Multi-specific molecules
Inventors
ROBERTS, Anthony Simon • Kopsidas, George • LUKE, Michael Ross • JENNINGS, Phil Anthony
Assignees
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Publication Number
US-11345736-B2
Publication Date
2022-05-31
Expiration Date
Abstract
The present disclosure relates to multi-specific molecules which are capable of simultaneously binding at least two different target antigens or epitopes. The molecules comprise at least one binding domain molecule (BDM) which hinds to a first target antigen or epitope, the BDM being modified for selective binding to a heterologous target, coupled to a pharmacologically active protein or peptide which is an antibody or antigen-binding fragment thereof or a non-antibody protein or peptide which binds to a second target antigen or epitope, the BDMs being coupled to a C-terminus of a polypeptide present within the pharmacologically active protein or peptide.
Core Innovation
The invention relates to a multi-specific molecule that binds to two or more different target antigens or epitopes. The molecule comprises at least one binding domain molecule (BDM) that binds to a first target antigen or epitope and a full length antibody or an antigen-binding fragment that binds to a second target antigen or epitope.
The at least one BDM has first, second, and third binding loops and includes the amino acid sequence set forth in SEQ ID NO:5. The multi-specific molecule is coupled by linking the BDM to the antibody or antigen-binding fragment such that the at least one BDM is coupled via its N-terminus to a C-terminus of a heavy and/or light chain of the antibody or antigen-binding fragment.
The coupling uses a peptide linker as set forth in SEQ ID NO:16 or SEQ ID NO:17. The provided content emphasizes generating multi-specific molecules and retaining binding and pharmacokinetics-related properties when forming bi-specific and tri-specific constructs. The approach provides modular coupling of BDMs to antibody formats including full length antibody and antigen-binding fragments, enabling multivalent multi-specific formats.
Claims Coverage
The consolidated claim coverage centers on three core inventive features: a multi-specific molecule, a defined BDM binding-loop architecture and sequence, and N-terminus-to-C-terminus coupling to an antibody chain using specified peptide linkers.
Multi-specific binding via BDM and antibody/antigen-binding fragment
A multi-specific molecule binds to two or more different target antigens or epitopes, comprising a BDM that binds to a first target antigen or epitope and a full length antibody or an antigen-binding fragment that binds to a second target antigen or epitope.
BDM binding-loop architecture with defined sequence
The at least one BDM has first, second, and third binding loops and has the amino acid sequence set forth in SEQ ID NO:5.
N-terminus-to-C-terminus coupling using defined peptide linker
The at least one BDM is coupled via its N-terminus to a C-terminus of a heavy and/or light chain of the antibody or antigen-binding fragment by a peptide linker as set forth in SEQ ID NO:16 or SEQ ID NO:17.
The claim coverage is directed to coupling a defined BDM to a full length antibody or antigen-binding fragment that binds a different antigen or epitope, using a specified peptide linker that connects the BDM N-terminus to an antibody heavy and/or light chain C-terminus.
Stated Advantages
Improved stability/half-life/avidity/therapeutic efficacy.
Retention of antibody function and avidity.
Stability/circulation time is improved when BDMs are added to proteins/antibodies.
Simpler generation of bi-specific or tri-specific molecules is achieved.
Retention of binding, avidity, structure/functions and pharmacokinetics is stated as an advantage.
Documented Applications
Detection and/or affinity purification using assay formats including Western blot and ELISA.
Biophysical binding characterization of constructs, including measurements of binding using tools such as ForteBio Blitz and SPR, including sensorgrams and binding parameters.
Immunofluorescence and radioimmunoassay are mentioned as assay formats within the provided content.
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