Polynucleotides encoding anti-amyloid beta monoclonal antibodies

• US 9,585,956 B2
• Filed: 09/22/2015
• Issued: 03/07/2017
• Est. Priority Date: 06/12/2007
• Status: Active Grant

• Current Assignee: AC Immune SA, Genentech, Inc. (Roche Holding AG)
• Original Assignee: AC Immune SA, Genentech, Inc. (Roche Holding AG)
• Inventors: Pfeifer, Andrea, Pihlgren, Maria, Muhs, Andreas, Watts, Ryan
• Primary Examiner(s): BALLARD, KIMBERLY
• Application Number:
  US14/861,001
• Publication Number:
  US 20160000910A1
• Time in Patent Office: 532 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• 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 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• 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 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: G01N 2333/4709 Amyloid plaque core protein
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

The antibodies enabled by the teaching of the present invention are particularly useful for the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer'"'"'s Disease (AD).

Claims

1. An isolated polynucleotide encoding an antibody or fragment thereof that binds to beta-amyloid, wherein said antibody or fragment thereof comprises:

(a) a light chain variable region (VL) complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO;

11;

(b) a VL CDR2 comprising the amino acid sequence of SEQ ID NO;

12;

(c) a VL CDR3 comprising the amino acid sequence of SEQ ID NO;

13;

(d) a heavy chain variable region (VH) CDR1 comprising the amino acid sequence of SEQ ID NO;

14;

(e) a VH CDR2 comprising the amino acid sequence of SEQ ID NO;

15; and

(f) a VH CDR3 comprising the amino acid sequence of SEQ ID NO;

16.

2. The isolated polynucleotide of claim 1, wherein the antibody or fragment thereof comprises:

(a) a VL comprising an amino acid sequence that is at least 85% identical to the sequence set forth in SEQ ID NO;

7;

(b) a VH comprising an amino acid sequence that is at least 85% identical to the sequence set forth in SEQ ID NO;

8;

or

(c) a VL comprising an amino acid sequence that is at least 85% identical to the sequence set forth in SEQ ID NO;

7 and a VH comprising an amino acid sequence that is at least 85% identical to the sequence set forth in SEQ ID NO;

8.

3. The isolated polynucleotide of claim 2, wherein the antibody or fragment thereof comprises a VL comprising an amino acid sequence that is at least 85% identical to the sequence set forth in SEQ ID NO:

7 and a VH comprising an amino acid sequence that is at least 85% identical to the sequence set forth in SEQ ID NO;

8.

4. The isolated polynucleotide of claim 2, wherein the VL comprises an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NO:

7.

5. The isolated polynucleotide of claim 2, wherein the VL comprises an amino acid sequence that is at least 95% identical to the sequence set forth in SEQ ID NO:

7.

6. The isolated polynucleotide of claim 2, wherein the VH comprises an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NO:

8.

7. The isolated polynucleotide of claim 2, wherein the VH comprises an amino acid sequence that is at least 95% identical to the sequence set forth in SEQ ID NO:

8.

8. The isolated polynucleotide of claim 2, wherein the antibody or fragment thereof comprises a VL comprising an amino acid sequence that is at least 95% identical to the sequence set forth in SEQ ID NO:

7 and a VH comprising an amino acid sequence that is at least 95% identical to the sequence set forth in SEQ ID NO;

8.

9. The isolated polynucleotide of claim 2, wherein

(a) the VL is encoded by a nucleotide sequence comprising SEQ ID NO:

17 or 19;

(b) the VH is encoded by a nucleotide sequence comprising SEQ ID NO;

18 or 20;

or

(c) the VL is encoded by a nucleotide sequence comprising SEQ ID NO;

17 or 19 and the VH is encoded by a nucleotide sequence comprising SEQ ID NO;

18 or 20.

10. The isolated polynucleotide of claim 9, wherein the VL is encoded by a nucleotide sequence comprising SEQ ID NO:

17 or 19.

11. The isolated polynucleotide of claim 9, wherein the VH is encoded by a nucleotide sequence comprising SEQ ID NO:

18 or 20.

12. An isolated polynucleotide encoding an antibody or fragment thereof that binds to beta-amyloid, wherein said antibody or fragment thereof comprises

a VL comprising an amino acid sequence that is at least 85% identical to the sequence set forth in SEQ ID NO:

7 and a VH comprising an amino acid sequence that is at least 85% identical to the sequence set forth in SEQ ID NO;

8.

13. The isolated polynucleotide of claim 12, wherein said antibody or fragment thereof comprises a VL comprising an amino acid sequence that is at least 95% identical to the sequence set forth in SEQ ID NO:

7.

14. The isolated polynucleotide of claim 12, wherein said antibody or fragment thereof comprises a VH comprising an amino acid sequence that is at least 95% identical to the sequence set forth in SEQ ID NO:

8.

15. The isolated polynucleotide of claim 12, wherein said antibody or fragment thereof comprises a VL comprising an amino acid sequence that is at least 95% identical to the sequence set forth in SEQ ID NO:

7 and a VH comprising an amino acid sequence that is at least 95% identical to the sequence set forth in SEQ ID NO;

8.

16. The isolated polynucleotide of claim 12, wherein said antibody or fragment thereof comprises a VL comprising the amino acid sequence of SEQ ID NO:

7 and a VH comprising the amino acid sequence of SEQ ID NO;

8.

17. An isolated polynucleotide or population of polynucleotides encoding an antibody or fragment thereof that binds to beta-amyloid, wherein the fragment is a Fab or a F(ab′

)₂ fragment, and wherein the antibody is produced by

(a) hybridoma FG1F9E4, deposited on May 25, 2007 and given deposit number DSM ACC2845;

or

(b) hybridoma FK2A6A6, deposited on May 25, 2007 and given deposit number DSM ACC2846.

18. The isolated polynucleotide or population of polynucleotides of claim 17, wherein the antibody is produced by hybridoma FG1F9E4, deposited on May 25, 2007 and given deposit number DSM ACC2845.

19. The isolated polynucleotide or population of polynucleotides of claim 17, wherein the antibody is produced by hybridoma FK2A6A6, deposited on May 25, 2007 and given deposit number DSM ACC2846.

20. A population of isolated polynucleotides, comprising a first polynucleotide and a second polynucleotide, wherein:

the first polynucleotide encodes a VL of an antibody or fragment thereof that binds to beta-amyloid, comprising;

(a) a VL CDR1 comprising the amino acid sequence of SEQ ID NO;

11;

(b) a VL CDR2 comprising the amino acid sequence of SEQ ID NO;

12; and

(c) a VL CDR3 comprising the amino acid sequence of SEQ ID NO;

13; and

the second polynucleotide encodes a VH of an antibody or fragment thereof that binds to beta-amyloid, comprising;

(d) a VH CDR1 comprising the amino acid sequence of SEQ ID NO;

14;

(e) a VH CDR2 comprising the amino acid sequence of SEQ ID NO;

15; and

(f) a VH CDR3 comprising the amino acid sequence of SEQ ID NO;

16.

21. The population of isolated polynucleotides of claim 20, wherein the first polynucleotide encodes a VL comprising SEQ ID NO:

7 and the second polynucleotide encodes a VH comprising SEQ ID NO;

8.