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US 12,559,546 B2Granted
Methods of identifying HIV patients sensitive to therapy with gp120 CD4 binding site-directed antibodies
AssigneeGilead Sciences, Inc.
InventorsStephen R. Martin, Brian Moldt, Aiyappa Parvangada
Life of this patent
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Abstract
Provided are methods for identifying patient populations infected with HIV that can be targeted by antibodies that bind to HIV gp120 CD4 binding site (CD4bs) region.
Claims43
A method of treating HIV in a human subject in need thereof, the method comprising the following ordered steps:
- a) First, identifying a human subject who is infected with an HIV or a population of HIV expressing a gp120 comprising the following amino acid residues:
- I201 and F353, wherein the amino acid positions are with reference to SEQ ID NO:
- 3;
- and
- b) Second, administering to the subject an effective amount of an antibody or antigen-binding fragment thereof that comprises a heavy-chain variable domain (VH) comprising a VH-complementarity determining region (CDR)1, a VH-CDR2, and a VH-CDR3;
- and a light-chain variable domain (VL) comprising a VL-CDR1, a VL-CDR2, and a VL-CDR3;
- (i) wherein the VH-CDR1, the VH-CDR2, the VH-CDR3, the VL-CDR1, the VL-CDR2, and the VL-CDR3 comprise the sequences set forth, respectively, in:
- SEQ ID NOs:
- 7, 8, 9, 10, 11 and 12;
- wherein the CDRs are according to Kabat;
- (ii) wherein the VH-CDR1, the VH-CDR2, the VH-CDR3, the VL-CDR1, the VL-CDR2, and the VL-CDR3 comprise the sequences set forth, respectively, in:
- SEQ ID NOs:
- 45, 46, 47, 48, 49 and 50;
- wherein the CDRs are according to Chothia;
- (iii) wherein the VH-CDR1, the VH-CDR2, the VH-CDR3, the VL-CDR1, the VL-CDR2, and the VL-CDR3 comprise the sequences set forth, respectively, in:
- SEQ ID NOs:
- 80, 81, 82, 48, 49 and 12;
- wherein the CDRs are according to IMGT;
- or
- (iv) wherein the VH-CDR1, the VH-CDR2, the VH-CDR3, the VL-CDR1, the VL-CDR2, and the VL-CDR3 comprise the sequences set forth, respectively, in:
- SEQ ID NOs:
- 105, 106, 107, 108, 109 and 50;
- wherein the CDRs are according to Honegger.
20 more elements
Dependencies are inferred from the claim text.