Soluble polypeptides
AssigneeAffinity Biosciences Pty Ltd
InventorsMatthew David Beasley, Keith Philip Niven, Ben Ross Kiefel
Life of this patent
Estimating the term…
Abstract
The invention relates generally to polypeptides, such as antibody molecules, that demonstrate high stability and solubility. In particular, the invention relates to polypeptides comprising paired VL and VH domains that demonstrate soluble expression and folding in a reducing or intracellular environment. The invention also relates to polynucleotides encoding such polypeptides, to libraries of such polypeptides or polynucleotides, and to methods of using such polypeptides in research, diagnostic and therapeutic applications.
Claims20
A polynucleotide library comprising a plurality of different polynucleotides, wherein each polynucleotide encodes a polypeptide comprising:
- i) an antibody heavy chain variable region (VH) comprising a scaffold region which is at least 90% identical to the scaffold region of IGHV3-23 as set out in SEQ ID NO:
- 3;
- and
- ii) an antibody light chain variable region (VL) comprising a scaffold region which is at least 90% identical to the scaffold region of any one of IGLV1-40 (as set out in SEQ ID NO:
- 18), IGLV1-44 (as set out in SEQ ID NO:
- 21), IGLV1-47 (as set out in SEQ ID NO:
- 24), IGLV1-51 (as set out in SEQ ID NO:
- 15), IGLV3-1 (as set out in SEQ ID NO:
- 6), IGLV3-19 (as set out in SEQ ID NO:
- 27), IGLV3-21 (as set out in SEQ ID NO:
- 9), IGLV6-57 (as set out in SEQ ID NO:
- 12);
- wherein the VH and the VL are capable of forming an antigen-binding site;
- and
- wherein at least two of the polynucleotides differ from one another by encoding polypeptides comprising one or more different CDRs in the VH and/or VL variable regions.
A method of constructing a polynucleotide library, the method comprising preparing a plurality of different polynucleotides encoding a polypeptide, which comprises:
- i) an antibody heavy chain variable region (VH) comprising a scaffold region which is at least 90% identical to the scaffold region of IGHV3-23 as set out in SEQ ID NO:
- 3;
- and
- ii) an antibody light chain variable region (VL) comprising a scaffold region which is at least 90% identical to the scaffold region of any one of IGLV1-40 (as set out in SEQ ID NO:
- 18), IGLV1-44 (as set out in SEQ ID NO:
- 21), IGLV1-47 (as set out in SEQ ID NO:
- 24), IGLV1-51 (as set out in SEQ ID NO:
- 15), IGLV3-1 (as set out in SEQ ID NO:
- 6), IGLV3-19 (as set out in SEQ ID NO:
- 27), IGLV3-21 (as set out in SEQ ID NO:
- 9), IGLV6-57 (as set out in SEQ ID NO:
- 12);
- wherein the VH and the VL are capable of forming an antigen-binding site;
- and
- wherein at least two of the polynucleotides differ from one another by encoding polypeptides comprising one or more different CDRs in the VH and/or VL variable regions.
An isolated and/or recombinant polypeptide comprising:
- i) an antibody heavy chain variable region (VH) comprising a scaffold region which is at least 90% identical to the scaffold region of IGHV3-23 as set out in SEQ ID NO:
- 3;
- and
- ii) an antibody light chain variable region (VL) comprising a scaffold region which is at least 90% identical to the scaffold region of any one of IGLV1-40 (as set out in SEQ ID NO:
- 18), IGLV1-44 (as set out in SEQ ID NO:
- 21), IGLV1-47 (as set out in SEQ ID NO:
- 24), IGLV1-51 (as set out in SEQ ID NO:
- 15), IGLV3-1 (as set out in SEQ ID NO:
- 6), IGLV3-19 (as set out in SEQ ID NO:
- 27), IGLV3-21 (as set out in SEQ ID NO:
- 9), IGLV6-57 (as set out in SEQ ID NO:
- 12);
- wherein the VH and the VL are capable of forming an antigen-binding site.
Dependencies are inferred from the claim text.