Focused libraries of genetic packages
First Claim
Patent Images
1. A focused library of vectors or genetic packages, comprising a first set of variegated DNAs each of which comprises a nucleotide sequence encoding an antibody heavy chain, which comprises a CDR1 region, a CDR2 region, and a CDR3 region, each nucleotide sequence in the first set of variegated DNAs being represented by the formula V:
- ;
nz;
;
JHn, or V;
;
nz;
;
D;
;
ny;
;
JHn, wherein V is a v gene, nz is a series of bases that are essentially random, D is a D segment, ny is a series of bases that are essentially random, and JHn is one of the six JH segments, wherein the CDR2s of the heavy chains encoded by the first set of variegated DNAs are seventeen amino acids in length, sixteen amino acids in length, and/or nineteen amino acids in length, and wherein the heavy chain CDR2s encoded by the first set of variegated DNAs are seventeen amino acids in length having the sequence;
<
2>
I<
2>
<
3>
SGG<
1>
T<
1>
YADSVKG (SEQ ID NO;
2), in which each <
1>
independently is selected from the group consisting of A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, and Y;
each <
2>
independently is an amino acid selected from the group consisting of Y, R, W, V, G and S; and
<
3>
is selected from the group consisting of P and S.
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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.
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Citations
22 Claims
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1. A focused library of vectors or genetic packages, comprising a first set of variegated DNAs each of which comprises a nucleotide sequence encoding an antibody heavy chain, which comprises a CDR1 region, a CDR2 region, and a CDR3 region, each nucleotide sequence in the first set of variegated DNAs being represented by the formula V:
- ;
nz;
;
JHn, or V;
;
nz;
;
D;
;
ny;
;
JHn, wherein V is a v gene, nz is a series of bases that are essentially random, D is a D segment, ny is a series of bases that are essentially random, and JHn is one of the six JH segments, wherein the CDR2s of the heavy chains encoded by the first set of variegated DNAs are seventeen amino acids in length, sixteen amino acids in length, and/or nineteen amino acids in length, and wherein the heavy chain CDR2s encoded by the first set of variegated DNAs are seventeen amino acids in length having the sequence;<
2>
I<
2>
<
3>
SGG<
1>
T<
1>
YADSVKG (SEQ ID NO;
2), in which each <
1>
independently is selected from the group consisting of A, D, E, F, G, H, I, K, L, M, N, P, Q, R, S, T, V, W, and Y;
each <
2>
independently is an amino acid selected from the group consisting of Y, R, W, V, G and S; and
<
3>
is selected from the group consisting of P and S. - View Dependent Claims (6, 7, 8, 9, 10, 11, 16, 17, 19, 20, 21, 22)
- ;
-
2. A focused library of vectors or genetic packages, comprising a first set of variegated DNAs each of which comprises a nucleotide sequence encoding an antibody heavy chain, which comprises a CDR1 region, a CDR2 region, and a CDR3 region, each nucleotide sequence in the first set of variegated DNAs being represented by the formula V:
- ;
nz;
;
JHn, or V;
;
nz;
;
D;
;
ny;
;
JHn, wherein V is a v gene, nz is a series of bases that are essentially random, D is a D segment, ny is a series of bases that are essentially random, and JHn is one of the six JH segments, wherein;(a) nz encodes the sequence <
1>
<
1>
1>
, in which each <
1>
independently is any amino acid residue other than C;
D encodes the sequence S<
2>
S<
3>
(SEQ ID NO;
450), in which <
2>
is S or G and <
3>
is Y or W;
ny encodes the sequence <
1>
<
1>
<
1>
, in which each <
1>
independently is any amino acid residue other than C; and
JHn encodes the sequence YFDY (SEQ ID NO;
449),(b) nz encodes the sequence <
1>
<
1>
<
1>
, in which each <
1>
independently is any amino acid residue other than C;
D encodes the sequence CSG<
1>
<
1>
CY (SEQ ID NO;
451), in which each <
1>
independently is any amino acid residue other than C;
ny encodes the sequence <
1>
, which is any amino acid residue other than C; and
JHn encodes the sequence YFDY (SEQ ID NO;
449),(c) nz encodes the sequence <
1>
<
1>
S<
1>
(SEQ ID NO;
452), in which each <
1>
independently is any amino acid residue other than C;
D encodes the sequence TIFG (SEQ ID NO;
453);
ny encodes the sequence <
1>
<
1>
<
1>
<
1>
<
1>
(SEQ ID NO;
454), in which each <
1>
independently is any amino acid residue other than C; and
JHn encodes the sequence YFDY (SEQ ID NO;
449),(d) nz encodes the sequence <
1>
<
1>
<
1>
, in which each <
1>
independently is any amino acid residue other than C;
D encodes the sequence YY<
2>
S<
3>
<
3>
YY (SEQ ID NO;
455), in which <
2>
is D or G, and each <
3>
independently is S or G;
ny encodes the sequence <
1>
<
1>
<
1>
, in which each <
1>
independently is any amino acid residue other than C; and
JHn encodes the sequence YFDY (SEQ ID NO;
449), or(e) nz encodes the sequence <
1>
<
1>
<
1>
<
1>
(SEQ ID NO;
456), in which each <
1>
independently is any amino acid residue other than C;
D encodes the sequence YC<
2>
<
2>
<
3>
<
1>
CY (SEQ ID NO;
457), in which <
1>
is any amino acid residue other than Cys, each <
2>
independently is S or G, and <
3>
is T, D or G;
ny encodes the sequence <
1>
<
1>
<
1>
, in which each <
1>
independently is any amino acid residue other than C; and
JHn encodes YFDY (SEQ ID NO;
449). - View Dependent Claims (3, 4, 5, 12, 13, 14, 15, 18)
- ;
Specification