Multi-specific antibodies and methods of making and using thereof
Inventors
Zhu, Yi • Olsen, Ole • Xia, Dong • JELLYMAN, David • BYKOVA, Katrina • ROUSSEAU, Anne-Marie K. • Brady, Bill • RENSHAW, Blair • Kovacevich, Brian • Liang, Yu • Gao, Zeren
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11787863-B2
Publication Date
2023-10-17
Expiration Date
Abstract
The disclosure provides a tetra-specific antibody monomer having a N-terminal and a C-terminal, comprising in tandem from the N-terminal to the C-terminal, a first scFv domain at the N-terminal, a Fab domain, a Fc domain, a second scFv domain, and a third scFv at the C-terminal, wherein the first scFv domain, the Fab domain, the second scFv domain, and the third scFv domain each has a binding specificity against a different antigen. In one embodiment, the antigen is a tumor antigen, an immune signaling antigen, or a combination thereof. Multi-specific antibodies comprising the disclosed tetra-specific antibodies are also provided.
Core Innovation
The disclosed invention relates to a tetra-specific antibody monomer having a tandem arrangement from an N-terminal to a C-terminal. The construct includes a first scFv domain at the N-terminal, a Fab domain, an Fc domain having an amino acid SEQ ID NO: 62, and second and third scFv domains at the C-terminal. The Fab domain comprises a CL having an amino acid SEQ ID NO: 64, and the monomer is defined to include particular combinations of binding specificities across the scFv and Fab domains.
The invention further specifies that the first scFv domain, the Fab domain, the second scFv domain, and the third scFv domain have a combination of binding specificities selected from defined sets. In one set, the first scFv domain has specificity against CD3, the Fab domain has specificity against EGFR VIII, the second scFv domain has specificity against PD-L1, and the third scFv domain has specificity against 4-1BB. In alternative sets, the defined combination replaces one or more targets, including CD19 and ROR1.
The tetra-specific antibody monomer is also defined by sequence elements, including that it comprises 3 CDRs of specified SEQ ID NOs for each of the first scFv, Fab, second scFv, and third scFv domains. The documented description supports binding of the construct to EGFRvIII, PD-L1, ROR1, and 4-1BB, and includes immune engagement through CD3 binding.
Claims Coverage
The independent claim defines a tetra-specific antibody monomer with four antigen-binding elements in tandem and restricts the construct to specific target-binding combinations, each tied to defined SEQ ID-based CDR content. The claim therefore covers a construct-level inventive framework with multiple alternative binding-specificity selections.
Tandem tetra-specific antibody monomer architecture
A tetra-specific antibody monomer having a N-terminal and a C-terminal, comprising in tandem from the N-terminal to the C-terminal: a first scFv domain at the N-terminal; a Fab domain comprising a CL having an amino acid SEQ ID NO. 64; an Fc domain having an amino acid SEQ ID NO. 62; a second scFv domain; and a third scFv domain at the C-terminal.
Defined binding-specificity combinations across the domains
Wherein the first scFv domain, the Fab domain, the second scFv domain and the third scFv domain have a combination of binding specificities selected from CD3/EGFR VIII/PD-L1/4-1BB, CD3/CD19/PD-L1/4-1BB, and 4-1BB/PD-L1/ROR1/CD3, with the further specific alternative stated for the CDR set selection within the last combination.
SEQ ID-based CDR composition for each binding element
Wherein the tetra-specific antibody monomer comprises 3 complementarity determining regions (CDRs) of SEQ ID NO. 2 and 3 CDRs of SEQ ID NO: 4, together with the specified 3 CDRs sets for the Fab, second scFv and third scFv elements as recited for each binding-specificity selection.
Overall, the claim coverage is centered on a tandem tetra-specific antibody monomer architecture that uses a Fab with a defined CL sequence and an Fc with a defined SEQ ID, and that restricts the monomer to particular four-target binding combinations. The additional limitation is a defined set of 3 CDRs (SEQ ID NO-based) associated with each binding element, providing structured control of the antigen-binding specificities.
Stated Advantages
Documented Applications
No documented applications found
Interested in licensing this patent?