Antibody Polypeptide Libray Screening and Selected Antibody Polypeptides
AssigneeBig Glucose Ltd.
InventorsJasper Clube, Laurent Jespers
Life of this patent
Estimating the term…
Abstract
The present invention provides further developments in the screening of antibody polypeptide libraries. The invention also provides novel isolated antibody polypeptides obtainable by the methods of the invention.
Claims77
A method for selecting, from a repertoire of antibody polypeptides, a population of functional variable domains which bind a target ligand and a generic ligand, which generic ligand is capable of binding functional members of the repertoire regardless of target ligand specificity, comprising the steps of:
- a) contacting the repertoire with said generic ligand and selecting functional variable domains bound thereto;
- and
- b) contacting the selected functional variable domains with the target ligand and selecting a population of variable domains which bind to the target ligand,
- wherein either (i) the variable domains are heavy chain variable domains and the generic ligand is an antibody light chain variable domain;
- or (ii) the variable domains are light chain variable domains and the generic ligand is an antibody heavy chain variable domain;
- and
- wherein optionally in (i) the heavy chain variable domains are Camelid variable domains (VHH) or derived from a Camelid heavy chain antibody (H2 antibody);
- or optionally in (i) and (ii) each variable domain is a human variable domain or derived from a human.
(canceled)
(canceled)
A method for selecting at least one antibody heavy chain variable domain from a population of antibody polypeptides, the method comprising:
- a) contacting the population with an antibody light chain variable domain and
- b) selecting at least one antibody heavy chain variable domain that binds to the light chain variable domain.
19-24. (canceled)
26-34. (canceled)
(canceled)
A method for selecting at least one antibody light chain variable domain from a population of antibody polypeptides, the method comprising:
- a) contacting the population with an antibody heavy chain variable domain and
- b) selecting at least one antibody light chain variable domain that binds to the heavy chain variable domain.
57-60. (canceled)
65-66. (canceled)
(canceled)
72-73. (canceled)
A method for separating IgG from Camelid VNH antibody single variable domain in a population of antibody polypeptides comprising single variable domains and IgG, the method comprising:
- a) contacting the population with a generic ligand and
- b) selecting a subpopulation that binds to the generic ligand, thereby separating IgG from the single variable domain,
- wherein the generic ligand has binding specificity for antibody CH1 domain, light chain constant domain (CL), IgG hinge or antibody light chain variable domain.
75-80. (canceled)
A method for separating a Camelid VHH single variable domain from IgG in a population of antibody polypeptides comprising Camelid VHH domains and IgG, the method comprising:
- a) contacting the population with a generic ligand and
- b) selecting a subpopulation that binds to the generic ligand, thereby separating the single variable domain from IgG,
- wherein the generic ligand has binding specificity for (i) VHH and not VH;
- or (ii) heavy chain antibody (H2) hinge.
82-91. (canceled)
A method for selecting, from a repertoire of antibody polypeptides, a single variable domain which binds a target ligand and a generic ligand, comprising the steps of:
- a) contacting the repertoire with a target ligand and selecting single variable domains bound thereto;
- and
- b) contacting the selected variable domains with the generic ligand and selecting a variable domain which binds to the generic ligand,
- wherein the generic ligand is an antibody variable domain selected from Annex 2 c) or e);
- and
- wherein (i) when the selected variable domain is a heavy chain variable domain the generic ligand is a light chain variable domain, or (ii) when the selected variable domain is a light chain variable domain the generic ligand is a heavy chain variable domain.
93-94. (canceled)
A method of producing a derivative of an antibody or antibody fragment in any of Annex 2c) (i) to (iv) that binds a target ligand, the method comprising:
- a) using a light chain variable domain of said antibody or fragment or an identical variable domain as the generic ligand in the method of claim, and wherein the target ligand used in step a) is the target ligand to which the antibody or fragment binds, thereby selecting a heavy chain single variable domain that binds the target ligand and the light chain variable domain;
- and
- b) replacing at least one of the heavy chain variable domains of the antibody or fragment with the selected heavy chain variable domain;
- an identical heavy chain variable domain or a derivative thereof.
- c)
106-107. (canceled)
109-112. (canceled)
Dependencies are inferred from the claim text.