Compound comprising Fc-binding unit, and conjugate prepared using same
Inventors
Chung, Sang Jeon • Oh, Yeong Soo • Kim, Juhwan • LEE, Younggeun • SEO, Jinwoo • LEE, Geonmin • KIM, Gahyeon • KWON, Sejeong • Park, Sunhee • YEOM, Hojin • OH, Hui Jo • SON, Jinyoung
Assignees
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Publication Number
US-12296020-B2
Publication Date
2025-05-13
Expiration Date
Abstract
Some embodiments of the present application provide a compound comprising Fc binding unit. The compound comprising Fc binding unit of the present application may be used to transfer a group of interest to an antibody in a position-specific manner. Furthermore, some embodiments of the present application provide a method for preparing an antibody conjugate comprising a group of interest (for example, a reactive group) using the compound comprising Fc binding unit.
Core Innovation
The invention provides a compound comprising an Fc binding unit (FcBU) having a defined Fc binding peptide or a modified Fc binding peptide. The framework includes spacer A that is an unsubstituted C3 alkylene, linker A that is a bond, an unsubstituted C1-30 alkylene, or an unsubstituted C1-30 heteroalkylene with heteroatoms independently selected from N, O, and S, X selected as —CH2— or —O—, and a reactive group (RG) defined by specified structures with hn as an integer of 1 to 3.
The Fc binding unit consists of a Fc binding peptide with defined attachment points and a modified Fc binding peptide. Two cysteine residues of the Fc binding peptide are optionally covalently linked to each other via a disulfide bond, and the modified Fc binding peptide is modified by at least one of amidation of the C terminal of the Fc binding peptide and conjugation of a polyethylene glycol (PEG) moiety to the N terminal of the Fc binding peptide.
The disclosure further specifies linker A variants that include ethylene glycol-containing segments and an unsubstituted C1-30 heteroalkylene containing 0 to 10 ethylene glycol units, together with PEG moiety structures having defined repeat-unit composition and terminal substituent RPEG. The document also describes antibody conjugate and antibody-payload conjugate architectures, including transfer of the reactive group to Fc lysines K246 and/or K248.
Claims Coverage
The provided claim sets center on one compound architecture built from an Fc binding unit, a spacer A/linker A framework, and a selectable reactive group RG, and they include one Fc binding peptide or modified Fc binding peptide. The merged claim coverage captures the recurring inventive features across the provided claim sets.
Fc binding unit with spacer, linker, and reactive-group architecture
A compound comprising Fc binding unit having a structure of formula 2-2, wherein spacer A is an unsubstituted C3 alkylene, linker A is a bond, unsubstituted C1-30 alkylene, or unsubstituted C1-30 heteroalkylene with heteroatoms independently selected from N, O, and S, X is —CH2— or —O—, R a1 is methyl, R a2 and R a3 are H, J is —C(=O)—, and RG is a reactive group having defined structures with hn being 1 to 3 and RH substituents selected from the listed set.
Fc binding peptide architecture with optional cysteine linkage
The Fc binding unit consists of a Fc binding peptide or a modified Fc binding peptide, wherein the Fc binding peptide has a defined structure and attachment points, and two cysteine residues of the Fc binding peptide are optionally covalently linked to each other via a disulfide bond.
Modified Fc binding peptide by C-terminal amidation and N-terminal PEG conjugation
The modified Fc binding peptide is modified by at least one of amidation of the C terminal of the Fc binding peptide and conjugation of a polyethylene glycol (PEG) moiety to the N terminal of the Fc binding peptide.
Reactive group selected from azide, norbornene, or DBCO
The reactive group (RG) is selected as an azide group, a norbornene group, or Dibenzocyclooctyne (DBCO).
Linker A with ethylene glycol-containing segments
Linker A is constructed as —La1—La2—La3—, with La1 and La3 being a bond or unsubstituted C1-10 alkylene, La2 being a bond or a repeating [EG] ethylene glycol unit, and at least one of La1, La2, or La3 not being a bond.
Unsubstituted C1-30 heteroalkylene linker containing ethylene glycol units
Linker A is an unsubstituted C1-30 heteroalkylene containing 0 to 10 ethylene glycol units defined by repeating ethylene glycol segment structures.
PEG moiety with defined repeat-unit composition and terminal substituent
A PEG moiety has a specified PEG structure including an EG repeat-unit pattern, an integer p, and a terminal substituent RPEG, with heteroatoms selected from O, N, and S and optional substituent options.
Fc binding peptide cysteine disulfide bond
Two cysteine residues of the Fc binding peptide are covalently linked to each other via a disulfide bond.
Overall, the claims focus on a compound platform defined by an Fc binding unit coupled through a constrained spacer/linker/reactive-group architecture, together with a specified Fc binding peptide or modified Fc binding peptide. Dependent claims further narrow the reactive group, linker ethylene-glycol-containing segments, PEG moiety structure, and disulfide linkage of cysteine residues.
Stated Advantages
Improved performance versus a prior FcBU approach.
Enables downstream ADC-like antibody-payload conjugates with branched linker/plasma stability.
Documented Applications
Antibody conjugate formation by transferring the reactive group from the FcBU compound to antibody Fc lysines K246 and/or K248.
Downstream ADC-like antibody-payload conjugates derived from the described antibody conjugates.
Antibody-payload conjugate architectures linked to anti-CLDN18.2 antibody units and payload attachment to Fc lysines K246 and K248.
Claudin 18.2-positive cancers.
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