formulas IIA-IIF.
  • each Y independently can be aliphatic or heteroaliphatic.
  • each of Y, Z 2 , R 1 , R 2 , R 3 , TG, and n can be as recited above for Formulas I and/or II.
  • the multivalent cation-binding ligand can be selected from:
  • the substrate comprises a ceramic material, a glass material, a metal material, a silica material, a synthetic polymeric material (e.g., polystyrene-containing polymers), a natural polymeric material (e.g., carbohydrate-based materials, such as polysaccharides, including cellulose materials and the like), or any combination thereof.
  • a synthetic polymeric material e.g., polystyrene-containing polymers
  • a natural polymeric material e.g., carbohydrate-based materials, such as polysaccharides, including cellulose materials and the like
  • the heteroatom-containing functional group of the substrate can comprise a heteroatom selected from an element belonging to Group 16 of the periodic table (e.g., oxygen, sulfur, selenium, tellurium, and polonium); nitrogen; boron; and the like.
  • the heteroatom is selected from (I) oxygen and the heteroatom-containing functional group is a hydroxyl group; or (II) sulfur and the heteroatom-containing functional group is a thiol group.
  • a plurality of heteroatomcontaining functional groups can be present on the surface of the substrate and thus one or more of the heteroatom-containing functional groups independently can be bound to a multivalent cation-binding ligands to provide a substrate comprising a plurality of multivalent cation-binding ligands.
  • the heteroatom of the heteroatom-containing functional group is bound directly to a Z 1 group of the multivalent cation-binding ligand, wherein Z 1 is -O[X(A)s(A’) m A”] q -Hr or -[X(A) s (A')mA”] q -Hr, as defined for Formula I.
  • a covalent bond typically is formed between the X atom of the Z 1 group and the heteroatom.
  • the heteroatom is bound to a carbon atom of the multivalent cation-binding ligand, which in turn is directly or indirectly bound to a Z 2 group of the multivalent cation-binding ligand, wherein Z 2 is -O[X(A) s (A’)mA”]q-Hr or -[X(A) s (A’)mA”]q-Hr, as defined for Formula II.
  • a covalent bond is formed between the carbon atom and the heteroatom.
  • the surface functional group is an aliphatic or aromatic group
  • the aliphatic group can be selected from an alkyl-, alkenyl-, or alkynyl-containing group and the aromatic group can be selected from an aryl or heteroaryl group.
  • the multivalent cation-binding ligand can be bound to a carbon atom of the aliphatic or aromatic group via a covalent bond.
  • the aliphatic group is a lower alkyl group (e.g., methyl, ethyl, propyl, butyl, pentyl, hexyl, septyl, octyl, nonyl, or decyl) and the aromatic group is phenyl.
  • the amine group of the multivalent cationbinding ligand can be bound to an aliphatic group (e.g., a CH2 group) that is part of an epoxide ring. In such aspects, the amine group becomes bound to the substrate by attacking a methylene group of the epoxide and ring-opening the epoxide ring.
  • Formulas III and IV showing binding options for attaching the multivalent cation-binding ligand to the substrate via the functional group are provided below, with Formulas IVA and IVB showing further representative formulas for Formula IV.
  • the multivalent cation-binding ligand can be bound to the substrate at the positions indicated.
  • X' represents a heteroatom provided by the heteroatom-containing functional group of the substrate that becomes bound to the multivalent cationbinding ligand; an aliphatic group; or an aromatic group.
  • X’ is O, S, NR’ (wherein R’ is hydrogen, aliphatic, or aromatic), Se, Te, Po, methyl, or phenyl; and the remaining variables of the Formula are as recited herein for Formulas I, IA, II, or IIA-IIF.
  • the composition can further comprise a positively-charged species, such as a multivalent cation species or a combination of a multivalent cation species and monovalent cation species.
  • a positively-charged species can be associated with the multivalent cation-binding ligand.
  • these two groups can be associated by chemical interactions, such as covalent bonds, ionic bonds, and/or electrostatic interactions.
  • the positively-charged species associates with the multivalent cation-binding ligand through chemical interactions between the positively-charged species and oxygen atoms of the multivalent cation-binding ligand, such as through negatively-charged oxygen atoms, lone pair electrons of the oxygen atoms, or combinations thereof.
  • the positively-charged species is a multivalent cationic species.
  • the multivalent cationic species has a 2+ oxidation state; however, other higher oxidations states, including 3+, 4+, or higher, are contemplated.
  • the multivalent cationic species can be selected from Ca 2+ , Mg 2+ , Fe 2+ , Zn 2+ , Cu 2+ , Cr 2+ , Ag 2+ , Co 2+ , Ni 2+ , Mn 2+ , Be 2+ , Sr 2+ , Ba 2+ , V 2+ , or any combination thereof.
  • the multivalent cation-binding ligand can be associated with a plurality of positively-charged species, wherein each positively-charged species is the same or different.
  • the positively-charged species is Ca 2+ , Ni 2+ , Co 2+ , or any combination thereof.
  • the composition can further comprise a target (also referred to as a target molecule).
  • a target also referred to as a target molecule
  • the target can become part of the composition upon exposure of the multivalent cation-binding ligand-bound substrate to the target, which can be present in a separate solution, solid mixture, or some combination thereof.
  • the target can either be associated or not associated with the multivalent cation-binding ligand.
  • the association of the target can occur through chemical interactions between functional groups of the target and (i) a positively-charged species that in turn is associated with the multivalent cation-binding ligand; and/or (ii) one or more A, A', and/or A” atoms of the multivalent cation-binding ligand (as defined for Formulas I and/or II).
  • the target can be in a free state such that it exists with the multivalent cation-binding ligand and the substrate but is not bound thereto by any chemical interactions.
  • the composition can further comprise contaminants that are desired to be separated from a target or other media.
  • the contaminants can become part of the composition upon exposure of the multivalent cation-binding ligand-bound substrate to the contaminants, which can be present in a separate solution, solid mixture, or some combination thereof.
  • the contaminants can either be associated or not associated with the multivalent cation-binding ligand.
  • the association of a contaminant can occur through chemical interactions between functional groups of a contaminant and (i) a positively-charged species that in turn is associated with the multivalent cation-binding ligand; and/or (ii) one or more A, A’, and/or A” atoms of the multivalent cation-binding ligand (as defined for Formulas I and/or II).
  • the contaminants can be in a free state such that they exist with the multivalent cation-binding ligand and the substrate but are not bound thereto by any chemical interactions.
  • the method of using compositions according to aspects of the present disclosure can comprise exposing a sample to a composition disclosed herein.
  • the method comprises exposing the sample to a composition comprising the substrate and the multivalent cation-binding ligand wherein the composition has first been exposed to the positively-charged species.
  • the sample can be exposed to the composition before or concurrently with the positively-charged species.
  • the sample can be exposed to the composition by flowing the sample through a column comprising the composition.
  • the method can comprise mixing the sample with the composition using suitable techniques (e.g., shaking, agitating, or the like).
  • the sample can be in the form of a solid or a solution.
  • the sample is in the form of a solution that can further comprise contaminants or other reagents (e.g., buffers, etc.).
  • the method can be performed such that target species contained within the sample are extracted by the composition.
  • the target species become associated with the multivalent cation-binding ligand and can thus be indirectly bound to the substrate.
  • the target species can thus be separated from extraneous contaminants and sample solution.
  • the method can be performed such that contaminants contained within the sample are extracted and removed from a target species also contained within the sample.
  • the contaminants become associated with the multivalent cation-binding ligand and can thus be indirectly bound to the substrate. The contaminants can thus be separated from any target species that might be present in the sample.
  • the method can comprise eluting, from the composition, any contaminants or target species that have been bound indirectly to the substrate.
  • the composition comprising the bound contaminant or target is subjected to an elution solution capable of removing the contaminant or the target from the composition and thus isolating the target, either by affirmatively eluting the target with the elution solution or eluting the contaminants with the elution solution, leaving the target associated with the substrate through the multivalent cation-binding ligand.
  • the target can be finally stripped from the composition using another suitable elution solution.
  • the composition can further be stripped of any positively-charged species that is associated with the multivalent cation-binding ligand using a stripping solution.
  • the stripping solution can comprise an acidic species that facilitates providing hydrogen ions that can displace positively-charged ion species that are associated with the multivalent cation-binding ligand.
  • the stripping solution can comprise a basic species that facilitates either providing 1 + or 2+ charged metal ions that can displace positively-charged ion species that are associated with the multivalent cation-binding ligand.
  • Exemplary stripping solutions can comprise an acid selected from hydrochloric acid, nitric acid, acetic acid, phosphoric acid, sulfuric acid, formic acid, boric acid, citric acid, and the like or a base selected from sodium hydroxide, lithium hydroxide, and the like.
  • a "target molecule" of interest may have pharmaceutical, diagnostic, agricultural, and/or any of a variety of other properties that are useful in commercial, experimental, or other applications.
  • a "target molecule” of interest can be an antibody or protein therapeutic.
  • the "target molecule” is an antibody.
  • Exemplary target molecules of interest are described herein in Table 1. [0078] In aspects where the method is used to separate one or more contaminants from a target, the contaminants can include unwanted species other than a target.
  • the disclosed composition can be used as an anion exchange resin.
  • the disclosed composition can be used as a cation exchange resin.
  • the composition can be used as a zwitterionic resin.
  • Table 1 below, details various applications in which compositions of the present disclosure that include a multivalent cation-binding ligand can be used, along with targeted modalities, conditions to be used (binding and elution conditions), the type of ion exchange involved, and the expected mode of operation. Those in the art will recognize how to conduct methods utilizing the conditions described in Table 1 with the benefit of the present disclosure.
  • compositions comprising: a substrate; and a multivalent cation-binding ligand covalently bound to a surface of the substrate, wherein the multivalent cation-binding ligand has a structure according to one of Formulas I or II
  • each Y independently for each occurrence, is a bond, an aliphatic group, or a heteroaliphatic group
  • each Z 1 is selected from -O[X(A) s (A')mA"]q-H r or -[X(A) s (A')mA”]q-H r
  • each X independently for each occurrence, is P, S, B, N, or C
  • each A independently for each occurrence, is selected from O or S
  • each A’ independently for each occurrence, is selected from -OH, -SH, -O', or -S'
  • each A”, independently for each occurrence, is selected from O, S, O', or S'
  • each s, independently for each occurrence is an integer selected from 0 or 1
  • each m independently for each occurrence, is an integer selected from 0 or 1
  • q is an integer selected from 1 to 10
  • r is an integer selected from 0 or 1
  • each Z 2 is selected from -O[
  • m is 1 when X is C, B, N, or S, and m is 2 when X is P.
  • each Y independently for each occurrence is selected from a bond, an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, or a heteroalkynyl group.
  • each Y is a bond, -Ph-CH2-N(H)-Ph, -Ph-CHz-. or - [NH2] + [CHzCH2]t-, or -[NH2] + [CH2CH2Y’]t-, wherein Y’ is O, S, or NH, and t is an integer ranging from 1 to 8.
  • Z 1 is selected from -OP(O)(OH)2, -P(O)(OH)2, -O- C(O)OH, -C(O)(OH), -O-S(O) 2 (OH), -S(O) 2 (OH), -OP(S)(OH) 2 , -P(S)(OH)2, -O-C(S)OH, -C(S)(OH), -O- S(S) 2 (OH), -S(S) 2 (OH), -OP(S)(SH) 2 , -P(S)(SH) 2 , -O-C(S)SH, -C(S)(SH), -O-S(S) 2 (SH), -S(S) 2 (SH), -OP(S)(OH)(SH), -P(S)(OH)(SH), -OP(O)(O ) 2 , -P(O)(O)(O) 2 , -P(O)(O
  • Z 1 is selected from -P(O)(OH)O-P(O)(OH)OH, -P(O)(OH)O- P(O)(OH)O-P(O)(OH)OH, -P(O)(OH)O-P(O)(OH)O-P(O)(OH)OH, -P(O)(O O-P(O)(O ) 2 , - P(O)(OH)O-P(O)(OH)O-P(O)(O')2, or -P(O)(OH)O-P(O)(OH)O-P(O)(OH)O-P(O)(O ) 2 .
  • At least one Z 2 is selected from -OP(O)(OH)2, -P(O)(OH)2, -O- C(O)OH, -C(O)(OH), -O-S(O) 2 (OH), -S(O) 2 (OH), -OP(S)(OH) 2J -P(S)(OH) 2 , -O-C(S)OH, -C(S)(OH), -O- S(S) 2 (OH), -S(S) 2 (OH), -OP(S)(SH) 2 , -P(S)(SH) 2 , -O-C(S)SH, -C(S)(SH), -O-S(S) 2 (SH), -S(S) 2 (SH), -OP(S)(OH)(SH), -P(S)(OH)(SH), -OP(O)(O ) 2 , -P(O) 2 , -P(O)(OH)(
  • At least one Z 2 is selected from -P(O)(OH) 2 , -C(O)(OH), - S(O) 2 (OH), -P(S)(OH) Z , -C(S)(OH), -S(S) 2 (OH), -P(S)(SH) Z , -C(S)(SH), -S(S) 2 (SH), -P(S)(OH)(SH), -P(O)(O- )2, -0(0)0-, -S(O) 2 (O ), -P(S)(O-)2, -C(S)O-, -S(S) 2 O-, -P(S)(S-)2, -C(S)S-, or -P(S)(O )(S ), -OB(OH) 2 , -B(OH) 2 , -OB(O')2, -B(O-)2, -B(O-)2,
  • At least one Z 2 is selected from -P(O)(OH)O-P(O)(OH)OH, - P(O)(OH)O-P(O)(OH)O-P(O)(OH)OH, -P(O)(OH)O-P(O)(OH)O-P(O)(OH)OH, -P(O)(O )O- P(O)(O') 2 , -P(O)(OH)O-P(O)(OH)O-P(O)(O-) 2 , or -P(O)(OH)O-P(O)(OH)O-P(O)(OH)O-P(O)(O ) 2 , - OP(O)(OH)O-P(O)(OH, -OP(O)(OH)O-P(O)(OH)OH, -OP(O)(OH)O-P(O-P(O)(OH)OH, -OP(O)(OH)O
  • At least one Z 2 is R 3 , wherein R 3 is hydrogen, an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, a heteroalkynyl group, an aryl group, or a heteroaryl group.
  • each of R 1 and R 2 independently, for each occurrence, is selected from hydrogen, an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, a heteroalkynyl group, an aryl group, or a heteroaryl group.
  • the TG group is hydrogen or hydroxyl.
  • the multivalent cation-binding ligand has a structure according to
  • the multivalent cation-binding ligand has a structure according to one of Formulas IIA-IIF
  • the multivalent cation-binding ligand is selected from any of the species disclosed herein.
  • the substrate is a porous material, a non-porous material, a microporous material, a woven material, a non-woven material, a polymeric material, a non-polymeric material, or a fibrous material.
  • the substrate is in the form of a resin, a bead, a sphere, a particle, a microcarrier, a membrane, a web, a bag, a bioreactor, a tube, a plate, an array, a filter, a fiber, a fabric, or any combination thereof.
  • the substrate comprises a ceramic material, a glass material, a metal material, a silica material, a synthetic or natural polymeric material, or any combination thereof.
  • the substrate comprises a functional group that extends from the surface of the substrate to which the multivalent cation-binding ligand according to Formula I is bound and wherein the multivalent cation-binding ligand is bound to the functional group via a direct covalent bond between Z 1 and the heteroatom.
  • the multivalent cation-binding ligand and the substrate are bound as illustrated in Formula III, wherein X' is O; S; NR' wherein R’ is hydrogen, aliphatic, or aromatic; Se; Te;
  • the substrate comprises a functional group that extends from the surface of the substrate to which the multivalent cation-binding ligand according to Formula II is bound and wherein the multivalent cation-binding ligand is bound to the functional group via a covalent bond formed between the heteroatom and a carbon atom to which Z 2 is bound, directly or indirectly.
  • the multivalent cation-binding ligand and the substrate are bound as illustrated in Formula IV wherein X’ is O; S; NR’ wherein R’ is hydrogen, aliphatic, or aromatic; Se; Te;
  • the functional group is a heteroatom-containing functional group that comprises a heteroatom selected from oxygen, sulfur, or nitrogen.
  • the functional group is a heteroatom-containing functional group selected from a thiol group, a hydroxyl group, or an amine group.
  • the composition further comprises a positively-charged species.
  • the positively-charged species is associated with the multivalent cation-binding ligand.
  • the positively-charged ion species is associated with the multivalent cation-binding ligand through coordination bonds formed between the positively-charged ion species and (i) negatively charged oxygen atoms of the multivalent cation-binding ligand, (ii) lone pair electrons of oxygen
  • the positively-charged ion species is a multivalent cationic species.
  • the multivalent cationic species has a 2+, 3+, or 4+ oxidation state.
  • the multivalent cationic species has a 2+ oxidation state.
  • the positively-charged ion species is selected from Ca 2+ , Mg 2+ , Fe 2+ , Zn 2+ , Cu 2+ , Cr 2+ , Ag 2+ , Co 2+ , Ni 2+ , Mn 2+ , V 2+ , or any combination thereof.
  • the composition comprises a plurality of positively-charged ion species, wherein each positively-charged ion species of the plurality is the same or different.
  • the composition further comprises a target, a contaminant, or a combination thereof.
  • the composition comprises the target and the target is associated with the substrate through interactions between the target and the positively-charged ion species.
  • the target is a biological molecule of interest.
  • the biological molecule of interest is selected from antibodies, proteins, peptides, glycoproteins, lipoproteins, enzymes, nucleic acids, nucleoproteins, viruses, virus-like particles, viral fragments, viral capsids, viral antigens, antigenic proteins, cellular markers, cells or particular cell types, a cellular component or cell parts, organelles, receptor proteins, vaccines, or any combinations thereof.
  • the composition comprises the contaminant and the contaminant is associated with the substrate through interactions between the contaminant and the positively-charged ion species.
  • kits comprising: the composition according to any or all of the above composition aspects; and a container configured to house the composition during use of the composition.
  • the sample comprises the target and one or more contaminants.
  • the target is a biological molecule.
  • the solution is an elution solution formulated to dissociate the target from the multivalent cation-binding ligand so as to isolate the target from the sample.
  • the method further comprises exposing the composition to a stripping solution after separating the target from the sample.
  • the method further comprises forming the composition prior to exposing the sample to the composition, wherein forming the composition comprises combining a composition according to any or all of the above composition aspects with a positively-charged ion species.
  • composition according to any or all composition aspects described above is used for capturing a recombinant protein, peptide, or enzyme; a virus or a virus-like particle; an adeno-associated virus; a nucleic acid; a plasma-derived protein; or any combination thereof.
  • composition comprising: a solid substrate; and an associating means for associating a positively-charged ion species with the solid substate.
  • the associating means is a multivalent cation-binding ligand.
  • reaction solid was isolated by filtration and washed (30 minutes per wash, 100 mL per wash) with a solution comprising 3 x Acetone:D.L water 1 :1 , 2 x D.l. Water, EthanokD.L Water and Acetone.
  • substrate-bound multivalent cation-binding ligand was isolated by filtration and dried under vacuum at 60°C until at constant weight.
  • reaction solid was isolated by filtration and washed with using 30 minutes per wash, 200 mL per wash. Washes comprised 7 x D.L water and 1 x Acetone. After the final wash, the substrate-bound multivalent cation-binding ligand was isolated by filtration and dried under vacuum at 60°C until at constant weight.
  • reaction was isolated by filtration to give an off-white solid.
  • the solid was then washed with washes consisting of 50-75mL of solvent, stirring for 10 mins/wash. Washes included a 1 :1 mixture of D.L water and methanol. Washes continued until pH of reaction wash was equal to pH of virgin methanol :D.L water solution.
  • the substrate-bound multivalent cation-binding ligand was dried under vacuum at 60 °C until at constant weight.
  • Aqueous prep To a single neck flask with magnetic stir bar was added 200ml of water followed by 1.76g polyvinyl alcohol (PVA). The flask was stirred while heating to 80°C. The solution was stirred until contents were fully dissolved. The solution was removed from heat and to the solution was added 12.88g of sodium chloride dissolved in 25mL water. The solution was stirred until uniform then transferred to a 500mL jacketed reactor with overhead stirring and stir shaft comprised of a lower PTFE, Turbine Agitator and upper four-Blade PTFE Agitator Stirrer Blades. The solution was stirred and brought to 20°C with external bath. The solution was stirred and degassed under N2 for20 minutes at 200rpm.
  • PVA polyvinyl alcohol
  • reaction quench After 18 hours, the reaction solid was isolated by filtration. The off-white solid was then washed with 75mL of solvent and stirring for 10 mins/wash. Washes included a 1 :1 mixture of D.L water and methanol. Washes continued until pH of reaction wash was equal to pH of virgin methanol:D.L water solution.
  • substrate-bound multivalent cation-binding ligands according to the examples above were evaluated for binding of different positively-charged species.
  • sample resin The substrate-bound multivalent cation-binding ligands (referred to herein as “sample resin”) are suspended in a 20mM solution of a positively-charged species, such as an M 2+ metal (10 mL per gram of sample resin).
  • a positively-charged species such as an M 2+ metal (10 mL per gram of sample resin).
  • the sample resin is slurried for 20-30 minutes then isolated by filtration. Solids are then washed with D.L water until the filtrate wash reaches a pH of 7.
  • the resulting chelate comprising the substrate-bound multivalent cation-binding ligand associated with the positively-charged species can then be used for multivalent metal retention separations.
  • M 2+ metal ion chelates were effectively chelated with the substrate-bound multivalent cation-binding ligand examples described above: magnesium 2 -, calcium 2 -, iron 2 -, colbalt 2 -, copper 2 -.
  • compositions according to the present disclosure were evaluated, wherein the substrates were bound directly or indirectly to at least one phosphate group.
  • the compositions were evaluated for their ability to selectively separate different target species (i.e., proteins including myoglobin, ovalbumin, chymotripsinogen A, and cytochrome C).
  • DBC dynamic binding capacity
  • FIGS. 2-6 show results for composition 4;
  • FIG. 3 shows results for composition 7 (as compared against CHT);
  • FIG. 4 shows results for composition 3 (as compared against CHT);
  • FIG. 5 shows results for composition 4 (as compared against CHT);
  • FIG. 6 shows results for composition 8 (as compared against CHT).
  • compositions disclosed herein to separate a target (e.g., myoglobin) from a sample was evaluated as well as the ability of the composition to be regenerated.
  • Table 4 provides results wherein no regeneration was conducted and
  • Table 5 provides results with Ca 2+ regeneration with Ca(OH)2, demonstrating that the composition can incorporate calcium and facilitate quantitative elutions of myoglobin from the composition.
  • a binding assay was performed to evaluate the effect of pH and salt on the efficacy of a composition comprising multivalent cation-binding ligands according to the present disclosure.
  • the multivalent cation-binding ligands used in this example are illustrated below (denoted as (550) Vinyl, (R6)PO3, and (150)P020P03), with the resin to which they are bound being illustrated as a circle.
  • a control (denoted as “CHT”), was also used as a comparison example. O 3 ,
  • the evaluations were conducted using 96-well plates, with each well containing 20 pL of a 50% slurry of resins comprising a multivalent cation-binding ligand according to the present disclosure.
  • the resins were equilibrated with buffers of either 10 mM or 25 mM sodium phosphate at pH levels of 5.0, 5.8, 6.8, and 9.2, respectively.
  • Concentrated Herceptin monoclonal antibodies (mAbs) containing 10% aggregates, were loaded onto the resins at loading densities of 20, 40, 60, or 80 gg/gL of resin. The plates were then shaken at 400 rpm for 30 minutes.
  • the mAbs were eluted using buffers containing either 0.2 M or 0.5 M NaCI at various pH levels. The eluates were collected in 1 mL deep 96-well plates. To measure protein concentration, 100 gL of each sample was transferred to a UV-transparent plate, and absorbance at 280 nm was read using a Varioskan plate reader. Protein concentrations were determined based on a standard curve for the monoclonal antibodies. Results are summarized in Tables 7- 10 for examples at pH 6.8 using 25 mM NaPC at 0.2 M NaCI (Table 7) or 0.5 M NaCI (Table 8), or using 10 mM NaPC>4 at 0.2 M NaCI (Table 9) or 0.5 M NaCI (Table 10).
  • Results are summarized in Tables 11 -14 for examples at pH 5.8 using 25 mM NaPC at 0.2 M NaCI (Table 11 ) or 0.5 M NaCI (Table 12), or using 10 mM NaPO at 0.2 M NaCI (Table 13) or 0.5 M NaCI (Table 14). Results are summarized in Tables 15 and 16 for examples at pH 9.2 using 10 mM NaPO4 at 0.2 M NaCI (Table 15) or 0.5 M NaCI (Table 16). Results are summarized in Tables 17 and 18 for examples at pH 5.0 using 10 mM NaPC>4 at 0.2 M NaCI (Table 17) or 0.5 M NaCI (Table 18).
  • an aggregation separation assay also was performed with these compositions.
  • Monomer purity and aggregate levels were analyzed by Size- Exclusion Chromatography using a Thermo Scientific MAbPac-1 column on a Thermo Fisher HPLC 3000 system. Twenty micrograms of loading materials and elution collections were loaded with sodium phosphate and sodium chloride mobile phase. Peak areas were used to calculate monomer recovery and aggregate removal percentages.
  • Results for monomer and aggregation purifications based on 10 mM NaPC , with elutions using 0.5M NaCI, and pH 6.8 are summarized in Table 19, below.
  • Results for monomer and aggregation purifications based on 10 mM NaPC>4, with elutions using 0.5M NaCI, and pH 5.8 are summarized in Table 20, below.
  • Results for monomer and aggregation purifications based on 10 mM NaPO4, with elutions using 0.5M NaCI, and pH 9.2 are summarized in Table 21 , below.
  • results for monomer and aggregation purifications based on 10 mM Sodium Acetate, with elutions using 0.5M NaCI, and pH 5.0 are summarized in Table 22, below.
  • the multivalent cation-binding ligands tested for MAb binding capacity performed well at lower phosphate buffer solutions (10mM NaPC ).
  • the multivalent cationbinding ligands tolerated buffers >pH 5.0 and had successful Mab binding capacity.
  • MAb recovery percentage varied between 25% to 85% for the different multivalent cation-binding ligands that were evaluated, monomer percent recovery was >90% and aggregate percent recovery ranged from 10 to 20.5% depending on the multivalent cation-binding ligand used and the differences in buffer composition and buffer pH.
  • compositions 12 and 13 Composition 14
  • DNA impurities such as templates (5-10%), are typically present, which can mislead the estimation of actual AAV concentration based on UV absorbance measurement at 260nm.
  • a procedure wherein a final product is allowed to flow through a composition according to the present disclosure can be used to thereby eliminate this issue including scale- up manufacturing.
  • DNA molecules incorporated into viral particle cannot be affected as viral DNA/RNA are protected by capsid structure.

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Abstract

L'invention concerne des compositions comprenant un substrat solide qui est lié à un ligand de liaison à un cation multivalent. La composition peut être utilisée pour associer des espèces ioniques chargées positivement au substrat solide de façon à faciliter des procédés de séparation dans la phase solide. L'invention concerne également des procédés de fabrication et d'utilisation de la composition.
PCT/US2025/016608 2024-02-21 2025-02-20 Ligands de liaison à des cations multivalents et compositions les comprenant pour des séparations par affinité de chélates ioniques Pending WO2025179026A1 (fr)

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Citations (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US41A (en) 1836-10-08 Frederick j
US5552A (en) 1848-05-09 Paul stillman
US3997482A (en) 1974-01-14 1976-12-14 Ceskoslovenska Akademie Ved Hydrophilic polymeric carriers of biologically active compounds and method of preparing the same
US5334310A (en) 1991-10-21 1994-08-02 Cornell Research Foundation, Inc. Column with macroporous polymer media
US5593729A (en) 1992-10-21 1997-01-14 Cornell Research Foundation, Inc. Pore-size selective modification of porous materials
US5605623A (en) 1989-07-06 1997-02-25 Perseptive Biosystems, Inc. Perfusive chromatography
US5728457A (en) 1994-09-30 1998-03-17 Cornell Research Foundation, Inc. Porous polymeric material with gradients
US5929214A (en) 1997-02-28 1999-07-27 Cornell Research Foundation, Inc. Thermally responsive polymer monoliths
US6238565B1 (en) 1998-09-16 2001-05-29 Varian, Inc. Monolithic matrix for separating bio-organic molecules
US20020043499A1 (en) 2000-03-14 2002-04-18 Hammen Richard F. Composite matrices with interstitial polymer networks
US6616825B1 (en) 2000-08-23 2003-09-09 The Regents Of The University Of California Electrochromatographic device for use in enantioselective separation, and enantioselective separation medium for use therein
US6884345B1 (en) * 1998-11-09 2005-04-26 Knut Irgum Chromatography method and a column material useful in said method
US7678269B2 (en) * 2005-09-19 2010-03-16 Millipore Corporation Asymmetric porous adsorptive bead
US20100160605A1 (en) 2008-12-18 2010-06-24 Tosoh Corporation Packing material for liquid chromatography and process for separation and purification of biopolymer by means of the packing material
US8356717B2 (en) 2007-10-11 2013-01-22 3M Innovative Properties Company Hydrophilic porous substrates
US20130245139A1 (en) 2012-03-12 2013-09-19 EMD Millpore Corporation Removal of protein aggregates from biopharmaceutical preparations in a flow-through mode
US20140316017A1 (en) 2011-12-22 2014-10-23 Lanxess Deutschland Gmbh Thiol group-containing acrylate resin
US8940172B2 (en) 2006-12-01 2015-01-27 Institute Of Process Engineering, Chinese Academy Of Sciences Super-macroporous polymeric microspheres and preparation method thereof
US9028683B2 (en) 2005-06-09 2015-05-12 Tosoh Corporation Packing material with excellent hydrophilicity and process for producing the same
US20160122368A1 (en) * 2014-10-29 2016-05-05 Dionex Corporation Chromatographic material and method for preparation thereof
WO2019169040A1 (fr) * 2018-02-27 2019-09-06 Life Technologies Corporation Milieux de séparation fonctionnalisés par un floculant

Patent Citations (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5552A (en) 1848-05-09 Paul stillman
US41A (en) 1836-10-08 Frederick j
US3997482A (en) 1974-01-14 1976-12-14 Ceskoslovenska Akademie Ved Hydrophilic polymeric carriers of biologically active compounds and method of preparing the same
US5605623A (en) 1989-07-06 1997-02-25 Perseptive Biosystems, Inc. Perfusive chromatography
US5833861A (en) 1989-07-06 1998-11-10 Perseptive Biosystems, Inc. Perfusive chromatography
US5334310A (en) 1991-10-21 1994-08-02 Cornell Research Foundation, Inc. Column with macroporous polymer media
US5453185A (en) 1991-10-21 1995-09-26 Cornell Research Foundation, Inc. Column with macroporous polymer media
US5593729A (en) 1992-10-21 1997-01-14 Cornell Research Foundation, Inc. Pore-size selective modification of porous materials
US5728457A (en) 1994-09-30 1998-03-17 Cornell Research Foundation, Inc. Porous polymeric material with gradients
US5929214A (en) 1997-02-28 1999-07-27 Cornell Research Foundation, Inc. Thermally responsive polymer monoliths
US6238565B1 (en) 1998-09-16 2001-05-29 Varian, Inc. Monolithic matrix for separating bio-organic molecules
US6884345B1 (en) * 1998-11-09 2005-04-26 Knut Irgum Chromatography method and a column material useful in said method
US20020043499A1 (en) 2000-03-14 2002-04-18 Hammen Richard F. Composite matrices with interstitial polymer networks
US6616825B1 (en) 2000-08-23 2003-09-09 The Regents Of The University Of California Electrochromatographic device for use in enantioselective separation, and enantioselective separation medium for use therein
US9028683B2 (en) 2005-06-09 2015-05-12 Tosoh Corporation Packing material with excellent hydrophilicity and process for producing the same
US7678269B2 (en) * 2005-09-19 2010-03-16 Millipore Corporation Asymmetric porous adsorptive bead
US20140073769A1 (en) 2005-09-19 2014-03-13 Emd Millipore Corporation Asymmetric porous adsorptive bead
US8940172B2 (en) 2006-12-01 2015-01-27 Institute Of Process Engineering, Chinese Academy Of Sciences Super-macroporous polymeric microspheres and preparation method thereof
US8356717B2 (en) 2007-10-11 2013-01-22 3M Innovative Properties Company Hydrophilic porous substrates
US20100160605A1 (en) 2008-12-18 2010-06-24 Tosoh Corporation Packing material for liquid chromatography and process for separation and purification of biopolymer by means of the packing material
US20140316017A1 (en) 2011-12-22 2014-10-23 Lanxess Deutschland Gmbh Thiol group-containing acrylate resin
US20130245139A1 (en) 2012-03-12 2013-09-19 EMD Millpore Corporation Removal of protein aggregates from biopharmaceutical preparations in a flow-through mode
US20160122368A1 (en) * 2014-10-29 2016-05-05 Dionex Corporation Chromatographic material and method for preparation thereof
WO2019169040A1 (fr) * 2018-02-27 2019-09-06 Life Technologies Corporation Milieux de séparation fonctionnalisés par un floculant

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HE XIAO-MEI ET AL: "Graft modification of cotton with phosphate group and its application to the enrichment of phosphopeptides", JOURNAL OF CHROMATOGRAPHY A, ELSEVIER, AMSTERDAM, NL, vol. 1484, 9 January 2017 (2017-01-09), pages 49 - 57, XP029891060, ISSN: 0021-9673, DOI: 10.1016/J.CHROMA.2017.01.020 *

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