MULTISPECIFIC ANTIBODY ANALOGS COMPRISING A COMMON LIGHT CHAIN, AND METHODS OF THEIR PREPARATION AND USE

摘要

Multispecific antibody analogs that co-engage at least two different antigens or epitopes (also referred to targets, used interchangeably throughout), said analogs comprising a common light chain, are provided, as well as methods for their production and use.

主权项

1. A method of making a multispecific antibody analog comprising at least two first antigen binding regions and at least two second antigen binding regions, said first and second antigen binding regions having a common light chain, wherein first antigen binding regions have a different antigen specificity than the second antigen binding regions, the method comprising;
i) obtaining at least one light chain from a first antigen binding region having specificity for the first antigen, wherein the first antigen binding region comprises said at least one light chain and a heavy chain; ii) obtaining heavy chains from the output of a selection performed from a naïve library against a second antigen; iii) preparing a restricted library comprising heavy chains obtained in step ii) and the at least one light chain obtained in step i); iv) performing a second selection against the second antigen from the library prepared in step iii); v) obtaining an multispecific antibody comprising the second antigen binding region from the selection performed in step iv), wherein the second antigen binding region comprises the at least one light chain obtained in step i); vi) incorporating the first antigen binding region and the second antigen binding region into a multispecific antibody format, wherein the format comprises: an IgG moiety comprising either: a) the first antigen binding region; or b) the second antigen binding region; and two Fab moieties, wherein each Fab moiety comprises either: a) the second antigen binding region; or b) the first antigen binding region; wherein the N-terminus of the heavy chain of one Fab moiety is linked to the C-terminus of the Fc region of one heavy chain of the IgG moiety via a linker moiety, and the N-terminus of the heavy chain of the other Fab moiety is linked to the C-terminus of the Fc region of the other heavy chain of the IgG moiety via a linker moiety; thereby generating the multispecific antibody analog.