Binding members with altered diversity scaffold domains
AssigneeMaxion Therapeutics Limited
InventorsAneesh Karatt Vellatt, John McCafferty, Sachin Surade, Tim Luetkens, Edward Masters, Michael Dyson
Life of this patent
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Abstract
This invention relates to libraries of binding members that each comprise a fusion protein which contains a donor diversity scaffold domain, such as a cysteine rich protein, inserted within a recipient diversity scaffold domain, such as an antibody constant or variable domain. Libraries and methods of generating libraries are provided, along with screening methods, binding members and methods of using the binding members.
Claims33
A library of binding members comprising:
- a diverse population of fusion proteins, each fusion protein comprising a donor diversity scaffold domain inserted into a recipient diversity scaffold domain,
- wherein the donor diversity scaffold domain comprises a donor scaffold and a donor interaction sequence and the recipient diversity scaffold domain comprises a recipient scaffold and a recipient interaction sequence,
- wherein the donor diversity scaffold domain is a knottin, and
- wherein the recipient diversity scaffold domain is an antibody variable domain and the donor diversity scaffold domain is a replacement for all or part of one of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 or VL CDR3 of the antibody variable domain,
- wherein the donor diversity scaffold domain:
- a) is a peptide that consists of 100 or fewer amino acids, and
- b) comprises two or more disulphide bridges formed by four or more cysteine residues within the donor scaffold,
- wherein the donor diversity scaffold is located 8 Angstroms to 13 Angstroms from the recipient diversity scaffold domain, calculated from the end of a preceding framework of the antibody variable domain of the recipient diversity scaffold domain to a first cysteine residue of the donor diversity scaffold domain
- wherein one or both of the donor interaction sequence and the recipient interaction sequence are diverse in said diverse population of fusion proteins.
A fusion protein comprising a donor diversity scaffold domain inserted into a recipient diversity scaffold domain,
- wherein the donor diversity scaffold domain comprises a donor scaffold and a donor interaction sequence and the recipient diversity scaffold domain comprises a recipient scaffold and a recipient interaction sequence,
- wherein the donor diversity scaffold domain is a knottin, and
- wherein the N terminal and C terminal of the donor diversity scaffold domain are linked to the recipient diversity scaffold domain without linkers or with linkers of up to 4 amino acids,
- wherein the recipient diversity scaffold domain is an antibody variable domain and the donor diversity scaffold domain is a replacement for all or part of one of VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 or VL CDR3 of the antibody variable domain,
- wherein the donor diversity scaffold domain:
- a) is a peptide that consists of 100 or fewer amino acids and
- b) comprises two or more disulphide bridges formed by four or more cysteine residues within the donor scaffold, and
- wherein the donor diversity scaffold is located 8 Angstroms to 13 Angstroms from the recipient diversity scaffold domain, calculated from the end of a preceding framework of the antibody variable domain of the recipient diversity scaffold domain to a first cysteine residue of the donor diversity scaffold domain.
Dependencies are inferred from the claim text.