Monoclonal antibody specifically binding to LAG-3 and use thereof
Inventors
Lee, Sang Pil • Shin, Ji-Young • Yoon, Sunha • Choi, Yunseon • Park, Jae Eun • Lee, Ji Su • Song, Youngja • BAEK, Gisun • Yoo, Seok Ho • KIM, Yeung-chul • LEE, Dong Jung • Park, Bum-Chan • Park, Young Woo
Assignees
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Publication Number
US-11945864-B2
Publication Date
2024-04-02
Expiration Date
Abstract
A monoclonal antibody or an antigen-binding fragment thereof according to an embodiment of the present invention can bind to lymphocyte-activation gene 3 (LAG-3) including a heavy chain variable region and a light chain variable region and inhibit the activity thereof. Thus it is expected to be useful for the development of immunotherapeutic agents for various disorders that are associated with LAG-3.
Core Innovation
The disclosed subject matter relates to a monoclonal antibody or an antigen-binding fragment thereof that specifically binds lymphocyte-activation gene 3 (LAG-3). The antibody is defined by a heavy chain variable region and a light chain variable region, with specific heavy chain CDR1, CDR2, and CDR3 sequences represented by SEQ ID NO: 1 or SEQ ID NO: 27, SEQ ID NO: 2, and SEQ ID NO: 3, respectively. The light chain variable region includes light chain CDR1 represented by SEQ ID NO: 8, SEQ ID NO: 53, or SEQ ID NO: 57, a light chain CDR2 represented by Asp Ala Ser, and light chain CDR3 represented by SEQ ID NO: 10, SEQ ID NO: 33, or SEQ ID NO: 60.
The antibody targets the extracellular Ig-V domain of LAG-3 and inhibits the formation of the LAG-3/MHC class II complex. By blocking this interaction, the antibody enhances T-cell activity. The document further expands embodiments to polynucleotides, vectors, and transformants that encode the antibody variable regions, and also includes cancer treatment and diagnosis compositions, kits, and drug conjugates built from the claimed antibody.
The disclosed embodiments also include chimeric antigen receptor (CAR) constructs that incorporate the monoclonal antibody or an antigen-binding fragment together with a transmembrane domain and an intracellular signaling domain. The document additionally includes multispecific antibodies in expanded embodiments. An experimental development workflow is described, including selection and conversion of antibody formats, expression and purification, binding specificity and cross-reactivity assessments, affinity measurements (K_D), epitope mapping using extracellular domain variants, and functional blockade and T-cell recovery measurements.
Claims Coverage
The independent claim set includes 1 independent claim covering a LAG-3-specific monoclonal antibody or antigen-binding fragment defined by precise heavy- and light-chain variable-region CDRs, totaling multiple alternative CDR/SEQ ID combinations and a defined light-chain CDR2 sequence (Asp Ala Ser). Dependent claims mainly refine the antibody format and sequence embodiment, and further define downstream pharmaceutical and engineered-cell modalities (polynucleotide/expressing constructs, drug conjugates, and CAR protein formats).
LAG-3-specific antibody defined by CDR sequences
A monoclonal antibody or an antigen-binding fragment thereof specifically binding to lymphocyte-activation gene 3 (LAG-3), comprising: a heavy chain variable region comprising heavy chain CDR1 represented by SEQ ID NO: 1 or SEQ ID NO: 27; heavy chain CDR2 represented by SEQ ID NO: 2; and heavy chain CDR3 represented by SEQ ID NO: 3; and a light chain variable region comprising light chain CDR1 represented by SEQ ID NO: 8, SEQ ID NO: 53 or SEQ ID NO: 57; light chain CDR2 represented by Asp Ala Ser; and light chain CDR3 represented by SEQ ID NO: 10, SEQ ID NO: 33 or SEQ ID NO: 60.
Claim coverage centers on a LAG-3-specific monoclonal antibody or antigen-binding fragment whose identity is set by specific heavy-chain and light-chain variable-region CDRs (including defined SEQ ID options and the light-chain CDR2 sequence Asp Ala Ser). Dependent claims extend the same antibody core into defined formats such as encoded polynucleotides, drug conjugates, and CAR protein architectures, and further narrow antibody format and specific sequence embodiments.
Stated Advantages
Enhances T-cell activity.
Documented Applications
Cancer treatment.
Cancer diagnosis compositions and kits.
CAR constructs incorporating the LAG-3-specific monoclonal antibody or antigen-binding fragment.
Multispecific antibodies.
Drug conjugates.
Antibody encoding polynucleotides, vectors, and transformants.
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