TRISPECIFIC ANTIBODY CONSTRUCTIONS TARGETED AT DLL3 AND METHODS OF USE THEREOF
Patent Information
- Application Number
- ARP20250100595
- Authority / Receiving Office
- AR · AR
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-12-10
- Filing Date
- 2025-03-05
- Publication Date
- 2026-09-02
Claims
This disclosure describes costimulatory trivalent and trispecific antibody constructs capable of binding to two different antigens on one or more cytotoxic effector cells and a TAA (such as DLL3) on a tumor cell. Pharmaceutical compositions comprising these antibody constructs and methods for preparing and using these constructs and compositions, for example, for cancer treatment, are also described.
1. An antibody construct comprising: (i) a first Fab domain capable of binding to CD3 on a cytotoxic effector cell; (ii) a first scFv domain capable of binding to CD28 on a cytotoxic effector cell; (iii) a third binding domain capable of binding DLL3 on a tumor cell; and (iv) a dimeric Fc domain comprising a first Fc polypeptide and a second Fc polypeptide, wherein: (a) the first Fab domain is coupled to the N-terminus of the first Fc polypeptide, (b) the third binding domain is coupled to the N-terminus of the second Fc polypeptide, and (c) the first scFv domain is coupled to: the C-terminus of the light chain of the first Fab domain.
33. A pharmaceutical composition comprising the antibody construct of any of claims 1-32, and a pharmaceutically acceptable carrier, excipient, diluent, or combination thereof.
34. A nucleic acid molecule or a set of nucleic acid molecules encoding one or more, two or more, three or more, or four or more polypeptide chains forming the antibody construct of any of claims 1-32.
35. A vector or a set of vectors comprising the nucleic acid molecule or the set of nucleic acid molecules of claim 34.
36. A cell comprising the nucleic acid molecule or set of nucleic acid molecules of claim 34, or the vector or set of vectors of claim 35.
37. A method for producing an antibody construct of any of claims 1-32, wherein the method comprises: (a) obtaining a host cell culture comprising at least one host cell comprising one or more nucleic acid molecules encoding one or more, two or more, three or more or four or more polypeptide chains forming the antibody construct and (b) recovering the antibody construct from the host cell culture.