Monoclonal antibodies against amyloid beta protein and uses thereof

• US 10,208,109 B2
• Filed: 07/21/2011
• Issued: 02/19/2019
• Est. Priority Date: 11/30/2005
• Status: Active Grant

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated), Abbvie Incorporated
• Inventors: Hillen, Heinz, Barghorn, Stefan, Labkovsky, Boris, Ebert, Ulrich, Striebinger, Andreas R., Keller, Patrick
• Primary Examiner(s): Ballard, Kimberly
• Application Number:
  US13/188,034
• Publication Number:
  US 20110287005A1
• Time in Patent Office: 2,770 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 monoclonal antibody comprising:

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 he 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;

wherein the monoclonal antibody binds amyloid beta globulomer.

2. The monoclonal antibody of claim 1, wherein the antibody binds with greater specificity to an amyloid beta (Aβ

) protein globulomer than to an amyloid beta protein monomer.

4. The monoclonal antibody of claim 1 or 3, wherein said antibody is murine or humanized.

18. A composition comprising the monoclonal antibody of claim 17 or claim 1.

19. A vaccine comprising the monoclonal antibody of claim 17 or claim 1 and a pharmaceutically acceptable adjuvant.

20. A kit comprising:

a) the monoclonal antibody of claim 17 or claim 1 and b) a conjugate comprising an antibody attached to a signal-generating compound, wherein said antibody of said conjugate is different from said monoclonal antibody.

3. A monoclonal antibody which specifically binds to forms of amyloid beta, wherein:

the light chain variable region of the monoclonal 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 monoclonal 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);

wherein the monoclonal antibody binds amyloid beta globulomer.

5. A monoclonal antibody comprising a variable heavy chain encoded by SEQ ID NO:

1, wherein the monoclonal antibody binds amyloid beta globulomer.

6. A monoclonal antibody comprising a variable light chain encoded by SEQ ID NO:

2, wherein the monoclonal antibody binds amyloid beta globulomer.

7. The monoclonal antibody of claim 6 further comprising a variable heavy chain encoded by SEQ ID NO:

1, wherein the monoclonal antibody binds amyloid beta globulomer.

8. A monoclonal antibody, wherein the variable heavy chain comprises SEQ ID NO:

3, wherein the monoclonal antibody binds amyloid beta globulomer.

9. A monoclonal antibody, wherein the variable light chain comprises SEQ ID NO:

4, wherein the monoclonal antibody binds amyloid beta globulomer.

10. The monoclonal antibody of claim 9 further comprising SEQ ID NO:

3.

11. A monoclonal antibody comprising the complementarity determining regions of SEQ ID NO:

3 and SEQ ID NO;

4, wherein said antibody is murine or humanized, wherein the monoclonal antibody binds amyloid beta globulomer.

12. A hybridoma that produces a monoclonal antibody having a variable heavy chain comprising SEQ ID NO:

3 and a variable light chain comprising SEQ ID NO;

4.

13. A monoclonal antibody produced by the hybridoma of claim 12.

14. A monoclonal antibody comprising:

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; and

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

10; and

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

3;

wherein the monoclonal antibody binds amyloid beta globulomer.

15. A monoclonal antibody comprising:

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

5;

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

6;

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

7; and

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

4;

wherein the monoclonal antibody binds amyloid beta globulomer.

16. A hybridoma having American Type Culture Collection designation number PTA-7238.

17. A monoclonal antibody (8F5) produced by said hybridoma of claim 16.