Focused libraries of genetic packages
OwnerRobert Charles Ladnerinventor
Life of this patent
Estimating the term…
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.
Claims43
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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) 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 variegated DNA sequences characterized by any of the above DNA sequences.
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, 0.27 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 variegated DNA sequences characterized by any of the above DNA sequences.
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.
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.
Dependencies are inferred from the claim text.