Muscle-targeting complexes and uses thereof
AssigneeDyne Therapeutics, Inc.
InventorsRomesh R. Subramanian, Mohammed T. Qatanani, Timothy Weeden, Jason P. Rhodes
Life of this patent
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Abstract
Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a disease allele associated with muscle disease. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.
Claims23
-91. (canceled)
A complex comprising a muscle-targeting agent covalently linked to a molecular payload configured to modulate expression or activity of a muscle disease gene that encodes a non-secreted product that functions within muscle cells, wherein the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells, wherein the muscle-targeting agent is a muscle-targeting antibody that specifically binds in the range of C89 to F760 of human transferrin receptor protein 1 (TfR1) having an amino acid sequence as set forth in SEQ ID NO:
- 1.
A complex comprising an anti-transferrin receptor antibody covalently linked to an oligonucleotide that targets an RNA encoded by a muscle disease gene in a muscle cell,
- wherein the oligonucleotide is 15-35 nucleotides in length and comprises a region of complementarity to the RNA, wherein the region of complementarity is at least 12 nucleotides in length;
- and
- wherein the anti-transferrin receptor antibody binds in the range of C89 to F760 of human transferrin receptor protein 1 (TfR1) having an amino acid sequence as set forth in SEQ ID NO:
- 1.
A method of modulating the expression or activity of a muscle disease gene in a muscle cell, the method comprising contacting the muscle cell with a complex comprising an anti-transferrin receptor antibody covalently linked to an oligonucleotide that targets an RNA encoded by a muscle disease gene in a muscle cell,
- wherein the oligonucleotide is 15-35 nucleotides in length and comprises a region of complementarity to the RNA, wherein the region of complementarity is at least 12 nucleotides in length;
- and
- wherein the anti-transferrin receptor antibody binds in the range of C89 to F760 of human transferrin receptor protein 1 (TfR1) having an amino acid sequence as set forth in SEQ ID NO:
- 1.
A method of treating a subject having a muscle disease, the method comprising administering to the subject a complex comprising an anti-transferrin receptor antibody covalently linked to an oligonucleotide that targets an RNA encoded by a muscle disease gene in a muscle cell,
- wherein the oligonucleotide is 15-35 nucleotides in length and comprises a region of complementarity to the RNA, wherein the region of complementarity is at least 12 nucleotides in length;
- and
- wherein the anti-transferrin receptor antibody binds in the range of C89 to F760 of human transferrin receptor protein 1 (TfR1) having an amino acid sequence as set forth in SEQ ID NO:
- 1.
Dependencies are inferred from the claim text.