Multigenome retroviral vector preparations and methods and systems for producing and using same

Inventors

Ter Meulen, Jan Henrik • BERGLUND, Peter Lars Aksel

Assignees

Immune Design Corp

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Publication Number

US-10584356-B2

Patent

Publication Date

2020-03-10

Expiration Date


Abstract

The present invention provides novel multigenome retroviral vectors, methods and packaging systems for making such retroviral vectors and methods of use.

Core Innovation

The patent discloses a recombinant multigenome retroviral vector preparation that comprises multiple retroviral particles carrying distinct retroviral vector genomes within a single preparation. A first retroviral particle includes two copies of a first retroviral vector genome encoding a first heterologous protein sequence of interest, and a second retroviral particle includes two copies of a second retroviral vector genome encoding a second heterologous protein sequence of interest. The preparation also includes a third retroviral particle that comprises one copy of the first retroviral vector genome and one copy of the second retroviral vector genome, wherein the first and second sequences of interest are different.

The sequences of interest encode heterologous proteins selected from a tumor antigen, neoantigen, infectious disease antigen, immunomodulatory molecule, chimeric antigen receptor, recombinant T cell receptor, and immunoglobulin antigen-binding domain. The preparation is pseudotyped with a heterologous envelope glycoprotein. The patent also describes packaging-system configurations that provide pseudotyped multigenome retroviral vector preparations from nucleic acid molecules encoding an envelope protein, gag and pol proteins, rev, and retroviral vector genomes encoding different sequences of interest.

The patent describes multigenome packaging system arrangements that include at least two nucleic acid molecules each comprising a retroviral vector genome with a unique sequence of interest encoding one of the listed heterologous protein categories. The system further includes one or more nucleic acid molecules encoding components necessary to generate pseudotyped retroviral vector particles and optionally a nucleic acid molecule encoding vpx, together with a packaging cell line.

Claims Coverage

The partial content includes three independent claims, covering a recombinant multigenome retroviral vector preparation, a retroviral vector packaging system, and a multigenome retroviral vector packaging system. The independent claims enumerate three inventive features centered on distinct sequences of interest and pseudotyped multigenome particle compositions.

Recombinant multigenome retroviral vector preparation with different heterologous sequences pseudotyped with a heterologous envelope glycoprotein

The preparation includes a first retroviral particle comprising two copies of a first retroviral vector genome encoding a first sequence of interest; a second retroviral particle comprising two copies of a second retroviral vector genome encoding a second sequence of interest; and a third retroviral particle comprising one copy of the first retroviral vector genome and one copy of the second retroviral vector genome, wherein the first and second sequences of interest are different, and wherein the retroviral vector preparation is pseudotyped with a heterologous envelope glycoprotein.

Retroviral vector packaging system providing pseudotyped multigenome retroviral vector preparation

The system comprises a first nucleic acid molecule encoding a viral envelope protein; a second nucleic acid molecule encoding gag and pol proteins; a third nucleic acid molecule encoding rev; a fourth nucleic acid molecule comprising a first retroviral vector genome encoding a first sequence of interest; a fifth nucleic acid molecule comprising a second retroviral vector genome encoding a second sequence of interest; optionally a sixth nucleic acid molecule encoding vpx; and a packaging cell or cell line.

Multigenome retroviral vector packaging system with at least two unique genome-encoding nucleic acids and pseudotyped particle components

The system comprises at least two nucleic acid molecules each comprising a retroviral vector genome comprising a unique sequence of interest; one or more nucleic acid molecules encoding components necessary to generate pseudotyped retroviral vector particles; optionally a nucleic acid molecule encoding vpx; and a packaging cell line.

Across the independent claims, the core coverage centers on multigenome retroviral vector preparations and corresponding packaging systems that combine distinct retroviral vector genomes encoding different heterologous protein sequences of interest, and that generate pseudotyped retroviral vector particles using nucleic acids for envelope and other required components, optionally including vpx, in a packaging cell or packaging cell line.

Stated Advantages

Documented Applications

No documented applications found

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