# US 12,110,319 B2 · Anti-yellow fever virus antibodies, and methods of their generation and use

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- Number: US 12,110,319 B2
- Document ID: US12110319B2
- Status: Granted
- Kind: B2
- Application number: 18/485,163
- Filed: 2023-10-11
- Published: 2024-07-04
- Granted: 2024-10-08
- Earliest claimed: 2019-11-25
- Assignees: Mabloc, Inc.
- Applicants: Mabloc, LLC
- Inventors: Anna Wec; Laura Walker
- Web page: https://patentgrep.com/patent/US12110319B2

## CPC

- A61K 39/42: viral
- A61P 31/14: for RNA viruses
- C07K 16/10: RNA viruses
- C07K 16/116: Togaviridae (F); Matonaviridae (F); Flaviviridae (F)
- 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 2317/76: 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
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Antibodies and antigen-binding fragments thereof specific to the YFV E protein and with neutralizing potency against YFV are provided. These antibodies and antigen-binding fragments are useful in treating YFV.

## Claims

### Claim 1

A method of treating or preventing a Yellow Fever Virus (YFV) infection or at least one symptom arising therefrom, comprising administering to a patient in need thereof or suspected of being in need thereof an isolated antibody or antigen-binding fragment thereof,
wherein the antibody or antigen-binding fragment thereof specifically binds to a YFV protein, wherein the antibody or antigen-binding fragment thereof comprises:
(i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:307 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:459;
(ii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:308 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:460;
(iii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:311 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:463;
(iv) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:320 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:471; or
(v) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:341 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:492.

### Claim 2 (depends on 1)

The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:307 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:459.

### Claim 3 (depends on 1)

The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:308 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:460.

### Claim 4 (depends on 1)

The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:311 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:463.

### Claim 5 (depends on 1)

The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:320 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:471.

### Claim 6 (depends on 1)

The method of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:341 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:492.

### Claim 7 (depends on 1)

The method of claim 1, wherein the at least one symptom associated with the YFV infection is treated, alleviated, or reduced in severity.

### Claim 8 (depends on 1)

The method of claim 1, wherein the at least one symptom associated with the YFV infection is fever, chills, headache, low back pain, myalgia, loss of appetite, nausea, vomiting, or fatigue.

### Claim 9 (depends on 1)

The method of claim 1, wherein the isolated antibody or antigen-binding fragment thereof:
(a) displays neutralization activity toward YFV in vitro;
(b) displays an in vitro neutralization potency (IC50) of between about 0.5 microgram/milliliter (μl/ml) to about 5 μl/ml; between about 0.05 μl/ml to about 0.5 μl/ml; or less than about 0.05 mg/ml; and/or
(c) binds to an envelope protein of YFV.

### Claim 10 (depends on 9)

The method of claim 9, wherein the isolated antibody or antigen-binding fragment thereof comprises at least two of characteristics (a), (b), and/or (c).

### Claim 11 (depends on 1)

The method of claim 1, wherein the isolated antibody or antigen-binding fragment thereof displays an equilibrium dissociation constant of between about 1×106 M to about 1×1010 M.

### Claim 12

A method of treating or preventing a Yellow Fever Virus (YFV) infection or at least one symptom arising therefrom, comprising administering to a patient in need thereof or suspected of being in need thereof an isolated nucleic acid encoding an antibody or antigen-binding fragment thereof,
wherein the antibody or antigen-binding fragment thereof specifically binds to a YFV protein, wherein the antibody or antigen-binding fragment thereof comprises:
(i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:307 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:459;
(ii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:308 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:460;
(iii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:311 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:463;
(iv) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:320 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:471; or
(v) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:341 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:492.

### Claim 13 (depends on 12)

The method of claim 12, wherein the at least one symptom associated with the YFV infection is fever, chills, headache, low back pain, myalgia, loss of appetite, nausea, vomiting, or fatigue.

### Claim 14

A method of treating or preventing a Yellow Fever Virus (YFV) infection or at least one symptom arising therefrom, comprising administering to a patient in need thereof or suspected of being in need thereof a pharmaceutical composition comprising a pharmaceutically acceptable excipient and an isolated antibody or antigen-binding fragment thereof
wherein the antibody or antigen-binding fragment thereof specifically binds to a YFV protein, wherein the antibody or antigen-binding fragment thereof comprises:
(i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:307 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:459;
(ii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:308 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:460;
(iii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:311 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:463;
(iv) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:320 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:471; or
(v) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:341 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:492.

### Claim 15 (depends on 14)

The method of claim 14, wherein the at least one symptom associated with the YFV infection is fever, chills, headache, low back pain, myalgia, loss of appetite, nausea, vomiting, or fatigue.

### Claim 16

A method of treating or preventing a Yellow Fever Virus (YFV) infection or at least one symptom arising therefrom, comprising administering to a patient in need thereof or suspected of being in need thereof a pharmaceutical composition comprising a pharmaceutically acceptable excipient and an isolated nucleic acid encoding an antibody or antigen-binding fragment thereof
wherein the antibody or antigen-binding fragment thereof specifically binds to a YFV protein, wherein the antibody or antigen-binding fragment thereof comprises:
(i) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:307 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:459;
(ii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:308 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:460;
(iii) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:311 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:463;
(iv) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:320 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:471; or
(v) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:341 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:492.

### Claim 17 (depends on 16)

The method of claim 16, wherein the at least one symptom associated with the YFV infection is fever, chills, headache, low back pain, myalgia, loss of appetite, nausea, vomiting, or fatigue.
