Anti-transferrin receptor (TFR) antibody, encoding nucleic acid thereof and method of use thereof to deliver an oligonucleotide to a subject
Inventors
Subramanian, Romesh R. • Qatanani, Mohammed T. • Weeden, Timothy • Desjardins, Cody A. • Quinn, Brendan • Najim, John
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12734246-B2
Publication Date
2026-09-15
Expiration Date
Abstract
Aspects of the disclosure relate to antibodies that bind to transferrin receptor (e.g., transferrin receptor 1) and complexes comprising the antibody covalently linked to a molecular payload. Methods of using the antibodies are also provided.
Core Innovation
The invention provides an antibody that binds human transferrin receptor (TfR/TfR1) comprising specified heavy-chain variable region (VH) and light-chain variable region (VL) amino acid sequences. Disclosed embodiments include antibody formats such as Fab fragments and single-chain variable fragments, sequence variants, Fc modifications, and covalent antibody-payload complexes linked to molecular payloads, such as oligonucleotides, via specified linkers and spacers. The background section and summary text are omitted in the supplied excerpts, and the problem being solved is not explicitly described.
The disclosed molecular payloads encompass oligonucleotides including siRNA, miRNAs, aptamers, ribozymes, guide RNAs, multimers, and splice-altering oligonucleotides, as well as peptide, protein, small-molecule, and diagnostic agents. Reported characterizations demonstrate anti-TfR Fab-oligonucleotide conjugates enhancing exon-51 skipping in DMD myotubes, increasing tissue accumulation, reducing DMPK mRNA in muscle tissues, and facilitating receptor-mediated uptake. The disclosure further covers pharmaceutical formulations and methods for delivering an oligonucleotide to target tissues including muscle and brain.
Claims Coverage
The supplied claims identify one independent claim comprising one inventive feature directed to an antibody that binds human transferrin receptor, with dependent claims directed to antibody-payload complexes and delivery methods.
Antibody binding human transferrin receptor
The independent claim recites an antibody that binds human transferrin receptor (TfR), comprising a heavy chain variable region (VH) with the amino acid sequence of SEQ ID NO: 76 and a light chain variable region (VL) with the amino acid sequence of SEQ ID NO: 75.
The claim coverage focuses on the specified human TfR-binding antibody defined by VH and VL sequences, while further claims encompass covalent antibody-molecular payload complexes, oligonucleotide payloads, and methods for delivering an oligonucleotide to a subject.
Stated Advantages
Selected Fab-oligonucleotide conjugates enhance exon-51 skipping compared with naked oligonucleotide in human DMD myotubes.
In cynomolgus monkeys, the conjugate produces greater tissue ASO accumulation than unconjugated ASO across evaluated muscles and heart, increasing oligonucleotide tissue distribution.
The conjugates reduce DMPK mRNA in muscle tissues in hTfR1 knock-in mice, demonstrating cellular uptake and in vivo muscle-tissue activity.
Certain siRNA strand chemistries tune RISC loading and reduce off-target effects.
The antibodies serve as high-affinity TfR1 binders for receptor-mediated delivery of molecular payloads to target tissues, including muscle and brain.
Documented Applications
Diagnostic or therapeutic delivery of an oligonucleotide to a subject using an anti-TfR antibody-payload or antibody-oligonucleotide complex to target tissues, including muscle and brain.
Methods of delivering an oligonucleotide to treat muscular disorders and neurological diseases, including muscular dystrophy and Duchenne muscular dystrophy (DMD).
Oligonucleotide-mediated exon-51 skipping in human DMD myotubes and DMPK mRNA reduction in muscle tissues.
Pharmaceutical formulations containing the disclosed conjugates.
Interested in licensing this patent?