Anti-ILT4 antibodies and antigen-binding fragments

Inventors

Blanusa, Milan • Joyce-Shaikh, Barbara • Schuster, Andrea Claudia • Schultze, Kornelia • Zuniga, Luis A.

Assignees

Merck Sharp and Dohme LLC • Agenus Inc

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Publication Number

US-12344670-B2

Patent

Publication Date

2025-07-01

Expiration Date


Abstract

The present invention provides antibodies and antigen-binding fragments thereof that bind to ILT4 (immunoglobulin-like transcript 4) and combinations thereof, e.g., with an anti-PD1 antibody. Also provided are methods of use thereof, for example, for treating or preventing cancer in a subject; and methods of making such antibodies and fragments.

Core Innovation

The invention relates to detecting an ILT4 peptide or fragment thereof in a sample by contacting the sample with an antibody or an antigen-binding fragment that binds human ILT4. Detection is based on the presence of a complex between the antibody or antigen-binding fragment and the ILT4 peptide or fragment, where the presence of the complex indicates the presence of the ILT4 peptide or fragment.

The disclosed antibody or antigen-binding fragment includes heavy chain variable domain CDR-H1, CDR-H2, and CDR-H3 sequences together with light chain variable domain CDR-L1, CDR-L2, and CDR-L3 sequences. Multiple alternative CDR-defined sets are provided, including arrangements with limited position options expressed as X, X1, and X2, and alternative heavy and light combinations are specified through enumerated SEQ ID numbers.

The document also describes anti-ILT4 antibody properties in functional contexts, including blockade of ILT4-HLA-G, interference with ILT4 suppression, effects on myeloid cytokine production, and tumor growth inhibition in humanized mouse models. It further includes measurement-related concepts involving protecting epitopes from deuterium-D2O exchange associated with hydrogen-deuterium exchange mass spectrometry, and therapeutic composition contexts including combinations with pembrolizumab and blocking ILT4 binding to HLA-G/A/B/F.

Claims Coverage

The document provides one independent claim focused on detecting an ILT4 peptide or fragment by antibody complex formation, using a binding antibody or antigen-binding fragment whose variable domains are defined by specific CDR sequences. Three inventive features are covered across the consolidated claims, with dependent coverage including alternative CDR sets and enumerated heavy and light chain variable domain sequences.

Antibody-based detection by ILT4 complex formation

A method for detecting an ILT4 peptide or fragment in a sample by contacting the sample with an antibody or antigen-binding fragment that binds human ILT4, wherein detecting the presence of a complex between the antibody or antigen-binding fragment and the ILT4 peptide or fragment indicates the presence of the ILT4 peptide or fragment.

CDR-defined heavy- and light-chain variable domains

The antibody or antigen-binding fragment comprises a heavy chain variable domain and a light chain variable domain defined by CDR-H1, CDR-H2, CDR-H3 and CDR-L1, CDR-L2, CDR-L3 amino-acid sequences specified by SEQ ID numbers, including variants with limited position substitutions.

Enumerated alternative heavy and light variable domain combinations

The antibody or antigen-binding fragment is provided with alternative heavy chain variable domain CDR sets and corresponding light chain variable domain CDR sets, including specified heavy-chain and light-chain amino acid sequences via enumerated SEQ ID numbers and sequence identity thresholds.

Overall claim coverage centers on a CDR-defined anti-ILT4 antibody or antigen-binding fragment used to detect ILT4 peptide or fragment presence by complex formation, with alternative heavy/light variable-domain configurations specified through CDR sequence constraints and SEQ ID numbers.

Stated Advantages

Detecting the presence of an ILT4 peptide or fragment is indicated by detection of a complex between the antibody or antigen-binding fragment and the ILT4 peptide or fragment.

The document states blockade of ILT4-HLA-G and interference with ILT4 suppression.

The document states effects on myeloid cytokine production.

The document states tumor growth inhibition in humanized mouse models.

Documented Applications

Detecting the presence of an ILT4 peptide or fragment in a sample using an antibody or antigen-binding fragment that binds human ILT4, where complex detection indicates ILT4 presence.

Therapeutic use of anti-ILT4 antibodies and antigen-binding fragments, including combinations with pembrolizumab, and blocking ILT4 binding to HLA-G/A/B/F.

Measurement and analysis context involving protecting epitopes from deuterium-D2O exchange associated with hydrogen-deuterium exchange mass spectrometry.

Functional evaluation in contexts including effects on myeloid cytokine production and tumor growth inhibition in humanized mouse models.

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