COMPOSITIONS AND METHODS FOR INHIBITING VIRAL ENTRY

• US 20150297677A1
• Filed: 12/12/2013
• Published: 10/22/2015
• Est. Priority Date: 12/13/2012
• Status: Active Grant

• Current Assignee: Children's Medical Center Corporation, Dana-Farber Cancer Institute
• Original Assignee: Children's Medical Center Corporation
• Inventors: Umetsu, Dale T., Freeman, Gordon J., Choe, Hyeryun, Jemielity, Stephanie, De Kruyff, Rosemarie H.
• Granted Patent: US 11,116,818 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/685 one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 38/1774 Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
• CPC Class Codes: A61K 45/00 Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07K 14/70503 Immunoglobulin superfamily
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/30 Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/17 Immunomodulatory nucleic acids
• CPC Class Codes: C12N 2310/531 Stem-loop; Hairpin

Abstract

The invention provides methods, compositions, and kits featuring agents that inhibit viral entry mediated by T-cell Immunoglobulin and Mucin-domain containing proteins (TIM proteins) and other phosphatidylserine receptors.

Claims

1. A method for treating or preventing a virus infection in a subject, comprising administering to the subject an effective amount of an agent that inhibits viral entry.

3. The method of claim 1, wherein the agent inhibits viral entry via a T-cell Immunoglobulin and Mucin-domain containing protein (TIM protein) or phosphatidylserine receptor.

4. The method of claim 3, wherein the TIM protein is selected from the group consisting of hTIM1, hTIM3, and hTIM4.

5. The method of claim 1, wherein the agent is an inhibitory nucleic acid molecule that is complementary to at least a portion of a TIM protein.

6. The method of claim 5, wherein the inhibitory nucleic acid molecule is selected from the group consisting of an antisense molecule, an siRNA, and an shRNA.

7. The method of claim 1, wherein the agent is an antibody or fragment thereof that selectively binds to a TIM protein.

8. The method of claim 7, wherein the antibody is a monoclonal or polyclonal antibody.

9. The method of claim 1, wherein the agent is an exogenous TIM protein or fragment thereof

10. The method of claim 1, wherein the agent is 1,2-diacyl-sn-glycero-3-phospho-L-serine (PS) or 1,2-diacyl-sn-glycero-3-phosphoethanolamine (PE).

11. The method of claim 1, wherein the agent is administered in one or more doses.

12. The method of claim 11, wherein the agent is administered at one, two, three, four, five, six, seven, or eight week intervals.

13. The method of claim 1, wherein the agent reduces viral entry by at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100%.

14. The method of claim 1, wherein the administration of the agent protects the subject against viremia or the inflammatory consequences of a viral infection.

15. The method of claim 1, wherein the administration of the agent protects the subject or cell from lethality.

16. The method of claim 1, wherein the virus is an enveloped virus

17. The method of claim 1, wherein the enveloped virus is an alphavirus, flavivirus, filovirus, or arenavirus.

18. The method of claim 17, wherein the virus is selected from the group consisting of Ebola virus (EBOV), Marburg virus (MARY), Amapari virus (AMAV), Tacaribe virus (TCRV), Junin virus (JUNV), Machupo virus (MACV), Chikungunya virus (CHKV), Eastern equine encephalitis virus (EEEV), Dengue virus (DENY), West Nile virus (WNV), Sinbis virus (SINN) or Ross River virus (RRV).

2. A method for treating or preventing viral entry of a cell, comprising contacting the cell with an effective amount of an agent that inhibits viral entry.

19. A kit comprising an agent that inhibits viral entry, and directions for the use of said agent to treat or prevent viral infection in a subject.

20. The kit of claim 19, wherein the agent inhibits viral entry via a T-cell Immunoglobulin and Mucin-domain containing protein (TIM protein) or phosphatidylserine receptor.

21-35. -35. (canceled)