Hokkaido University

Fuso Pharmaceutical Industries, Ltd.

Yasuhiko Suzuki

Kazuhiko Ohashi

Naoya Maekawa

Tomohiro Okagawa

Shiro Murata

Satoru Konnai

Keiichi Yamamoto

Asami Nishimori

Chie Nakajima

Yusuke Suzuki

Hiroshi Tahara

Yuzuru Kitahara

Satoshi Takagi

Yumiko Kagawa

Miki Nakagawa

Yayoi Kameda

Shinya Goto

Yamato Sajiki

The present invention provides mammalian cell expression vectors that impart to mammalian host cells an ability to produce high levels of foreign gene-derived proteins. A ubiquitously acting chromatin opening element (UCOE) is introduced into an expression vector that has a plasmid DNA integrated into a transcriptional hot spot on the chromosome of a dihydrofolate reductase gene-deficient host cell so that it allows for selection of strains that grow in hypoxanthine-thymidine (hereinafter denoted as HT)-free medium, whereby transformants will produce a protein of interest in increased amounts.

Vector including a translation-impaired dihydrofolate reductase gene cassette and ubiquitously acting chromatin opening element

The present invention provides an anti-PD-L1 antibody capable of staining tumor cells such as melanoma cells. An anti-PD-L1 antibody comprising (a) a light chain comprising CDR1 having the amino acid sequence of KSISKY (SEQ ID NO: 1), CDR2 having the amino acid sequence of SGS and CDR3 having the amino acid sequence of QQHNEYPLT (SEQ ID NO: 2) and (b) a heavy chain comprising CDR1 having the amino acid sequence of GYTFTDYI (SEQ ID NO: 3), CDR2 having the amino acid sequence of INPDSGGN (SEQ ID NO: 4) and CDR3 having the amino acid sequence of ARGITMMVVISHWKFDP (SEQ ID NO: 5). A composition for detecting PD-L1, comprising the above antibody as an active ingredient. A method for preparing the above antibody is also provided.

Anti-PD-L1 antibody for detecting PD-L1

The present invention provides an anti-PD-L1 antibody capable of repeated administration even to animals other than rat. An anti-PD-L1 antibody comprising (a) a light chain comprising a light chain variable region containing CDR1 having the amino acid sequence of QSLLYSENQKDY (SEQ ID NO: 37), CDR2 having the amino acid sequence of WAT and CDR3 having the amino acid sequence of GQYLVYPFT (SEQ ID NO: 38) and the light chain constant region of an antibody of an animal other than rat; and (b) a heavy chain comprising a heavy chain variable region containing CDR1 having the amino acid sequence of GYTFTSNF (SEQ ID NO: 39), CDR2 having the amino acid sequence of IYPEYGNT (SEQ ID NO: 40) and CDR3 having the amino acid sequence of ASEEAVISLVY (SEQ ID NO: 41) and the heavy chain constant region of an antibody of an animal other than rat. A pharmaceutical composition comprising the above anti-PD-L1 antibody as an active ingredient. A method for preparing the above anti-PD-L1 antibody is also provided.

Anti-PD-L1 antibody

The present invention provides an anti-LAG-3 antibody capable of repeated administration even to animals other than rat. An anti-LAG-3 antibody comprising (a) a light chain comprising a light chain variable region containing CDR1 having the amino acid sequence of QSLLDSDGNTY (SEQ ID NO: 16), CDR2 having the amino acid sequence of SVS and CDR3 having the amino acid sequence of MQATHVPFT (SEQ ID NO: 17) and the light chain constant region of an antibody of an animal other than rat; and (b) a heavy chain comprising a heavy chain variable region containing CDR1 having the amino acid sequence of GFDFDTYP (SEQ ID NO: 18), CDR2 having the amino acid sequence of ITIKTHNYAT (SEQ ID NO: 19) and CDR3 having the amino acid sequence of NREDFDY (SEQ ID NO: 20) and the heavy chain constant region of an antibody of an animal other than rat. A pharmaceutical composition comprising the above anti-LAG-3 antibody as an active ingredient. A method for preparing the above anti-LAG-3 antibody is also provided.

Anti-LAG-3 antibody

The present invention provides an anti-PD-L1 antibody capable of staining tumor cells such as melanoma cells. An anti-PD-L1 antibody comprising (a) a light chain comprising CDR1 having the amino acid sequence of KSISKY (SEQ ID NO: 1), CDR2 having the amino acid sequence of SGS and CDR3 having the amino acid sequence of QQHNEYPLT (SEQ ID NO: 2) and (b) a heavy chain comprising CDR1 having the amino acid sequence of GYTFTDYI (SEQ ID NO: 3), CDR2 having the amino acid sequence of INPDSGGN (SEQ ID NO: 4) and CDR3 having the amino acid sequence of ARGITMMVVISHWKFDF (SEQ ID NO: 5). A composition for detecting PD-L1, comprising the above antibody as an active ingredient. A method for preparing the above antibody is also provided.

The present inventors conducted dedicated studies and successfully constructed expression vectors that enable high-level production of foreign gene-derived proteins in mammalian host cells, which comprise a translation-impaired dihydrofolate reductase gene cistron whose expression has been attenuated by altering the codons to the least frequently used codons in mammals; and a gene cassette which has a cloning site for incorporation of a foreign gene between a highly transcriptionally active promoter and a highly stable polyadenylation signal.

Expression vector for producing protein derived from foreign gene in large quantity using animal cells, and use thereof

The present inventors successfully constructed expression vectors that enable high-level production of foreign gene-derived proteins in mammalian host cells, which comprise a translation-impaired drug resistance gene cistron whose expression has been attenuated by altering the codons to the least frequently used codons in mammals; and a gene cassette which has a cloning site for incorporation of a foreign gene between a highly transcriptionally active promoter and a highly stable polyadenylation signal.

Expression vector for mass production of foreign gene-derived protein using animal cell and use thereof

As a result of dedicated research, the present inventors have successfully invented a collagen gene construct which can be easily purified and maintains a triple helix structure equivalent to that of naturally-occurring collagen while having a low molecular weight. Specifically, one-step purification by affinity purification is enabled because CR-D (a signal peptide) has a carbohydrate recognition domain. By substituting a portion of a human collagen structural gene of the present invention with the collagen-like structural gene portion of MBL, a low-molecular-weight collagen which maintains a triple helix structure and is thermally stable can be obtained with high purity and in large quantities.

Growing community of inventors

Hokkaido, Japan

Yasuhiko Suzuki