Focused libraries of genetic packages
First Claim
1. A focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody family, the vectors or genetic packages being characterized by variegated DNA sequences that encode a heavy chain CDR1 selected from the group consisting of:
- (1) <
1>
1Y2<
1>
3M4<
1>
5, 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. 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) V1S2G3G4S5I6S7<
<
1>
8<
1>
9<
1>
10Y11Y12W13<
1>
14, 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) mixtures of vectors or genetic packages characterized by any of the above DNA sequences.
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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.
126 Citations
43 Claims
-
1. A focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody family, the vectors or genetic packages being characterized by variegated DNA sequences that encode a heavy chain CDR1 selected from the group consisting of:
-
(1) <
1>
1Y2<
1>
3M4<
1>
5, 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. 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) V1S2G3G4S5I6S7<
<
1>
8<
1>
9<
1>
10Y11Y12W13<
1>
14, 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) mixtures of vectors or genetic packages characterized by any of the above DNA sequences. - View Dependent Claims (2, 19, 40, 42)
-
-
3. A focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody facility, the vectors or genetic packages being characterized by variegated DNA sequences that encode a heavy chain CDR2 selected from the group consisting of:
-
(1) <
2>
I<
2>
<
3>
SGG<
1>
T<
1>
YADSVKG, 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>
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, 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, 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, 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) mixtures of vectors or genetic packages characterized by any of the above DNA sequences. - View Dependent Claims (4, 20)
-
-
5. A focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody family, the vectors or genetic packages being characterized by variegated DNA sequences that encode a heavy chain CDR3 selected from the group consisting of:
-
(1) YYCA21111YFDYWG, 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, 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, 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, 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, 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) YYCA211S1TIFG11111YFDYWG, 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, 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, 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) mixtures of vectors or genetic packages characterized by any of the above DNA sequences. - View Dependent Claims (6, 7, 8)
-
-
9. A focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody family, the vectors or genetic packages being characterized by variegated DNA sequences that encodes a kappa light chain CDR1 selected from the group consisting of:
-
(1) RASQ<
1>
V<
2>
<
2>
<
3>
LA(2) RASQ<
1>
V<
2>
<
2>
<
2>
<
3>
LA;
wherein <
1>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVWY;
<
2>
is 0.2 S and 0.044 of each of ADEFGHIKLMNPQRTVWY; and
<
3>
is 0.2Y and 0.044 each of ADEFGHIKLMNPQRTVW and Y; and
(3) mixtures of vectors or genetic packages characterized by any of the above DNA sequences. - View Dependent Claims (10, 21)
-
-
11. A focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody family, the vectors or genetic packages being characterized by variegated DNA sequences that encode a kappa light chain CDR2 having the sequence:
-
<
1>
AS<
2>
R<
4>
<
1>
,wherein <
1>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVWY;
<
2>
is 0.2 S and 0.044 of each of ADEFGHIKLMNPQRTVWY; and
<
4>
is 0.2 A and) 0.044 each of DEFGHIKLMNPQRSTVWY.
-
-
12. A focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody family, the vectors or genetic packages being characterized by variegated DNA sequences that encode a kappa light chain CDR3 selected from the groups consisting of:
-
(1) QQ<
3>
<
1>
<
1>
<
1>
P<
1>
T,wherein <
1>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVWY;
<
3>
is 0.2 Y and 0.044 each of ADEFGHIKLMNPQRTVW;
(2) QQ33111P, wherein 1 and 3 are as defined in (1) above;
(3) QQ3211PP1T, wherein 1 and 3 are as defined in (1) above and 2 is 0.2 S and 0.044 each of ADEFGHIKLMNPQRTVWY; and
(4) mixtures of vectors or genetic packages characterized by any of the above DNA sequences. - View Dependent Claims (13)
-
-
14. A focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody family, the vectors or genetic packages being characterized by variegated DNA sequences that encode a lambda light chain CDR1 selected from the group consisting of:
-
(1) TG<
1>
SS<
2>
VG<
1>
<
3>
<
2>
<
3>
VS,wherein <
1>
is 0.27 T, 0.27 G and 0.027 each of ADEFHIKLMNPQRSVWY, <
2>
is 0.27 D, 0.27 N and 0.027 each of AEFGHIKLMPQRSTVWY, and <
3>
is 0.36 Y and 0.036 each of ADEFGHIKLMNPQRSTVW;
(2) G<
2>
<
4>
L<
4>
<
4>
<
4>
<
3>
<
4>
<
4>
, wherein <
2>
is as defined in (1) above and <
4>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVWY; and
(3) mixtures of vectors or genetic packages characterized by any of the above DNA sequences. - View Dependent Claims (15)
-
-
16. A focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody family, the vectors or genetic packages being characterized by variegated DNA sequences that encode a lambda light chain CDR2 has the sequence:
-
<
4>
<
4>
<
4>
<
2>
RPS,wherein <
2>
is 0.27 D, 0.27 N, and 0.027 each of AEFGHIKLMPQRSTVWY and <
4>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVW.
-
-
17. A focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody family, the vectors or genetic packages being characterized by variegated DNA sequences that encode a lambda light chain CDR3 selected from the group consisting of:
-
(1) <
4>
<
5>
<
4>
<
2>
<
4>
S<
4>
<
4>
<
4>
<
4>
V,wherein <
2>
is 0.27 D, 0.27 N, and 0.027 each of AEFGHIKLMPQRSTVWY;
<
4>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVW; and
<
5>
is 0.36 S and 0.0355 each of ADEFGHIKLMNPQRTVWY;
(2) <
5>
SY<
1>
<
5>
S<
5>
<
1>
<
4>
V, wherein <
1>
is an equimolar mixture of ADEFGHIKLMNPQRSTVWY; and
<
4> and
<
5>
are as defined in (1) above; and
(3) mixtures of vectors or genetic packages characterized by any of the above DNA sequences. - View Dependent Claims (18)
-
-
22. A population of variegated DNA sequences that encode a heavy chain CDR1 selected from the group consisting of:
-
(1) <
1>
1Y2<
1>
3M4<
1>
5, 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 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) V1S2G3G4S5I6S7<
1>
8<
1>
9<
1>
10Y11Y12W13<
1>
14, 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) mixtures of variegated DNA sequences characterized by any of the above DNA sequences. - View Dependent Claims (23, 43)
-
-
24. A population of variegated DNA sequences that encode a heavy chain CDR2 selected from the group consisting of:
-
(1) <
2>
I<
2>
<
3>
SGG<
1>
T<
1>
YADSVKG, 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>
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, 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, 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, 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) mixtures of variegated DNA sequences characterized by any of the above DNA sequences. - View Dependent Claims (25, 41)
-
-
26. A population of variegated DNA sequences that encode a heavy chain CDR3 selected from the group consisting of:
-
(1) YYCA21111YFDYWG, 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, 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, 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, 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, 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) YYCA211S1TIFG11111YFDYWG, 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, 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, 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) mixtures of variegated DNA sequences characterized by any of the above DNA sequences. - View Dependent Claims (27, 28, 29)
-
-
30. A population of variegated DNA sequences that encode a kappa light chain CDR1 selected from the group consisting of:
-
(1) RASQ<
1>
V<
2>
<
2>
<
3>
LA(2) RASQ<
1>
V<
2>
<
2>
<
2>
<
3>
LA;
wherein <
1>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVWY;
<
2>
is 0.2 S and 0.044 of each of ADEFGHIKLMNPQRTVWY; and
<
3>
is 0.2Y and 0.044 each of ADEFGHIKLMNPQRTVW and Y; and
(3) mixtures of variegated DNA sequences characterized by any of the above DNA sequences. - View Dependent Claims (31)
-
-
32. A population of variegated DNA sequences that encode a kappa light chain CDR2 having the sequence:
-
<
1>
AS<
2>
R<
4>
<
1>
,wherein <
1>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVWY;
<
2>
is 0.2 S and 0.044 of each of ADEFGHIKLMNPQRTVWY; and
<
4>
is 0.2 A and) 0.044 each of DEFGHIKLMNPQRSTVWY.
-
-
33. A population of variegated DNA sequences that encode a kappa light chain CDR3 selected from the groups consisting of:
-
(1) QQ<
3>
<
1>
<
1>
<
1>
P<
1>
T,wherein <
1>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVWY;
<
3>
is 0.2 Y and 0.044 each of ADEFGHIKLMNPQRTVW;
(2) QQ33111P, wherein 1 and 3 are as defined in (1) above;
(3) QQ3211PPlT, wherein 1 and 3 are as defined in (1) above and 2 is 0.2 S and 0.044 each of ADEFGHIKLMNPQRTVWY; and
(4) mixtures of variegated DNA sequences characterized by any of the above DNA sequences. - View Dependent Claims (34)
-
-
35. A population of variegated DNA sequences that encode a lambda light chain CDR1 selected from the group consisting of:
-
(1) TG<
1>
SS<
2>
VG<
1>
<
3>
<
2>
<
3>
VS,wherein <
1>
is 0.27 T, 0.2.7 G and 0.027 each of ADEFHIKLMNPQRSVWY, <
2>
is 0.27 D, 0.27 N and 0.027 each of AEFGHIKLMPQRSTVWY, and <
3>
is 0.36 Y and 0.036 each of ADEFGHIKLMNPQRSTVW;
(2) G<
2>
<
4>
L<
4>
<
4>
<
4>
<
3>
<
4>
<
4>
,wherein <
2>
is as defined in (1) above and <
4>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVWY; and
(3) mixtures of variegated DNA sequences characterized by any of the above DNA sequences. - View Dependent Claims (36)
-
-
37. A population of variegated DNA sequences that encode a lambda light chain CDR2 has the sequence:
-
<
4>
<
4>
<
4>
<
2>
RPS,wherein <
2>
is 0.27 D, 0.27 N, and 0.027 each of AEFGHIKLMPQRSTVWY and <
4>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVW.
-
-
38. A population of variegated DNA sequences that encode a lambda light chain CDR3 selected from the group consisting of:
-
(1) <
4>
<
5>
<
4>
<
2>
<
4>
S<
4>
<
4>
<
4>
<
4>
V,wherein <
2>
is 0.27 D, 0.27 N, and 0.027 each of AEFGHIKLMPQRSTVWY;
<
4>
is an equimolar mixture of amino acid residues ADEFGHIKLMNPQRSTVW; and
<
5>
is 0.36 S and 0.0355 each of ADEFGHIKLMNPQRTVWY;
(2) <
5>
SY<
1>
<
5>
S<
5>
<
1>
<
4>
V, wherein <
1>
is an equimolar mixture of ADEFGHIKLMNPQRSTVWY; and
<
4> and
<
5>
are as defined in (1) above; and
(3) mixtures of variegated. DNA sequence characterized by any of the above DNA sequences. - View Dependent Claims (39)
-
Specification