CDCP1 antibodies and antibody drug conjugates
Inventors
Cantley, Lewis C. • SOLTOFF, Stephen P. • EMERLING, Brooke M. • Poulogiannis, Georgios • HODAKOSKI, Cindy M. • Liu, Hui • Apostolou, Irina • Bates, Brian Gaither • Marquette, Kimberly Ann • Bennett, Eric M. • Mosyak, Lidia • TCHISTIAKOVA, Lioudmila G. • Rosfjord, Edward Christian • Rondon, Isaac J. • Huang, Chao Bai
Assignees
Cornell University • Beth Israel Deaconess Medical Center Inc • Pfizer Inc
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Publication Number
US-12371507-B2
Publication Date
2025-07-29
Expiration Date
Abstract
The present disclosure provides materials and methods for CUB domain-containing protein 1 (CDCP1)-targeted therapy.
Core Innovation
The invention provides an isolated antibody, or an antigen-binding fragment thereof, that specifically binds CDCP1. The antibody is defined by Kabat-defined complementarity determining regions in both the VH and VL regions, including CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 sequence definitions. This sequence-defined specificity is directed to CUB Domain-Containing Protein-1 (CDCP1).
The invention also provides an antibody drug conjugate comprising an antibody, or antigen-binding fragment thereof, that specifically binds CDCP1. In the antibody drug conjugate, the antibody is conjugated to a drug moiety and contains fixed VH and VL CDR sequences with selected CDRH3 and CDRL3 options. The disclosure further includes CDCP1-directed antibody drug conjugates, antigen-binding fragments, and references to payload, linker, and conjugation-related content.
The ADC aspect of the invention includes conjugation strategies and payload/linker combinations for CDCP1-directed drug delivery. It describes ADCs where the antibody is conjugated to a drug moiety and supports site-specific conjugation using engineered cysteines and an acyl donor glutamine tag. The document enumerates linker options, including val-cit, mc, PEG variants, and PABC-containing linkers, and it describes auristatin-based payloads and corresponding linker-drug moieties.
Claims Coverage
The consolidated claims coverage includes two independent claim scopes: one directed to an isolated antibody, or antigen-binding fragment thereof, that specifically binds CDCP1 and is defined by VH and VL CDR amino-acid sequences; and one directed to a CDCP1-specific antibody drug conjugate in which the antibody is conjugated to a drug moiety and contains defined VH and VL CDR sequences with selected CDRH3 and CDRL3 options. Two inventive features are identified.
Sequence-defined CDCP1-binding isolated antibody
An isolated antibody, or antigen-binding fragment thereof, that specifically binds CDCP1, comprising a VH with CDRH1 comprising the amino acid sequence of SEQ ID NO:2, CDRH2 comprising the amino acid sequence of SEQ ID NO:3, and CDRH3 comprising the amino acid sequence of SEQ ID NO:27, and a VL with CDRL1 comprising the amino acid sequence of SEQ ID NO:12, CDRL2 comprising the amino acid sequence of SEQ ID NO:13, and CDRL3 comprising the amino acid sequence of SEQ ID NO:31.
CDCP1-binding antibody drug conjugate with selected CDRH3 and CDRL3
An antibody drug conjugate comprising an antibody, or antigen-binding fragment thereof, that specifically binds CDCP1, wherein the antibody is conjugated to a drug moiety, and wherein the antibody comprises a VH with CDRH1 comprising the amino acid sequence of SEQ ID NO:2, CDRH2 comprising the amino acid sequence of SEQ ID NO:3, and a CDRH3 selected from SEQ ID NO:27, SEQ ID NO:4, SEQ ID NO:40, and SEQ ID NO:45, and a VL with CDRL1 comprising the amino acid sequence of SEQ ID NO:12, CDRL2 comprising the amino acid sequence of SEQ ID NO:13, and a CDRL3 selected from SEQ ID NO:31 and SEQ ID NO:14.
Across the independent claims, coverage centers on CDCP1-specific binding defined by Kabat-defined VH and VL CDR amino-acid sequences, and extends to antibody drug conjugates in which the defined CDCP1-binding antibody is conjugated to a drug moiety.
Stated Advantages
ADC homogeneity is addressed, as indicated by engineered variant notes related to ADC homogeneity.
The document states binding affinity at pH 7.4 and pH 6.8, melting transition temperature, and IC50 values in CDCP1-expressing cells for exemplary CDCP1 ADCs.
Tumor-volume reduction is reported in NSCLC PDX and head-and-neck PDX models.
Documented Applications
Use as an antibody drug conjugate targeting CDCP1, including an antibody conjugated to a drug moiety.
Binding of CDCP1 by an isolated antibody or antigen-binding fragment defined by VH and VL CDR sequences.
Therapeutic use as described in the document’s therapeutic and combination-treatment use cases.
Diagnostic use as described in the document’s therapeutic/diagnostic use cases.
Tumor-volume reduction in NSCLC PDX models.
Tumor-volume reduction in head-and-neck PDX models.
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