Agents, uses and methods for the treatment of synucleinopathy

• US 10,640,554 B2
• Filed: 06/17/2019
• Issued: 05/05/2020
• Est. Priority Date: 07/13/2015
• Status: Active Grant

• Current Assignee: H. Lundbeck A/S (Lundbeck Foundation)
• Original Assignee: H. Lundbeck A/S (Lundbeck Foundation)
• Inventors: Kallunki, Pekka, Fog, Karina, Vesterager, Louise Buur, Bergstrom, Ann-Louise, Sotty, Florence, Satijn, David, Van Den Brink, Edward, Parren, Paul, Rademaker, Rik, Vink, Tom, Malik, Ibrahim John, Montezinho, Liliana Christina Pereira
• Primary Examiner(s): Hayes, Robert C
• Application Number:
  US16/443,249
• Publication Number:
  US 20190367595A1
• Time in Patent Office: 323 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 51/00 Preparations containing radioactive substances for use in therapy or testing in vivo
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: G01N 2800/2835 Movement disorders, e.g. Parkinson, Huntington, Tourette
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The invention relates to novel monoclonal anti-alpha-synuclein antibodies. The antibodies can be used for treating a synucleinopathy such as Parkinson'"'"'s disease (including idiopathic and inherited forms of Parkinson'"'"'s disease), Diffuse Lewy Body Disease (DLBD), Lewy body variant of Alzheimer'"'"'s disease (LBV), Combined Alzheimer'"'"'s and Parkinson disease, pure autonomic failure and multiple system atrophy.

Claims

1. A method of treating Parkinson'"'"'s disease or other synucleinopathy in a human subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody which specifically binds to human alpha-synuclein and comprises heavy chain CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NOs:

1, 35, and 3, respectively, and light chain CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NOs;

4, 5, and 6, respectively.

2. The method of claim 1, wherein the Parkinson'"'"'s disease is an idiopathic or inherited form of Parkinson'"'"'s disease.

3. The method of claim 1, wherein the synucleinopathy is selected from Gaucher'"'"'s Disease, Diffuse Lew Body Disease, Lewy body variant of Alzheimer'"'"'s disease, combined Alzheimer'"'"'s and Parkinson'"'"'s disease, pure autonomic failure, and multiple system atrophy.

4. The method of claim 1, wherein the antibody is which is a single chain Fv, a disulphide-bonded Fv, an Fab fragment, a Fab′

fragment, or a F(ab)₂ fragment.

5. The method of claim 1, wherein the antibody is a human antibody.

6. The method of claim 1, wherein the antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:

32 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO;

8.

7. The method of claim 1, wherein the antibody binds an epitope within amino acid residues 112-117 (SEQ ID NO:

9) of human alpha-synuclein (SEQ ID NO;

10).

8. The method of claim 1, wherein the antibody is formulated in a pharmaceutical composition.

9. A method of treating Parkinson'"'"'s disease in a human subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of an antibody which specifically binds to human alpha-synuclein and comprises heavy chain CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NOs:

1, 35, and 3, respectively, and light chain CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NOs;

4, 5, and 6, respectively.

10. The method of claim 9, wherein the antibody is which is a single chain Fv, a disulphide-bonded Fv, an Fab fragment, a Fab′

fragment, or a F(ab)₂ fragment.

11. The method of claim 9, wherein the antibody is a human antibody.

12. The method of claim 9, wherein the antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:

32 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO;

8.

13. The method of claim 9, wherein the antibody binds an epitope within amino acid residues 112-117 (SEQ ID NO:

9) of human alpha-synuclein (SEQ ID NO;

10).

14. The method of claim 9, wherein the antibody is formulated in a pharmaceutical composition.