# US 12,595,305 B2 · TREM2 stabilizing antibodies

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- Number: US 12,595,305 B2
- Document ID: US12595305B2
- Status: Granted
- Kind: B2
- Application number: 17/934,795
- Filed: 2022-09-23
- Published: 2023-06-01
- Granted: 2026-04-07
- Earliest claimed: 2018-10-15
- Assignees: Novartis AG
- Applicants: Novartis AG
- Inventors: Verena Brand; Dominik Feuerbach; Fabrizio Gasparini; Nathalie George; Eveline Schaadt; Derya Shimshek; Honnappa Srinivas; Markus Waldhuber; Rainer Wilcken
- Web page: https://patentgrep.com/patent/US12595305B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/70: Vectors or expression systems specially adapted for E. coli
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/75: Agonist effect on antigen
- C07K 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- C07K 2319/21: containing a His-tag
- C12N 2750/14143: viral genome or elements thereof as genetic vector
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

The present invention provides antibodies that bind to and stabilize human Triggering Receptor Expressed on Myeloid cells 2 (TREM2) protein and methods of using these antibodies.

## Claims

### Claim 1

A nucleic acid molecule or set of nucleic acid molecules encoding an anti-TREM2 antibody or antigen-binding fragment thereof, wherein the anti-TREM2 antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDR1, HCDR2, and HCDR3) and three light chain complementarity determining regions (LCDR1, LCDR2, and LCDR3), wherein:
(i) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 7, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 17, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 18, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 19, as defined by the Kabat numbering system;
(ii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 8, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 9, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 20, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 21, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 22, as defined by the Chothia numbering system;
(iii) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 10, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 11, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 12, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 23, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 21, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 19, as defined by the IMGT numbering system;
(iv) the HCDR1 comprises the amino acid sequence of SEQ ID NO: 4, the HCDR2 comprises the amino acid sequence of SEQ ID NO: 5, the HCDR3 comprises the amino acid sequence of SEQ ID NO: 6, the LCDR1 comprises the amino acid sequence of SEQ ID NO: 17, the LCDR2 comprises the amino acid sequence of SEQ ID NO: 18, and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 19, as defined by the Combined numbering system.

### Claim 2 (depends on 1)

The nucleic acid molecule or set of nucleic acid molecules of claim 1, wherein the anti-TREM2 antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 13 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 24.

### Claim 3 (depends on 1)

The nucleic acid molecule or set of nucleic acid molecules of claim 1, wherein the anti-TREM2 antibody or antigen-binding fragment thereof comprises a modified Fc domain that has reduced antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) activity compared to the antibody or antigen-binding fragment thereof without the modified Fc domain.

### Claim 4 (depends on 1)

The nucleic acid molecule or set of nucleic acid molecules of claim 1, wherein the anti-TREM2 antibody or antigen-binding fragment thereof comprises:
a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 and a light chain comprising the amino acid sequence of SEQ ID NO: 26.

### Claim 5 (depends on 4)

The nucleic acid molecule or set of nucleic acid molecules of claim 4, wherein:
the heavy chain variable region is encoded by the nucleic acid sequence of SEQ ID NO: 28 and the light chain variable region is encoded by the nucleic acid sequence of SEQ ID NO: 31.

### Claim 6 (depends on 1)

A vector comprising the nucleic acid molecule or set of nucleic acid molecules of claim 1.

### Claim 7 (depends on 6)

The vector of claim 6, wherein the vector is selected from a DNA vector, an RNA vector, a plasmid, a cosmid, or a viral vector.

### Claim 8 (depends on 1)

A cell comprising the nucleic acid molecule or set of nucleic acid molecules of claim 1.

### Claim 9 (depends on 8)

A method of producing an anti-TREM2 antibody or antigen-binding fragment thereof, the method comprising: (i) culturing the cell of claim 8 under conditions suitable to produce an anti-TREM2 antibody or antigen-binding fragment thereof and (ii) isolating the anti-TREM2 antibody or antigen-binding fragment thereof from the culture.

### Claim 10 (depends on 4)

The nucleic acid molecule or set of nucleic acid molecules of claim 4, wherein the heavy chain is encoded by the nucleic acid sequence of SEQ ID NO: 38 and the light chain is encoded by the nucleic acid sequence of SEQ ID NO: 32.