Abstract: There is provided a plasmid system for transfection into a cell to create a producer cell, the system comprising: a. a helper plasmid comprising a first nucleotide sequence encoding Murine leukemia virus (MLV)-derived Gag and Pol poly-proteins; b. an envelope plasmid comprising a second nucleotide sequence encoding an Env protein; c. a genome plasmid comprising a third nucleotide sequence encoding a retroviral genome, wherein the first nucleotide sequence is codon-shuffled to remove any significant regions of homology with the third nucleotide sequence; and wherein the second nucleotide sequence is codon-optimised for expression in the producer cell.

Abstract: The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.

Abstract: The present invention provides a method of preparing a population of genetically modified cells which comprise a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR) comprising: providing a starting population of cells; depleting said starting population of cells which express a target antigen; and introducing into a cell in the depleted starting population a nucleic acid sequence which encodes a CAR or transgenic TCR against the target antigen. The present invention also provides genetically modified cells, pharmaceutical compositions and pharmaceutical compositions for use in the treatment and/or prevention of disease.

Abstract: The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.

Abstract: The present invention provides a kit of vectors comprising a first and second viral vector, wherein the first viral vector comprises a transgene of interest (TOI), and presence of the second viral vector in a host cell is required for integration of the first viral vector TOI into the host cell genome.

Abstract: The present invention provides methods of reducing the levels of a titratable selectable pressure required, the number of amplification cycles, and the time taken to generate protein expressing cell lines by altering the codons of the desired open-reading-frames. Through the use of codon adaptation for this purpose the methods of the invention consistently provide sufficient yields in faster time frames saving many weeks in cell line development activities. Furthermore the methods of the invention also generate cell lines with lower concentrations of selection and amplification agent than previously achievable. Accordingly lower levels of selection and amplification marker in the final cells lines are observed.

Abstract: The present invention provides a method of preparing a population of genetically modified cells which comprise a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR) comprising: providing a starting population of cells; depleting said starting population of cells which express a target antigen; and introducing into a cell in the depleted starting population a nucleic acid sequence which encodes a CAR or transgenic TCR against the target antigen. The present invention also provides genetically modified cells, pharmaceutical compositions and pharmaceutical compositions for use in the treatment and/or prevention of disease.

Abstract: The present invention provides a retroviral or lentiviral vector having a viral envelope which comprises a mitogenic T-cell activating transmembrane protein which comprises: (i) a mitogenic domain which binds a mitogenic tetraspanin, and (ii) a transmembrane domain; wherein the mitogenic T-cell activating transmembrane protein is not part of a viral envelope glycoprotein. When cells such as T-cells or Natural Killer cells are transduced by such a viral vector, they are activated by the mitogenic T-cell activating transmembrane protein.

Abstract: The invention provides methods for the rapid identification and selection of cell lines suitable for biopharmaceuticals production, which do no utilize animal derived components.

Abstract: The present invention provides methods of reducing the levels of a titratable selectable pressure required, the number of amplification cycles, and the time taken to generate protein expressing cell lines by altering the codons of the desired open-reading-frames. Through the use of codon adaptation for this purpose the methods of the invention consistently provide sufficient yields in faster time frames saving many weeks in cell line development activities. Furthermore the methods of the invention also generate cell lines with lower concentrations of selection and amplification agent than previously achievable. Accordingly lower levels of selection and amplification marker in the final cells lines are observed.

Abstract: The present invention provides methods of reducing the levels of a titratable selectable pressure required, the number of amplification cycles, and the time taken to generate protein expressing cell lines by altering the codons of the desired open-reading-frames. Through the use of codon adaptation for this purpose the methods of the invention consistently provide sufficient yields in faster time frames saving many weeks in cell line development activities. Furthermore the methods of the invention also generate cell lines with lower concentrations of selection and amplification agent than previously achievable. Accordingly lower levels of selection and amplification marker in the final cells lines are observed.

Abstract: The present invention provides novel antigen-binding proteins derived from human germline VH domains, having improved expression and improved biophysical characteristics.

Abstract: The invention provides methods for the rapid identification and selection of cell lines suitable for biopharmaceuticals production, which do no utilize animal derived components.

Abstract: The present invention provides methods of reducing the levels of a titratable selectable pressure required, the number of amplification cycles, and the time taken to generate protein expressing cell lines by altering the codons of the desired open-reading-frames. Through the use of codon adaptation for this purpose the methods of the invention consistently provide sufficient yields in faster time frames saving many weeks in cell line development activities. Furthermore the methods of the invention also generate cell lines with lower concentrations of selection and amplification agent than previously achievable. Accordingly lower levels of selection and amplification marker in the final cells lines are observed.

Abstract: A method of producing a replication defective retrovirus comprising transfecting a producer cell with the following: iii) a retroviral genome; iv) a nucleotide sequence coding for retroviral gag and pot proteins; and iii) nucleotide sequences encoding other essential viral packaging components not encoded by the nucleotide sequence of (ii); characterised in that the nucleotide sequence coding for retroviral gag and pot proteins is codon optimised for expression in the producer cell.

Abstract: A method of producing a replication defective retrovirus comprising transfecting a producer cell with the following: iii) a retroviral genome; iv) a nucleotide sequence coding for retroviral gag and pol proteins; and iii) nucleotide sequences encoding other essential viral packaging components not encoded by the nucleotide sequence of (ii); characterised in that the nucleotide sequence coding for retroviral gag and pol proteins is codon optimised for expression in the producer cell.

Abstract: A selection system suitable for use in vivo is provided, the system comprising: I) a plurality of first nucleotide sequences encoding a gene product capable of binding to and effecting the cleavage, directly or indirectly, of a nucleotide sequence, or a transcription product thereof; wherein a region of the first nucleotide sequence required for binding to the nucleotide sequence is heterogeneous within the plurality of first nucleotide sequences; and ii) a second nucleotide sequence comprising: (a) a coding region encoding a detectable marker operably linked to sequences required for mRNA stability and/or translation; and (b) a third nucleotide sequence positioned between the coding region and at least one of the sequences required for mRNA stability and/or translation; wherein (a) and (b) are operably linked to a regulatory sequence capable of directing expression of (a) and (b) as a contiguous RNA molecule in a host cell; and wherein the first nucleotide sequence encoding a gene product is capable of bindi

Abstract: Provided herein are methods for producing a replication defective retrovirus, which comprises transfecting a producer cell with (1) a retroviral genome; (2) a nucleotide sequence coding for retroviral gag and pol proteins that is codon-optimized for expression in the producer cell; and (3) nucleotide sequences encoding other essential viral packaging components not encoded by the nucleotide sequence of (1).

Abstract: A selection system suitable for use in vivo is provided, the system comprising: I) a plurality of first nucleotide sequences encoding a gene product capable of binding to and effecting the cleavage, directly or indirectly, of a nucleotide sequence, or a transcription product thereof; wherein a region of the first nucleotide sequence required for binding to the nucleotide sequence is heterogeneous within the plurality of first nucleotide sequences; and ii) a second nucleotide sequence comprising: (a) a coding region encoding a detectable marker operably linked to sequences required for mRNA stability and/or translation; and (b) a third nucleotide sequence positioned between the coding region and at least one of the sequences required for mRNA stability and/or translation; wherein (a) and (b) are operably linked to a regulatory sequence capable of directing expression of (a) and (b) as a contiguous RNA molecule in a host cell; and wherein the first nucleotide sequence encoding a gene product is capable of bindi