Humanized antibodies that sequester amyloid beta peptide

• US 7,892,545 B2
• Filed: 02/08/2008
• Issued: 02/22/2011
• Est. Priority Date: 02/24/2000
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company, Washington University In St Louis
• Original Assignee: Eli Lilly and Company, Washington University In St Louis
• Inventors: Tsurushita, Naoya, Paul, Steven M., Bales, Kelly R., Holtzman, David M, DeMattos, Ronald, Vasquez, Maximiliano
• Primary Examiner(s): Kolker; Daniel E
• Assistant Examiner(s): Emch; Gregory S
• Application Number:
  US12/028,641
• Publication Number:
  US 20090238821A1
• Time in Patent Office: 1,110 Days
• Field of Search: None
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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: 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 2317/34 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 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 Framework region [FR]
• 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

Abstract

A method to treat conditions characterized by formation of amyloid plaques both prophylactically and therapeutically is described. The method employs humanized antibodies which sequester soluble Aβ peptide from human biological fluids or which preferably specifically bind an epitope contained within position 13-28 of the amyloid beta peptide Aβ.

Claims

1. A method to inhibit the formation of amyloid plaques or to inhibit the formation of toxic soluble Aβ

species in humans, comprising administering to a human subject in need of such inhibition an effective amount of a humanized antibody, wherein said antibody comprises;

a. a light chain comprising a light chain variable region comprising the following sequence;

2. The method of claim 1 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

3. The method of claim 2 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

4. A method to reduce the formation of amyloid plaques or to reduce the formation of toxic soluble Aβ

species in a human, comprising administering to a human subject in need of such reduction an effective amount of a humanized antibody, wherein said antibody comprises;

a. a light chain comprising a light chain variable region comprising the following sequence;

5. The method of claim 4 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

6. The method of claim 5 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

7. A method of treating, preventing, or reversing cognitive decline in a subject having clinical or pre-clinical Alzheimer'"'"'s disease, Down'"'"'s syndrome, or clinical or pre-clinical cerebral amyloid angiopathy, comprising administering to the subject an effective amount of a humanized antibody, wherein said antibody comprises:

a. a light chain comprising a light chain variable region comprising the following sequence;

8. The method of claim 7 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

9. The method of claim 8 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

10. A method of treating, preventing, or reversing cognitive decline in a human subject having clinical or pre-clinical Alzheimer'"'"'s disease, Down'"'"'s syndrome, or clinical or pre-clinical cerebral amyloid angiopathy, comprising expressing recombinant sequences of a humanized antibody in human tissue, wherein said antibody comprises:

a. a light chain comprising a light chain variable region comprising the following sequence;

11. The method of claim 10 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

12. The method of claim 11 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

13. A method of improving cognition in a human subject having clinical or pre-clinical Alzheimer'"'"'s disease, Down'"'"'s syndrome, or clinical or pre-clinical cerebral amyloid angiopathy, comprising administering to the subject an effective amount of a humanized antibody, wherein said antibody comprises:

a. a light chain comprising a light chain variable region comprising the following sequence;

14. The method of claim 13 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

15. The method of claim 14 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

16. A method of therapeutically treating Alzheimer'"'"'s disease, comprising administering to a patient in need thereof an effective amount of a humanized antibody, wherein said antibody comprises:

a. a light chain comprising a light chain variable region comprising the following sequence;

17. The method of claim 16 wherein said Alzheimer'"'"'s disease is pre-clinical Alzheimer'"'"'s disease.

18. The method of claim 17 wherein said light chain comprises the sequence given by SEQ ID NO:

11 and said heavy chain comprises the sequence given by SEQ ID NO;

12.

19. The method of claim 18 wherein said Alzheimer'"'"'s disease is pre-clinical Alzheimer'"'"'s disease.

20. The method of claim 18 wherein said Alzheimer'"'"'s disease is clinical Alzheimer'"'"'s disease.

21. The method of claim 16 wherein said Alzheimer'"'"'s disease is clinical Alzheimer'"'"'s disease.

22. The method of claim 16 wherein said light chain variable region comprises the sequence given by SEQ ID NO:

9 and said heavy chain variable region comprises the sequence given by SEQ ID NO;

10.

23. The method of claim 22 wherein said Alzheimer'"'"'s disease is pre-clinical Alzheimer'"'"'s disease.

24. The method of claim 22 wherein said Alzheimer'"'"'s disease is clinical Alzheimer'"'"'s disease.