Abeta conformer selective anti-Abeta globulomer monoclonal antibodies

• US 9,359,430 B2
• Filed: 04/15/2013
• Issued: 06/07/2016
• Est. Priority Date: 11/30/2006
• Status: Active Grant

• Current Assignee: Abbvie Incorporated
• Original Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated), Abbvie Incorporated
• Inventors: Barghorn, Stefan, Hillen, Heinz, Striebinger, Andreas R., Labkovsky, Boris, Ebert, Ulrich, Keller, Patrick
• Primary Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US13/862,865
• Publication Number:
  US 20130287799A1
• Time in Patent Office: 1,149 Days
• Field of Search: None
• US Class Current: 1/1
• 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: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/10 characterized by their source of isolation or production
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• 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 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The subject invention relates to monoclonal antibodies that may be used in the treatment and diagnosis of Alzheimer'"'"'s Disease. In particular, the present invention relates to monoclonal antibodies referred to as 10F4 and 3C5 and to other monoclonal antibodies (e.g., murine, human or humanized) having similar properties thereto.

Claims

1. An isolated nucleic acid molecule encoding an antibody comprising a set of six CDRs comprising SEQ ID NOs:

15-20;

or a set of six CDRs comprising SEQ ID NOs;

9-14.

2. The isolated nucleic acid molecule of claim 1 wherein the nucleotide sequence of said molecule comprises at least one sequence selected from the group consisting of SEQ ID NO:

1, SEQ ID NO;

2, SEQ ID NO;

3 and SEQ ID NO;

4.

3. A vector comprising said isolated nucleic acid molecule of claim 1.

4. A host cell comprising said vector of claim 3.

5. A method of producing an antibody, comprising culturing said host cell of claim 4 in a culture medium for a time and under conditions suitable for production of said antibody.

6. An isolated antibody produced by said method of claim 5, wherein the antibody has an affinity for Aβ

(1-42) globulomer.

7. The isolated nucleic acid molecule of claim 1, wherein the antibody has a higher affinity to Aβ

(1-42) globulomer than to at least one amyloid beta protein selected from the group consisting of Aβ

(1-42) peptide present in cerebrospinal fluid (CSF) and b) Aβ

(1-40) peptide present in CSF;

or wherein the antibody has a binding affinity to Aβ

(1-42) globulomer which is greater than the binding affinity to at least one amyloid beta protein selected from the group consisting of a) Aβ

(1-42) monomer, b) Aβ

(1-40) monomer, c) Aβ

(1-42) fibril, and d) soluble amyloid precursor protein-alpha (sAPPα

).