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US 11,535,665 B2Granted
AAV-mediated expression of anti-influenza antibodies and methods of use thereof
AssigneeThe Trustees of the University of Pennsylvania
InventorsMaria P. Limberis, Anna P. Tretiakova, James M. Wilson
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Abstract
AAV vectors expressing anti-influenza antibodies are provided. Also described are pharmaceutical compositions useful in delivery same for prophylactic or anti-viral purposes. Methods of delivering such vectors are provided.
Claims21
A composition useful for delivering a combination of two anti-influenza antibody constructs for passive immunization against influenza infection, the composition comprising:
- (a) a first non-replicating recombinant adeno-associated virus having an AAV9 capsid (rAAV9) and having a vector genome which comprises:
- (i) an AAV inverted terminal repeat (ITR), (ii) an enhancer, (iii) a chicken beta-actin promoter, (iv) an intron, (v) a 5′ UTR, (vi) a nucleic acid sequence encoding a leader peptide operably linked to an FI6v3 heavy chain (HC) variable region, (vii) a nucleic acid sequence encoding the FI6v3 HC variable region having an amino acid sequence of SEQ ID NO:2, (viii) a nucleic acid sequence encoding a human heavy chain (HC constant region), (ix) a furin recognition site, (x) an F2A linker, (xi) a nucleic acid sequence encoding a leader peptide operably linked to an immunoglobulin light chain (LC), (xii) a nucleic acid sequence encoding the immunoglobulin light chain (LC) which is a germline antibody sequence with no defined specificity comprising an amino acid sequence of SEQ ID NO:
- 6 and SEQ ID NO:
- 7, (xiii) a polyadenylation signal, and (xiv) an AAV inverted terminal repeat;
- and
- (b) a second non-replicating rAAV9, wherein the second rAAV9 has an AAV9 capsid and a vector genome which comprises:
- (i) an AAV inverted terminal repeat (ITR), (ii) an enhancer, (iii) a chicken beta-actin promoter, (iv) an intron, (v) a 5′ UTR, (vi) a nucleic acid encoding a leader peptide operably linked to a CR8033 heavy chain (HC) variable region, (vii) a nucleic acid sequence encoding the CR8033 HC variable region having an amino acid sequence of SEQ ID NO:
- 9, (viii) a nucleic acid sequence encoding a human heavy chain (HC) constant region, (ix) a nucleic acid sequence encoding a furin recognition site, (x) an F2A linker, (xi) a nucleic acid sequence encoding a leader peptide operably linked to an immunoglobulin light chain (LC), (xii) a nucleic acid sequence encoding the immunoglobulin light chain (LC) which is a germline antibody sequence with no defined specificity comprising an amino acid sequence of SEQ ID NO:
- 12 and SEQ ID NO:
- 13, (xiii) a polyadenylation signal, and (xiv) an AAV inverted terminal repeat;
- and an aqueous liquid suspension base.
8 more elements
A composition useful for delivering a combination of two anti-influenza antibody constructs for passive immunization against influenza infection, the composition comprising:
- (a) a first non-replicating recombinant adeno-associated virus (rAAV) having a vector genome which comprises:
- (i) an AAV inverted terminal repeat (ITR), (ii) an enhancer, (iii) a promoter, (iv) an intron, (v) a 5′ UTR, (vi) a nucleic acid sequence encoding a leader peptide operably linked to an FI6v3 heavy shain (HC) variable region, (vii) a nucleic acid sequence encoding the FI6v3 heavy chain variable region, the FI6v3 HC variable region having an amino acid sequence of SEQ ID NO:2, (viii) a nucleic acid sequence encoding a human HC constant region, (ix) a nucleic acid sequence encoding a suitable linker, (x) a nucleic acid sequence encoding a leader peptide operably linked to an immunoglobulin light chain, (xi) at least one nucleic acid sequence encoding the immunoglobulin light chain which is a germline sequence with no defined specificity comprising an amino acid sequence of SEQ ID NO:
- 6 and SEQ ID NO:
- 7, (xii) a polyadenylation signal, and (xiii) an AAV inverted terminal repeat;
- and
- (b) a second non-replicating rAAV, wherein the second rAAV has a vector genome which comprises:
- (i) an AAV inverted terminal repeat (ITR), (ii) an enhancer, (iii) a promoter, (iv) an intron, (v) a 5′ UTR, (vi) a nucleic acid encoding a leader peptide operably linked to a CR8033 heavy chain (HC) variable region, (vii) a nucleic acid sequence encoding the CR8033 HC variable region having an amino acid sequence of SEQ ID NO:
- 9, (viii) a nucleic acid sequence encoding a human HC constant region, (ix) a nucleic acid sequence encoding a suitable linker, (x) a nucleic acid sequence encoding a leader peptide operably linked to an immunoglobulin light chain, (xi) at least one nucleic acid sequence encoding the immunoglobulin light chain which is a germline sequence with no defined specificity comprising an amino acid sequence of SEQ ID NO:
- 12 and SEQ ID NO:
- 13, (xii) a polyadenylation signal, and (xiii) an AAV inverted terminal repeat;
- and an aqueous liquid suspension base.
8 more elements
Dependencies are inferred from the claim text.