Bispecific anti-human CD20/human transferrin receptor antibodies and methods of use
Inventors
DUERR, HARALD • Fenn, Sebastian • Goepfert, Ulrich • Imhof-Jung, Sabine • Klein, Christian • LARIVIERE, Laurent • MOLHOJ, MICHAEL • Regula, Joerg Thomas • Rueger, Petra • Schaefer, Wolfgang
Assignees
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Publication Number
US-11603411-B2
Publication Date
2023-03-14
Expiration Date
Abstract
Herein are provided bispecific anti-human CD20/human transferrin receptor antibodies and methods of using the same.
Core Innovation
The invention provides a bispecific antibody that includes an antibody comprising two pairs of an antibody light chain and an antibody heavy chain, wherein the binding sites formed by each pair specifically bind to human CD20 protein. The antibody also includes one additional Fab fragment fused to the C-terminus of one of the heavy chains, where the additional Fab fragment specifically binds to human transferrin receptor.
The additional Fab fragment is engineered to comprise a domain crossover such that the constant light chain domain (CL) and the constant heavy chain domain 1 (CH1) are replaced by each other. This configuration maintains separate specificity for human CD20 and human transferrin receptor while using engineered constant-region crossover and heterodimerization concepts.
In the described embodiments and architectures, the bispecific antibody is implemented with defined sequence identifiers: the light chain amino acid sequence is SEQ ID NO: 1, the heavy chain amino acid sequence is SEQ ID NO: 2, a Fab fragment light chain amino acid sequence is SEQ ID NO: 3, and a Fab fragment heavy chain amino acid sequence is SEQ ID NO: 4.
Claims Coverage
The independent claim defines one bispecific antibody architecture with 2 antigen specificities and 4 specified polypeptide sequence roles, using a C-terminal fused additional Fab fragment with a domain crossover that replaces CL and CH1.
Bispecific antibody with CD20 and transferrin receptor binding
A bispecific antibody comprising one antibody comprising two pairs each of an antibody light chain and an antibody heavy chain, wherein the binding sites formed by each of the pairs of the heavy chain and the light chain specifically bind to a first antigen, and one additional Fab fragment fused to the C-terminus of one of the heavy chains, wherein the binding site of the additional Fab fragment specifically binds to a second antigen; the first antigen is human CD20 protein and the second antigen is human transferrin receptor.
C-terminal fused additional Fab with CL/CH1 domain crossover
The additional Fab fragment specifically binding to the second antigen comprises a domain crossover such that the constant light chain domain (CL) and the constant heavy chain domain 1 (CH1) are replaced by each other.
Defined SEQ ID NO composition for the bispecific antibody
The bispecific antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 1, a heavy chain comprising the amino acid sequence of SEQ ID NO: 2, a Fab fragment comprising a light chain comprising the amino acid sequence of SEQ ID NO: 3, and a heavy chain comprising the amino acid sequence of SEQ ID NO: 4.
The claim coverage is centered on a bispecific antibody that binds human CD20 and human transferrin receptor using an additional Fab fragment fused to the C-terminus and configured with a domain crossover that replaces CL and CH1, with the antibody composition defined by SEQ ID NOs for the light chain, heavy chain, and Fab fragment components.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating an individual with multiple sclerosis by administering an effective amount of the antibody of claim 1.
Depleting brain-sequestered CD20-expressing B-cells in an individual by administering an effective amount of the antibody of claim 1.
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