abstract |
The present invention relates to bispecific antibodies against human A-beta and the human transferrin receptor, methods for their production, pharmaceutical compositions containing these antibodies, and uses thereof. Said bispecific antibodies are formed by: a) an antibody formed by two pairs, each of them has a short chain of antibody and a long chain of antibody, in which the binding sites formed by each of the pairs of the chain long and short chain specifically bind to a human A-beta protein and b) an additional Fab fragment, said additional Fab fragment is fused with the C-terminus of one of the long chains of the antibody, in which the binding site. of the additional Fab fragment binds specifically to a human transferrin receptor, in which each of the short antibody chains contains in the short chain constant domain (CL) with mutations E123R and Q124K (numbering according to Kabat), in that each of the long chains of antibody contains in the first long chain constant domain (CH1) with mutations K147E and K213E (numbering according to the Kabat EU index), in which the additional Fab fragment that specifically binds to the second antigen contains a cross-domain of domains, such that the short-chain constant domain (CL) and the long-chain constant domain 1 (CH1) replace each other. |