Single domain antibodies that bind to human CD20
Inventors
Liu, Jinny Lin • Zabetakis, Daniel • Goldman, Ellen R. • Anderson, George P.
Assignees
Publication Number
US-10246514-B2
Publication Date
2019-04-02
Expiration Date
2037-09-12
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Abstract
Described herein is the development of recombinant single domain antibodies, also known as nanobodies, that may provide better therapeutic results or be useful for diagnostic applications of B-cell lymphomas, or in other applications where an antibody to CD20 may be useful.
Core Innovation
The invention relates to the development of recombinant single domain antibodies, also known as nanobodies, that bind to human CD20. These nanobodies are designed to provide better therapeutic results or be useful for diagnostic applications particularly in B-cell lymphomas or other contexts where an antibody to CD20 is useful. The single domain antibodies are small antigen binding domains (~15 kD) derived from heavy chain variable regions of camelid antibodies, possessing better tissue penetration than conventional antibodies.
The background describes the problem that while human CD20 is an ideal therapeutic target for B-lymphomas due to its stable expression on the cell surface and induction of apoptotic cell signaling upon antibody binding, existing monoclonal antibodies like Rituximab exhibit limited complete responses in treated patients. There is a need to develop alternative CD20-specific antibodies that may provide better therapeutic outcomes or improved diagnostic performance. Current CD20 immuno-reagents are mainly monoclonal antibodies or their scFv derivatives; the invention addresses this by developing stable, small, single domain antibodies specific to human CD20 which have improved tumor penetration and rapid clearance, enabling use with imaging radionuclides and targeted radiotherapy.
Claims Coverage
The patent contains three independent claims covering isolated single domain antibodies and pharmaceutical compositions comprising them, each specifying particular amino acid sequences.
Isolated anti-CD20 single domain antibody comprising specific amino acid sequences
An isolated anti-CD20 single domain antibody that comprises the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 5, or SEQ ID NO: 6.
Isolated anti-CD20 single domain antibody comprising a specific consensus amino acid sequence
An isolated anti-CD20 single domain antibody comprising the amino acid sequence of SEQ ID NO: 16, which corresponds to a consensus CDR3 sequence.
Pharmaceutical composition comprising isolated anti-CD20 single domain antibodies and carrier
A pharmaceutical composition comprising an isolated anti-CD20 single domain antibody of SEQ ID NO: 2, SEQ ID NO: 5, or SEQ ID NO: 6, or alternatively SEQ ID NO: 16, together with a pharmaceutically acceptable carrier.
The claims cover isolated single domain antibodies specific to human CD20 possessing defined amino acid sequences and pharmaceutical compositions containing these antibodies, focusing on their unique binding sequences and formulation as compositions for therapeutic use.
Stated Advantages
Improved penetration in tissues compared to conventional antibodies, supporting better diagnostic and therapeutic applications in B-cell lymphomas.
Higher affinity and sensitivity potential for diagnostic tests through fusion with streptavidin or its derivatives.
High stability and solubility conferring long shelf life and compatibility with harsh radiolabeling conditions for imaging or radiotherapy.
Ability to be produced in bacteria or yeast, substantially reducing production costs relative to mammalian cell expression systems.
Documented Applications
Therapeutic applications in treating B-cell lymphomas.
Diagnostic applications for detecting or imaging B-cell lymphomas.
Use in other applications where an antibody to CD20 is useful, including potentially in auto-immune diseases such as rheumatoid arthritis as discussed in the background context.
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