Control of trace metals during production of anti-CD38 antibodies
AssigneeJanssen Biotech, Inc.
InventorsNicole Larmore, Balasubramanian Ramanathan, Richard Yeager
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Abstract
The disclosure relates to methods to control trace metals during production of anti-CD38 antibodies, drug substances and drug products generated using the methods, and uses of the generated drug substances and drug products.
Claims77
A method of producing an anti-CD38 antibody expressed from a polynucleotide encoding a heavy chain variable region (VH) of SEQ ID NO:
- 7 and a light chain variable region (VL) of SEQ ID NO:
- 8 having an asialo, mono-galacto core-fucosylated biantennary glycan (G1F) oligosaccharide content between 15% and 27%, comprising:
- a) preparing a culture medium comprising between 2 parts per billion (ppb) and 8.5 manganese (Mn);
- and
- b) controlling the G1F oligosaccharide content of the anti-CD38 antibody by culturing a host cell comprising the polynucleotide encoding the VH of SEQ ID NO:
- 7 and the VL of SEQ ID NO:
- 8 in the culture medium prepared in step a), thereby producing the anti-CD38 antibody expressed from the polynucleotide encoding the VH of SEQ ID NO:
- 7 and the VL of SEQ ID NO:
- 8 having the G1F oligosaccharide content between 15% and 27%.
A method of producing an anti-CD38 antibody expressed from a polynucleotide encoding the VH of SEQ ID NO:
- 7 and a VL of SEQ ID NO:
- 8 having a G1F oligosaccharide content between 15% and 27%, comprising:
- a) culturing a host cell expressing the polynucleotide encoding the VH of SEQ ID NO:
- 7 and the VL of SEQ ID NO:
- 8 in conditions that the anti-CD38 antibody is produced;
- and
- b) controlling the G1F oligosaccharide content of the anti-CD38 antibody by monitoring the concentration of Mn in the culture medium during biosynthesis of the anti-CD38 antibody and regulating the concentration of Mn in the culture medium during biosynthesis of the anti-CD38 antibody, wherein the concentration of Mn in the culture medium is regulated to comprise between 2 ppb and 8.5 ppb Mn, thereby producing the anti-CD38 antibody having the G1F oligosaccharide content between 15% and 27%.
A method of producing a drug product comprising an anti-CD38 antibody expressed from a polynucleotide encoding the VH of SEQ ID NO:
- 7 and the VL of SEQ ID NO:
- 8 and having a G1F oligosaccharide content between 15% and 27%, comprising:
- a) preparing a culture medium comprising between 2 ppb and 8.5 ppb Mn;
- b) controlling the G1F oligosaccharide content of the anti-CD38 antibody by culturing a host cell comprising the polynucleotide encoding the VH of SEQ ID NO:
- 7 and the VL of SEQ ID NO:
- 8 in the culture medium prepared in step a), thereby producing the anti-CD38 antibody having the G1F oligosaccharide content between 15% and 27%;
- and
- c) formulating the anti-CD38 antibody as a drug product.
Dependencies are inferred from the claim text.