Single domain antibodies against SOD1 and their use in medicine

• US 9,862,777 B2
• Filed: 05/28/2014
• Issued: 01/09/2018
• 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, Rousseau, Frederic, Schymkowitz, Joost
• Primary Examiner(s): Ballard, Kimberly A.
• Assistant Examiner(s): MACFARLANE, STACEY NEE
• Application Number:
  US14/894,980
• Publication Number:
  US 20160115245A1
• Time in Patent Office: 1,322 Days
• Field of Search: None
• 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 the enzyme superoxide dismutase (“

SOD1”

),

wherein the single-domain antibody comprises a peptide that binds with both wild-type and mutant SOD 1, wherein the single-domain antibody is able to block fibril formation by SOD 1, and wherein;

(a) the single-domain antibody comprises a peptide selected from the group consisting of SEQ ID NOS;

1-14, or

(b) the single-domain antibody comprises an amino acid sequence comprising a set of three complementarity determining regions (CDRs), wherein the set of CDRs is selected from;

i. SEQ ID NOs;

15, 16 and 17;

ii. SEQ ID NOs;

18, 20 and 21;

iii. SEQ ID NOs;

19, 20 and 21;

iv. SEQ ID NOs;

22, 24 and 25;

v. SEQ ID NOs;

23, 24 and 25;

or

vi. SEQ ID NOs;

26, 27 and 28.

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

3. The single-domain antibody of claim 2, wherein the tag is a His-tag, HA-tag, or Myc-tag.

4. A medicament comprising:

the single-domain antibody of claim 1, and

a pharmaceutically acceptable excipient.

5. The single-domain antibody of claim 1, wherein the mutant SOD1 is characterized by an A4V, G93A, and/or G113W mutation.

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 14, wherein the single-domain antibody is administered through injection or pump to the subject.

6. A single-domain antibody against the enzyme superoxide dismutase (“

SOD1”

),

wherein the single-domain antibody comprises a peptide selected from the group consisting of SEQ ID NOs;

1-14 or

wherein a complementarity-determining region (“

CDR”

) thereof is selected from SEQ ID NOs;

15-28.

7. The single-domain antibody of claim 6, wherein the single-domain antibody comprises a peptide comprising SEQ ID NO:

1.

8. The single-domain antibody of claim 6, wherein the single-domain antibody comprises the CDR of SEQ ID NO:

16.

9. The single-domain antibody of claim 6, wherein the single-domain antibody comprises the CDR of SEQ ID NO:

17.

10. The single-domain antibody of claim 6, wherein the single-domain antibody comprises the CDR of SEQ ID NO:

18.

11. The single-domain antibody of claim 6, wherein the single-domain antibody comprises the CDR of SEQ ID NO:

19.

12. The single-domain antibody of claim 6, wherein the single-domain antibody comprises the CDR of SEQ ID NO:

20.