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US 8,980,646 B2Granted
Proteolytic and covalent antibodies
AssigneePaul, Sudhir
InventorsSudhir Paul, Yasuhiro Nishiyama
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Abstract
Improved methods for the production, selection and inhibition of catalytic and covalent antibodies are disclosed.
Claims15
A method of obtaining covalent or catalytic antibodies from an organism, comprising identifying and isolating said covalent or catalytic antibodies by contacting antibodies from the organism with a covalently reactive polypeptide antigen analog (pCRA) of formula (I)
- L-E (I)
- wherein L is a polypeptide comprising an antigenic epitope recognized by said covalent or catalytic antibodies, wherein said antigenic epitope is linear or discontinuous
- wherein E is an electrophilic group conjugated to an amino acid side chain functional group of L having the formula
- Y-Y′-Y″-
- wherein
- Y″ is an atom, covalent bond or linker,
- Y′ is an atom, bond or chemical group that connects Y and L or Y″,
- Y is a covalently reactive electrophilic group which forms a covalent bond with a nucleophilic group of said covalent or catalytic antibody;
- wherein said organism is optionally immunized with said pCRA.
6 more elements
A water-binding, covalently reactive polypeptide antigen analogue (pCRAW) of formula (I):
- L-E (I)
- wherein L is a polypeptide comprising an antigenic epitope recognized by an antibody, wherein said antigenic epitope is linear or discontinuous;
- wherein E is an electrophilic group conjugated to an amino acid side chain functional group of L having the formula
- Y-Y′-Y″-
- wherein
- Y″ is an atom, covalent bond or linker,
- Y′ is an atom, bond or chemical group that connects Y and L or Y″,
- Y is a covalently reactive electrophilic group which forms a covalent bond with a nucleophilic group of said antibody,
- Y″, Y′ or Y contains a water-binding group as a terminal or internal component with a site that binds a zinc, copper, nickel, cobalt, calcium or magnesium ion which chelates one or more water molecules in which the metal binding site is -(His)n- where n=2 or more, or Cys-X-Cys-Cys or -Cys-X-Cys- wherein X is an amino acid residue, ethylene diamine tetraacetic acid or diaminomethyl pyridine.
6 more elements
Dependencies are inferred from the claim text.