Focused libraries of genetic packages
First Claim
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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Accused Products
Abstract
Focused libraries of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of antibody peptides, polypeptides or proteins and collectively display, display and express, or comprise at least a portion of the focused diversity of the family. The libraries have length and sequence diversities that mimic that found in native human antibodies.
-
Citations
22 Claims
-
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. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
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Specification