# US 9,000,127 B2 · Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1)

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- Number: US 9,000,127 B2
- Document ID: US9000127B2
- Status: Granted
- Kind: B2
- Application number: 13/690,748
- Filed: 2012-11-30
- Published: 2013-08-15
- Granted: 2015-04-07
- Earliest claimed: 2012-02-15
- Assignees: Novo Nordisk A/S
- Applicants: Novo Nordisk A/S
- Inventors: Vibeke Westphal Stennicke; Christine Brender Read; Susanne Nedergaard Grell; Charlotte Wiberg; Rune Salbo; Anette Henriksen; Soeren Padkjaer
- Web page: https://patentgrep.com/patent/US9000127B2

## CPC

- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/74: Inducing cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The invention relates to antibodies that are capable of specifically binding TREM-1 and preventing the activation of TREM-1, a protein expressed on monocytes, macrophages and neutrophils. Such antibodies find utility in the treatment of individuals with an inflammatory disease, such as rheumatoid arthritis and inflammatory bowel disease.

## Claims

### Claim 1

An isolated antibody or fragment thereof, wherein the antibody or fragment thereof competes with mAb 0170 for binding to and blocking a triggering receptor expressed on myeloid cells-1 (TREM-1) having an amino acid sequence set for as SEQ ID NO:1 (human TREM-1), SEQ ID NO:12 or SEQ ID NO:21 (cynomolgus monkey TREM-1).

### Claim 2 (depends on 1)

The antibody or fragment thereof according to claim 1, which is capable of blocking peptidoglycan recognition protein 1 (PGLYRP1)-induced activation of TREM-1.

### Claim 3 (depends on 1)

The antibody or fragment thereof according to claim 1, which is capable of specifically binding a polypeptide comprising amino acids D38 to F48 of SEQ ID NO:1 (human TREM-1).

### Claim 4 (depends on 1)

The antibody or fragment thereof according to claim 1, which is capable of specifically binding a polypeptide comprising amino acid residues E19 to L26 of SEQ ID NO: 12 (cynomolgus monkey TREM-1).

### Claim 5 (depends on 1)

The antibody or fragment thereof according to claim 1, which has an epitope comprising one, two, three, four, five, six, seven or all of the amino acid residues D38, V39, K40, C41, D42, Y43, T44 and L45 and one, two or all of the amino acid residues E46, K47, F48 of SEQ ID NO: 1 (human TREM-1).

### Claim 6 (depends on 5)

The antibody or fragment thereof according to claim 5, which has an epitope further comprising one, two or all of the amino acid residues L31, I86 and V101 of SEQ ID NO: 1 (human TREM-1).

### Claim 7 (depends on 1)

The antibody or fragment thereof according to claim 1, which has an epitope comprising one, two, three or all of the amino acid residues D42, E46, D92 and H93 of SEQ ID NO: 1 (human TREM-1).

### Claim 8 (depends on 7)

The antibody or fragment thereof according to claim 7, which has an epitope further comprising one, two or all of the amino acid residues L31, I86 and V101 of SEQ ID NO: 1 (human TREM-1).

### Claim 9 (depends on 1)

The antibody according to claim 1, which is capable of specifically binding SEQ ID NO: 13 (K20A-hTREM-1-Cmyc2-His6).

### Claim 10 (depends on 1)

The antibody according to claim 1, which is capable of specifically binding SEQ ID NO: 14 (A24T/Y28F/N30S/R32Q/P70H-cTREM-1-Cmyc2-His6).

### Claim 11 (depends on 1)

The antibody according to claim 1, which is capable of specifically binding SEQ ID NO: 15 (A24T/Y28F/N30S/R32Q/E54K-cTREM-1-Cmyc2-His6).

### Claim 12 (depends on 1)

The antibody according to claim 1, wherein mAb 0170 further comprises a heavy chain having an amino acid sequence set forth as SEQ ID NO:4 and a light chain having an amino acid sequence set forth as SEQ ID NO:5; wherein the heavy chain comprises a CDRH1 sequence corresponding to amino acid residues 31 to 35 of SEQ ID NO:4, and/or a CDRH2 sequence corresponding to amino acids 50 to 68 of SEQ ID NO:4, and/or a CDRH3 sequence corresponding to amino acid residues 101 to 110 of SEQ ID NO:4; and wherein the light chain comprises a CDRL1 sequence corresponding to amino acid residues 24 to 38 of SEQ ID NO:5, and/or a CDRL2 sequence corresponding to amino acid residues 54 to 60 of SEQ ID NO:5, and/or a CDRL3 sequence corresponding to amino acid residues 93 to 101 of SEQ ID NO:5.

### Claim 13 (depends on 12)

The antibody of claim 12, wherein the CDRH1, CDRH2, CDRH3 sequences may be modified by substituting one, two or three of the amino acid residues.

### Claim 14 (depends on 12)

The antibody of claim 12, wherein the CDRL1, CDRL2, and CDRL3 sequences may be modified by substituting one, two or three of the amino acid residues.