Aβ conformer selective anti-aβ globulomer monoclonal antibodies

• US 8,455,626 B2
• Filed: 11/26/2007
• Issued: 06/04/2013
• Est. Priority Date: 11/30/2006
• Status: Active Grant

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbott Laboratories
• Inventors: Barghorn, Stefan, Hillen, Heinz, Striebinger, Andreas R., Labkovsky, Boris, Ebert, Ulrich, Keller, Patrick
• Primary Examiner(s): Kemmerer, Elizabeth C
• Assistant Examiner(s): Ballard, Kimberly A
• Application Number:
  US11/945,124
• Publication Number:
  US 20090035307A1
• Time in Patent Office: 2,017 Days
• Field of Search: None
• US Class Current: 530/388.1
• 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 antibody comprising SEQ ID NO:

5, 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 (a) Aβ

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

(1-40) peptide present in CSF.

2. An isolated antibody comprising SEQ ID NO:

6, 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 (a) Aβ

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

(1-40) peptide present in CSF.

3. The isolated antibody of claim 2 further comprising SEQ ID NO:

5.

4. A hybridoma designated by American Type Culture Collection deposit number PTA-7406.

5. A monoclonal antibody (3C5) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7406.

6. An isolated antibody comprising SEQ ID NO:

7, 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 (a) Aβ

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

(1-40) peptide present in CSF.

7. An isolated antibody comprising SEQ ID NO:

8, 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 (a) Aβ

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

(1-40) peptide present in CSF.

8. The isolated antibody of claim 7 further comprising SEQ ID NO:

7.

9. A hybridoma designated by American Type Culture Collection deposit number PTA-7808.

10. A monoclonal antibody (10F4) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7808.

11. An isolated monoclonal antibody comprising a heavy chain encoded by the nucleic acid sequence set forth in SEQ ID NO:

1 or SEQ ID NO;

3, or a light chain encoded by the nucleic acid sequence set forth in SEQ ID NO;

2 or SEQ ID NO;

4, 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 (a) Aβ

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

(1-40) peptide present in the CSF.

12. The isolated antibody of claim 11 wherein said antibody is selected from the group consisting of a monoclonal antibody produced by a hybridoma designated by American Type Culture Collection deposit number PTA-7406 and a monoclonal antibody produced by a hybridoma designated by American Type Culture Collection deposit number PTA-7808.

13. The isolated antibody of claim 11 wherein said antibody comprises at least one amino acid sequence from the group consisting of SEQ ID NO:

5, SEQ ID NO;

6, SEQ ID NO;

7 and SEQ ID NO;

8.