Antibodies and antibody-drug conjugates specific for CD123 and uses thereof
Inventors
CHARATI, Manoj Baburao • Han, Yoon-Chi • Katragadda, Madan • PICHÉ-NICHOLAS, Nicole Melissa • Tumey, Lawrence Nathan
Assignees
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Publication Number
US-11613581-B2
Publication Date
2023-03-28
Expiration Date
Abstract
The present invention provides antibodies that specifically bind to CD123. The invention further relates to immunoconjugates (e.g., antibody-drug conjugates, or ADCs) comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and ADCs for the treatment of a condition associated with cells expressing CD123 (e.g., cancer or autoimmune disease).
Core Innovation
The invention is directed to isolated antibodies that specifically bind to CD123, including antibodies defined by particular heavy chain variable region and light chain variable region sequence identifiers and by specified VH and VL CDR amino acid sequences. The disclosed antibodies are also described in engineered forms with defined antibody variable region sequence content and structural constraints.
A related aspect is directed to antibody-drug conjugates and antibody-agent conjugates that link a CD123-binding antibody to an agent through an acetyl-lysine-valine-citrulline-p-aminobenzyloxycarbonyl (Ac-Lys-Val-Cit-PABC) linker. The agent is selected from cytotoxic agents, immunomodulating agents, imaging agents, therapeutic proteins, biopolymers, and oligonucleotides, and in particular examples the agent is a cyclopropylpyrroloindoline (CPI) dimer.
The invention also describes an antibody hinge/tag architecture concept, including LLQG tag replacement and hinge position modification such as K222R, and further discusses pharmaceutical compositions and treatment contexts for conditions associated with CD123-associated cancers or autoimmune disorders.
Claims Coverage
The provided independent claims cover CD123-specific isolated antibodies defined by exact VH/VL sequences or CDR sequences, and CD123 antibody-drug conjugates defined by specific antibody chain sequence identifiers plus an Ac-Lys-Val-Cit-PABC linker and selected agent categories, including CPI dimer. The inventive features center on sequence-defined CD123 binding and linker-defined conjugate architecture.
CD123-specific isolated antibody with sequence-defined VH/VL pairs
An isolated antibody which specifically binds to CD123, selected from antibodies comprising particular heavy chain variable region amino acid sequences and particular light chain variable region amino acid sequences given by SEQ ID NOs.
CD123-specific isolated antibody defined by VH and VL CDR sequence sets
An isolated antibody which specifically binds to CD123, selected from antibodies defined by specified VH complementarity determining region sequences together with specified VL CDR sequences.
CD123-specific isolated antibody defined by fixed VH and VL CDR SEQ ID NOs
An isolated antibody which specifically binds to CD123, wherein the VH comprises VH CDR1, VH CDR2, and VH CDR3 sequences identified by SEQ ID NOs and the VL comprises VL CDR1, VL CDR2, and VL CDR3 sequences identified by SEQ ID NOs.
CD123-specific isolated antibody defined by heavy and light chain amino acid sequences
An isolated antibody which specifically binds to CD123, wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 30 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 27.
CD123-specific isolated antibody produced from specified expression vectors
An isolated antibody which specifically binds to CD123, wherein the antibody comprises a heavy chain variable region produced by the expression vector with ATCC Accession No. PTA-124283 and a light chain variable region produced by the expression vector with ATCC Accession No. PTA-124284.
CD123 antibody-drug conjugate with Ac-Lys-Val-Cit-PABC linker and selected agent category
An antibody-drug conjugate comprising an antibody which specifically binds to CD123 and comprises a heavy chain comprising SEQ ID NO: 27 and a light chain comprising SEQ ID NO: 30, an Ac-Lys-Val-Cit-PABC linker, and an agent selected from cytotoxic agents, immunomodulating agents, imaging agents, therapeutic proteins, biopolymers, and oligonucleotides, wherein the linker conjugates the antibody and the agent.
CD123 antibody-drug conjugate with Ac-Lys-Val-Cit-PABC linker and CPI dimer payload
An antibody-drug conjugate comprising an antibody which specifically binds to CD123 and comprises a heavy chain comprising SEQ ID NO: 27 and a light chain comprising SEQ ID NO: 30, an Ac-Lys-Val-Cit-PABC linker, and a cyclopropylpyrroloindoline (CPI) dimer, wherein the linker conjugates the antibody and the CPI dimer.
Overall, the claims center on CD123-specific isolated antibodies precisely defined by VH/VL sequence or CDR sequence identifiers, including antibodies produced from specified expression vectors, and on antibody-drug conjugates that require an Ac-Lys-Val-Cit-PABC linker to conjugate a CD123-binding antibody to selected agent categories or specifically to a CPI dimer.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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