Immunotherapy regimes dependent on ApoE status

• US 9,644,025 B2
• Filed: 10/17/2008
• Issued: 05/09/2017
• Est. Priority Date: 10/17/2007
• Status: Active Grant

• Current Assignee: Janssen Sciences Ireland UC (Johnson & Johnson), Wyeth LLC (Pfizer Inc.)
• Original Assignee: Janssen Sciences Ireland UC (Johnson & Johnson), Wyeth LLC (Pfizer Inc.)
• Inventors: Black, Ronald, Ekman, Lars, Lieberburg, Ivan, Grundman, Michael, Callaway, James, Gregg, Keith M., Jacobsen, Jack Steven, Gill, Davinder, Tchistiakova, Lioudmila, Widom, Angela
• Primary Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US12/738,396
• Publication Number:
  US 20100266505A1
• Time in Patent Office: 3,126 Days
• 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: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• 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 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/71 Decreased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: G06Q 99/00 Subject matter not provided for in other groups of this subclass

Abstract

The invention provides methods of immunotherapy of Alzheimer'"'"'s and similar diseases in which the regime administered to a patient depends on the ApoE genotype of the patient.

Claims

1. A method of treating a disease characterized by Aβ

deposits in the brain of patient comprising intravenously or subcutaneously administering an effective regime of a humanized antibody to a population of patients suffering from the disease;

wherein the humanized antibody comprises a mature light chain variable region sequence of SEQ ID NO;

2 and a mature heavy chain variable region sequence of SEQ ID NO;

3, and a human heavy chain constant region of IgG1 isotype with L234A, L235A, and G237A mutations, wherein positions are numbered by the EU numbering system, and thereby treating the disease in the patients, wherein the regime administered to different patients in the population does not depend on the number of ApoE4 alleles present in a patient.

2. The method of claim 1, wherein the dose is 0.15-1 mg/kg.

3. The method of claim 1, wherein the dose is 0.15-2 mg/kg.

4. The method of claim 1, wherein the dosage is 10 mg/kg.

5. The method of claim 1, further comprising monitoring the patient by MRI for vasogenic edema.

6. The method of claim 1, wherein the antibody is an L234A, L235A, G237A variant of bapineuzumab.

7. The method of claim 2, wherein the antibody is an L234A, L235A, G237A variant of bapineuzumab.

8. The method of claim 3, wherein the antibody is an L234A, L235A, G237A variant of bapineuzumab.

9. The method of claim 5, wherein the antibody is an L234A, L235A, G237A variant of bapineuzumab.

10. The method of claim 1, wherein the disease is Alzheimer'"'"'s disease.

11. The method of claim 6, wherein the disease is Alzheimer'"'"'s disease.

12. The method of claim 7, wherein the disease is Alzheimer'"'"'s disease.

13. The method of claim 8, wherein the disease is Alzheimer'"'"'s disease.

14. The method of claim 9, wherein the disease is Alzheimer'"'"'s disease.

15. A method of reducing the risk, lessening the severity or delaying the outset of a disease characterized by Aβ

deposits in the brain of patient comprising administering an effective regime of a humanized antibody to a population of patients susceptible to the disease;

wherein the humanized antibody comprises a mature light chain variable region sequence of SEQ ID NO;

2 and a mature heavy chain variable region sequence of SEQ ID NO;

3, and a human heavy chain constant of IgG1 isotype with L234A, L235A, and G237A mutations, wherein positions are numbered by the EU numbering system, thereby reducing the risk, lessening the severity or delaying the outset of the disease in the patients, wherein the regime administered to different patients in the population does not depend on the number of ApoE4 alleles present in a patient.

16. The method of claim 15, wherein the dose is 0.15-1 mg/kg.

17. The method of claim 15, wherein the dose is 0.15-2 mg/kg.

18. The method of claim 15, further comprising monitoring the patient by MRI for vasogenic edema.

19. The method of claim 15, wherein the antibody is an L234A, L235A, G237A variant of bapineuzumab.

20. The method of claim 16, wherein the antibody is an L234A, L235A, G237A variant of bapineuzumab.

21. The method of claim 17, wherein the antibody is an L234A, L235A, G237A variant of bapineuzumab.

22. The method of claim 18, wherein the antibody is an L234A, L235A, G237A variant of bapineuzumab.

23. The method of claim 15, wherein the disease is Alzheimer'"'"'s disease.

24. The method of claim 19, wherein the disease is Alzheimer'"'"'s disease.

25. The method of claim 20, wherein the disease is Alzheimer'"'"'s disease.

26. The method of claim 21, wherein the disease is Alzheimer'"'"'s disease.

27. The method of claim 22, wherein the disease is Alzheimer'"'"'s disease.