Aβ binding molecules

• US 8,623,365 B2
• Filed: 12/21/2011
• Issued: 01/07/2014
• Est. Priority Date: 02/10/2003
• Status: Expired due to Fees

• Current Assignee: Applied Molecular Evolution, Inc. (Eli Lilly and Company)
• Original Assignee: Applied Molecular Evolution, Inc. (Eli Lilly and Company)
• Inventors: Davies, Julian, Tang, Ying, Watkins, Jeffry Dean
• Primary Examiner(s): Emch, Gregory S
• Application Number:
  US13/332,753
• Publication Number:
  US 20120114560A1
• Time in Patent Office: 748 Days
• Field of Search: None
• US Class Current: 424/145.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• 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

Abstract

The present invention encompasses isolated antibodies, or fragments thereof, that are humanized variants of murine antibody 266 which employ complementarity determining regions derived from murine antibody 266. The variant antibodies are useful for treatment or prevention of conditions and diseases associated with Aβ, including Alzheimer'"'"'s disease, Down'"'"'s syndrome, cerebral amyloid angiopathy, mild cognitive impairment, and the like.

Claims

1. An antibody, or antigen-binding portion thereof, that binds human Aβ

, comprising a light chain and a heavy chain,

wherein the light chain comprises;

a) the CDR1 of SEQ ID NO;

7

b) the CDR2 of SEQ ID NO;

23

c) the CDR3 of SEQ ID NO;

30; and

the heavy chain comprises;

a) the CDR1 of SEQ ID NO;

37

b) the CDR2 of SEQ ID NO;

41

c) the CDR3 of SEQ ID NO;

71.

2. The antibody or antigen-binding portion of claim 1 which is a humanized antibody.

3. The antigen-binding portion of claim 1 which is a Fab fragment.

4. The antigen-binding portion of claim 1 which is a F(ab'"'"')2 fragment.

5. The antibody or antigen-binding portion of claim 1, wherein said antibody or antigen-binding portion thereof has an IgG isotype selected from the group consisting of heavy chain constant regions IgG1 and IgG4.

6. A pharmaceutical composition comprising the antibody or antigen-binding portion thereof of claim 1.

7. A method of treating Alzheimer'"'"'s disease comprising administering to a subject in need thereof of an effective amount of the antibody or antigen-binding portion thereof of claim 1.

8. A method of diagnosing Alzheimer'"'"'s disease comprising administering to a subject having brain amyloids a diagnostic amount of the antibody or antigen-binding portion thereof of claim 1.

9. An antibody, or antigen-binding portion thereof, that binds human Aβ

, comprising a light chain and a heavy chain,

wherein the light chain comprises;

a) the CDR1 of SEQ ID NO;

7

b) the CDR2 of SEQ ID NO;

23

c) the CDR3 of SEQ ID NO;

30; and

the heavy chain comprises;

a) the CDR1 of SEQ ID NO;

37

b) the CDR2 of SEQ ID NO;

48

c) the CDR3 of SEQ ID NO;

75.

10. The antibody or antigen-binding of claim 9 which is a humanized antibody.

11. The antigen-binding portion of claim 9 which is a Fab fragment.

12. The antigen-binding portion of claim 9 which is a F(ab'"'"')2 fragment.

13. The antibody or antigen-binding portion of claim 9, wherein said antibody or antigen-binding portion thereof has and IgG isotype selected from the group consisting of heavy chain constant regions IgG1 and IgG4.

14. A pharmaceutical composition comprising the antibody or antigen-binding portion thereof of claim 9.

15. A method of treating Alzheimer'"'"'s disease comprising administering to a subject in need thereof an effective amount of the antibody or antigen-binding portion thereof of claim 9.

16. A method of diagnosing Alzheimer'"'"'s disease comprising administering to a subject having brain amyloids a diagnostic amount of the antibody or antigen-binding portion thereof of claim 9.