Amyloid-beta binding proteins

• US 9,822,171 B2
• Filed: 02/10/2015
• Issued: 11/21/2017
• Est. Priority Date: 04/15/2010
• Status: Active Grant

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated), Abbvie Incorporated
• Inventors: Barghorn, Stefan, Hillen, Heinz, Striebinger, Andreas, Giaisi, Simone, Ebert, Ulrich, Benatuil, Lorenzo
• Primary Examiner(s): Sang, Hong
• Application Number:
  US14/618,632
• Publication Number:
  US 20150218261A1
• Time in Patent Office: 1,015 Days
• Field of Search: None
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 47/6835 the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
• CPC Class Codes: A61K 49/00 Preparations for testing in vivo
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• CPC Class Codes: C07K 16/18 against material from animals or humans
• 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 2317/30 : characterized by aspects of specificity or valency
• CPC Class Codes: C07K 2317/31 : multispecific
• CPC Class Codes: C07K 2317/54 : F(ab')2
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• 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 2317/569 : Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/624 : Disulfide-stabilized antibody (dsFv)
• CPC Class Codes: C07K 2317/626 : Diabody or triabody
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention relates to amyloid-beta (Aβ) binding proteins. Antibodies of the invention have high affinity to Aβ(20-42) globulomer or any Aβ form that comprises the globulomer epitope. Method of making and method of using the antibodies of the invention are also provided.

Claims

1. A method for treating a subject for Alzheimer'"'"'s disease by administering to the subject an effective amount of an anti-Aβ

(20-42) globulomer antibody comprising;

a first amino acid sequence which is at least 90% identical to SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, or SEQ ID NO;

11; and

a second amino acid sequence which is at least 90% identical to SEQ ID NO;

1, SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, or SEQ ID NO;

16,

wherein the first amino acid sequence comprises three complementarity determining regions consisting of amino acids 31-35, 50-65, and 98-101, respectively, of SEQ ID NO;

2 or SEQ ID NO;

3; and

wherein the second amino acid sequence comprises three complementarity determining regions consisting of amino acids 24-39, 55-61, and 94-102, respectively, of SEQ ID NO;

1.

2. The method of claim 1, wherein the first amino acid sequence is at least 90% identical to SEQ ID NO:

2 or SEQ ID NO;

3; and

a second amino acid sequence is at least 90% identical to SEQ ID NO;

1.

3. The method of claim 1, wherein the first amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:

4, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, and SEQ ID NO;

11.

4. The method of claim 1, wherein the second amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, and SEQ ID NO;

16.

5. The method of claim 1, wherein the first amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:

4, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, and SEQ ID NO;

11; and

the second amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, and SEQ ID NO;

16.

6. The method of claim 1, wherein the antibody is selected from the group consisting of:

an immunoglobulin molecule, a monoclonal antibody, a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a multispecific antibody, a dual variable domain, and a bispecific antibody.

7. The method of claim 1, wherein the antibody further comprises an immunoglobulin light chain constant region having an amino acid sequence selected from the group consisting of SEQ ID NO:

27 and SEQ ID NO;

28.

8. The method of claim 1, wherein the antibody further comprises an agent selected from the group consisting of:

an immunoadhesion molecule;

an imaging agent, and a therapeutic agent.

9. The method of claim 1, wherein the antibody possesses a human glycosylation pattern.

12. The method of claim 1, wherein the antibody has a binding affinity to an Aβ

(20-42) globulomer that is greater than the binding affinity of the antibody to an Aβ

(1-42) globulomer.

14. The method of claim 1, wherein the first amino acid sequence is selected from the group consisting of SEQ ID NO:

4, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, and SEQ ID NO;

11; and

the second amino acid sequence is selected from the group consisting of SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, and SEQ ID NO;

16.

10. A method for treating a subject for Alzheimer'"'"'s disease by administering to the subject an effective amount of a pharmaceutical composition comprising:

an anti-Aβ

(20.42) globulomer antibody comprising;

a first amino acid sequence which is at least 90% identical to SEQ ID NO;

2, SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, or SEQ ID NO;

11; and

a second amino acid sequence which is at least 90% identical to SEQ ID NO;

1, SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, or SEQ ID NO;

16,

wherein the first amino acid sequence comprises three complementarity determining regions consisting of amino acids 31-35, 50-65, and 98-101, respectively, of SEQ ID NO;

2 or SEQ ID NO;

3; and

wherein the second amino acid sequence comprises three complementarity determining regions consisting of amino acids 24-39, 55-61, and 94-102, respectively, of SEQ ID NO;

1; and

a pharmaceutically acceptable carrier.

11. The method of claim 10, wherein the pharmaceutical composition further comprises at least one additional therapeutic agent.

13. The method of claim 10, wherein the antibody has a binding affinity to an Aβ

(20-42) globulomer that is greater than the binding affinity of the antibody to an Aβ

(1-42) globulomer.

15. The method of claim 10, wherein the first amino acid sequence is selected from the group consisting of SEQ ID NO:

4, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, SEQ ID NO;

10, and SEQ ID NO;

11; and

the second amino acid sequence is selected from the group consisting of SEQ ID NO;

12, SEQ ID NO;

13, SEQ ID NO;

14, SEQ ID NO;

15, and SEQ ID NO;

16.