CD33 antibodies and methods of using the same to treat cancer
Inventors
Cheung, Nai-Kong V. • Hoseini, Sayed Shahabuddin • Ahmed, Mahiuddin
Assignees
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Publication Number
US-12441793-B2
Publication Date
2025-10-14
Expiration Date
Abstract
The present disclosure relates generally to immunoglobulin-related compositions (e.g., antibodies or antigen binding fragments thereof) that can bind to the CDS 3 protein. The antibodies of the present technology are useful in methods for detecting and treating Alzheimer's disease or a CDS 3-associated cancer in a subject in need thereof.
Core Innovation
The disclosure provides antibodies and antigen binding fragments comprising a heavy chain immunoglobulin variable domain and a light chain immunoglobulin variable domain, where the variable domains include specified CDR sequences or selected amino acid sequences from defined SEQ ID sets. The antibody or antigen binding fragment optionally binds the IgC2 domain of CD33 and is described in monoclonal, chimeric, humanized, and bispecific formats.
The invention further encompasses bispecific antibody and antigen binding fragment formats that bind T cells, B-cells, myeloid cells, plasma cells, or mast-cells, and that bind CD3, CD4, CD8, CD20, CD19, CD21, CD23, CD46, CD80, HLA-DR, CD74, CD22, CD14, CD15, CD16, CD123, TCR gamma/delta, NKp46, or KIR. In addition, the invention includes binding to a small molecule DOTA hapten, and covers antibody binding characteristics described using CD33-binding kinetics/affinity and redirected T-cell cytotoxicity.
The disclosure also includes engineered CD33-targeting bispecific antibody and fusion protein constructs, Fc and glycosylation modifications, detectable labels and imaging modalities including radiolabels used for PET/SPECT, and pretargeted radioimmunotherapy using a DOTA radiolabeled hapten complex. SADA self-assembly/disassembly conjugate domains are described together with reduced off-target binding/toxicity and Fc modifications to alter Fc receptor/complement interactions.
Claims Coverage
The independent claims cover three core inventive feature groups: specified immunoglobulin variable-domain CDR sequences, selected heavy-chain and light-chain amino-acid sequences from defined SEQ ID sets, and paired heavy-chain and light-chain amino-acid sequence sets. Across these claims, the coverage is centered on CD33 IgC2 domain binding and optional bispecific formats, including optional binding to a small molecule DOTA hapten.
Specified variable-domain CDRs for CD33 IgC2 binding
An antibody or antigen binding fragment having a heavy chain variable domain with VH-CDR1 sequence GYSFTDYN (SEQ ID NO: 154), VH-CDR2 sequence IDPYKGGT (SEQ ID NO: 155), and VH-CDR3 sequence AREMITAYYFDY (SEQ ID NO: 156), and having a light chain variable domain with VL-CDR1 sequence QDINKY (SEQ ID NO: 157), VL-CDR2 sequence YAS (SEQ ID NO: 158), and VL-CDR3 sequence LQYDNLLT (SEQ ID NO: 159), optionally binding the IgC2 domain of CD33 and optionally configured as a monoclonal, chimeric, humanized, or bispecific antibody with optional bispecific binding to specified immune-cell targets or CD3 and optionally binding to a small molecule DOTA hapten.
Selected VH and VL amino-acid sequences from defined SEQ ID sets
An antibody or antigen binding fragment comprising a heavy chain variable domain comprising an amino acid sequence selected from SEQ ID NOs: 2, 3, 4, 5, 6, 7, and 133, and a light chain variable domain comprising an amino acid sequence selected from SEQ ID NOs: 9, 10, 11, 12, and 13, optionally binding the IgC2 domain of CD33 and optionally being a monoclonal, chimeric, humanized, or bispecific antibody with optional bispecific binding to specified cell targets or specified binding partners or a small molecule DOTA hapten, and optionally wherein the bispecific antibody comprises an amino acid sequence selected from SEQ ID NOs 30-113 or 142-153.
Specified HC and LC amino-acid sequences paired for CD33 binding
An antibody comprising a heavy chain amino acid sequence comprising SEQ ID NO: 16, 20, 22, 136, 139, 141 and a light chain amino acid sequence comprising SEQ ID NO: 14, 18, 24, 26, 27, 28, 29, 134, 138, 140, optionally binding the IgC2 domain of CD33, and optionally being a monoclonal, chimeric, humanized, or bispecific antibody with optional bispecific binding to specified immune-cell targets or binding partners or a small molecule DOTA hapten.
Across the independent claims, the inventive coverage is directed to antibodies and antigen binding fragments with defined immunoglobulin variable-domain sequence content, including CDR sequence specification and listed VH/VL amino-acid sequence selection, with optional CD33 IgC2 domain binding and optional bispecific configurations targeting selected immune-cell markers or binding to a small molecule DOTA hapten.
Stated Advantages
Reduced off-target binding/toxicity.
Alter Fc receptor/complement interactions.
Documented Applications
Detecting and diagnosing CD33-associated cancers using in vivo radioisotope labeling with PET/SPECT.
Treating CD33-associated cancers, including leukemia and AML, using administration of anti-CD33 antibodies or immunoconjugates.
Treating leukemia and/or increasing sensitivity of leukemic cells to radiation therapy using a CD33-localizing antibody and a radiolabeled DOTA hapten that binds the antibody.
Pretargeted radioimmunotherapy using a radiolabeled DOTA hapten–antibody or binding fragment complex.
Application of bispecific antibody formats that bind CD3, B-cells, myeloid cells, plasma cells, mast-cells, or other listed targets and optionally bind a small molecule DOTA hapten.
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