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US 2026/0250331 A1Published application
Recombinant hiv env polypeptides and their use
AssigneesInternational AIDS Vaccine Initiative, The Scripps Research Institute
InventorsJon M. STEICHEN, William R. SCHIEF
Life of this patent
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Abstract
The present disclosure relates to recombinant HIV Env polypeptides and their use in the treatment and prevention of HIV/AIDS.
Claims19
An isolated polypeptide comprising a variant HIV Env gp120 polypeptide, wherein the variant HIV Env gp120 polypeptide comprises one or more of
- (a) a V1 loop comprising positions 131-154, wherein the V1 loop comprises an amino acid sequence of
- (i)
- (SEQ ID NO:
- 71)
- CTNVTNNITDDMRGEL,
- (ii)
- (SEQ ID NO:
- 72)
- CTNYAPNLLSNMRGEL,
- (iii)
- (SEQ ID NO:
- 73)
- CTNYAPNLLSNMRGEI,
- (iv)
- (SEQ ID NO:
- 74)
- CTNYAPKLLSNMRGEI
- (v)
- (SEQ ID NO:
- 75)
- CTNYAPKLRSMMRGEI
- or
- (vi)
- (SEQ ID NO:
- 76)
- CTNYAPNLRSDMRGEI;
- (b) a V3 loop comprising positions 297-334, wherein positions 297-303 of the V3 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 77)
- (i)
- TRPNNNT,
- or
- (SEQ ID NO:
- 78)
- (ii)
- TRPSNNT;
- (c) a V3 loop comprising positions 297-334, wherein positions 319-334 of the V3 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 79)
- (i)
- TGDIIGDIRQAHCNVS,
- (SEQ ID NO:
- 80)
- (ii)
- FGDIIGDIRMAHCNVS,
- (SEQ ID NO:
- 81)
- (iii)
- FGDVLGDVRMAHCNIS,
- (SEQ ID NO:
- 82)
- (iv)
- FGDVLGHVRMAHCNIS,
- or
- (SEQ ID NO:
- 83)
- (v)
- FGDVLGDVDMAKCTIS;
- and
- (d) a β19 sheet comprising positions 413-419, wherein the β19 sheet comprises an amino acid sequence of
- (SEQ ID NO:
- 84)
- (i)
- SITLPCR,
- (SEQ ID NO:
- 85)
- (ii)
- SIVLPCR,
- (SEQ ID NO:
- 86)
- (iii)
- SLILPCR,
- or
- (SEQ ID NO:
- 87)
- (iv)
- SLILPCW,
- wherein HIV Env gp120 polypeptide positions correspond to the HXB2 reference;
- or
- wherein the variant HIV Env gp120 polypeptide comprises
- (e) a V1 loop comprising positions 131-154, wherein the V1 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 71)
- (i)
- CTNVTNNITDDMRGEL,
- (SEQ ID NO:
- 72)
- (ii)
- CTNYAPNLLSNMRGEL,
- (SEQ ID NO:
- 73)
- (iii)
- CTNYAPNLLSNMRGEI,
- (SEQ ID NO:
- 74)
- (iv)
- CTNYAPKLLSNMRGEI,
- (SEQ ID NO:
- 75)
- (v)
- CTNYAPKLRSMMRGEI,
- or
- (SEQ ID NO:
- 76)
- (vi)
- CTNYAPNLRSDMRGEI;
- (f) a V3 loop comprising positions 297-334, wherein positions 297-303 of the V3 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 77)
- (i)
- TRPNNNT,
- or
- (SEQ ID NO:
- 78)
- (ii)
- TRPSNNT;
- (g) a V3 loop comprising positions 297-334, wherein positions 319-334 of the V3 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 79)
- (i)
- TGDIIGDIRQAHCNVS,
- (SEQ ID NO:
- 80)
- (ii)
- FGDIIGDIRMAHCNVS,
- (SEQ ID NO:
- 81)
- (iii)
- FGDVLGDVRMAHCNIS,
- (SEQ ID NO:
- 82)
- (iv)
- FGDVLGHVRMAHCNIS,
- or
- (SEQ ID NO:
- 83)
- (v)
- FGDVLGDVDMAKCTIS;
- and
- (h) a β19 sheet comprising positions 413-419, wherein the β19 sheet comprises an amino acid sequence of
- (SEQ ID NO:
- 84)
- (i)
- SITLPCR,
- (SEQ ID NO:
- 85)
- (ii)
- SIVLPCR,
- (SEQ ID NO:
- 86)
- (iii)
- SLILPCR,
- or
- (SEQ ID NO:
- 87)
- (iv)
- SLILPCW,
- wherein HIV Env gp120 polypeptide positions correspond to the HXB2 reference;
- or
- wherein the variant HIV Env gp120 polypeptide comprises one or more of
- (i) a V1 loop comprising positions 131-154, wherein the V1 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 71)
- (i)
- CTNVTNNITDDMRGEL,
- (SEQ ID NO:
- 72)
- (ii)
- CTNYAPNLLSNMRGEL,
- (SEQ ID NO:
- 73)
- (iii)
- CTNYAPNLLSNMRGEI,
- (SEQ ID NO:
- 74)
- (iv)
- CTNYAPKLLSNMRGEI,
- (SEQ ID NO:
- 75)
- (v)
- CTNYAPKLRSMMRGEI,
- or
- (SEQ ID NO:
- 76)
- (vi)
- CTNYAPNLRSDMRGEI;
- (j) a V3 loop comprising positions 297-334, wherein positions 297-303 of the V3 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 77)
- (i)
- TRPNNNT,
- or
- (SEQ ID NO:
- 78)
- (ii)
- TRPSNNT;
- (k) a V3 loop comprising positions 297-334, wherein positions 319-334 of the V3 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 79)
- (i)
- TGDIIGDIRQAHCNVS,
- (SEQ ID NO:
- 80)
- (ii)
- FGDIIGDIRMAHCNVS,
- (SEQ ID NO:
- 81)
- (iii)
- FGDVLGDVRMAHCNIS,
- (SEQ ID NO:
- 82)
- (iv)
- FGDVLGHVRMAHCNIS,
- or
- (SEQ ID NO:
- 83)
- (v)
- FGDVLGDVDMAKCTIS;
- and
- (l) a β19 sheet comprising positions 413-419, wherein the β19 sheet comprises an amino acid sequence of
- (SEQ ID NO:
- 84)
- (i)
- SITLPCR,
- (SEQ ID NO:
- 85)
- (ii)
- SIVLPCR,
- (SEQ ID NO:
- 86)
- (iii)
- SLILPCR,
- or
- (SEQ ID NO:
- 87)
- (iv)
- SLILPCW,
- wherein HIV Env gp120 polypeptide positions correspond to the HXB2 reference, or
- wherein the variant HIV Env gp120 polypeptide comprises
- (m) a V1 loop comprising positions 131-154, wherein the V1 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 71)
- (i)
- CTNVTNNITDDMRGEL,
- (SEQ ID NO:
- 72)
- (ii)
- CTNYAPNLLSNMRGEL,
- (SEQ ID NO:
- 73)
- (iii)
- CTNYAPNLLSNMRGEI,
- (SEQ ID NO:
- 74)
- (iv)
- CTNYAPKLLSNMRGEI,
- (SEQ ID NO:
- 75)
- (v)
- CTNYAPKLRSMMRGEI,
- or
- (SEQ ID NO:
- 76)
- (vi)
- CTNYAPNLRSDMRGEI;
- (n) a V3 loop comprising positions 297-334, wherein positions 297-303 of the V3 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 77)
- (i)
- TRPNNNT,
- or
- (SEQ ID NO:
- 78)
- (ii)
- TRPSNNT;
- (o) a V3 loop comprising positions 297-334, wherein positions 319-334 of the V3 loop comprises an amino acid sequence of
- (SEQ ID NO:
- 79)
- (i)
- TGDIIGDIRQAHCNVS,
- (SEQ ID NO:
- 80)
- (ii)
- FGDIIGDIRMAHCNVS,
- (SEQ ID NO:
- 81)
- (iii)
- FGDVLGDVRMAHCNIS,
- (SEQ ID NO:
- 82)
- (iv)
- FGDVLGHVRMAHCNIS,
- or
- (SEQ ID NO:
- 83)
- (v)
- FGDVLGDVDMAKCTIS;
- and
- (p) a β19 sheet comprising positions 413-419, wherein the β19 sheet comprises an amino acid sequence of
- (SEQ ID NO:
- 84)
- (i)
- SITLPCR,
- (SEQ ID NO:
- 85)
- (ii)
- SIVLPCR,
- (SEQ ID NO:
- 86)
- (iii)
- SLILPCR,
- or
- (SEQ ID NO:
- 87)
- (iv)
- SLILPCW,
- wherein HIV Env gp 120 polypeptide positions correspond to the HXB2 reference or wherein the variant HIV Env gp120 polypeptide comprises a V1 loop comprising positions 131-154, a V3 loop comprising positions 297-334, and a β19 sheet comprising positions 413-419, wherein the V1 loop, positions 297-303 of the V3 loop, positions 319-334 of the V3 loop, and the β19 sheet comprises the amino acid sequence of
- (q) CTNYAPKLLSNMRGEI (SEQ ID NO:
- 74), TRPNNNT (SEQ ID NO:
- 77), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCR (SEQ ID NO:
- 86), respectively,
- (r) CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPNNNT (SEQ ID NO:
- 77), FGDVLGDVRMAHCNIS (SEQ ID NO:
- 81), and SLILPCR (SEQ ID NO:
- 86), respectively,
- (s) CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPNNNT (SEQ ID NO:
- 77), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCR (SEQ ID NO:
- 86), respectively,
- (t) CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPSNNT (SEQ ID NO:
- 78), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCR (SEQ ID NO:
- 86), respectively,
- (u) CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPSNNT (SEQ ID NO:
- 78), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCW (SEQ ID NO:
- 87), respectively,
- (v) CTNYAPNLRSDMRGEI (SEQ ID NO:
- 76), TRPNNNT (SEQ ID NO:
- 77), FGDVLGDVDMAKCTIS (SEQ ID NO:
- 83), and SLILPCR (SEQ ID NO:
- 86), respectively,
- (w) CTNYAPKLLSNMRGEI (SEQ ID NO:
- 74), TRPNNNT (SEQ ID NO:
- 77), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCR (SEQ ID NO:
- 86), respectively,
- (x) CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75) TRPNNNT (SEQ ID NO:
- 77), FGDVLGDVRMAHCNIS (SEQ ID NO:
- 81), and SLILPCR (SEQ ID NO:
- 86), respectively,
- (y) CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPNNNT (SEQ ID NO:
- 77), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCR (SEQ ID NO:
- 86), respectively,
- (z) CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPSNNT (SEQ ID NO:
- 78), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCR (SEQ ID NO:
- 86), respectively,
- (aa) CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPSNNT (SEQ ID NO:
- 78), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCW (SEQ ID NO:
- 87), respectively, or
- (bb) CTNYAPNLRSDMRGEI (SEQ ID NO:
- 76), TRPNNNT (SEQ ID NO:
- 77), FGDV LGDVDMAKCTIS (SEQ ID NO:
- 83), and SLILPCR (SEQ ID NO:
- 86), respectively,
- and wherein HIV Env gp120 polypeptide positions correspond to the HXB2 reference. or wherein the variant HIV Env gp120 polypeptide comprises a V1 loop comprising positions 131-154, a V3 loop comprising positions 297-334, and a β19 sheet comprising positions 413-419, wherein the V1 loop, positions 297-303 of the V3 loop, positions 319-334 of the V3 loop, and the β19 sheet comprises the amino acid sequence of CTNYAPKLLSNMRGEI (SEQ ID NO:
- 74), TRPNNNT (SEQ ID NO:
- 77), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCR (SEQ ID NO:
- 86), respectively, and wherein HIV Env gp120 polypeptide positions correspond to the HXB2 reference or
- wherein the variant HIV Env gp120 polypeptide comprises a V1 loop comprising positions 131-154, a V3 loop comprising positions 297-334, and a β19 sheet comprising positions 413-419, wherein the V1 loop, positions 297-303 of the V3 loop, positions 319-334 of the V3 loop, and the β19 sheet comprises the amino acid sequence of CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPNNNT (SEQ ID NO:
- 77), FGDVLGDVRMAHCNIS (SEQ ID NO:
- 81), and SLILPCR (SEQ ID NO:
- 86), respectively, and wherein HIV Env gp120 polypeptide positions correspond to the HXB2 reference or
- wherein the variant HIV Env gp120 polypeptide comprises a V1 loop comprising positions 131-154, a V3 loop comprising positions 297-334, and a β19 sheet comprising positions 413-419, wherein the V1 loop, positions 297-303 of the V3 loop, positions 319-334 of the V3 loop, and the β19 sheet comprises the amino acid sequence of CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPNNNT (SEQ ID NO:
- 77), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCR (SEQ ID NO:
- 86), respectively, and wherein HIV Env gp120 polypeptide positions correspond to the HXB2 reference or
- wherein the variant HIV Env gp120 polypeptide comprises a V1 loop comprising positions 131-154, a V3 loop comprising positions 297-334, and a β19 sheet comprising positions 413-419, wherein the V1 loop, positions 297-303 of the V3 loop, positions 319-334 of the V3 loop, and the β19 sheet comprises the amino acid sequence of CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPSNNT (SEQ ID NO:
- 78), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCR (SEQ ID NO:
- 86), respectively, and wherein HIV Env gp120 polypeptide positions correspond to the HXB2 reference or
- wherein the variant HIV Env gp120 polypeptide comprises a V1 loop comprising positions 131-154, a V3 loop comprising positions 297-334, and a β19 sheet comprising positions 413-419, wherein the V1 loop, positions 297-303 of the V3 loop, positions 319-334 of the V3 loop, and the β19 sheet comprises the amino acid sequence of CTNYAPKLRSMMRGEI (SEQ ID NO:
- 75), TRPSNNT (SEQ ID NO:
- 78), FGDVLGHVRMAHCNIS (SEQ ID NO:
- 82), and SLILPCW (SEQ ID NO:
- 87), respectively, and wherein HIV Env gp120 polypeptide positions correspond to the HXB2 reference.
399 more elements
An isolated polypeptide comprising
- (a) an amino acid sequence having at least about 80%, at least about 90%, at least about 95%, at least about 97%, at least about 99%, or 100% sequence identity to the amino acid sequence of BG505 MD39 N332-GT1,
- (b) an amino acid sequence having at least about 80%, at least about 90%, at least about 95%, at least about 97%, at least about 99%, or 100% sequence identity to the amino acid sequence of BG505 MD39 N332-GT2,
- (c) an amino acid sequence having at least about 80%, at least about 90%, at least about 95%, at least about 97%, at least about 99%, or 100% sequence identity to the amino acid sequence of BG505 MD39 N332-GT3,
- (d) an amino acid sequence having at least about 80%, at least about 90%, at least about 95%, at least about 97%, at least about 99%, or 100% sequence identity to the amino acid sequence of BG505 MD39 N332-GT4,
- (e) an amino acid sequence having at least about 80%, at least about 90%, at least about 95%, at least about 97%, at least about 99%, or 100% sequence identity to the amino acid sequence of BG505 MD39 N332-GT5, or
- (f) an amino acid sequence having at least about 80%, at least about 90%, at least about 95%, at least about 97%, at least about 99%, or 100% sequence identity to the amino acid sequence of BG505 MD39 N332-GT2-KO.
3 more elements
An isolated antibody comprising
- (a) the VHCDR1, VH CDR2, and VH CDR3 of BG18, BG18.11, BG18.6, BG18 iGL0, BG18 iGL1, BG18 iGL2, PRE1, PRE2, PRE3, PRE4, PRE5, PRE6, PRE7, PRE8, PRE9, PRE10, PRE11, PRE12, PRE13, PRE14, PRE15, VH4-595, VH1-69, VH5-51, VH3-33, or VH3-23;
- and
- (b) the VL CDR1, VL CDR2, and VL CDR3 of BG18, BG18.11, BG18.6, BG18 iGL0, BG18 iGL1, BG18 iGL2, PRE1, PRE2, PRE3, PRE4, PRE5, PRE6, PRE7, PRE8, PRE9, PRE10, PRE11, PRE12, PRE13, PRE14, PRE15, VL3-10, VL3-19, VL3-1, VL3-21, or VL2-8 or an isolated antibody comprising VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 of BG18.11, BG18.6, BG18 iGL0, BG18 iGL1, BG18 iGL2, PRE1, PRE2, PRE3, PRE4, PRE5, PRE6, PRE7, PRE8, PRE9, PRE10, PRE11, PRE12, PRE13, PRE14, or PRE15 orr an isolated antibody comprising the 3 VH CDRs and 3 VL CDRs of
- (c) VH4-59 and BG18 iGL, respectively;
- (d) VH1-69 and BG18 iGL, respectively;
- (e) VH5-51 and BG18 iGL, respectively;
- (f) VH3-33 and BG18 iGL, respectively;
- (g) VH3-23 and BG18 iGL, respectively;
- (h) BG18 iGL1 and VL3-19, respectively;
- (i) BG18 iGL1 and VL3-10, respectively;
- (j) BG18 iGL1 and VL3-1, respectively;
- (k) BG18 iGL1 and VL3-21, respectively;
- or
- (l) BG18 iGL1 and VL2-8, respectively or an isolated antibody comprising
- (m) the VH of BG18, BG18.11, BG18.6, BG18 iGL0, BG18 iGL1, BG18 iGL2, PRE1, PRE2, PRE3, PRE4, PRE5, PRE6, PRE7, PRE8, PRE9, PRE10, PRE11, PRE12, PRE13, PRE14, PRE15, VH4-595, VH1-69, VH5-51, VH3-33, or VH3-23;
- and
- (n) the VL of BG18, BG18.11, BG18.6, BG18 iGL0, BG18 iGL1, BG18 iGL2, PRE1, PRE2, PRE3, PRE4, PRE5, PRE6, PRE7, PRE8, PRE9, PRE10, PRE11, PRE12, PRE13, PRE14, PRE15, VL3-10, VL3-19, VL3-1, VL3-21, or VL2-8 or
- an isolated antibody comprising the VH and VL of BG18.11, BG18.6, BG18 iGL0, BG18 iGL1, BG18 iGL2, PRE1, PRE2, PRE3, PRE4, PRE5, PRE6, PRE7, PRE8, PRE9, PRE10, PRE11, PRE12, PRE13, PRE14, or PRE15.
- an isolated antibody comprising the VH and VL of
- (o) VH4-59 and BG18 iGL, respectively;
- (p) VH1-69 and BG18 iGL, respectively;
- (q) VH5-51 and BG18 iGL, respectively;
- (r) VH3-33 and BG18 iGL, respectively;
- (s) VH3-23 and BG18 iGL, respectively;
- (t) BG18 iGL1 and VL3-19, respectively;
- (u) BG18 iGL1 and VL3-10, respectively;
- (v) BG18 iGL1 and VL3-1, respectively;
- (w) BG18 iGL1 and VL3-21, respectively;
- or
- (x) BG18 iGL1 and VL2-8, respectively.
27 more elements
Dependencies are inferred from the claim text.