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Anti-trem2 antibodies and methods of use thereof

a technology of anti-trem2 and antibodies, which is applied in the field of anti-trem2 and anti-dap12 antibodies, can solve the problems of a 3 fold increase in the risk of developing alzheimer's disease, the loss of function of trem2, and the effect of carrying these mutations is just as serious, so as to induce antigen-specific t-cell proliferation, reduce the expression of tnf-, and increase the expression of c-

Inactive Publication Date: 2019-01-10
ALECTOR LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present patent is about methods and compositions that involve using antibodies that target a protein called TREM2 and its signaling adaptor molecule DAP12, which are involved in the development of dementia and inflammatory diseases such as Alzheimer's disease, frontotemporal dementia, nasu-Hakola disease, and multiple sclerosis. The patent describes different types of antibodies that can either activate or inhibit TREM2 and DAP12 activities, and the use of these antibodies in preventing or treating these diseases. The patent also describes the specific cells that express TREM2 and DAP12, and how these antibodies can affect the immune system. Overall, the patent provides new methods and compositions for targeting TREM2 and DAP12 for research and development purposes.

Problems solved by technology

Some of these mutations lead to truncation and likely loss-of-function of TREM2.
Although these TREM2 mutations are rarer than the known risk variants of Alzheimer's disease (e.g., APOE4), the effect of carrying these mutations is just as serious; around a 3 fold increase in the risk of developing Alzheimer's disease.
Moreover, even individuals without Alzheimer's disease who carry a heterozygous TREM2 mutation show worse cognition as compared to individuals with two normal TREM2 alleles.
The presence of M2-macrophages in tumors is associated with poor prognosis.

Method used

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  • Anti-trem2 antibodies and methods of use thereof

Examples

Experimental program
Comparison scheme
Effect test

embodiment 1

2. The isolated antibody of embodiment 1, wherein the TREM2 protein, the DAP12 protein, or both is a mammalian protein or a human protein.

embodiment 2

3. The isolated antibody of embodiment 2, wherein the TREM2 protein, the DAP12 protein, or both is a wild-type protein.

4. The isolated antibody of embodiment 2, wherein the TREM2 protein, the DAP12 protein, or both is a naturally occurring variant.

5. The isolated antibody of any one of embodiments 1-4, wherein the one or more TREM2 activities comprise TREM2 binding to DAP12.

6. The isolated antibody of any one of embodiments 1-4, wherein the one or more DAP12 activities comprise DAP12 binding to TREM2.

7. The isolated antibody of any one of embodiments 1-6, wherein the one or more TREM2 activities, DAP12 activities, or both comprise DAP12 phosphorylation.

embodiment 7

8. The isolated antibody of embodiment 7, wherein DAP12 phosphorylation is induced by one or more SRC family tyrosine kinases.

9. The isolated antibody of any one of embodiments 1-8, wherein the one or more TREM2 activities, DAP12 activities, or both comprise PI3K activation.

10. The isolated antibody of any one of embodiments 1-9, wherein the one or more TREM2 activities, DAP12 activities, or both comprise increased expression of one or more anti-inflammatory mediators selected from the group consisting of IL-12p70, IL-6, and IL-10.

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Abstract

The invention is generally directed to methods and compositions that include antibodies, e.g., monoclonal, chimeric, humanized antibodies, antibody fragments, etc., that specifically bind a TREM2 protein, e.g., a mammalian TREM2 and / or human TREM2. The methods provided herein find use in preventing, reducing risk, or treating an individual having dementia, frontotemporal dementia, Alzheimer's disease, Nasu-Hakola disease, or multiple sclerosis.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 62 / 035,336, filed Aug. 8, 2014, U.S. Provisional Application No. 62 / 135,110, filed Mar. 18, 2015, and U.S. Provisional Application No. 62 / 135,122, filed Mar. 18, 2015, each of which is hereby incorporated by reference in its entirety.SUBMISSION OF SEQUENCE LISTING ON ASCII TEXT FILE[0002]The content of the following submission on ASCII text file is incorporated herein by reference in its entirety: a computer readable form (CRF) of the Sequence Listing (file name: 735022000440SEQLISTING.TXT, date recorded: Aug. 7, 2015, size: 240 KB).FIELD OF THE INVENTION[0003]This invention relates to anti-TREM2 and anti-DAP12 antibodies and therapeutic uses of such antibodies.BACKGROUND OF THE INVENTION[0004]Triggering receptor expressed on myeloid cells-2 (TREM2) is an immunoglobulin-like receptor that is expressed primarily on myeloid lineage cells, such as macrophages, dendritic ...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K16/28A61K39/00
CPCC07K2317/92C07K2317/76C07K2317/75C07K2317/55C07K2317/34C07K2317/33C07K2317/31C07K2317/21A61K2039/505C07K16/2803C07K16/28C07K2317/56C07K16/283C07K2317/52A61P25/00A61P25/28
Inventor MONROE, KATESCHWABE, TINAAVOGADRI-CONNORS, FRANCESCATASSI, ILARIALAM, HELENROSENTHAL, ARNON
Owner ALECTOR LLC
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