Antibody-oligonucleotide conjugates
Inventors
Jaminet, Paul A. • JAMINET, Shou-Ching S. • Ha, Edward
Assignees
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Publication Number
US-12458705-B2
Publication Date
2025-11-04
Expiration Date
Abstract
Conjugates are provided, comprising a targeting protein, e.g., an anti-TM4SFI antibody or antigen or binding fragments thereof. Methods of manufacture and use of said conjugates are also described.
Core Innovation
The invention relates to an anti-TM4SF1 antibody or an antigen binding fragment thereof conjugated to an oligonucleotide. The antibody is specifically characterized by particular heavy chain CDR1, CDR2, and CDR3 sequences together with particular light chain CDR1, CDR2, and CDR3 sequences, with the option that the antibody comprises an alternative heavy chain sequence and an alternative light chain sequence.
The oligonucleotide is either a DNA molecule or an RNA molecule. The RNA molecule includes antisense oligonucleotides, siRNA, antisense RNA, miRNA, antisense miRNA, antagomir, shiRNA, and mRNA, and the DNA molecule includes modified DNA and triple helical DNA, supercoiled DNA, Z-DNA, and combinations thereof.
The conjugates are constructed using linker-mediated assembly between the antibody and the oligonucleotide. The disclosed conjugation strategies include covalent coupling and noncovalent coupling, with linker chemistry described using terminal functional groups and examples of cyclooctyne, cyclopropene, azide, tetrazine, and related cycloaddition chemistries, as well as leaving-group and alkoxy-amine terminus concepts.
The disclosure further includes alternative conjugation approaches, including copper-free or copper reaction concepts and cycloaddition families such as Huisgen cycloaddition, Diels-Alder, and Hetero Diels-Alder, and an mTGase-based strategy. The document also describes an optional viral protein p19-based siRNA carrier fused to the antibody, and an engineered-cysteine workflow using NHS, SPDB, or SMCC linkers and thio-ester reactive adducts.
Claims Coverage
The provided independent claim covers one inventive feature centered on a conjugate that specifies an anti-TM4SF1 antibody or antigen binding fragment and couples it to an oligonucleotide.
Anti-TM4SF1 antibody oligonucleotide conjugate defined by cdr sequence sets
A conjugate comprising an anti-TM4SF1 antibody or an antigen binding fragment thereof conjugated to an oligonucleotide, wherein the anti-TM4SF1 antibody or antigen binding fragment comprises specified heavy chain CDR1, CDR2, and CDR3 sequences and specified light chain CDR1, CDR2, and CDR3 sequences, with optional alternative heavy chain and light chain sequences.
The independent claim is centered on antibody-oligonucleotide conjugates where the antibody identity is constrained by specific heavy- and light-chain CDR1, CDR2, and CDR3 sequence sets, optionally including alternative heavy and light chain sequences.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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