Libraries of genetic packages comprising novel HC CDR1, CDR2, and CDR3 and novel LC CDR1, CDR2, and CDR3 designs
Provided are compositions and methods for preparing and identifying antibodies having CDR3s that vary in sequence and in length from very short to very long which in certain embodiments may bind to a carbohydrate moiety or the active site of an enzyme. Libraries coding for antibodies with the CDR3s are also provided. The libraries can be provided by modifying a pre-existing nucleic acid library.
1. A library of vectors or genetic packages, wherein the vectors or genetic packages comprise variegated DNA sequences, each encoding a heavy chain (HC) variable region, which comprises three complementarity determining regions (CDRs) 1-3 and framework regions (FRs) 1-4, arranged from the amino-terminus to the carboxy-terminus in an order of FR1-CDR2-FR2-CDR2-FR3-CDR3-FR4, wherein the HC CDR3 region contains 3-35 amino acid residues, and wherein more than 20% of the HC CDR3 sequence consists of Tyr residues;
wherein D regions and J stumps of the HC CDR3 consist of more than 20% of Tyr residues;
wherein the D regions are selected from the group consisting of 3-3.2 (SEQ ID NO: 177), 3-22.2 (SEQ ID NO: 88), 6-19.1 (SEQ ID NO: 218), 6-13.1 (SEQ ID NO: 215) and 4-17.2 (SEQ ID NO: 760); and
wherein the J stumps are selected from the libraries consisting of 5.002 (SEQ ID NO: 984), 5.003 (SEQ ID NO: 985), 5.005 (SEQ ID NO: 985) and 5.006 (SEQ ID NO: 990).
2. The library of claim 1 , wherein the library is a library of genetic packages.
3. The library of claim 2 , wherein the genetic packages are bacteriophages.
4. The library of claim 3 , wherein the library is a phage display library.
5. The library of claim 1 , wherein the library is a library of vectors.
6. The library of claim 5 , wherein the vectors are phage vectors or phagemid vectors.
7. The library of claim 1 , wherein the library comprises at least 1×10 9 members.