Abstract

The invention relates to a pharmaceutical formulation comprising at least three recombinant transgene expressing Newcastle Disease Virus (NDV) strains, which have been demonstrated to possess significant oncolytic activity against mammalian cancers and an improved safety profile, a non-recombinant NDV strain, a reovirus type-3 and optionally a vaccinia virus. At least one of the recombinant NDV strains comprises in its viral genome a nucleic acid sequence comprising at least one foreign gene, the at least one foreign gene encoding a checkpoint modulator, and at least one of the recombinant NDV strains comprises in its viral genome a nucleic acid sequence comprising at least one foreign gene, the at least one foreign gene encoding an angiogenesis inhibitor. The viral genome of each of the at least three recombinant NDV strains comprises a mutation in the HN gene, said mutation allowing replication of said rgNDV in a cancer cell to a higher level than replication of an otherwise identical NDV not having said mutation in the HN gene. The pharmaceutical formulation provides an improved treatment of cancer, because instead of a monotherapy, a mixture of oncolytic viruses is applied.

IPC Classes  ?

• A61K 35/768 - Oncolytic viruses not provided for in groups

Abstract

The invention relates to a novel Newcastle Disease Viruses (NDV) and transgene expressing Newcastle Disease Viruses (NDV), which have been demonstrated to possess significant oncolytic activity against mammalian cancers and an improved safety profile. The invention provides novel oncolytic viruses through the use of genetic engineering, including the transfer of foreign genes or parts thereof. The present invention also provides nucleic acids encoding a reverse genetically engineered (rg-)NDV comprising one or more of these foreign genes and having a mutation in the HN gene, said mutation allowing replication of said rgNDV in a cancer cell to a higher level than replication of an otherwise identical rgNDV not having said mutation in the HN gene, as well as a mutation in the F gene, said mutation resulting in a reduced ICPI value as compared to an otherwise identical rgNDV not having said at least one mutation in the F gene.

IPC Classes  ?

• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 14/125 - Newcastle disease virus
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 7/02 - Recovery or purification

Abstract

The invention relates to transgene expressing Newcastle Disease Viruses (NDV), which have been demonstrated to possess significant oncolytic activity against mammalian cancers and/or an improved safety profile. The invention provides novel oncolytic viruses through the use of genetic engineering, including the transfer of foreign genes or parts thereof, such as genes encoding Atezolizumab or Bevacizumab. The present invention also provides nucleic acids encoding a reverse genetically engineered (rg-)NDV comprising one or more of these foreign genes and having a mutation in the HN gene, said mutation allowing replication of said rgNDV in a cancer cell to a higher level than replication of an otherwise identical rgNDV not having said mutation in the HN gene.

IPC Classes  ?

• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• C07K 14/125 - Newcastle disease virus
• C07K 16/22 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors
• C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 7/02 - Recovery or purification
• C12N 15/86 - Viral vectors

Abstract

The invention relates to transgene expressing Newcastle Disease Viruses (NDV), which have been demonstrated to possess significant oncolytic activity against mammalian cancers. The invention provides novel oncolytic viruses through the use of genetic engineering, including the transfer of foreign genes or parts thereof, such as genes encoding Ipilimumab, interleukin-12 or NS1. The present invention also provides nucleic acids encoding a reverse genetically engineered (rg-)NDV comprising one or more of these foreign genes and having a mutation in the HN gene, said mutation allowing replication of said rgNDV in a cancer cell to a higher level than replication of an otherwise identical rgNDV not having said mutation in the HN gene.

IPC Classes  ?

• A61K 35/768 - Oncolytic viruses not provided for in groups
• C07K 14/125 - Newcastle disease virus
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
• C12N 7/02 - Recovery or purification
• C12N 15/86 - Viral vectors