Abstract

The present invention relates to an alphavirus RNA replicase coding sequence, an optimized self-amplifying nucleic acid molecule, a pharmaceutical composition, and a use. The optimized self-amplifying nucleic acid molecule is a self-amplifying nucleic acid molecule comprising the alphavirus RNA replicase coding sequence, a tissue-specific self-amplifying nucleic acid molecule, or an improved self-amplifying mRNA comprising a mutated replicase; and the mutated replicase comprises a mutated macro domain. The present invention further relates to a preparation method for the self-amplifying nucleic acid molecule.

IPC Classes  ?

• C12N 15/54 - Transferases (2)
• C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
• C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61P 35/00 - Antineoplastic agents

Abstract

Provided herein is a lipid compound that can be used in combination with other lipid components such as a neutral lipid, cholesterol, and a polymer-bound lipid to form a lipid nanoparticle for the delivery of a therapeutic agent (e.g. a nucleic acid molecule), thereby achieving therapeutic or preventive purposes, including vaccination. Further provided herein is a lipid nanoparticle composition containing the lipid compound.

IPC Classes  ?

• C07J 41/00 - Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
• A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
• A61K 47/28 - Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
• A61K 9/51 - Nanocapsules
• B82Y 5/00 - Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

A pharmaceutical combination where a checkpoint inhibitor is combined with a recombinant oncolytic virus and the use of said combination for the treatment of cancer.

IPC Classes  ?

• A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
• A61K 35/768 - Oncolytic viruses not provided for in groups
• A61K 39/00 - Medicinal preparations containing antigens or antibodies

Abstract

Compositions and methods are provided for eliciting an immune response in a subject, by (a) administering to a subject a first vaccine, wherein the first vaccine includes a macromolecule or an oncolytic virus capable of inducing an immune response in a subject, and (b) administering a second vaccine, wherein the second vaccine includes an oncolytic virus. Within preferred embodiments of the invention the immune response is used to treat a patient having cancer.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/12 - Viral antigens
• A61K 39/02 - Bacterial antigens
• C12N 15/869 - Herpesviral vectors
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 35/00 - Antineoplastic agents

Abstract

Compositions and methods are provided for eliciting an immune response in a subject, by (a) administering to a subject a first vaccine, wherein the first vaccine includes a macromolecule or an oncolytic virus capable of inducing an immune response in a subject, and (b) administering a second vaccine, wherein the second vaccine includes an oncolytic virus. Within preferred embodiments, the immune response is used to treat a patient having cancer.

IPC Classes  ?

• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• A61K 39/12 - Viral antigens
• A61K 39/02 - Bacterial antigens
• C12N 15/869 - Herpesviral vectors
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• A61P 35/00 - Antineoplastic agents

Abstract

A nucleic acid molecule, kit and method for detecting a monkey pox virus. The nucleic acid molecule comprises primer molecules having nucleic acid sequences as shown in SEQ ID NO: 5-6 and a probe molecule optionally having a nucleic acid sequence as shown in SEQ ID NO: 7.

IPC Classes  ?

• C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
• C12Q 1/686 - Polymerase chain reaction [PCR]
• C12N 15/11 - DNA or RNA fragmentsModified forms thereof
• C12R 1/93 - Animal viruses

Abstract

Provided in the present application is a method for preparing a nucleic acid-encapsulation body complex, comprising introducing a nucleic acid into an empty encapsulation body by means of a mode selected from microfluidic mixing and oscillation mixing, so as to obtain a nucleic acid-encapsulation body complex capable of being directly administrated to subjects. Also provided in the present application is a device for preparing a nucleic acid-encapsulation body complex, comprising: a micro-fluidic chip, more than one first feeding containers, more than one second feeding containers and a collection container. Further provided in the present application is a method for preparing a nucleic acid-encapsulation body complex, comprising: in a microfluidic mixing mode, encapsulating a nucleic acid with an encapsulant capable of being self-assembled into an encapsulation body capable of encapsulating the nucleic acid, so as to obtain the nucleic acid-encapsulation body complex capable of being directly administrated to subjects.

IPC Classes  ?

• A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
• C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
• A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
• B01F 33/301 - Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions

Abstract

A messenger ribonucleic acid (mRNA) molecule, comprising: an expression cassette 1 containing a coding sequence of RNA replicase, and an expression cassette 2 containing a coding sequence of an antigen. Further provided are a mRNA vaccine, which is obtained by encapsulating the mRNA molecule into lipid nanoparticles (LNPs); a DNA molecule, which can be transcribed into the mRNA molecule; and the use of the mRNA molecule in preparing a mRNA vaccine capable of eliciting an anti-HER2 immune response. Further provided is a method for preparing the mRNA molecule, comprising: (1) on the basis of the DNA sequence of the genome of a virus, replacing in a coding sequence of a structural polyprotein the moiety following the promoter of the structural polyprotein with the coding sequence of the antigen; (2) adding a promoter site of RNA polymerase to the 5'-end of 5'-UTR; (3) adding poly-A to the 3'-end of 3'-UTR; and (4) transcribing into a mRNA molecule the DNA molecule constructed by steps (1)-(3).

IPC Classes  ?

• C12N 15/86 - Viral vectors
• C07K 14/71 - ReceptorsCell surface antigensCell surface determinants for growth factorsReceptorsCell surface antigensCell surface determinants for growth regulators
• C12N 15/12 - Genes encoding animal proteins
• A61K 38/04 - Peptides having up to 20 amino acids in a fully defined sequenceDerivatives thereof
• A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
• A61K 35/76 - VirusesSubviral particlesBacteriophages
• A61K 39/00 - Medicinal preparations containing antigens or antibodies
• C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof

Abstract

Immunogenic proteins are provided which have been derived from a strain of HPV which causes or is associated with causing cancer, which are mutated so that they do not cause increased cell proliferation. In various embodiments, the immunogenic protein is derived (e.g., mutated) from an HPV strain such as HPV 16, 18, 31, 33,35, 39, 45, 51, 52, 56, 58, 59, 66 or 68. Also provided are compositions (e.g., mRNA compositions) encoding such immunogenic proteins, as well as method for treating and preventing HPV infections.

IPC Classes  ?

• A61K 39/12 - Viral antigens
• C07K 16/08 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from viruses
• A61P 35/00 - Antineoplastic agents
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
• C12N 15/62 - DNA sequences coding for fusion proteins

Abstract

Immunogenic proteins are provided which have been derived from a strain of HPV which causes or is associated with causing cancer, which are mutated so that they do not cause increased cell proliferation. Within various embodiments of the invention the immunogenic protein is derived (e.g., mutated) from an HPV strain such as HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 or 68. Also provided are compositions (e.g., mRNA compositions) encoding such immunogenic proteins, as well as method for treating and preventing HPV infections.

IPC Classes  ?

• C12N 15/62 - DNA sequences coding for fusion proteins
• C07K 19/00 - Hybrid peptides
• A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy

Abstract

The present invention relates to an anti-poxvirus vaccine, which comprises an mRNA molecule encoding the following proteins and/or fusion proteins: (a) more than one monkey poxvirus protein selected from the following: an A35R protein, an M1R protein, a B6R protein, and an A29L protein, and/or (b) a fusion protein formed by fusing two or more monkey poxvirus proteins or parts of proteins selected from the following: an A35R protein, an M1R protein, a B6R protein, and an A29L protein. The present invention also relates to a kit for preparing the anti-poxvirus vaccine, which comprises: (i) a DNA molecule encoding the described protein and/or fusion protein, and optionally (ii) a reagent for transcribing the DNA molecule of (i) into an mRNA molecule. The present invention also relates to a DNA molecule or mRNA molecule encoding the described protein and fusion protein.

IPC Classes  ?

• A61K 39/275 - Poxviridae, e.g. avipoxvirus
• A61K 9/51 - Nanocapsules
• C12N 15/39 - Poxviridae, e.g. vaccinia virus, variola virus
• C12N 15/62 - DNA sequences coding for fusion proteins
• A61P 31/20 - Antivirals for DNA viruses

Abstract

An HSV vector with ICP27 under control of CXCR4 promoter and miRNA-223/125b and ICP34.5 under control of miRNA-124/143, and deletion of one RL and one RS region of the viral genome. Within optional embodiments the mutation is a deletion containing the second copy of the ICP34.5 gene. The HSV vector also incorporates a virus-expressed cytokine cassette encoding IL-12, IL-15/1 L-15RA under the control of CMV promoter.

IPC Classes  ?

• C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
• A61K 35/763 - Herpes virus
• A61P 35/00 - Antineoplastic agents
• C12R 1/93 - Animal viruses

Abstract

An HSV vector with ICP27 under control of CXCR4 promoter and miRNA-223/125b and ICP34.5 under control of miRNA-124/143, and deletion of one RL and one RS region of the viral genome. Within optional embodiments the mutation is a deletion containing the second copy of the ICP34.5 gene. The HSV vector also incorporates a virus-expressed cytokine cassette encoding IL-12, IL-15/IL-15RA under the control of CMV promoter.

IPC Classes  ?

• C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
• C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
• A61K 35/763 - Herpes virus
• A61P 35/00 - Antineoplastic agents
• C12R 1/93 - Animal viruses

Abstract

Recombinant multivalent proteins are provided having two or more angiotensin-converting enzyme 2 (ACE2) fragments and a human immunoglobin Fc domain, wherein the ACE2 fragments are capable of binding to a coronavirus. Within one embodiment the human immunoglobin Fc domain has an N-terminal flexible hinge region which is joined to the C-terminal ends of a first and a second of the two or more ACE2 fragments. Also provided are expression vectors and host cells for producing the recombinant multivalent proteins, as well as pharmaceutical compositions comprising recombinant multivalent proteins, and methods of using the same (e.g., for the treatment and/or prevention of coronavirus infections).

IPC Classes  ?

• C12N 9/48 - Hydrolases (3.) acting on peptide bonds, e.g. thromboplastin, leucine aminopeptidase (3.4)
• G01N 33/573 - ImmunoassayBiospecific binding assayMaterials therefor for enzymes or isoenzymes
• G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
• G01N 33/569 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses

Abstract

Recombinant multivalent proteins are provided having two or more angiotensin-converting enzyme 2 (ACE2) fragments and a human immunoglobin Fc domain, wherein the ACE2 fragments are capable of binding to a coronavirus. Within one embodiment the human immunoglobin Fc domain has an N-terminal flexible hinge region which isjoined to the C-terminal ends of a first and a second of the two or more ACE2 fragments. Also provided are expression vectors and host cells for producing the recombinant multivalent proteins, as well as pharmaceutical compositions comprising recombinant multivalent proteins, and methods of using the same (e.g., for the treatment and/or prevention of coronavirus infections).

IPC Classes  ?

• C07K 19/00 - Hybrid peptides
• C12N 15/62 - DNA sequences coding for fusion proteins
• A61K 38/48 - Hydrolases (3) acting on peptide bonds (3.4)
• A61P 31/14 - Antivirals for RNA viruses