Monoclonal antibodies against amyloid beta protein and uses thereof

• US 10,323,084 B2
• Filed: 07/27/2017
• Issued: 06/18/2019
• Est. Priority Date: 11/30/2005
• Status: Active Grant

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated), Abbvie Incorporated
• Original Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated), Abbvie Incorporated
• Inventors: Hillen, Heinz, Barghorn, Stefan, Labkovsky, Boris, Ebert, Ulrich, Striebinger, Andreas, Keller, Patrick
• Primary Examiner(s): Ballard, Kimberly
• Application Number:
  US15/662,224
• Publication Number:
  US 20180066044A1
• Time in Patent Office: 691 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: 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 37/04 Immunostimulants
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/20 characterized by taxonomic origin
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• 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 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: G01N 2333/4709 Amyloid plaque core protein
• CPC Class Codes: G01N 2500/20 cell-free systems
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/577 involving monoclonal antibodies binding reaction mechanisms characterised by the use of monoclonal antibodies; monoclonal antibodies per se are classified with their corresponding antigens; G01N33/53 - G01N33/576 take precedence
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The subject invention relates to monoclonal antibodies (e.g., 8F5 and 8C5) that may be used, for example, in the prevention, treatment and diagnosis of Alzheimer'"'"'s Disease or other neurodegenerative disorders.

Claims

1. A method of treating Alzheimer'"'"'s Disease in a patient in need of said treatment comprising administering an isolated antibody that binds with greater specificity to an amyloid beta (Aβ

) protein globulomer than to an amyloid beta protein monomer in an amount sufficient to effect said treatment, wherein the antibody comprises

a) a light chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO;

8;

b) a light chain variable region CDR 2 comprising the amino acid sequence of SEQ ID NO;

9;

c) a light chain variable region CDR 3 comprising the amino acid sequence of SEQ ID NO;

10;

d) a heavy chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO;

5;

e) a heavy chain variable region CDR 2 comprising the amino acid sequence of SEQ ID NO;

6; and

f) a heavy chain variable region CDR 3 comprising the amino acid sequence of SEQ ID NO;

7.

2. The method of claim 1 wherein said isolated antibody is administered via a route selected from the group consisting of intramuscular administration, intravenous administration and subcutaneous administration.

3. The method of claim 1, wherein the antibody is humanized.

4. A method of treating Alzheimer'"'"'s Disease in a patient in need of said treatment comprising the step of administering a composition comprising an antibody with greater specificity to an amyloid beta (Aβ

) protein globulomer than to an amyloid beta protein monomer to said patient in an amount sufficient to effect said treatment wherein the antibody comprises

a) a light chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO;

8;

b) a light chain variable region CDR 2 comprising the amino acid sequence of SEQ ID NO;

9;

c) a light chain variable region CDR 3 comprising the amino acid sequence of SEQ ID NO;

10;

d) a heavy chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO;

5;

e) a heavy chain variable region CDR 2 comprising the amino acid sequence of SEQ ID NO;

6; and

f) a heavy chain variable region CDR 3 comprising the amino acid sequence of SEQ ID NO;

7.

5. The method of claim 4, wherein the antibody is humanized.

6. A method of treating Alzheimer'"'"'s Disease in a patient in need of said treatment comprising the step of administering a vaccine comprising an isolated antibody with greater specificity to an amyloid beta (Aβ

) protein globulomer than to an amyloid beta protein monomer and a pharmaceutically acceptable adjuvant to said patient in an amount sufficient to effect said treatment, wherein the antibody comprises

a) a light chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO;

8;

b) a light chain variable region CDR 2 comprising the amino acid sequence of SEQ ID NO;

9;

c) a light chain variable region CDR 3 comprising the amino acid sequence of SEQ ID NO;

10;

d) a heavy chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO;

5;

e) a heavy chain variable region CDR 2 comprising the amino acid sequence of SEQ ID NO;

6; and

f) a heavy chain variable region CDR 3 comprising the amino acid sequence of SEQ ID NO;

7.

7. The method of claim 6, wherein the antibody is humanized.

8. A method of treating Alzheimer'"'"'s Disease in a patient in need of said treatment comprising administering an isolated antibody that binds with greater specificity to an amyloid beta (Aβ

) protein globulomer than to an amyloid beta protein monomer in an amount sufficient to effect said treatment, wherein the antibody comprises the complementarity determining regions of SEQ ID NO;

3 and SEQ ID NO;

4, wherein the antibody is humanized.

9. A method of treating Alzheimer'"'"'s Disease in a patient in need of said treatment comprising the step of administering a composition comprising an antibody with greater specificity to an amyloid beta (Aβ

) protein globulomer than to an amyloid beta protein monomer to said patient in an amount sufficient to effect said treatment wherein the antibody comprises the complementarity determining regions of SEQ ID NO;

3 and SEQ ID NO;

4, wherein the antibody is humanized.

10. A method of treating Alzheimer'"'"'s Disease in a patient in need of said treatment comprising the step of administering a vaccine comprising an isolated antibody with greater specificity to an amyloid beta (Aβ

) protein globulomer than to an amyloid beta protein monomer and a pharmaceutically acceptable adjuvant to said patient in an amount sufficient to effect said treatment, wherein the antibody comprises the complementarity determining regions of SEQ ID NO;

3 and SEQ ID NO;

4, wherein the antibody is humanized.

11. A method of treating Alzheimer'"'"'s Disease in a patient in need of said treatment comprising administering an isolated antibody that binds with greater specificity to an amyloid beta (Aβ

) protein globulomer than to an amyloid beta protein monomer in an amount sufficient to effect said treatment, wherein

the light chain variable region of the antibody comprises the amino acid sequence of RSSQSLVYSNGDTYLH (SEQ ID NO;

     8);

the amino acid sequence of KVSNRFS (SEQ ID NO;

     9); and

the amino acid sequence of SQSTHVPWT (SEQ ID NO;

     10); and

the heavy chain variable region of the antibody comprises the amino acid sequence of GFTFSSYGMS (SEQ ID NO;

     24);

the amino acid sequence of SINSNGGSTYYPDSVKG (SEQ ID NO;

     6); and

the amino acid sequence of GDY (SEQ ID NO;

     25).

12. The method of claim 11, wherein the antibody is humanized.

13. A method of treating Alzheimer'"'"'s Disease in a patient in need of said treatment comprising the step of administering a composition comprising an antibody with greater specificity to an amyloid beta (Aβ

) protein globulomer than to an amyloid beta protein monomer to said patient in an amount sufficient to effect said treatment wherein

the light chain variable region of the antibody comprises the amino acid sequence of RSSQSLVYSNGDTYLH (SEQ ID NO;

     8);

the amino acid sequence of KVSNRFS (SEQ ID NO;

     9); and

the amino acid sequence of SQSTHVPWT (SEQ ID NO;

     10); and

the heavy chain variable region of the antibody comprises the amino acid sequence of GFTFSSYGMS (SEQ ID NO;

     24);

the amino acid sequence of SINSNGGSTYYPDSVKG (SEQ ID NO;

     6); and

the amino acid sequence of GDY (SEQ ID NO;

     25).

14. The method of claim 13, wherein the antibody is humanized.

15. A method of treating Alzheimer'"'"'s Disease in a patient in need of said treatment comprising the step of administering a vaccine comprising an isolated antibody with greater specificity to an amyloid beta (Aβ

) protein globulomer than to an amyloid beta protein monomer and a pharmaceutically acceptable adjuvant to said patient in an amount sufficient to effect said treatment, wherein

the light chain variable region of the antibody comprises the amino acid sequence of RSSQSLVYSNGDTYLH (SEQ ID NO;

     8);

the amino acid sequence of KVSNRFS (SEQ ID NO;

     9); and

the amino acid sequence of SQSTHVPWT (SEQ ID NO;

     10); and

the heavy chain variable region of the antibody comprises the amino acid sequence of GFTFSSYGMS (SEQ ID NO;

     24);

the amino acid sequence of SINSNGGSTYYPDSVKG (SEQ ID NO;

     6); and

the amino acid sequence of GDY (SEQ ID NO;

     25).

16. The method of claim 15, wherein the antibody is humanized.