Methods of reducing clinical symptoms of viral infection by administering a toll-like receptor 3 antagonist

Patent metadata

Field	Value
Publication number	US-9932404-B2
Application number	US-201615345860-A
Country	US
Kind code	B2
Filing date	Nov 8, 2016
Priority date	Oct 31, 2008
Publication date	Apr 3, 2018
Grant date	Apr 3, 2018

Abstract

Toll Like Receptor 3 (TLR3) antibody antagonists, polynucleotides encoding TLR3 antibody antagonists or fragments thereof, and methods of making and using the foregoing are disclosed.

First claim

The invention claimed is:

1. A method of reducing a clinical symptom of a respiratory viral infection in an individual, the method comprising administering a therapeutically effective amount of an isolated antibody or fragment thereof to the individual for a time sufficient to reduce the clinical symptom, wherein the antibody binds toll-like receptor 3 (TLR3) amino acid residues K416, K418, L440, N441, E442, Y465, N466, K467, Y468, R488, R489, A491, K493, N515, N516, N517, H539, N541, 5571, L595, and K619 of SEQ ID NO: 2.

2. The method of claim 1 , wherein the viral infection is influenza A virus infection.

3. The method of claim 1 , wherein the antibody is fully human.

4. The method of claim 1 , wherein the antibody is human adapted.

5. The method of claim 1 , wherein the antibody is conjugated to poly(ethylene glycol).

6. The method of claim 1 , wherein the antibody is of an IgG4 isotype.

7. The method of claim 1 , wherein the antibody comprises an Fc domain comprising S229P, P235A or L236A substitutions.

8. The method of claim 1 , wherein the viral infection is caused by a double-stranded RNA (dsRNA) virus or a virus that has dsRNA as a replication intermediate.

9. The method of claim 1 , wherein the clinical symptom is inflammation.

10. A method of reducing a clinical symptom of a respiratory viral infection in an individual, the method comprising administering a therapeutically effective amount of an isolated antibody or fragment thereof to the individual for a time sufficient to reduce the clinical symptom, wherein the isolated antibody comprises a heavy chain variable region and a light chain variable region or fragment thereof and the isolated antibody heavy chain variable region Chothia residues W33, F50, D52, D54, Y56, N58, P61, E95, Y97, Y100, and D100b and the isolated antibody light chain variable region Chothia residues Q27, Y32, N92, T93, L94, and S95 bind toll-like receptor 3 (TLR3) that has the amino acid sequence shown in SEQ ID NO: 2.

11. The method of claim 10 , wherein the viral infection is influenza A virus infection.

12. The method of claim 10 , wherein the antibody is fully human.

13. The method of claim 10 , wherein the antibody is human adapted.

14. The method of claim 10 , wherein the antibody is conjugated to poly(ethylene glycol).

15. The method of claim 10 , wherein the antibody is of an IgG4 isotype.

16. The method of claim 10 , wherein the antibody comprises an Fc domain comprising S229P, P235A or L236A substitutions.

17. The method of claim 10 , wherein the viral infection is caused by a double-stranded RNA (dsRNA) virus or a virus that has dsRNA as a replication intermediate.

18. The method of claim 10 , wherein the clinical symptom is inflammation.

Assignees

• Janssen Biotech Inc

Inventors

• Cunningham Mark
• Feng Yiqing
• Heeringa Katharine
• Luo Jinquan
• Rauchenberger Robert
• Rutz Mark
• San Mateo Lani
• Sarisky Robert
• Sweet Raymond
• Teng Fang
• Teplyakov Alexey
• Wu Sheng-Jiun

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title