Anti-TREM2 antibodies and related methods
Inventors
Streuli, Michel • Sriram, Venkataraman • Pal, Aritra • Presta, Leonard G.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10508148-B2
Publication Date
2019-12-17
Expiration Date
Abstract
Provided herein are anti-TREM2 antibodies and related methods of making and using anti-TREM2 antibodies. Also provided are methods and compositions for enhancing an immune response and/or for the treatment of an immune-related condition in an individual, e.g., cancer, comprising killing, disabling, or depleting non-stimulatory myeloid cells using an anti-TREM2 antibody or antigen binding fragment thereof.
Core Innovation
The invention relates to an isolated anti-TREM2 humanized antibody comprising a human IgG1 Fc and explicitly defined heavy-chain and light-chain variable regions. The heavy chain variable region includes CDR-H1, CDR-H2, and CDR-H3, and the light chain variable region includes CDR-L1, CDR-L2, and CDR-L3, defined by SEQ ID NOs 9 to 14. The antibody binds human TREM2 and includes cross-competing binding to mouse TREM2.
The disclosure further describes production and selection of glycosylated anti-TREM2 antibodies in stable mammalian cells, using optimized nucleic acid input ratios to enrich a glycosylated antibody. Desired glycoforms are identified and purified, including analytical identification by liquid chromatography and mass spectrometry, and purification by ion-exchange chromatography and Fc/Fab affinity purification approaches.
The invention also describes functional use of anti-TREM2 to disable, kill, deplete, and modulate TREM2+ myeloid cells in a cancer tumor microenvironment. The disclosure reports apoptosis, necrosis, growth arrest, CDC, ADCC, ADCP, cross-presentation to CD8+ T cells through MHCI and TCR signaling, cytokine production, enhanced immune response, and diagnostic and response-prediction approaches based on measuring TREM2 protein expression and mRNA encoding TREM2.
Claims Coverage
The partial content identifies three independent claim families: an isolated anti-TREM2 humanized antibody with defined VH/VL CDR sequences; a cancer treatment method using the defined antibody; and a method of killing, disabling, or depleting TREM2+ myeloid cells by contacting the cells with the defined antibody. Across these independent claims, the document specifies an anti-TREM2 antibody having a human IgG1 Fc and explicitly defined CDR sequences.
Isolated anti-TREM2 humanized antibody with defined CDR sequences
An isolated anti-TREM2 humanized antibody comprising a human IgG1 Fc, a heavy chain variable region with CDR-H1, CDR-H2, and CDR-H3, and a light chain variable region with CDR-L1, CDR-L2, and CDR-L3, wherein CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3 are defined by SEQ ID NOs 9 to 14.
Treating cancer by administering the defined anti-TREM2 humanized antibody
A method of treating cancer in a subject in need thereof comprising administering an effective amount of an anti-TREM2 antibody comprising a human IgG1 Fc and the defined heavy chain and light chain CDR sequences.
Killing, disabling, or depleting TREM2+ myeloid cells by contacting with the defined antibody
A method of killing, disabling, or depleting TREM2+ myeloid cells of a subject having cancer comprising contacting the myeloid cells with an anti-TREM2 antibody comprising a human IgG1 Fc and the defined heavy chain and light chain CDR sequences.
The claim coverage centers on an isolated anti-TREM2 humanized antibody with a human IgG1 Fc and explicitly defined CDR sequences. This antibody is used either to treat cancer by administering an effective amount, or to kill, disable, or deplete TREM2+ myeloid cells by contacting the cells.
Stated Advantages
Cancer treatment by administering an effective amount of the specified anti-TREM2 humanized antibody.
Killing, disabling, or depleting TREM2+ myeloid cells.
Functional activity directed to TREM2+ myeloid cells via ADCC, ADCP, and/or CDC activity.
Enhanced efficacy in combination with checkpoint blockade, including improved tumor growth inhibition and complete responses.
Improved efficacy with limited overt toxicity.
Predominant expression of TREM2 on TAMs and limited in healthy tissues, supporting targeted activity.
Documented Applications
Treating cancer in a subject in need thereof using an effective amount of the specified anti-TREM2 humanized antibody.
Killing, disabling, or depleting TREM2+ myeloid cells of a subject having cancer by contacting the myeloid cells with the specified anti-TREM2 humanized antibody.
Detecting the presence or level of TREM2 in a sample by contacting the sample with the antibody.
Marker-based characterization and detection or quantification of TREM2 or non-stimulatory myeloid cells.
Diagnosing or predicting response by measuring TREM2 expression and using anti-TREM2 binding for detection and quantification in samples.
Treating cancer in a subject using an anti-TREM2 antibody, including combination with checkpoint blockade such as anti-PD-1, anti-PD-L1, or anti-CTLA-4.
Killing, disabling, or depleting TREM2+ myeloid cells in a cancer tumor microenvironment to modulate immune-stimulatory capacity and localization.
Interested in licensing this patent?