Universal antibody libraries

Patent metadata

Field	Value
Publication number	US-11674240-B2
Application number	US-57171005-A
Country	US
Kind code	B2
Filing date	Jul 6, 2005
Priority date	Jul 6, 2004
Publication date	Jun 13, 2023
Grant date	Jun 13, 2023

Abstract

Universal antibody libraries are described which are synthetic and derived from expressed human antibody sequences selected accordingly to certain criteria, for example, that the sequences are derived from naturally-occurring antibodies expressed in response to a certain antigen class (e.g., small molecule, polysaccharide, peptide, or protein) and having CDR regions engineered for optimal diversity. Methods for making and screening such libraries for isolating therapeutics suitable for treating disease are also disclosed.

First claim

The invention claimed is:

1. A library of polynucleotides encoding antibody binding regions comprising:
a) a light chain human framework region selected from a light chain human framework clone of the V K -I sub-family;
b) four heavy chain framework regions, wherein each heavy chain framework region comprises a heavy chain human framework clone selected from the group consisting of 1-e, 3-07, 3-11, 3-21, 3-23, 3-30.5, 3-33, 3-48, and 3-74;
c) a V K I CDR-L1 region of length seven according to the contact definition of CDR comprising the amino acid sequence SX 1 X 2 LAWY (SEQ ID NO: 22) wherein X 1 is S or N and X 2 is N or Y;
d) a V K I CDR-L2 region of length ten according to the contact definition of CDR comprising the amino acid sequence of LLIYAASAL(Q/E) (SEQ ID NO: 29);
e) a V K I CDR-L3 region is of length eight or nine according to the contact definition of CDR comprising the amino acid sequence QQYNSTPL (SEQ ID NO: 34);
f) a CDR-H1 region of length six according to the contact definition of CDR comprising the amino acid sequence (T/S)SYA(I/M)S (SEQ ID NO: 19);
g) a CDR-H2 region of length thirteen according to the contact definition of CDR comprising the amino acid sequence of WMGGINPISGT(T/A)N(SEQ ID NO: 27); and
h) a CDR-H3 region consisting of the amino acid sequence of: ARX 1 X 2 X 3 X 4 X 5 FD (SEQ ID NO: 99) wherein Xi is A, D, S, I, P, R, Y, H, N, G, E, L or V and X 2 is A, D, S, I, P, R, Y, H, N, G, L or Q and X 3 is A, D, S, I, P, R, Y, H, N, G, V, T, L or Q and X 4 is A, D, S, I, P, R, Y, H, N, G, W or L and X 5 is A, D,S, I, P, R, Y, H, N, G, L, J or V;
ARX 1 X 2 X 3 X 4 X 5 X 6 FD (SEQ ID NO: 100) wherein X 1 is A, D, S, I, P, R, Y, H, N, G, E, L, V or M and X 2 is A, D, S, I, P, R, Y, H, N, G, L, V, K or Q and X 3 is A, D, S, I, P, R, Y, H, N, G, T, E, L, V, Q or W and X 4 is A, D, S, I, P, R, Y, H, N, G, L, V, W or Q and X 5 is A, D, S, I, P, R, Y, H, N, G, T, E, W or L and X 6 is A, D, S, I, P, R, Y, H, N, G, L or F;
ARX 1 X 2 X 3 X 4 X 5 X 6 X 7 FD (SEQ ID NO: 101) wherein Xi is A, D, S, I, P, R, Y, H, N, K, G, E or L and X 2 is A, D, S, I, P, R, Y, H, N, T, G, F, L or V and X 3 is A, D, S, I, P, R, Y, H, N, G, V or T and X 4 is A, D, S, I, P, R, Y, H, N, G, J or W and X 5 is A, D, S, I, P, R, Y, H, N, G, T or L and X 6 is A, D, S, I, P, R, Y, H, N, G or W and X 7 is A, D, S, I, P, R, Y, H, N, G, W, F or L;
ARX 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 FD (SEQ ID NO: 102) wherein X 1 is A, D, S, I, P, R, Y, H, N, G, E or V and X 2 is A, D, S, I, P, R, Y, H, N, G, L, Q or T and X 3 is A, D, S, I, P, R, Y, H, N, G, L, T, V or W and X 4 is A, D, S, I, P, R, Y, H, N, G, W, L or V and X 5 is A, D, S, I, P, R, Y, H, N, G, V, F, T or L and X 6 is A, D, S, I, P, R, Y, H, N, G, L, T or E and X 7 is A, D, S, I, P, R, Y, H, N, G, J, W or F and X 8 is A, D, S, I, P, R, Y, H, N, G, F, T or W;
ARX 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 FD (SEQ ID NO: 103) wherein Xi is A, D, S, I, P, R, Y, H, N, G, E, V, L or K and X 2 is A, D, S, I, P, R, Y, H, N, G, L, Q or K and X 3 is A, D, S, I, P, R, Y, H, N, G, L, V, K or M and X 4 is A, D, S, I, P, R, Y, H, N, G, T, L or V and X 5 is A, D, S, I, P, R, Y, H, N, G, T, W, L or Q and X 6 is A, D, S, I, P, R, Y, H, N, G, V, L, E or T and X 7 is A, D, S, I, P, R, Y, H, N, L, V, T, W or G and X 8 is A, D, S, I, P, R, Y, H, N, G or F and X 9 is A, D, S, I, P, R, Y, H, N, G, F, W or T; or ARX 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 FD (SEQ ID NO: 104) wherein X 1 is A, D, S, I, P, R, Y, H, N, G, E, or V and X 2 is A, D, S, I, P, R, Y, H, N, G, L, T, Q or K and X 3 is A, D, S, I, P, R, Y, H, N, G, L, V, T or E and X 4 is A, D, S, I, P, R, Y, H, N, G, L, F, T or Q and X 5 is A, D, S, I, P, R, Y, H, N, G, V, T or L and X 6 is A, D, S, I, P, R, Y, H, N, G, T, L or V and X 7 is A, D, S, I, P, R, Y, H, N, G, T, L, E or V and X 8 is A, D, S, I, P, R, Y, H, N, G, T, F, E or L and X 9 is A, D, S, I, P, R, J, H, N, G, W or T and X 10 is A, D, S, I, P, R, Y, H, N, G, F, W or L;
ARX 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 FD (SEQ ID NO: 105) wherein X 1 is A, D, S, I, P, R, Y, H, N, G, E, V or T and X 2 is A, D, S, I, P, R, Y, H, N, G, W, L, T or V and X 3 is A, D, S, I, P, R, Y, H, N, G, E, T, F, L or W and X 4 is A, D, S, I, P, R, Y, H, N, G, E, C, T or F and X 5 is A, D, S, I, P, R, Y, H, N, G, T, W or L and X 6 is A, D, S, I, P, R, Y, H, N, G, T or E and X 7 is A, D, S, I, P, R, Y, H, N, G, T, V or W and X 8 is A, D, S, I, P, R, Y, H, N, G, T, L, F, V, M or W and X 9 is A, D, S, I, P, R, Y, H, N, G, V, C or K and X 10 is A, D, S, I, P, R, Y, H, N, G, W or Q and X 11 is A, D, S, I, P, R, Y, H, N, G, W, For L;
ARX 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 FD (SEQ ID NO: 106) wherein X 1 is A, D, S, I, P, R, Y, H, N, G, L, V or E and X 2 is A, D, S, I, P, R, Y, H, N, G, L, V or E and X 3 is A, D, S, I, P, R, Y, H, N, G, or L and X 4 is A, D, S, I, P, R, Y, H, N, G, L, T or E and X 5 is A, D, SJ, P, R, Y, H, N, G, V, F, T or M and X 6 is A, D, S, I, P, R, Y, H, N, G, T, F or W and X 7 is A, D, S, I, P, R, Y, H, N, G J, V, L or E and X 8 is A, D, S, I, P, R, Y, H, N, G, T, E or W and X 9 is A, D, S, I, P, R, Y, H, N, G, L, F or W and X 10 is A, D, S, I, P, R, Y, H, N, G, L, T or F and X 11 is A, D, S, I, P, R, Y, H, N, G, W or T and X 12 is A, D, S, I, P, R, Y, H, N, G, W or F;
ARX 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 X 13 FD (SEQ ID NO: 107) wherein X 1 is A, D, S, I, P, R, Y, H, N, G, V, E or L and X 2 is A, D, S, I, P, R, Y, H, N, G, L or Q and X 3 is A, D, S, I, P, R, Y, H, N, G, L, T, V or M and X 4 is A, D, S, I, P, R, Y, H, N, G, V or C and X 5 is A, D, S, I, P, R, Y, H, N, G, V or T and X 6 is A, D, S, I, P, R, Y, H, N, G, F, V or T and X 7 is A, D, S, I, P, R, Y, H, N, G, W, T, V or F and X 8 is A, D, S, I, P, R, Y, H, N, G, L or V and X 9 is A, D, S, I, P, R, Y, H, N, G, V, F, L or C and X 10 is A, D, S, I, P, R, Y, H, N, G, F or L and X 11 is A, D, S, I, P, R, Y, H, N, G, L, V or C and X 12 is A, D, S, I, P, R, Y, H, N or G and X 13 is A, D, S, I, P, R, Y, H, N, G or W; or
ARX 1 X 2 X 3 X 4 X 5 X 6 X 7 X 8 X 9 X 10 X 11 X 12 X 13 X 14 FD (SEQ ID NO: 108) wherein X 1 is A, D, S, I, P, R, Y, H, N, G, E, V or L and X 2 is A, D, S, I, P, R, Y, H, N, G, L or K and X 3 is A, D, S, I, P, R, Y, H, N, G, T, V, L or F and X 4 is A, D, S, I, P, R, Y, H, N, G, V or T and X 5 is A, D, S, I, P, R, Y, H, N, G, C, F, K, L or M and X 6 is A, D, S, I, P, R, Y, H, N, G, V, F, T, W or C and X 7 is A, D, S, I, P, R, Y, H, N, G, T, W or F and X 8 is A, D, S, I, P, R, Y, H, N, G, W, V or F and X 9 is A, D, S, I, P, R, Y, H, N, G, L or V and X 10 is A, D, S, I, P, R, Y, H, N, G, C, L or F and X 11 is A, D, S, I, P, R, Y, HN, F, G or W and X 12 is A, D, S, I, P, R, Y, H, N, G, T, L or F and X 13 is A, D, S, I, P, R, Y, H, N, G or W and X 14 is A, D, S, I, P, R, Y, H, N, G, W or T.

2. The library of claim 1 , wherein antibody binding region is selected from the group consisting of an antibody, an antibody heavy chain (VH), and a single chain antibody (scFv).

3. The library of claim 1 , wherein the predetermined antigen class is a class of antigens selected from the group consisting of proteins, peptides, small molecules, polysaccharides, and polynucleotides.

4. The library of claim 1 , wherein the antibody binding regions further comprise one or more amino acid substitutions corresponding to a naturally occurring somatic mutation.

5. The library of claim 1 , wherein the library is an expression library.

6. The library of claim 5 , wherein the expression library is selected from the group consisting of a ribosome display library, a polysome display library, a phage display library, a bacterial expression library, and a yeast display library.

7. The library of clai

Assignees

• Crea Roberto
• Rajpal Arvind
• Cappuccilli Guido
• Shen Randy
• Takeuchi Toshihiko
• Pfizer

Inventors

• Crea Roberto
• Rajpal Arvind
• Cappuccilli Guido
• Shen Randy
• Takeuchi Toshihiko

Classifications

• C07K16/00 Primary

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• C07K2317/21

  from primates, e.g. man · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/567

  Framework region [FR] · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title