Long-acting anti-ccr5 binding agents for the prevention and treatment of hiv
OwnerJonah Sacha, Scott Kelly +4inventors
InventorsJonah Sacha, Scott Kelly, Helen Wu, Gabriela Webb, Diogo Magnani, Kathleen Engelman
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Abstract
The present disclosure provides CCR5 binding agents with increased effector function and circulation half-life that are useful for preventing or treating HIV.
Claims20
A method of preventing HIV infection in a subject comprising administering to the subject an effective amount of 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 conferring long-term CCR5 receptor occupancy (RO) in the vaginal or rectal tissue of a subject, the method comprising administering to the subject an effective amount of a CCR5 antibody comprising a human IgG Fc amino acid substitution, 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,
- wherein full receptor occupancy of CCR5 on CD4+ T cells in vaginal or rectal tissue of the subject persists for at least four weeks subsequent to administration.
A method of conferring long-term CCR5 receptor occupancy (RO) in the peripheral blood cells of a subject, the method comprising administering to the subject an effective amount of a CCR5 antibody comprising a human IgG Fc amino acid substitution, 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,
- wherein full receptor occupancy of CCR5 on CD4+ peripheral blood T cells of the subject persists for at least thirteen weeks subsequent to administration.
Dependencies are inferred from the claim text.