Methods for treating malaria by administering an antibody that specifically binds angiopoietin-2 (ang-2)

Patent metadata

Field	Value
Publication number	US-9371379-B2
Application number	US-201314134880-A
Country	US
Kind code	B2
Filing date	Dec 19, 2013
Priority date	Jul 29, 2009
Publication date	Jun 21, 2016
Grant date	Jun 21, 2016

Abstract

The present invention provides methods for treating malaria by administering to a patient in need thereof a pharmaceutical composition comprising an antibody that specifically binds human angiopoietin-2 (Ang-2).

First claim

What is claimed is:

1. A method for treating a symptom of cerebral malaria, the method comprising administering to a patient in need thereof a pharmaceutical composition comprising a therapeutically effective amount of an isolated antibody or antigen-binding fragment thereof that specifically binds human angiopoietin-2 (hAng-2) but does not substantially bind hAng-1, and a pharmaceutically acceptable carrier, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain CDR-1 (HCDR1) having the amino acid sequence of SEQ ID NO:4, an HCDR-2 having the amino acid sequence of SEQ ID NO:6, an HCDR-3 having the amino acid sequence of SEQ ID NO:8, a light chain CDR-1 (LCDR-1) having the amino acid sequence of SEQ ID NO:12, an LCDR-2 having the amino acid sequence of SEQ ID NO:14, and an LCDR-3 having the amino acid sequence of SEQ ID NO:16.

2. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof binds an epitope on hAng-2 (SEQ ID NO:518) comprising an amino acid selected from the group consisting of F-469, Y-475, and S-480.

3. The method of claim 2 , wherein the antibody or antigen-binding fragment thereof binds an epitope on hAng-2 comprising amino acids F-469, Y-475, and S-480.

4. The method of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) having the amino acid sequence of SEQ ID NO: 18 and a light chain variable region (LCVR) having the amino acid sequence of SEQ ID NO:20.

5. The method of claim 1 , wherein the symptom of cerebral malaria is a level of sICAM-1 or vWF, and treating the symptom comprises reducing the level of sICAM-1 or vWF as compared to an untreated patient in need thereof.

6. The method of claim 1 , wherein the symptom of cerebral malaria is loss of blood-brain barrier vascular integrity, and treating the symptom comprises reducing the loss of blood-brain barrier vascular integrity as compared to an untreated patient in need thereof.

7. The method of claim 1 , wherein the symptom of cerebral malaria is parasite accumulation in the brain, and treating the symptom comprises reducing parasite accumulation in the brain as compared to an untreated patient in need thereof.

8. The method of claim 1 , wherein the symptom of cerebral malaria is duration of survival, and treating the symptom comprises increasing duration of survival as compared to an untreated patient in need thereof.

Assignees

• Regeneron Pharma

Inventors

• Thurston Gavin
• Daly Christopher
• Ngambo Lisa Purcell

Classifications

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · 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