Acceptor framework for CDR grafting
The present invention relates to an antibody acceptor framework and to methods for grafting non-human antibodies, e.g., rabbit antibodies, using a particularly well suited antibody acceptor framework. Antibodies generated by the methods of the invention are useful in a variety of diagnostic and therapeutic applications.
1. A human heavy chain acceptor framework comprising a sequence that is at least 95% identical to SEQ ID NO: 1.
2. The human heavy chain acceptor framework of claim 1 , comprising an amino acid substitution at position 12, 103, and 144 (Aho numbering).
3. The human heavy chain acceptor framework of claim 2 , wherein the substitution is
(a) Serine (S) at position 12;
(b) Serine (S) or Threonine (T) at position 103; and/or
(c) Serine (S) or Threonine (T) at position 144.
4. An immunobinder specific to a desired antigen comprising:
(a) a light chain acceptor framework comprising the three variable light chain CDRs and of a lagomorph immunobinder specific for a desired antigen; and
(b) the human heavy chain acceptor framework of claim 1 comprising the three variable heavy chain CDRs of said lagomorph immunobinder.
5. The immunobinder of claim 4 , wherein the light chain acceptor framework has at least 85% identity to SEQ ID NO: 2.
6. The immunobinder of claim 4 , further comprising a linker sequence that links the variable light chain framework and the heavy chain acceptor framework, wherein the linker sequence is SEQ ID NO: 4.
7. The immunobinder of claim 4 , further comprising donor framework residues involved in antigen binding.
8. The immunobinder of claim 4 , wherein the immunobinder is a scFv antibody, a full-length immunoglobulin or a Fab fragment.
9. A humanized immunobinder specific for a desired antigen comprising:
(a) the three heavy chain CDRs of a donor rabbit immunobinder specific for said desired antigen grafted into a heavy chain acceptor framework having at least 95% identity to SEQ ID NO: 1; and
(b) the three light chain CDRs of said donor rabbit immunobinder grafted into a light chain acceptor framework having at least 85% identity to SEQ ID NO: 2.