# US 12,599,668 B2 · Antibodies

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- Number: US 12,599,668 B2
- Document ID: US12599668B2
- Status: Granted
- Kind: B2
- Application number: 17/432,745
- Filed: 2020-02-20
- Published: 2022-09-01
- Granted: 2026-04-14
- Earliest claimed: 2019-02-20
- Assignees: Harbour Antibodies BV; Universiteit Utrecht Holding B.V.; Erasmus University Medical Center Rotterdam
- Applicants: Harbour Antibodies BV; Universiteit Utrecht Holding B.V.; Erasmus University Medical Center Rotterdam
- Inventors: Franklin Gerardus Grosveld; Marinus Johannes Van Haperen; Dubravka Drabek; Berend Jan Bosch; Ivy Widjaja; Chunyan Wang; Brenda Van Dieren; Wentao Li; Frank J.M. Van Kuppeveld; Bart L. Haagmans; Nisreen M.A. Okba
- Web page: https://patentgrep.com/patent/US12599668B2

## CPC

- A61K 47/00: Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61P 31/14: for RNA viruses
- C07K 16/08: against material from viruses
- C07K 16/102: Coronaviridae (F)
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- 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 2317/565: Complementarity determining region [CDR]
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- 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
- 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
- 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)

## Abstract

The invention relates to antibodies and antigen-binding fragments thereof that recognize coronavirus spike proteins(CoV-S), such as the spike protein of Middle East respiratory syndrome coronavirusspike protein(MERS-S). In some embodiments, the antibodiesbind to CoV-S with high affinity, inhibit CoV infection of human cells, inhibit CoV sialic acid-binding activity and/or bind to multiple types of CoV-S. In some embodiments, the antibodies provide a means of preventing, treating or ameliorating CoV infection.

## Claims

### Claim 1

An antibody that binds to Middle East Respiratory Syndrome coronavirus (MERS-CoV) spike protein (MERS-S), wherein the antibody comprises a heavy chain that comprises a heavy chain variable region (VH) and a light chain that comprises a light chain variable region (VL):
wherein:
(a) the VH comprises a heavy chain complementarity determining region (CDR) 1 with a sequence of SEQ ID NO: 83, a heavy chain CDR2 with a sequence of SEQ ID NO: 84, and a heavy chain CDR3 with a sequence of SEQ ID NO: 85; and the VL comprises a light chain CDR1 with a sequence of SEQ ID NO: 86; a light chain CDR2 with a sequence of SEQ ID NO: 87, and a light chain CDR3 with a sequence of SEQ ID NO: 88,
(b) the VH comprises a heavy chain CDR1 with a sequence of SEQ ID NO: 89, a heavy chain CDR2 with a sequence of SEQ ID NO: 90, and a heavy chain CDR3 with a sequence of SEQ ID NO: 91; and the VL comprises a light chain CDR1 with a sequence of SEQ ID NO: 92, a light chain CDR2 with a sequence of SEQ ID NO: 93, and a light chain CDR3 with a sequence of SEQ ID NO: 94,
(c) the VH comprises a heavy chain CDR1 with a sequence of SEQ ID NO: 139, a heavy chain CDR2 with a sequence of SEQ ID NO: 140, and a heavy chain CDR3 with a sequence of SEQ ID NO: 141; and the VL comprises a light chain CDR1 with a sequence of SEQ ID NO: 142, a light chain CDR2 with a sequence of SEQ ID NO: 143, and a light chain CDR3 with a sequence of SEQ ID NO: 144,
(d) the VH comprises a heavy chain CDR1 with a sequence of SEQ ID NO: 133, a heavy chain CDR2 with a sequence of SEQ ID NO: 134, and a heavy chain CDR3 with a sequence of SEQ ID NO: 135; and the VL comprises a light chain CDR1 with a sequence of SEQ ID NO: 136, a light chain CDR2 with a sequence of SEQ ID NO: 137, and a light chain CDR3 with a sequence of SEQ ID NO: 138,
(e) the VH comprises a heavy chain CDR1 with a sequence of SEQ ID NO: 127, a heavy chain CDR2 with a sequence of SEQ ID NO: 128, and a heavy chain CDR3 with a sequence of SEQ ID NO: 129; and the VL comprises a light chain CDR1 with a sequence of SEQ ID NO: 130, a light chain CDR2 with a sequence of SEQ ID NO: 131, and a light chain CDR3 with a sequence of SEQ ID NO: 132,
(f) the VH comprises a heavy chain CDR1 with a sequence of SEQ ID NO: 95, a heavy chain CDR2 with a sequence of SEQ ID NO: 96, and a heavy chain CDR3 with a sequence of SEQ ID NO: 97; and the VL comprises a light chain CDR1 with a sequence of SEQ ID NO: 98, a light chain CDR2 with a sequence of SEQ ID NO: 99, and a light chain CDR3 with a sequence of SEQ ID NO: 100,
(g) the VH comprises a heavy chain CDR1 with a sequence of SEQ ID NO: 101, a heavy chain CDR2 with a sequence of SEQ ID NO: 102, and a heavy chain CDR3 with a sequence of SEQ ID NO: 103; and the VL comprises a light chain CDR1 with a sequence of SEQ ID NO: 104, a light chain CDR2 with a sequence of SEQ ID NO: 105, and a light chain CDR3 with a sequence of SEQ ID NO: 106,
(h) the VH comprises a heavy chain CDR1 with a sequence of SEQ ID NO: 109, a heavy chain CDR2 with a sequence of SEQ ID NO: 110, and a heavy chain CDR3 with a sequence of SEQ ID NO: 111; and the VL comprises a light chain CDR1 with a sequence of SEQ ID NO: 112, a light chain CDR2 with a sequence of SEQ ID NO: 113, and a light chain CDR3 with a sequence of SEQ ID NO: 114,
(i) the VH comprises a heavy chain CDR1 with a sequence of SEQ ID NO: 145, a heavy chain CDR2 with a sequence of SEQ ID NO: 146, and a heavy chain CDR3 with a sequence of SEQ ID NO: 147; and the VL comprises a light chain CDR1 with a sequence of SEQ ID NO: 148, a light chain CDR2 with a sequence of SEQ ID NO: 149, and a light chain CDR3 with a sequence of SEQ ID NO: 150, or
(j) the VH comprises a heavy chain CDR1 with a sequence of SEQ ID NO: 617, a heavy chain CDR2 with a sequence of SEQ ID NO: 618, and a heavy chain CDR3 with a sequence of SEQ ID NO: 619; and the VL comprises a light chain CDR1 with a sequence of SEQ ID NO: 614, a light chain CDR2 with a sequence of SEQ ID NO: 615, and a light chain CDR3 with a sequence of SEQ ID NO: 616.

### Claim 2 (depends on 1)

The antibody of claim 1, wherein the antibody comprises the VH, which comprises the amino acid sequence of SEQ ID NO: 70 and the VL, which comprises the amino acid sequence of SEQ ID NO: 74; or wherein the antibody comprises the VH, which comprises the amino acid sequence of SEQ ID NO: 69 and the VL, which comprises the amino acid sequence of SEQ ID NO: 72.

### Claim 3 (depends on 1)

The antibody of claim 1, wherein
the antibody comprises the VH, which comprises the amino acid sequence of SEQ ID NO: 17 and the VL, which comprises the amino acid sequence of SEQ ID NO: 67;
the antibody comprises the VH, which comprises the amino acid sequence of SEQ ID NO: 32 and the VL, which comprises the amino acid sequence of SEQ ID NO: 56;
the antibody comprises the VH, which comprises the amino acid sequence of SEQ ID NO: 22 and the VL, which comprises the amino acid sequence of SEQ ID NO: 59;
the antibody comprises the VH, which comprises the amino acid sequence of SEQ ID NO: 28 and the VL, which comprises the amino acid sequence of SEQ ID NO: 63;
the antibody comprises the VH, which comprises the amino acid sequence of SEQ ID NO: 26 and the VL, which comprises the amino acid sequence of SEQ ID NO: 65; or
the antibody comprises the VH, which comprises the amino acid sequence of SEQ ID NO: 107 and the VL, which comprises the amino acid sequence of SEQ ID NO: 108.

### Claim 4 (depends on 1)

The antibody of claim 1, wherein the antibody comprises the VH, which comprises the amino acid sequence of SEQ ID NO: 18 and the VL, which comprises the amino acid sequence of SEQ ID NO: 58.

### Claim 5 (depends on 1)

The antibody of claim 1, wherein the antibody comprises the VH, which comprises the amino acid sequence of SEQ ID NO: 480 and the VL, which comprises the amino acid sequence of SEQ ID NO: 458.

### Claim 6 (depends on 1)

The antibody of claim 1, wherein the antibody is an Fab, Fab′, F(ab′)2, Fv, a single-chain Fv (scFv) or a disulfide-linked Fv (sdFv).

### Claim 7 (depends on 1)

An isolated nucleic acid encoding the antibody of claim 1.

### Claim 8 (depends on 1)

A pharmaceutical composition comprising the antibody of claim 1, and a pharmaceutically acceptable carrier.

### Claim 9 (depends on 1)

A method for treating or ameliorating MERS-CoV infection in a subject in need thereof, wherein the method comprises administrating an effective amount of the antibody of claim 1 to the subject.

### Claim 10

An antibody that binds to Middle East Respiratory Syndrome coronavirus (MERS-CoV) spike protein (MERS-S), wherein the antibody comprises a heavy chain that comprises a heavy chain variable region (VH), which comprises the amino acid sequence of SEQ ID NO: 28 and a light chain that comprises a light chain variable region (VL), which comprises the amino acid sequence of SEQ ID NO: 63.

### Claim 11 (depends on 10)

A method for treating or ameliorating MERS-CoV infection in a subject in need thereof, wherein the method comprises administrating an effective amount of the antibody of claim 10 to the subject.