Method for treating a complement mediated disorder caused by an infectious agent in a patient

Patent metadata

Field	Value
Publication number	US-2016168237-A1
Application number	US-201514966921-A
Country	US
Kind code	A1
Filing date	Dec 11, 2015
Priority date	Dec 12, 2014
Publication date	Jun 16, 2016
Grant date	—

Abstract

The present disclosure relates to, inter alia, a method of treating a complement mediated disorder caused by an infectious agents in a patient, comprising administering an effective amount of a C5 inhibitor, such as eculizumab or an eculizumab variant, to the patient.

First claim

1 . A method of treating a complement mediated disorder caused by an infectious agent in a human patient comprising administering an effective amount of a polypeptide inhibitor of human complement C5 protein to the human patient.

2 . The method of claim 1 , wherein the infectious agent is selected from the group consisting of virus, bacteria, protozoa, fungi, prion and worm.

3 . The method of claim 1 , wherein the infectious agent is a virus that can cause hemorrhagic fever in the patient.

4 . (canceled)

5 . The method of claim 1 , wherein the complement mediated disorder is sepsis.

6 . (canceled)

7 . The method of claim 1 , wherein the infectious agent is a virus that can cause VHF or the complement mediated disorder is sepsis.

8 . The method of claim 1 , wherein the polypeptide inhibitor is a monoclonal antibody.

9 . The method of claim 1 , wherein the polypeptide inhibitor comprises a variable region of an antibody.

10 . The method of claim 1 , wherein the polypeptide inhibitor is eculizumab or an eculizumab variant, or antigen-binding fragment of either.

11 - 13 . (canceled)

14 . The method of claim 3 , wherein the virus is a filovirus and wherein the filovirus is an Ebola virus.

15 . The method of claim 1 , further comprising administering a second therapeutic agent to the patient.

16 - 23 . (canceled)

24 . The method of claim 1 , wherein the polypeptide inhibitor of complement C5 is a polypeptide comprising one or more of the amino acid sequence depicted in SEQ ID NOs:1-3, 5-8, or 24, 26-33, or an antigen binding fragment of any of the above.

25 . The method of claim 1 , wherein the polypeptide inhibitor of complement C5 is a polypeptide comprising one or more of the amino acid sequence depicted in SEQ ID NOs:9-16.

26 . (canceled)

27 . A method of treating a complement mediated disorder caused by an infectious agent in a human patient, comprising administering an effective amount of an anti-C5 antibody, or antigen binding fragment thereof, to the patient, wherein the complement mediated disorder is Shiga toxin-producing E. coli hemolytic uremic syndrome (STEC-HUS), wherein the method comprises an administration cycle comprising an induction phase followed by a maintenance phase, wherein:
the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 900 mg weekly for 4 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 1200 mg in week 5 and then 1200 mg every two weeks; or the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 2 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 900 mg in week 3, and then 900 mg every two weeks; or the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 2 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 600 mg in week 3, and then 600 mg every two weeks; or the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 1 week, starting at day 0, and is administered during the maintenance phase at a dose of 600 mg every week; or the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 300 mg weekly for 1 week, starting at day 0, and is administered during the maintenance phase at a dose of 300 mg at week 2 and then every 3 weeks.

28 . The method of claim 27 , wherein the anti-C5 antibody, or antigen binding fragment thereof, comprises CDR1, CDR2, and CDR3 heavy chain sequences as set forth in SEQ ID NOs:33, 29, and 11, respectively, and CDR1, CDR2, and CDR3 light chain sequences as set forth in SEQ ID NOs:12, 13, and 14, respectively.

29 . (canceled)

30 . The method of claim 27 , wherein the anti-C5 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region sequence as set forth in SEQ ID NO:15, and light chain variable region sequence as set forth in SEQ ID NO:16.

31 . The method of claim 27 , wherein the anti-C5 antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region depicted in SEQ ID NO:24 and a light chain variable region depicted in SEQ ID NO:16.

32 . (canceled)

33 . The method of claim 27 , wherein the anti-C5 antibody, or antigen binding fragment thereof, comprises a heavy chain sequence as set for in SEQ ID NO:5, and light chain sequence as set forth in SEQ ID NO:6 or SEQ ID NO:8.

34 . The method of claim 27 , wherein the antibody, or antigen-binding fragment thereof, comprises a heavy chain sequence depicted in SEQ ID NO:7 and a light chain sequence depicted in SEQ ID NO:6 or SEQ ID NO:8.

35 - 57 . (canceled)

58 . A kit for treating Shiga toxin-producing E. coli hemolytic uremic syndrome (STEC-HUS) in a human patient, the kit comprising:
(a) a dose of an anti-C5 antibody, or antigen binding fragment thereof; and (b) Instructions for using the anti-C5 antibody, or antigen binding fragment thereof, in the method of claim 27 .

59 . An anti-C5 antibody, or antigen binding fragment thereof, comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region from the sequence set forth in SEQ ID NO:15 or SEQ ID NO:24, and CDR1, CDR2 and CDR3 domains of the light chain variable region from the sequence set forth in SEQ ID NO:16, for administration in a cycle comprising an induction phase followed by a maintenance phase, wherein:
the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 900 mg weekly for 4 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 1200 mg in week 5 and then 1200 mg every two weeks; or the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 2 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 900 mg in week 3, and then 900 mg every two weeks; or the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 2 weeks, starting at day 0, and is administered during the maintenance phase at a dose of 600 mg in week 3, and then 600 mg every two weeks; or the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 600 mg weekly for 1 week, starting at day 0, and is administered during the maintenance phase at a dose of 600 mg every week; or the anti-C5 antibody, or antigen binding fragment thereof, is administered during the induction phase at a dose of 300 mg weekly for 1 week, starting at day 0, and is administered during the maintenance phase at a dose of 300 mg at week 2 and then every 3 weeks.

Assignees

• Alexion Pharma Inc

Inventors

• Fontenot Darrell
• Puffer Bridget
• Andrien Bruce
• Doyle Mittie
• Tamburini Paul
• Bedrosian Camille

Classifications

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title