PEGYLATED ABETA FAB

• US 20100015155A1
• Filed: 01/09/2008
• Published: 01/21/2010
• Est. Priority Date: 01/18/2007
• Status: Active Grant

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Chow, Chi-Kin, Hansen, Ryan John, Kuchibhotla, Uma, Demattos, Ronald Bradley, Bumol, Thomas Frank, McDonnell, Peter Colon, Bales, Kelly Renee, Lu, Jirong
• Granted Patent: US 8,066,999 B2
• Time in Patent Office: Days
• US Class Current: 424/139.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/6093 Synthetic polymers, e.g. polyethyleneglycol [PEG], Polymers or copolymers of (D) glutamate and (D) lysine
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/6893 clearing therapy or enhanced clearance, i.e. using an antibody clearing agents in addition to T-A and D-M
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• 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 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2319/31 fusions, other than Fc, for prolonged plasma life, e.g. albumin
• CPC Class Codes: Y10S 530/866 involving immunoglobulin or antibody fragment, e.g. fab', fab, fv, fc, heavy chain or light chain

Abstract

A method to treat conditions associated with Aβ peptide activity both prophylactically and therapeutically is described. The method employs humanized antibody fragments that specifically bind human Aβ peptide between amino acid positions 13-28, wherein the antibody fragments are covalently attached to a polyethylene glycol (PEG) molecule.

Claims

1-19. -19. (canceled)

20. A molecule comprising an antibody fragment that specifically binds human Aβ

peptide between amino acid positions 13-28, wherein the antibody fragment comprises a light chain variable region of SEQ ID NO;

1 and a heavy chain variable region of SEQ ID NO;

2, and wherein a polyethylene glycol molecule is covalently attached to a CDR of the heavy chain variable region of the antibody fragment.

21. The molecule of claim 20 wherein the antibody fragment is a Fab fragment.

22. The molecule of claim 21 wherein the polyethylene glycol molecule is covalently attached to the cysteine at amino acid position 56 of the heavy chain variable region of the said SEQ ID NO:

2.

23. The molecule of claim 21 wherein the polyethylene glycol molecule has a molecular weight of about 0.5 kD to about 30 kD.

24. The molecule of claim 23 wherein the polyethylene glycol molecule has a molecular weight of about 20 kD.

25. A molecule comprising an antibody Fab fragment with a light chain variable region of SEQ ID NO:

1 and a heavy chain variable region of SEQ ID NO;

2, wherein the said antibody fragment is covalently attached to a 20 kD polyethylene glycol molecule at position 56 of the heavy chain variable region of the SEQ ID NO;

2.

26. A composition comprising the molecule of claim 25.

27. A composition of claim 26 further comprising a pharmaceutically acceptable carrier.

28. A method of treating or preventing a condition associated with Aβ

peptide activity, comprising administering to a human subject in need thereof an effective amount of a molecule of claim 25.

29. A method of treating a condition selected from a group consisting of Alzheimer'"'"'s disease, Down'"'"'s syndrome, cereberal amyloid angiopathy (CAA), cognitive deficit, stroke, brain hemorrhage, and general mental debilitation, comprising administering to a human an effective amount of a molecule of claim 25.

30. The method according to claim 29, wherein Alzheimer'"'"'s disease is pre-clinical Alzheimer'"'"'s disease.

31. The method according to claim 29, wherein Alzheimer'"'"'s disease is clinical Alzheimer'"'"'s disease.