LAG-3 binding members
Inventors
Tuna, Mihriban • Wollerton Van Horck, Francisca • Everett, Katy Louise • Gaspar, Miguel • Kraman, Matthew • Kmiecik, Katarzyna • Fosh, Natalie
Assignees
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Publication Number
US-11214618-B2
Publication Date
2022-01-04
Expiration Date
Abstract
The present invention relates to specific binding members which bind to lymphocyte-activation gene 3 (LAG-3). The specific binding members preferably comprise a LAG-3 antigen-binding site which may be located in two or more structural loops of a CH3 domain of the specific binding member. The specific binding members of the invention find application, for example, in cancer therapy.
Core Innovation
The disclosure provides specific binding members that bind lymphocyte-activation gene 3 (LAG-3). The LAG-3 antigen-binding site is located in a CH3 domain and comprises the amino acid sequences WDEPWGED (SEQ ID NO: 1) and PYDRWVWPDE (SEQ ID NO: 3), with WDEPWGED located in a first structural loop and PYDRWVWPDE located in a second structural loop of the CH3 domain.
The binding member does not comprise a CDR-based antigen binding site for PD-L1. The disclosure also includes LAG-3 sequence variants in the LAG-3 antigen-binding site definitions, with alternative amino-acid sequences incorporated into the CH3-domain structural loop locations corresponding to the defined LAG-3 binding-site regions.
The disclosure also provides antibody molecules that bind both an immune system modulator and LAG-3. In such antibody molecules, the immune system modulator binding is provided by a CDR-based antigen binding site that is not a binding site for PD-L1, while the LAG-3 antigen-binding site remains located in a CH3 domain comprising WDEPWGED (SEQ ID NO: 1) and PYDRWVWPDE (SEQ ID NO: 3) positioned in the first and second structural loops of the CH3 domain.
Claims Coverage
The provided material identifies two independent claims. They cover a LAG-3 binding member with a CH3-domain antigen-binding site defined by two specific LAG-3 motifs and lacking a CDR-based PD-L1 binding site, and an antibody that simultaneously binds an immune system modulator and LAG-3 while ensuring PD-L1 is not bound by the immune-modulator CDR-based site.
Ch3-domain LAG-3 antigen-binding site defined by WDEPWGED and PYDRWVWPDE motifs in structural loops without CDR-based PD-L1 binding
A specific binding member binds LAG-3 with a LAG-3 antigen-binding site located in a CH3 domain, wherein the binding site comprises WDEPWGED (SEQ ID NO: 1) and PYDRWVWPDE (SEQ ID NO: 3), with WDEPWGED located in a first structural loop and PYDRWVWPDE located in a second structural loop, and wherein the specific binding member does not comprise a CDR-based antigen binding site for PD-L1.
Dual-specific antibody binding immune system modulator and CH3-domain LAG-3 motifs in structural loops
An antibody molecule binds an immune system modulator and LAG-3, comprising a CDR-based antigen binding site for the immune system modulator that is not a binding site for PD-L1, and a LAG-3 antigen-binding site located in a CH3 domain comprising WDEPWGED (SEQ ID NO: 1) and PYDRWVWPDE (SEQ ID NO: 3), with WDEPWGED in a first structural loop and PYDRWVWPDE in a second structural loop of the CH3 domain.
Overall, claim coverage is centered on CH3-domain LAG-3 antigen-binding sites defined by WDEPWGED and PYDRWVWPDE motifs positioned in first and second structural loops, and on maintaining non-overlap with PD-L1 binding by requiring the absence of a CDR-based PD-L1 binding site or by requiring that the immune-modulator CDR-based site is not a PD-L1 binding site.
Stated Advantages
Documented Applications
Not explicitly described in patent.
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