SINGLE DOMAIN ANTIBODIES AGAINST SOD1 AND THEIR USE IN MEDICINE

• US 20160115245A1
• Filed: 05/28/2014
• Published: 04/28/2016
• Est. Priority Date: 05/28/2013
• Status: Active Grant

• Current Assignee: EHS Manufacturing Pty Ltd, Katholieke Universiteit Leuven, Life Sciences Research Partners V.Z.W., VIB VZW
• Original Assignee: Katholieke Universiteit Leuven, Life Sciences Research Partners V.Z.W., VIB VZW
• Inventors: Robberecht, Wim, Schymkowitz, Joost, Rousseau, Frederic
• Granted Patent: US 9,862,777 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/22 from camelids, e.g. camel, llama or dromedary
• CPC Class Codes: C07K 2317/569 Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/21 containing a His-tag
• CPC Class Codes: C07K 2319/41 containing a Myc-tag
• CPC Class Codes: C07K 2319/42 containing a HA(hemagglutinin)-tag

Abstract

The present application relates to the field of single-domain antibodies (also called nanobodies), more particularly single-domain antibodies against SOD1 protein isoforms. It also relates to the use of these nanobodies in medicine. Accordingly, methods to treat a disease using these nanobodies are provided herein. The single-domain antibodies are particularly envisaged for treatment of ALS.

Claims

1. A single-domain antibody against SOD1.

2. The single-domain antibody according to claim 1, wherein SOD1 is human SOD1.

3. The single-domain antibody according to claim 1, wherein the single-domain antibody binds mutant SOD1.

4. The single-domain antibody according to claim 3, wherein the mutant SOD1 is characterized by a mutation of amino acids at positions 4, 93 and/or 113.

5. The single-domain antibody of claim 1, wherein the single-domain antibody binds both wild-type and mutant SOD1.

6. The single-domain antibody of claim 1, wherein the single-domain antibody is an inhibitory single-domain antibody against SOD1.

7. The single-domain antibody of claim 1, which has a peptide selected from the group consisting of SEQ ID NOS:

1-14, or wherein the CDRs are selected from SEQ ID NOS;

15-28.

8. The single-domain antibody of claim 1, which is fused to a tag.

9. The single-domain antibody claim 1, which is able to enter cells.

10. A nucleic acid molecule encoding the single-domain antibody of claim 1.

11. A vector comprising the nucleic acid molecule according to claim 10.

12. A host cell comprising the nucleic acid molecule according to claim 10.

13. A method of treating amyotrophic lateral sclerosis (ALS) or improving symptoms of ALS in a subject, the method comprising:

administering the single-domain antibody of claim 1 to the subject.

14. The method according to claim 13, wherein the single-domain antibody is administered intracerebroventricularly.

15. The method according to claim 13, wherein the single-domain antibody is administered through gene therapy.

16. A medicament comprising:

the single-domain antibody of claim 1, and

a pharmaceutically acceptable excipient.

17. A method of treating amyotrophic lateral sclerosis (ALS) or improving symptoms of ALS in a subject, the method comprising:

utilizing the vector according to claim 11 to treat the subject'"'"'s ALS.

18. A kit comprising:

the vector according to claim 11, and

a pharmaceutically acceptable excipient.

19. The single-domain antibody of claim 4, wherein the mutant SOD1 is characterized by an A4V, G93A, and/or G113W mutation.

20. The single-domain antibody of claim 8, wherein the tag is a His-tag, HA-tag, or Myc-tag.

21. The method according to claim 14, wherein the single domain antibody is administered through injection or pump.