Ph-sensitive antibodies

A major challenge in the field of antibody-based therapeutics is the development of antibodies with enhanced duration of action, prolonged half-life and which can be delivered at lower dose to patients. Current approaches to achieve this rely on engineering of pH-dependent antigen binding properties to antibodies which are laborious, and typically require further optimization of pH-sensitive interactions in a low- throughput, case-to-case manner as they largely rely on introduction of histidines mutations to the specific antibody complementarity-determining regions (CDRs). In the present invention, the inventors provide antibodies and other antigen-binding proteins carrying mutations outside of the paratope conferring universal pH sensitive binding properties to antibodies. The invention also relates to methods of isolating and generating said antigen-binding proteins, compositions and medical uses thereof.