Anti-Aβ globulomer 4D10 antibodies

• US 10,538,581 B2
• Filed: 10/11/2016
• Issued: 01/21/2020
• Est. Priority Date: 11/30/2005
• Status: Active Grant

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbvie Incorporated
• Inventors: Barghorn, Stefan, Hillen, Heinz, Labkovsky, Boris, Striebinger, Andreas R., Keller, Patrick, Ebert, Ulrich
• Primary Examiner(s): Kolker, Daniel E
• Assistant Examiner(s): Dutt, Aditi
• Application Number:
  US15/290,699
• Publication Number:
  US 20170022269A1
• Time in Patent Office: 1,197 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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 37/00 Drugs for immunological or allergic disorders
• 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 2317/41 Glycosylation, sialylation, or fucosylation
• 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 2800/2821 Alzheimer
• CPC Class Codes: G01N 2800/387 Down syndrome; Trisomy 18; Trisomy 13
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

Anti-Aβ globulomer antibodies, antigen-binding moieties thereof, corresponding hybridomas, nucleic acids, vectors, host cells, methods of producing said antibodies, compositions comprising said antibodies, uses of said antibodies and methods of using said antibodies.

The present invention relates to anti-Aβ globulomer antibodies having a binding affinity to Aβ(20-42) globulomer that is greater than the binding affinity of the antibody to Aβ(1-42) globulomer, antigen-binding moieties thereof, hybridomas producing said antibodies, nucleic acids encoding said antibodies, vectors comprising said nucleic acids, host cells comprising said vectors, methods of producing said antibodies, compositions comprising said antibodies, therapeutic and diagnostic uses of said antibodies and corresponding methods relating to Alzheimer'"'"'s disease and other amyloidoses.

Claims

1. An anti-Aβ

(20-42) globulomer antibody comprising;

a heavy chain variable region (VH) having

a VH CDR1 having amino acid residues 31-35 of SEQ ID NO;

27,

a VH CDR2 having amino acid residues 50-65 of SEQ ID NO;

27, and

a VH CDR3 having amino acid residues 98-101 of SEQ ID NO;

27; and

a light chain variable region (VL) having

a VL CDR1 having amino acid residues 24-39 of SEQ ID NO;

28,

a VL CDR2 having amino acid residues 55-61 of SEQ ID NO;

28, and

a VL CDR3 having amino acid residues 94-102 of SEQ ID NO;

28.

2. The antibody 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.

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

(20-42) globulomer that is at least 10 times greater than the binding affinity of the antibody to an Aβ

(1-42) globulomer.

4. The antibody of claim 1, wherein the VH has an amino acid sequence represented by SEQ ID NO:

27.

5. The antibody of claim 1, wherein the VL has an amino acid sequence represented by SEQ ID NO:

28.

6. The antibody of claim 1, wherein the VH has an amino acid sequence represented by SEQ ID NO:

27 and the VL has an amino acid sequence represented by SEQ ID NO;

28.

7. The antibody of claim 1, wherein the antibody comprises a constant region.

8. The antibody of claim 7, wherein the antibody comprises a heavy chain constant region selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgM, IgA, IgD and IgE constant regions.

9. The antibody of claim 8, wherein the antibody comprises an IgG1 heavy chain constant region.

10. The antibody of claim 8, wherein the constant region is a human constant region.

11. The antibody of claim 7, wherein the constant region comprises the amino acid sequence of SEQ ID NO:

39.

12. The antibody of claim 11, wherein the antibody possesses a human glycosylation pattern.

13. The antibody of claim 1, wherein the antibody is monoclonal antibody (4D10) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7405.

14. A hybridoma capable of producing the antibody of claim 1.

15. The hybridoma of claim 14, wherein the hybridoma is designated by American Type Culture Collection deposit number PTA-7405.

16. A composition comprising the antibody of claim 1.

17. The composition of claim 16, wherein the composition is a pharmaceutical composition and further comprises a pharmaceutically acceptable carrier.