ANTI-AMYLOID BETA ANTIBODIES CONJUGATED TO SIALIC ACID-CONTAINING MOLECULES

• US 20110202000A1
• Filed: 05/26/2010
• Published: 08/18/2011
• Est. Priority Date: 05/14/2007
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: THAKKER, DEEPAK R., SHAFER, LISA L., BENZ, MICHAEL
• Granted Patent: US 8,323,654 B2
• Time in Patent Office: Days
• US Class Current: 604/93.01
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 47/6807 the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense
• CPC Class Codes: A61K 47/6843 the antibody targeting a material from animals or humans
• 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 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/515 Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL

Abstract

Antibody complexes including anti-Aβ antibodies conjugated with a sialic acid-containing molecule show improved bioavailability with no significant adverse effects on binding to amyloid beta.

Claims

1. An antibody complex comprising:

an isolated anti-amyloid beta antibody; and

sialic acid-containing molecule conjugated to the antibody.

2. An antibody complex according to claim 1, wherein the isolated antibody is a humanized antibody.

3. An antibody complex according to claim 1 or claim 2, wherein the isolated antibody comprises:

a variable heavy chain region including an amino acid sequence selected from the group consisting of SEQ ID NOs;

42, 44, 46, 47, 48, 49, 50 and 51; and

a variable light chain region including an amino acid sequence selected from the group consisting of SEQ ID NOs;

43, 45, 52, 53 and 54.

4. An antibody complex according to claim 3, wherein the variable heavy chain region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

47, SEQ ID NO;

48, SEQ ID NO;

49, SEQ ID NO;

50 and SEQ ID NO;

51.

5. An antibody complex according to claim 4, wherein the variable light chain region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

52, SEQ ID NO;

53, and SEQ ID NO;

54.

6. An antibody complex according to 3, wherein the variable heavy chain region comprises an amino acid sequence of SEQ ID NO:

47 and the variable light chain region comprises an amino acid sequence of SEQ ID NO;

52.

7. An antibody complex according to claim 3, wherein the variable heavy chain region comprises an amino acid sequence of SEQ ID NO:

48 and the variable light chain region comprises an amino acid sequence of SEQ ID NO;

54.

8. An antibody complex according to claim 3, wherein the variable heavy chain region comprises an amino acid sequence of SEQ ID NO:

50 and the variable light chain region comprises an amino acid sequence of SEQ ID NO;

52.

9. An antibody complex according to claim 3, wherein the variable heavy chain region comprises an amino acid sequence of SEQ ID NO:

51 and the variable light chain region comprises an amino acid sequence of SEQ ID NO;

52.

10. An antibody complex according to claim 3, wherein the variable heavy chain region comprises an amino acid sequence of SEQ ID NO:

50 and the variable light chain region comprises an amino acid sequence of SEQ ID NO;

53.

11. An antibody complex according to claim 3, wherein the variable heavy chain region comprises an amino acid sequence of SEQ ID NO:

51 and the variable light chain region comprises an amino acid sequence of SEQ ID NO;

53.

12. An antibody complex according to any of claims 1-11, wherein the isolated antibody further comprises an immunoglobulin domain.

13. An antibody complex according to claim 12, wherein the immunoglobulin domain is selected from the group consisting of IgG-1, IgG-4, and IgGM.

14. An antibody complex according to any of claims 1-13, wherein the antibody is a monoclonal antibody.

15. An antibody complex according to claim 14, wherein the antibody is a F(ab)′

₂ antibody.

16. An antibody complex according to any of claims 1-15, wherein the sialic acid-containing molecule comprises a lipid head-group and a sialic acid group.

17. An antibody complex according to claim 16, wherein the lipid head-group is a phospholipid.

18. An antibody complex according to any of claims 1-15, wherein the sialic acid-containing molecule is selected from the group consisting of capsular polysialic acid, sialic acid-containing gangliosides, and colominic acid.

19. The liposome complex of claim 9, wherein the sialic acid-containing molecule is a capsular polysialic acid.

20. A composition comprising an antibody complex according to any of claims 1-19.

21. A composition according to claim 20, further comprising a pharmaceutically acceptable diluent.

22. A composition according to claim 20 or 21, wherein the antibody is present in the composition in an amount effective to treat a disease associated with increased or aberrant soluble Aβ

, Aβ

fibrils or Aβ

plaques when administered to a subject in need thereof.

23. A method for treating a disease associated with increased or aberrant soluble Aβ

, Aβ

fibrils or Aβ

plaques in a subject in need thereof, comprising;

administering an effective amount of the antibody of claim 1 to the subject.

24. A method according to claim 23, wherein the subject is suffering from or at risk of Alzheimer'"'"'s disease.

25. A method according to claim 23 or 24, wherein the subject is suffering from or at risk of Lewy body dimentia.

26. A method according to any of claims 23-25, wherein the subject is suffering from or at risk of Down'"'"'s Syndrome.

27. A method according to any of claims 23-26, wherein the subject is suffering from or at risk of cerebral amyloid angiopathy.

28. A method according to any of claims 23-27, wherein administering the antibody to the subject comprises administering the antibody directly to the subject'"'"'s central nervous system.

29. A method according to claim 28, wherein administering the antibody directly to the subject'"'"'s central nervous system comprises administering the antibody directly to cerebrospinal fluid of the subject.

30. A method according to any of claims 23-29, wherein the antibody is administered via an infusion device implanted in the subject.

31. A system comprising an implantable infusion device and a composition according to any of claims 20-22, wherein the composition is an injectable composition, wherein the infusion device comprises a reservoir for housing the composition, and wherein the composition is housed in the reservoir.