MODIFIED PROTEINS AND PEPTIDES
1 Assignment
0 Petitions
Accused Products
Abstract
The present disclosure relates to modified proteins and peptides that have reduced ability to bind to pre-existing antibodies. Such modified protein/peptide molecules can comprise C-terminal additions, extensions or tags and/or certain amino acid substitutions. Such modified molecules (e.g., fusions and conjugates) comprise proteins, peptides, antigen binding molecules, antibodies or antibody fragments such as single variable domains. The disclosure further relates to uses and formulations of compositions comprising such modified C-terminally extended and/or amino acid substituted molecules and also to methods of production and expression of these.
6 Citations
95 Claims
-
1-59. -59. (canceled)
-
60. A single immunoglobulin variable domain (dAb) which is selected from the group consisting of:
- a human VH dAb, a human VL dAb (e.g. a V kappa) and a Camelid VHH and which monovalently binds to a target antigen, comprising;
a. three complementarity determining (CDR) regions specific for said target antigen;
such that said dAb binds said antigen with a KD in the range from 5 μ
M to 1 pMb. four framework (FW) regions; and c. a C-terminal sequence consisting of the sequence VTVS(S)nX or VEIKpRqX; and
optionallyd. one or more amino acid substitutions at positions 14, 41, 108, 110, or 112 compared to a human germline framework sequence wherein; n represents an integer independently selected from 0 or 1; p and q each represent 0 or 1 such that when p represents 1 q may be 0 or 1 and such that when p represents 0, q also represents 0; X may be present or absent, and if present represents an amino acid extension of 1 to 5 amino acids residues; with the further proviso that if X is absent; i. n is 0 and/or the dAb ending in VTVS(S)n comprises one or more of said amino acid substitutions; ii. p and/or q is 0, and/or the dAb ending in VEIKpRq comprises one or more of said amino acid substitutions. - View Dependent Claims (61, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95)
- a human VH dAb, a human VL dAb (e.g. a V kappa) and a Camelid VHH and which monovalently binds to a target antigen, comprising;
-
62. A single immunoglobulin variable domain (dAb),) which is selected from the group consisting of:
- a human VH dAb, a human VL dAb (e.g. a V kappa) and a Camelid VHH and which comprises one or more modifications selected from;
(a) a C-terminal extension which comprises an amino acid extension of from one amino acid to 5 amino acids;
or(b) one or more amino acid framework substitutions wherein at least one substitution is a substitution selected from;
a P14A substitution, a P41A substitution and a L108A substitution;(c) a C terminal deletion and which has reduced binding to pre-existing ADAs compared to the unmodified single immunoglobulin variable domain (dAb).
- a human VH dAb, a human VL dAb (e.g. a V kappa) and a Camelid VHH and which comprises one or more modifications selected from;
Specification