Methods of treating C5-associated diseases comprising administering anti-C5 antibodies

Patent metadata

Field	Value
Publication number	US-11479602-B2
Application number	US-202016819989-A
Country	US
Kind code	B2
Filing date	Mar 16, 2020
Priority date	Jun 14, 2016
Publication date	Oct 25, 2022
Grant date	Oct 25, 2022

Abstract

The present invention provides monoclonal antibodies that bind to the complement factor 5 (C5) protein, and methods of use thereof. In various embodiments of the invention, the antibodies are fully human antibodies that bind to C5 protein. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing C5 activity, thus providing a means of treating or preventing a C5-related disease or disorder in humans. In some embodiments, the invention provides for an anti-C5 antibody that has improved pharmacokinetic and pharmacodynamic properties, e.g., a half-life of more than 10 days.

First claim

What is claimed is:

1. A method of treating or ameliorating at least one symptom or indication of a disease or disorder associated with C5 in a human subject in need thereof, the method comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an antibody or antigen-binding fragment thereof that specifically binds C5 comprising
a heavy chain variable region that comprises
an HCDR1 that comprises an amino acid sequence as set forth in SEQ ID NO: 100,
an HCDR2 that comprises an amino acid sequence as set forth in SEQ ID NO: 102, and
an HCDR3 that comprises an amino acid sequence as set forth in SEQ ID NO: 104;

and a light chain variable region that comprises
an LCDR1 that comprises an amino acid sequence as set forth in SEQ ID NO: 108,
an LCDR2 that comprises an amino acid sequence as set forth in SEQ ID NO: 110, and
an LCDR3 that comprises an amino acid sequence as set forth in SEQ ID NO: 112;

to the human subject.

2. The method of claim 1 , wherein the disease or disorder is selected from the group consisting of atypical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria, age-related macular degeneration, geographic atrophy, uveitis, neuromyelitis optica, multiple sclerosis, stroke, Guillain Barre Syndrome, traumatic brain injury, Parkinson's disease, a disorder of inappropriate or undesirable complement activation, a hemodialysis complication, hyperacute allograft rejection, xenograft rejection, interleukin-2 induced toxicity during IL-2 therapy, an inflammatory disorder, inflammation of an autoimmune disease, Crohn's disease, adult respiratory distress syndrome, thermal injury, burns, frostbite, a post-ischemic reperfusion condition, myocardial infarction, capillary leak syndrome, obesity, diabetes, Alzheimer's disease, schizophrenia, stroke, epilepsy, atherosclerosis, vasculitis, bullous pemphigoid, C3 glomerulopathy, membraneproliferative glomerulonephritis, diabetic nephropathy, Alport's syndrome, progressive kidney failure, proteinuric kidney disease, renal ischemia-reperfusion injury, lupus nephritis, post-pump syndrome in cardiopulmonary bypass, post-pump syndrome in renal bypass, hemodialysis, renal ischemia, mesenteric artery reperfusion after aortic reconstruction, infectious disease, sepsis, an immune complex disorder, an autoimmune disease, a renal disorder, rheumatoid arthritis, systemic lupus erythematosus, systemic lupus erythematosus nephritis, proliferative nephritis, hemolytic anemia, asthma, chronic obstructive pulmonary disease, emphysema, pulmonary embolism, pulmonary infarct, pneumonia, and myasthenia gravis.

3. The method of claim 1 , wherein the disease or disorder is atypical hemolytic uremic syndrome.

4. The method of claim 1 , wherein the disease or disorder is paroxysmal nocturnal hemoglobinuria.

5. The method of claim 1 , wherein the pharmaceutical composition is administered in combination with a second therapeutic agent.

6. The method of claim 5 , wherein the second therapeutic agent is selected from the group consisting of an anti-coagulant, an anti-inflammatory drug, an antihypertensive, an immunosuppressive agent, a lipid-lowering agent, an anti-CD20 agent, rituximab, an anti-TNF agent, infliximab, an anti-seizure agent, a C3 inhibitor, a second anti-05 antibody, and an anti-thrombotic agent.

7. The method of claim 1 , wherein the pharmaceutical composition is administered subcutaneously, intravenously, intradermally, intraperitoneally, orally, intramuscularly or intracranially.

8. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 98.

9. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 106.

10. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 98 and a light chain variable region that comprises the amino acid sequence set forth in SEQ ID NO: 106.

11. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain that comprises an amino acid sequence of SEQ ID NO: 353.

12. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a light chain that comprises an amino acid sequence of SEQ ID NO: 354.

13. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain that comprises an amino acid sequence of SEQ ID NO: 353; and a light chain that comprises an amino acid sequence of SEQ ID NO: 354.

14. The method of claim 13 , wherein the antibody or antigen-binding fragment thereof is an antibody.

15. The method of claim 14 , wherein the disease or disorder is paroxysmal nocturnal hemoglobinuria (PNH).

16. The method of claim 14 , wherein the disease or disorder is myasthenia gravis.

17. The method of claim 14 , wherein the disease or disorder is neuromyelitis optica.

18. The method of claim 15 , wherein the antibody is administered to the subject intravenously and subcutaneously.

19. The method of claim 16 , wherein the antibody is administered to the subject intravenously and subcutaneously.

20. The method of claim 17 , wherein the antibody is administered to the subject intravenously and subcutaneously.

21. The method of claim 18 , wherein the antibody is administered in combination with a second therapeutic agent.

22. The method of claim 19 , wherein the antibody is administered in combination with a second therapeutic agent.

23. The method of claim 20 , wherein the antibody is administered in combination with a second therapeutic agent.

Assignees

• Regeneron Pharma
• Regeneren Pharmaceuticals Inc

Inventors

• Hu Ying
• Latuszek Adrianna
• Romano Carmelo
• Olson William

Classifications

• C07K16/00 Primary

  Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K39/3955

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

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title