Anti-Aβ globulomer 7C6 antibodies

• US 9,540,432 B2
• Filed: 05/14/2013
• Issued: 01/10/2017
• 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: 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:
  US13/893,780
• Publication Number:
  US 20140127191A1
• Time in Patent Office: 1,337 Days
• Field of Search: None
• US Class Current: 1/1
• 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 antibody selected from the group consisting of an isolated antibody, a monoclonal antibody and a recombinant antibody, wherein

(a) said 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;

(b) the binding affinity of the antibody to the Aβ

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

(1-42) globulomer;

(c) the antibody is humanized and binds to the same epitope as a monoclonal antibody 7C6 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7240;

(d) the antibody comprises (i) a VH 7C6 CDR1 consisting of amino acid residues 31-35 of SEQ ID NO;

11, (ii) a VH 7C6 CDR2 consisting of amino acid residues 50-65 of SEQ ID NO;

11, (iii) a VH 7C6 CDR3 consisting of amino acid residues 98-107 of SEQ ID NO;

11, (iv) a VL 7C6 CDR1 consisting of amino acid residues 24-39 of SEQ ID NO;

12, (v) a VL 7C6 CDR2 consisting of amino acid residues 55-61 of SEQ ID NO;

12, and (vi) a VL 7C6 CDR3 consisting of amino acid residues 94-102 of SEQ ID NO;

12.

2. Antigen-binding moiety of an antibody of claim 1.

3. The antigen-binding moiety of claim 2, wherein the moiety is selected from the group consisting of a Fab fragment, a F(ab′

)₂ fragment and a single chain Fv fragment of the antibody.

4. A composition comprising said antibody of claim 1 or said antigen-binding moiety of claim 2.

5. The composition of claim 4, wherein said composition is a pharmaceutical composition and further comprises a pharmaceutical acceptable carrier.

6. An antibody selected from the group consisting of an isolated antibody, a monoclonal antibody and a recombinant antibody, wherein said antibody comprises two variable domains, wherein said two variable domains are SEQ ID NO:

11 and SEQ ID NO;

12.

7. The antibody of claim 6, 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. Monoclonal antibody (7C6) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7240.

14. Hybridoma designated by an American Type Culture Collection deposit number PTA-7240.