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US-20260124288-A1 - NOVEL VSV VIRUS FORMULATIONS

US20260124288A1US 20260124288 A1US20260124288 A1US 20260124288A1US-20260124288-A1

Abstract

Described herein are novel compositions comprising a virus or viral vector that may express viral glycoproteins, and methods of treatment using the same.

Inventors

  • Rockey BANDLISH
  • Ryan Paul DUFFIN
  • Amish Patel
  • Christopher POON

Assignees

  • EMERGENT PRODUCT DEVELOPMENT GAITHERSBURG INC.

Dates

Publication Date
20260507
Application Date
20231004

Claims (20)

  1. 1 .- 20 . (canceled)
  2. 22 .- 50 . (canceled)
  3. 51 . A pharmaceutical composition comprising: (a) about 5% to about 40% of one or more sugars; (b) about 50 mM to about 600 mM of one or more amino acids; (c) about 0.1 g/L to about 15 g/L of one or more protein; and (d) a virus or viral vector.
  4. 52 . The composition of claim 51 , wherein the virus or viral vector is a Rhabdovirus vector.
  5. 53 . The composition of claim 51 , wherein the virus or viral vector is a Vesicular Stomatitis Virus (VSV) vector.
  6. 54 . The composition of claim 51 , wherein the virus or vector does not encode a homologous viral glycoprotein or fragment thereof.
  7. 55 . The composition of claim 51 , wherein the vector encodes a heterologous viral transgene.
  8. 56 . The composition of claim 55 , wherein the heterologous viral transgene is a Lassa virus transgene, a Ebola virus transgene, a Sudan virus transgene or a Marburg virus transgene.
  9. 57 . The composition of claim 55 , wherein the heterologous viral transgene is located at position of 1 of the viral genome.
  10. 58 . The composition of claim 56 , wherein a nucleocapsid N gene is located at position 4 of the viral genome.
  11. 59 . The composition of claim 56 , wherein the heterologous Lassa virus transgene encodes a Lassa virus glycoprotein or fragment thereof.
  12. 60 . The composition of claim 56 , wherein the heterologous Lassa virus transgene encodes a Lassa virus immunogen.
  13. 61 . The composition of claim 55 , wherein the heterologous viral transgene is a Marburg virus transgene.
  14. 62 . The composition of claim 61 , wherein the heterologous Marburg virus transgene encodes a Marburg virus glycoprotein or fragment thereof.
  15. 63 . The composition of claim 61 , wherein the heterologous Marburg virus transgene encodes a Marburg virus immunogen.
  16. 64 . The composition of claim 55 , wherein the heterologous viral transgene is an Ebola virus transgene.
  17. 65 . The composition of claim 64 , wherein the heterologous Ebola virus transgene encodes an Ebola virus glycoprotein or fragment thereof.
  18. 66 . The composition of claim 64 , wherein the heterologous Ebola virus transgene encodes a Sudan virus immunogen.
  19. 67 . The composition of claim 55 , wherein the heterologous viral transgene is a Sudan virus transgene.
  20. 68 . The composition of claim 67 , wherein the heterologous Sudan virus transgene encodes a Sudan virus glycoprotein or fragment thereof.

Description

TECHNICAL FIELD Described herein are novel compositions comprising a Vesicular stomatitis virus (VSV) or VSV viral vectors that may express viral glycoproteins, and methods of treatment using the same. BACKGROUND OF THE INVENTION Vesicular stomatitis virus (VSV), a member of the Rhabdoviridae family, has shown increasing promise as a cancer therapeutic (Cook et al. Blood Adv (2022) 6 (11): 3268-3279) and in live vaccine development as a viral vector. It is an enveloped, single-stranded RNA virus with a simple genome encoding a nucleocapsid, phosphoprotein, matrix protein, glycoprotein, and a large polymerase. Genetic manipulation of VSV makes it suitable for therapeutic and vaccine uses e.g., transgenes may be inserted in the VSV genome and the native glycoprotein may be replaced by the desired antigen. The VSV virus or VSV viral vector may by attenuated, e.g., limiting replication and decreasing its already low pathogenicity in humans. Expression of antigens on the surface of the viral particle allows stimulation of an immune response for long-term immunity. VSV vectors have the ability to produce significant amounts of viral particles, and a low seroprevalence in humans due to the natural host being livestock and insects. Viral hemorrhagic fever is prevalent in Africa, and may be caused by several viruses. Lassa fever is a viral hemorrhagic disease that is prevalent in West Africa. Mainly found in Sierra Leone, Liberia, Guinea, and Nigeria, there is an increasing worry of spread to other countries. Lassa virus (LASV) belongs to the Arenaviridae family and is an enveloped, single-stranded, bipartite RNA virus that typically spreads to humans through exposure to its rodent host reservoir. Secondary transmission from person-to-person has also been identified in close contact dwellings or health care settings where infection control practices are limited. Lassa virus (LASV) has an incubation period of 2 to 21 days with hospitalization rates of approximately 15% and a 1% fatality rate. Most infected are asymptomatic (˜80%) but those displaying symptoms may have fever, malaise, chest pain, sore throat, cough, difficulty breathing, and abdominal distress such as cramps, vomiting, or diarrhea. Those with severe manifestations may exhibit bleeding from mucosal surfaces, pleural and pericardial effusion, seizures, and unconsciousness. Individuals most susceptible to severe or fatal LASV are children and pregnant women. The greatest risk of getting the disease still results from rodent exposure such as households having a large numbers of rats or poor sanitary conditions often found in rural areas and migrant/refugee camps. In addition to LASV, Marburg virus (MARV) and Ebola virus (EBOV) belong to the Filoviridae family and are single-stranded negative sense RNA viruses that cause severe hemorrhagic fever. Sudan virus (SUDV) is a species of EBOV. Transmission of these viruses is believed to occur via fruit bats, infected animals or humans. Symptoms of infection may include muscle aches, weakness, diarrhea, vomiting, and in some cases, severe bleeding and may result in a high mortality rate. One remaining challenge related to VSV based vectors/vaccines, however, is stability. To this end, this disclosure addresses the need for a stable VSV based viral vaccine/vector formulation, e.g., a VSV based vaccine for viral hemorrhagic fever. INCORPORATION BY REFERENCE All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference with regard to their background teachings to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. SUMMARY OF THE INVENTION One embodiment described herein is a pharmaceutical composition comprising: (a) one or more sugars; (b) one or more amino acids; (c) one or more proteins; and (d) a virus or viral vector. In one aspect, the virus or viral vector is a Rhabdovirus vector. In one aspect, the virus or viral vector is a Vesicular Stomatitis Virus (VSV) vector. In another aspect, the virus or vector does not encode a homologous viral glycoprotein or fragment thereof. In one aspect, the vector encodes a heterologous viral transgene. In one aspect, the heterologous viral transgene is a Lassa virus transgene, a Ebola virus transgene, a Sudan virus transgene or a Marburg virus transgene. In other aspects, the heterologous viral transgene is located at position of 1 of the viral genome. In one aspect, a nucleocapsid N gene is located at position 4 of the viral genome. In other aspects, the heterologous Lassa virus transgene encodes a Lassa virus glycoprotein or fragment thereof. In one aspect, the heterologous Lassa virus transgene encodes a Lassa virus immunogen. In one aspect, the heterologous viral transgene is a Marburg virus transgene. In one aspect, the heterologous Marburg virus transgene encodes a Marburg virus glycoprotein or fragment ther