Focused libraries of genetic packages
View Patent ↗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.
1. A focused library of vectors or genetic packages, the focused library comprising vectors or genetic packages which are characterized by variegated DNAs, each of which comprises a sequence that encodes a human antibody heavy chain comprising a synthetic heavy chain CDR1, CDR2 and CDR3,
wherein the human antibody heavy chain comprises a human heavy chain variable region, wherein the heavy chain variable region consists of a sequence represented by the formula 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 v gene is 3-23, 4-34, 3-30, 3-30.3, or 4-30.1;
wherein JH is JH4 or JH3;
wherein the CDR1 segments encoded by the variegated DNAs comprise CDR1 segments that consist of a length of 5 amino acid residues;
wherein the CDR2 segments encoded by the variegated DNAs comprise CDR2 segments that consist of a length of 17 amino acid residues;
wherein the CDR3 segments encoded by the variegated DNAs comprise an embedded human antibody heavy chain D segment, wherein the CDR3 segments consist of a length of 7-15 amino acid residues between YYCAR and WG;
wherein the CDR3 segments in the library comprise amino acid sequence variation and amino acid length variation;
wherein the variegation is focused so as to closely mimic the naturally-occurring diversity of the specific family that the library represents, both in sequence and in length.
2. The focused library of vectors or genetic packages of claim 1 , further comprising vectors or genetic packages which are characterized by variegated DNA sequences that encode a light chain comprising CDR1, CDR2 and CDR3, the light chain being a kappa light chain.
3. The library of claim 2 , wherein the library is a library of yeast vectors.
4. The library of claim 1 , wherein the library is a library of genetic packages.
5. The library of claim 1 , wherein the library is a library of yeast vectors.
6. The focused library of claim 1 , wherein the v gene is 3-23 and the JH is JH4.
7. The focused library of claim 1 , wherein the synthetic heavy chain CDR1 segments encoded by the variegated DNAs comprise amino acid sequence variation.
8. The focused library of claim 1 , wherein the synthetic heavy chain CDR2 segments encoded by the variegated DNAs comprise amino acid sequence variation.
9. The focused library of claim 1 , wherein the synthetic heavy chain CDR1 segments further comprise lengths of 7 amino acid residues.
10. The focused library of claim 1 , wherein the synthetic heavy chain CDR1 segments further comprise lengths of 14 amino acid residues.
11. The focused library of claim 1 , wherein the synthetic heavy chain CDR2 segments further comprise lengths of 16 amino acid residues.
12. The focused library of claim 1 , wherein the synthetic heavy chain CDR2 segments further comprise lengths 19 amino acid residues.
13. The library of claim 2 , wherein the library is a library of genetic packages.