Compbody—a multivalent target binder
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Publication Number
US-12043651-B2
Publication Date
2024-07-23
Expiration Date
Abstract
Herein is reported a multimeric fusion polypeptide comprising five monomeric fusion polypeptides each comprising at least a Fab fragment and a COMP-domain of SEQ ID NO: 01 or a functional fragment thereof.
Core Innovation
The invention relates to “Compbody” multimeric, multispecific fusion polypeptides built from pentamerized full-length IgG antibody monomers. Each fusion polypeptide includes a full length IgG antibody and a coiled coil domain of human cartilage oligomeric matrix protein (COMP)-domain consisting of the amino acid sequence of SEQ ID NO: 1, conjugated via a peptidic linker.
In the disclosed fusion polypeptide, the COMP-domain is conjugated to the C-terminus of the IgG heavy chain of the full length IgG antibody. The COMP-domain functions as a pentamerizing coiled-coil arrangement, producing five-unit multivalent binders.
Disclosed Compbody formats include binding-site architectures such as VH/VL, Fab variants including DAF/CrossFab/DutaFab, and scFv, as well as IgG knob-into-hole heterodimerizing schemes using CH3 mutation schemes. Recombinant production concepts are described for generating COMP-Fab pentamer and COMP-IgG pentamer.
Claims Coverage
The partial claims provided include two independent claims. Across the structure claim, the core inventive coverage comprises five monomeric IgG fusion polypeptides pentamerized via a COMP coiled-coil domain and conjugated through a peptidic linker at a defined IgG heavy-chain position; across the production claim, the coverage comprises transforming a host cell with expression vectors, culturing under synthesis-permitting conditions, and recovering the multimeric fusion polypeptide from host cell culture.
Pentamerized full-length IgG fused to COMP-domain coiled-coil
A multimeric, multispecific fusion polypeptide comprising pentamerized full-length IgG antibodies, wherein the fusion polypeptide comprises five monomeric fusion polypeptides each comprising a full length IgG antibody and a coiled coil domain of human cartilage oligomeric matrix protein (COMP)-domain consisting of the amino acid sequence of SEQ ID NO: 1.
Peptidic linker conjugating COMP-domain to IgG heavy-chain C-terminus
The fusion polypeptide wherein the full length IgG antibody is conjugated via a peptidic linker to the COMP-domain, and wherein the COMP-domain is conjugated to the C-terminus of the IgG heavy chain of the full length IgG antibody.
Production by transformation, culturing, and recovering from host cell culture
A multimeric fusion polypeptide produced by steps of transforming a host cell with expression vectors comprising nucleic acids encoding the multimeric fusion polypeptide, culturing said host cell under conditions that allow synthesis of said multimeric fusion polypeptide, and recovering said multimeric fusion polypeptide from said host cell culture.
The claim coverage centers on a pentamerized multimeric fusion polypeptide in which each IgG monomer is fused to a COMP-domain coiled-coil (SEQ ID NO: 1) via a peptidic linker conjugated at the C-terminus of the IgG heavy chain, yielding five-unit multivalent binders. A separate independent claim covers producing the multimeric fusion polypeptide by transforming a host cell with expression vectors, culturing to synthesize the fusion polypeptide, and recovering it from host cell culture.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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