Bispecific molecule comprising an anti-cr1 antibody cross-linked to an antigen-binding antibody fragment
OwnerNehal Mohamed, Leslie Casey +3inventors
InventorsNehal Mohamed, Leslie Casey, James Porter, Xiaoliang Wang, Muctarr Sesay
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Abstract
The invention provides a bispecific molecule comprising an antibody that binds a C3b-like to one or more antigen-binding antibody fragments, each of which binds an antigenic molecule. The invention also provides methods of producing such bispecific molecules and to therapeutic uses of such bispecific molecules. The invention further provides bispecific molecules in which the antigen-binding antibody fragment binds the protective antigen protein of Bacillus anthracis (Anthrax) exotoxin for treatment of Anthrax infection.
Claims93
A bispecific molecule comprising an antibody cross-linked to one or more antigen-binding antibody fragments via a chemical cross-linker, wherein said antibody binds a C3b-like receptor, and wherein each of said one or more antigen-binding antibody fragments binds an antigenic molecule.
A method of producing a bispecific molecule, comprising
- (a) producing an antigen-binding antibody fragment comprising a cysteine residue by a host cell such that said cysteine residue in said antigen-binding antibody fragment is maintained as a free thiol;
- (b) recovering said antigen-binding fragment having said free thiol;
- and
- (c) contacting said antigen-binding antibody fragment having said free thiol with a derivatized antibody that binds a C3b-like receptor under appropriate conditions such that said derivatized antibody cross-links to said antigen-binding antibody fragment at said free thiol;
- thereby producing said bispecific molecule.
A method of producing a bispecific molecule, comprising cross-linking an antibody with an antigen-binding antibody fragment, wherein said antibody binds a C3b-like receptor and said antigen-binding antibody fragment binds an antigenic molecule.
A method of producing a bispecific molecule, comprising
- (a) producing a thiol-derivatized antigen-binding antibody fragment such that said antigen-binding antibody fragment comprises a free thiol;
- (b) producing a maleimide-derivatized antibody that binds a C3b-like receptor such that said antibody comprises a maleimide;
- and
- (c) contacting said antigen-binding antibody fragment containing said free thiol with said antibody containing said maleimide under conditions such that said antibody and said antigen-binding antibody fragment cross-link via said maleimide and said free thiol;
- thereby producing said bispecific molecule.
A polyclonal population of bispecific molecules comprising a plurality of different bispecific molecules, each bispecific molecule in said plurality comprising an antibody cross-linked via a chemical cross-linker to one or more antigen-binding antibody fragments, wherein said antibody binds a C3b-like receptor, and wherein said antigen-binding fragments bind an antigenic molecule.
A method of treating a mammal having an undesirable condition associated with the presence of an antigenic molecule in its circulation, comprising the step of administering to the mammal a therapeutically effective amount of a bispecific molecule comprising an antibody cross-linked to one or more antigen-binding antibody fragments via a chemical cross-linker, wherein said antibody binds a C3b-like receptor on a blood cell of said mammal, and wherein each of said one or more antigen-binding antibody fragments binds said antigenic molecule.
A method of producing a bispecific molecule, comprising
- (a) producing a maleimide-derivatized antigen-binding antibody fragment such that said antigen-binding antibody fragment comprises a maleimide;
- (b) producing a thiol-derivatized antibody that binds a C3b-like receptor such that said antibody comprises a free thiol;
- and
- (c) contacting said antigen-binding antibody fragment containing said maleimide with said antibody containing said free thiol under conditions such that said antibody and said antigen-binding antibody fragment cross-link via said maleimide and said free thiol,
- thereby producing said bispecific molecule.
Dependencies are inferred from the claim text.