Mammalian receptors as targets for antibody and active vaccination therapy against mold infections

• US 9,259,467 B2
• Filed: 12/23/2013
• Issued: 02/16/2016
• Est. Priority Date: 09/01/2009
• Status: Active Grant

• Current Assignee: Los Angeles Biomedical Research Institute At Harbor-Ucla Medical Center (University of California)
• Original Assignee: Los Angeles Biomedical Research Institute At Harbor-Ucla Medical Center (University of California)
• Inventors: Ibrahim, Ashraf S., Liu, Mingfu, Spellberg, Brad, Filler, Scott, Fu, Yue, Edwards, John E.
• Primary Examiner(s): Devi, S.
• Application Number:
  US14/139,683
• Publication Number:
  US 20140112941A1
• Time in Patent Office: 785 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 39/0002 Fungal antigens, e.g. Trichophyton, Aspergillus, Candida
• CPC Class Codes: A61K 39/0005 Vertebrate antigens from snakes A61K39/38
• CPC Class Codes: A61K 39/39575 against materials from other living beings excluding bacteria and viruses, e.g. protozoa, fungi, plants
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: C07K 16/14 against material from fungi, algea or lichens
• 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
• CPC Class Codes: C07K 2317/77 Internalization into the cell
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/531 Stem-loop; Hairpin
• CPC Class Codes: C12N 2799/027 where the vector is derived from a retrovirus
• CPC Class Codes: C12N 2799/06 in vitro

Abstract

The present invention provides therapeutic compositions and methods for treating and preventing fungal disease or conditions including mucormycosis. The therapeutic methods and compositions of the invention include antibody, antibody fragment, siRNA and vaccine compositions having or directed against a GRP78 polypeptide or an antigenic fragment of the polypeptide.

Claims

1. A method of treating mucormycosis comprising administering to a human subject having mucormycosis a composition, wherein the composition comprises a therapeutically effective amount of an isolated antibody or an antibody fragment thereof that specifically binds the human glucose-regulated protein, 78 kD polypeptide (GRP78) or an antigenic fragment thereof in said human subject, wherein said mucormycosis is caused by a Rhizopus species.

2. The method of claim 1, wherein said Rhizopus species is Rhizopus oryzae.

3. The method of claim 1, wherein the human subject is immunocompromised.

4. The method of claim 1, wherein the human subject is suffering from diabetes mellitus.

5. The method of claim 1, wherein the human subject is suffering from diabetic ketoacidosis.

6. The method of claim 1, wherein the human subject is suffering from trauma.

7. The method of claim 1, wherein the antibody or the antibody fragment thereof blocks the GRP78 and abrogates endocytosis of the Rhizopus species by endothelial cells expressing the GRP78 in said human subject.

8. The method of claim 1, wherein the antibody is a monoclonal antibody, or the antibody fragment is a fragment of said monoclonal antibody.

9. The method of claim 1, wherein the antibody is a humanized monoclonal antibody, or the antibody fragment is a fragment of said humanized monoclonal antibody.