Aav-mediated expression of long-acting anti-ccr5 binding agents for the treatment and prevention of hiv
OwnerJonah Sacha, Scott Kelly +2inventors
InventorsJonah Sacha, Scott Kelly, Helen Wu, Gabriela Webb
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Abstract
The present disclosure provides recombinant adenovirus-associated viral vectors for the delivery of CCR5 binding agents with increased effector function and circulation half-life that are useful for treating and preventing HIV and methods of use thereof.
Claims20
A recombinant adeno-associated virus (rAAV) vector comprising a heterologous nucleic acid encoding a CCR5 antibody comprising the following human IgG Fc amino acid substitutions:
- (i) M428L and N434S;
- (ii) L234A and L235A;
- and
- (iii) S131C
- wherein the antibody comprises:
- (a) a heavy chain variable region (VH) comprising a heavy chain complementary determining region 1 (HCDR1) of SEQ ID NO:11, a heavy chain complementary determining region 2 (HCDR2) of SEQ ID NO:12, and a heavy chain complementary determining region 3 (HCDR3) of SEQ ID NO:13;
- and
- (b) a light chain variable region (VL) comprising a light chain complementary determining region 1 (LCDR1) of SEQ ID NO:9, a light chain complementary determining region 2 (LCDR2) of SEQ ID NO:
- 10, and a light chain complementary determining region 3 (LCDR3) of SEQ ID NO:11.
A method of treating a HIV infection in a subject comprising administering to the subject an effective amount of a recombinant adeno-associated virus (rAAV) vector comprising a heterologous nucleic acid encoding a CCR5 antibody comprising the following human IgG Fc amino acid substitutions:
- (i) M428L and N434S;
- (ii) L234A and L235A;
- and
- (iii) S131C
- wherein the antibody comprises:
- (a) a heavy chain variable region (VH) comprising a heavy chain complementary determining region 1 (HCDR1) of SEQ ID NO:11, a heavy chain complementary determining region 2 (HCDR2) of SEQ ID NO:12, and a heavy chain complementary determining region 3 (HCDR3) of SEQ ID NO:13;
- and
- (b) a light chain variable region (VL) comprising a light chain complementary determining region 1 (LCDR1) of SEQ ID NO:9, a light chain complementary determining region 2 (LCDR2) of SEQ ID NO:
- 10, and a light chain complementary determining region 3 (LCDR3) of SEQ ID NO:11.
Dependencies are inferred from the claim text.