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Focused libraries of genetic packages

  • US 8,399,384 B2
  • Filed: 06/15/2011
  • Issued: 03/19/2013
  • Est. Priority Date: 12/18/2000
  • Status: Expired due to Term
First Claim
Patent Images

1. A focused library of vectors or genetic packages, comprising a first set of variegated DNA molecules, each of which comprises a DNA sequence that encodes an antibody heavy chain (FTC) variable region comprising a CDR1 region, a CDR2 region, and a CDR3 region, wherein the first set of variegated DNA molecules collectively encode a plurality of:

  • (a) HC CDR1 regions selected from the group consisting of;

    (1) <

    1>

    1Y2<

    1>

    3M4<

    1>

    5 (SEQ ID NO;

    100), wherein <

    1>

    is an equimolar mixture of each of amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, and Y;

    (2) (S/T)1(S/G/X)2(S/G/X)3Y4Y5W6(S/G/X)7 (SEQ ID NO;

    101), wherein (S/T) is a 1;

    1 mixture of S and T residues, (S/G/X) is a mixture of 0.2025 S, 0.2025, G and 0.035 of each of amino acid residues A, D, E, F, H, I, K, L, M, N, P, Q, R, T, V, W, and Y;

    (3) VIS2G3G4S5I6S7<

    <

    1>

    8<

    1>

    9<

    1>

    10Y11Y12W13<

    1>

    14 (SEQ ID NO;

    1), wherein <

    1>

    is an equimolar mixture of each of amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, and Y; and

    (4) a mixture of any of (1) to (3) set forth above;

    (b) HC CDR2 regions selected from the group consisting of;

    (1) <

    2>

    I<

    2>

    <

    3>

    SGG<

    1>

    T<

    1>

    YADSVKG (SEQ ID NO;

    2), wherein <

    1>

    is an equimolar mixture of each of amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, 5, T, V, W, and Y;

    <

    2>

    is an equimolar mixture of each of amino acid residues Y, R, W, V, G, and S; and

    <

    3>

    is an equimolar mixture of each of amino acid residues P, S, and G or an equimolar mixture of P and S;

    (2) <

    1>

    I<

    4>

    <

    1>

    <

    1>

    <

    G>

    <

    5>

    <

    1>

    <

    1>

    -<

    1>

    YADSVKG (SEQ ID NO;

    3), wherein <

    1>

    is an equimolar mixture of each of amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, and Y;

    <

    4>

    is an equimolar mixture of residues D, I, N, S, W, Y; and

    <

    5>

    is an equimolar mixture of residues S, G, D and N;

    (3) <

    1>

    I<

    4>

    <

    1>

    <

    1>

    G<

    5>

    <

    1>

    <

    1>

    YNPSLKG (SEQ ID NO;

    4), wherein <

    1>

    is an equimolar mixture of each of amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y; and

    <

    4> and

    <

    5>

    are as defined above;

    (4) <

    1>

    I<

    8>

    S<

    1>

    <

    1>

    <

    1>

    GGYY<

    1>

    YAASVKG (SEQ ID NO;

    5), wherein <

    1>

    is an equimolar mixture of each amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y;

    <

    8>

    is 0.27 R and 0.027 of each of ADEFGHIKLMNPQSTVWY; and

    (5) a mixture of any of (1) to (4) set forth above;

    or(c) HC CDR3 regions selected from the group consisting of;

    (1) YYCA21111YFDYWG (SEQ ID NO;

    6), wherein 1 is an equimolar mixture of each amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y; and

    2 is an equimolar mixture of K and R;

    (2) YYCA2111111YFDYWG (SEQ ID NO;

    7), wherein 1 is an equimolar mixture of each amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y; and

    2 is an equimolar mixture of K and R;

    (3) YYCA211111111YFDAYTG (SEQ ID NO;

    8), wherein 1 is an equimolar mixture of each amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y; and

    2 is an equimolar mixture of K and R;

    (4) YYCAR111S2S3111YFDYWG (SEQ ID NO;

    9), wherein 1 is an equimolar mixture of each amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y; and

    2 is an equimolar mixture of S and G; and

    3 is an equimolar mixture of Y and W;

    (5) YYCA2111CSG11CY1YFDYWG (SEQ ID NO;

    10), wherein 1 is an equimolar mixture of each amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y; and

    2 is an equimolar mixture of K and R;

    (6) YYCA211SITIFG11111YFDYWG (SEQ ID NO;

    11), wherein 1 is an equimolar mixture of each amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y; and

    2 is an equimolar mixture of K and R;

    (7) YYCAR111YY2S3344111YFDYWG (SEQ ID NO;

    12), wherein 1 is an equimolar mixture of each amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y;

    2 is an equimolar mixture of D and S; and

    3 is an equimolar mixture of S and G;

    (8) YYCAR1111YC2231CY111YFDYWG (SEQ 1D NO;

    13), wherein 1 is an equimolar mixture of each amino acid residues A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W and Y;

    2 is an equimolar mixture of S and G; and

    3 is an equimolar mixture of T, D and G; and

    (9) a mixture of any of (1) to (8) set forth above.

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