Anti-vegf antibody constructs and related methods for treating vestibular schwannoma associated symptoms
AssigneeAkouos, Inc.
InventorsEmmanuel John Simons, Robert Ng, Michael John McKenna
Life of this patent
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Abstract
The present disclosure provides a construct comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a vascular endothelial growth factor (VEGF) binding agent or a portion thereof. In some embodiments, a construct is an AAV construct. In some embodiments, an AAV construct is a part of an AAV particle. Compositions comprising constructs and AAV particles described herein can be useful in treating hearing loss, for example, hearing loss associated with vestibular schwannoma.
Claims26
1-26. (canceled)
A method comprising contacting an inner ear cell with an adeno-associated virus (AAV) particle, comprising:
- (i) a nucleic acid construct comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a vascular endothelial growth factor (VEGF) binding agent or a portion thereof;
- and
- (ii) AAV Anc80 capsid,
- wherein the coding sequence includes a first nucleic acid sequence that encodes a first polypeptide of the VEGF binding agent and a second nucleic acid sequence that encodes a second polypeptide of the VEGF binding agent, and wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO:
- 16, and the second polypeptide comprises the amino acid sequence of SEQ ID NO:
- 20, and
- wherein the coding sequence is flanked by (a) a 5′ ITR comprising the nucleic acid sequence of SEQ ID NO:
- 45 and (b) a 3′ ITR comprising the nucleic acid sequence of SEQ ID NO:
- 46.
(canceled)
A method comprising introducing into an inner ear of a subject an adeno-associated virus (AAV) particle, comprising:
- (i) a nucleic acid construct comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a vascular endothelial growth factor (VEGF) binding agent or a portion thereof;
- and
- (ii) AAV Anc80 capsid,
- wherein the coding sequence includes a first nucleic acid sequence that encodes a first polypeptide of the VEGF binding agent and a second nucleic acid sequence that encodes a second polypeptide of the VEGF binding agent, and wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO:
- 16, and the second polypeptide comprises the amino acid sequence of SEQ ID NO:
- 20, and
- wherein the coding sequence is flanked by (a) a 5′ ITR comprising the nucleic acid sequence of SEQ ID NO:
- 45 and (b) a 3′ ITR comprising the nucleic acid sequence of SEQ ID NO:
- 46.
A method of treating hearing loss comprising administering an adeno-associated virus (AAV) particle, comprising:
- (i) a nucleic acid construct comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a vascular endothelial growth factor (VEGF) binding agent or a portion thereof;
- and
- (ii) AAV Anc80 capsid,
- wherein the coding sequence includes a first nucleic acid sequence that encodes a first polypeptide of the VEGF binding agent and a second nucleic acid sequence that encodes a second polypeptide of the VEGF binding agent, and wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO:
- 16, and the second polypeptide comprises the amino acid sequence of SEQ ID NO:
- 20, and
- wherein the coding sequence is flanked by (a) a 5′ ITR comprising the nucleic acid sequence of SEQ ID NO:
- 45 and (b) a 3′ ITR comprising the nucleic acid sequence of SEQ ID NO:
- 46.
A method of treating an inner ear disorder in a mammal comprising administering an adeno-associated virus (AAV) particle, comprising:
- (i) a nucleic acid construct comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a vascular endothelial growth factor (VEGF) binding agent or a portion thereof;
- and
- (ii) AAV Anc80 capsid,
- wherein the coding sequence includes a first nucleic acid sequence that encodes a first polypeptide of the VEGF binding agent and a second nucleic acid sequence that encodes a second polypeptide of the VEGF binding agent, and wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO:
- 16, and the second polypeptide comprises the amino acid sequence of SEQ ID NO:
- 20, and
- wherein the coding sequence is flanked by (a) a 5′ ITR comprising the nucleic acid sequence of SEQ ID NO:
- 45 and (b) a 3′ ITR comprising the nucleic acid sequence of SEQ ID NO:
- 46.
A method of treating vestibular schwannoma in a mammal comprising administering an adeno-associated virus (AAV) particle, comprising:
- (i) a nucleic acid construct comprising a coding sequence operably linked to a promoter, wherein the coding sequence encodes a vascular endothelial growth factor (VEGF) binding agent or a portion thereof;
- and
- (ii) AAV Anc80 capsid,
- wherein the coding sequence includes a first nucleic acid sequence that encodes a first polypeptide of the VEGF binding agent and a second nucleic acid sequence that encodes a second polypeptide of the VEGF binding agent, and wherein the first polypeptide comprises the amino acid sequence of SEQ ID NO:
- 16, and the second polypeptide comprises the amino acid sequence of SEQ ID NO:
- 20, and
- wherein the coding sequence is flanked by (a) a 5′ ITR comprising the nucleic acid sequence of SEQ ID NO:
- 45 and (b) a 3′ ITR comprising the nucleic acid sequence of SEQ ID NO:
- 46.
41-50. (canceled)
Dependencies are inferred from the claim text.