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OwnerLawrence Chasin, Qinghao Zhang +1inventors
InventorsLawrence Chasin, Qinghao Zhang, Zhimei Du
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The present invention provides, inter alia, a multiply auxotrophic cell line that is deficient in genes encoding enzymes that catalyze steps in the de novo synthesis of the pyrimidine and purine pathways, such as, e.g., uridine monophosphate synthetase (UMPS) and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), respectively, for the production of recombinant proteins such as recombinant monoclonal and bispecific antibodies. Methods for preparing the multiply auxotrophic, in particular the doubly auxotrophic and octa-auxotrophic cell lines disclosed herein, methods for selecting a cell expressing a protein of interest, methods for producing a protein of interest, methods for optimizing the activity of a protein of interest, and kits for selecting a cell expressing a protein of interest, are also provided. In addition, recombinant proteins such as antibodies, including monoclonal and bispecific antibodies, made by the methods of the present disclosure are also provided.
A multiply auxotrophic cell line that is deficient in (i) at least one gene encoding an enzyme in the de novo pathway for pyrimidine nucleotide synthesis and (ii) at least one gene encoding an enzyme in the de novo pathway for purine nucleotide synthesis.
A doubly auxotrophic cell line that is deficient in the gene encoding uridine monophosphate synthetase (UMPS) and the gene encoding 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC).
The method of 44, wherein:
A multiply auxotrophic cell line that is deficient in the gene encoding uridine monophosphate synthetase (UMPS), the gene encoding dihydroorotate dehydrogenase (DHODH), the genes encoding CTP synthase 1 and 2 (CTPS1/2), the gene encoding thymidylate synthetase (TYMS), and the gene encoding 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC).
A multiply auxotrophic cell line that is deficient in the gene encoding uridine monophosphate synthetase (UMPS), the gene encoding dihydroorotate dehydrogenase (DHODH), the genes encoding CTP synthase 1 and 2 (CTPS1/2), the gene encoding thymidylate synthetase (TYMS), the gene encoding 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), the gene encoding phosphoribosylaminoimidazole carboxylase (PAICS), and the gene encoding guanosine monophosphate synthetase (GMPS).
A multiply auxotrophic cell line that is deficient in the gene encoding uridine monophosphate synthetase (UMPS), the gene encoding dihydroorotate dehydrogenase (DHODH), the genes encoding CTP synthase 1 and 2 (CTPS1/2), the gene encoding thymidylate synthetase (TYMS), the gene encoding 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), the gene encoding phosphoribosylaminoimidazole carboxylase (PAICS), the genes encoding inosine-5′-monophosphate dehydrogenase 1 and 2 (IMPDH1/2), and the gene encoding guanosine monophosphate synthetase (GMPS).
A multiply auxotrophic cell line that is deficient in the gene encoding uridine monophosphate synthetase (UMPS), the gene encoding dihydroorotate dehydrogenase (DHODH), the genes encoding CTP synthase 1 and 2 (CTPS1/2), the gene encoding thymidylate synthetase (TYMS), the gene encoding 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), the gene encoding phosphoribosylaminoimidazole carboxylase (PAICS), the gene encoding adenylosuccinate lyase (ADSL), the genes encoding inosine-5′-monophosphate dehydrogenase 1 and 2 (IMPDH1/2), the gene encoding guanosine monophosphate synthetase (GMPS), and the genes encoding adenylosuccinate synthase and adenylosuccinate synthase like 1 (ADSS/ADSSL1).
An octa-auxotrophic cell line that is deficient in the gene encoding uridine monophosphate synthetase (UMPS), the gene encoding dihydroorotate dehydrogenase (DHODH), the genes encoding CTP synthase 1 and 2 (CTPS1/2), the gene encoding thymidylate synthetase (TYMS), the gene encoding 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), the gene encoding phosphoribosylaminoimidazole carboxylase (PAICS), the genes encoding inosine-5′-monophosphate dehydrogenase 1 and 2 (IMPDH1/2), and the gene encoding guanosine monophosphate synthetase (GMPS).
A method for modulating recombinant monoclonal antibody production, comprising:
A method for modulating recombinant monoclonal antibody production, comprising:
A method for protein production, comprising:
Dependencies are inferred from the claim text.