Methods and compositions for the treatment of antibody mediated neuropathies

• US 9,388,235 B2
• Filed: 09/05/2007
• Issued: 07/12/2016
• Est. Priority Date: 09/05/2006
• Status: Active Grant

• Current Assignee: Alexion Pharmaceuticals Incorporated (Astrazeneca PLC)
• Original Assignee: Alexion Pharmaceuticals Incorporated (Astrazeneca PLC)
• Inventors: Halstead, Susan, Willison, Hugh, Rother, Russell P.
• Primary Examiner(s): ULM, JOHN D
• Application Number:
  US12/439,070
• Publication Number:
  US 20100143343A1
• Time in Patent Office: 3,233 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The use of a therapeutic capable of inhibiting complement, e.g., an anti-C5 antibody, to treat antibody mediated neuropathies is disclosed.

Claims

1. A method of treating a mammal having Guillain-Barré

syndrome, said method comprising administering to the mammal a therapeutically effective amount of a complement cascade inhibitor, wherein said inhibitor is an antibody or antigen-binding fragment thereof which specifically binds;

(i) to complement component C5 and inhibits the cleavage of C5 into fragments C5a and C5b; and

/or (ii) to C5b, wherein said antibody or antigen-binding fragment thereof inhibits membrane attack complex (MAC) formation.

2. The method of claim 1 wherein said mammal has the Miller Fisher variant of Guillain-Barré

syndrome.

3. The method of claim 1 wherein said mammal is a human.

4. The method of claim 1 wherein said antibody or antigen-binding fragment thereof is at least one selected from the group consisting of:

a polyclonal antibody, a monoclonal antibody or antigen-binding fragment thereof, a diabody, a chimerized or chimeric antibody or antigen-binding fragment thereof, a humanized antibody or antigen-binding fragment thereof, a deimmunized antibody or antigen-binding fragment thereof, a fully human antibody or antigen-binding fragment thereof, a single chain antibody, an Fv, an Fab, an Fab′

, and an F(ab′

)₂.

5. The method of claim 1 wherein said antibody is eculizumab.

6. The method of claim 1 wherein said antigen-binding fragment thereof is pexelizumab.

7. The method of claim 5 wherein said treating is chronic.

8. The method of claim 6 wherein said treating comprises treating an acute episode.

9. The method of claim 1 wherein said antibody or antigen-binding fragment thereof is formulated to be administrable to said mammal intravenously.

10. The method of claim 1 wherein said antibody or antigen-binding fragment thereof is formulated to be administrable to said mammal systemically.

11. The method of claim 1, wherein said antibody or antigen-binding fragment thereof is formulated to be administrable to said mammal locally.

12. The method of claim 1 wherein said treating results in decreased neural injury in said mammal.

13. The method of claim 1 wherein said treating results in decreased membrane attack complex (MAC) formation at presynaptic neuromuscular junctions.

14. The method of claim 1 wherein said treating restores a normal frequency of miniature endplate potentials.

15. The method of claim 1 wherein said treating restores synaptic transmission at the neuromuscular junctions.

16. The method of claim 1 wherein said treating inhibits loss of terminal integrity at the neuromuscular junctions.