Antibody against human DLK1 and use thereof
Inventors
Lim, Jung Chae • Shin, Ji-Young • Yoon, Sunha • Lee, Sang Pil • Choi, Yunseon • LEE, Jisu • Cho, Young-Gyu • Yoo, Seok Ho • KIM, Yeung Chul • LEE, Si Hyung • Park, Jae Eun • Song, Youngja • Baek, Gi Sun • Park, Bum-Chan • Park, Young Woo
Assignees
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Publication Number
US-11306141-B2
Publication Date
2022-04-19
Expiration Date
Abstract
The present invention relates to an antibody against delta-like 1 homolog (Drosophila) (DLK1) or an antigen-binding fragment thereof, a nucleic acid encoding the same, a vector comprising the nucleic acid, a cell transformed with the vector, a method for producing the antibody or an antigen-binding fragment thereof, an antibody drug conjugate (ADC) comprising the same, a pharmaceutical composition for treating cancer, a composition for diagnosing cancer, and a chimeric antigen receptor (CAR) and a T-cell engager comprising the same.
Core Innovation
The invention provides an antibody or an antigen-binding fragment that specifically binds delta-like 1 homolog (DLK1). The antibody is defined by a heavy-chain variable region and a light-chain variable region comprising particular heavy-chain CDR1, CDR2, and CDR3 sequences and particular light-chain CDR1, CDR2, and CDR3 sequences, each identified by SEQ ID NOs. The description further includes selected parental monoclonal antibodies and affinity-matured variants directed to human DLK1 extracellular domain epitopes.
The described antibody binding includes characterization of high-affinity binding to extracellular DLK1 and epitope mapping to DLK1 regions including EGF-like repeat domains and membrane-proximity domain regions. Species cross-reactivity results and cell-surface binding are reported as dependent on DLK1 knockdown, together with internalization into DLK1-positive cells and lysosomal trafficking. These findings characterize the binding behavior of the DLK1-targeting antibody and antigen-binding fragments.
The invention extends the DLK1-binding antibody into conjugate and engineered therapeutic formats. The description supports ADC feasibility and includes assays showing cytotoxicity associated with a DLK1-binding conjugate, and further outlines additional therapeutic formats including CAR/T-cell engager constructs that use DLK1-binding antigen-binding domains. Pharmaceutical compositions and diagnostic compositions for treating and diagnosing DLK1-expressing cancers are also described in the summary content.
Claims Coverage
The independent claim set includes one independent antibody claim defining the DLK1-specific binding based on heavy- and light-chain CDR sequence identities, with multiple dependent claims further specifying frameworks and extending the antibody into therapeutic formats and conjugates. The independent claim is focused on the molecular definition of the DLK1-binding antibody or antigen-binding fragment, and the dependent claims broaden coverage to engineered modalities and compositions.
Cdr-defined dlk1-binding antibody or antigen-binding fragment
An antibody or an antigen-binding fragment thereof specifically binding to delta-like 1 homolog (DLK1), comprising a heavy-chain variable region and a light-chain variable region with specified heavy-chain CDR1/2/3 and light-chain CDR1/2/3 sequences defined by SEQ ID NOs.
Overall, claim coverage centers on DLK1-specific antibody binding defined by multiple alternative CDR sequence combinations. Coverage is then refined by additional exact region sequence identities and expanded into engineered therapeutic formats, including ADCs, CAR antigen-binding domains, and T-cell engager constructs, as well as pharmaceutical and diagnostic compositions as described.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating DLK1-expressing cancers using pharmaceutical compositions containing the DLK1-binding antibody/antigen-binding fragment and related therapeutic formats described in the summary content.
Diagnosing DLK1-expressing cancers using diagnostic compositions described in the summary content.
ADC-based therapy using antibody-drug conjugates that incorporate the DLK1-binding antibody/fragment.
CAR/T-cell engager immunotherapy formats using DLK1-binding antigen-binding domains for CAR and T-cell engager constructs.
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