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Huwentoxin-IV variants and methods of use

  • US 9,102,751 B2
  • Filed: 03/15/2013
  • Issued: 08/11/2015
  • Est. Priority Date: 05/18/2012
  • Status: Active Grant
First Claim
Patent Images

1. An isolated non-natural Huwentoxin-IV variant comprising the sequence X1CX2X3X4FX5X6CX7X8X9X10X11X12CCX13X14 X15X16X17X18CX19X20X21X22X23 X24CKX25X26IX27X28 (SEQ ID NO:

  • 357);

    whereini) X1 is K, R, H, D, Y, F, N, Q, S, T, G, L, I, P or E;

    ii) X2 is R, F, W, N, S or L;

    iii) X3 is R, H, D, Y, N, Q, L, I, P or E;

    iv) X4 is Y, V or I;

    v) X5 is R, W, Q, S or K;

    vi) X6 is R, E, Y, F, V or A;

    vii) X7 is K, R, E, Y, F, S, V or N;

    viii) X8 is P or V;

    ix) X9 is R, F, Q, V or S;

    x) X10 is H, D, Y, W, Q, S, T, G, A, V, L, I, P or N;

    xi) X11 is D, P or W;

    xii) X12 is K, R, D, E, Y, W, N, T, A, L or Q;

    xiii) X13 is R, Y, Q, S, T, G, L, I, P or K;

    xiv) X14 is K, R, Y, F, N, Q, G, A, V, L, I, P or S;

    xv) X15 is R, H, D, Y, W, N, Q, T, V, I, P or S;

    xvi) X16 is R, H, D, F, W, N, Q, S, T, G, A, L or K;

    xvii) X17 is K, R, Y, F, W, P or L;

    xviii) X18 is K, R, T, A, L or V;

    xix) X19 is S or I;

    xx) X20 is K, W, G, A, I, R or D;

    xxi) X21 is Y, W, A, H or K;

    xxii) X22 is T or V;

    xxiii) X23 is K, H, W, N, G, A, L or R;

    xxiv) X24 is W or K;

    xxv) X25 is W, T, I or Y;

    xxvi) X26 is K, R, Y, F, S, T, G, A, V, L, I or Q;

    xxvii) X27 is K, R, H, F, W, V, L, I, G or deleted; and

    xxviii) X28 is R, H, Y, F, W, N, G, V, P, K or deleted, andthe non-natural Huwentoxin-IV variant has an IC50 value of about 300×

    10

    9
    M or less for human Nav1.7 (SEQ ID NO;

         263), with the proviso that the non-natural Huwentoxin-IV variant is not a polypeptide comprising the sequence shown in SEQ ID NO;

    1.

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