University of Pittsburgh

Oki Electric Industry Co., Ltd.

Daiichi Sankyo Company, Limited

Kyorin Pharmaceutical Co., Ltd.

The University of Tokyo

Oki Semiconductor Co., Ltd.

Universal Can Corporation

Hiroaki Uchida

Joseph C Glorioso, Iii

Justus B Cohen

Paola Grandi

Takeshi Masuda

Kensuke Nakamura

Takashi Nakada

Yusuke Ota

Shinji Ashida

Narihiro Toda

Ichiro Hayakawa

Daisuke Okajima

Mitsuhiro Iwamoto

Hirofumi Hamada

Tomoko Terauchi

Masaki Meguro

Fuminao Doi

Naoya Harada

Tsutomu Irikura

Seigo Suzue

Susumu Kinoshita

Satoshi Murayama

Hirotaka Shinoda

Kazuya Suzuki

Hirotaka Mori

Hideaki Tahara

Minoru Yoshida

Toshio Nagata

Hidetsugu Uchida

Takeshi Yamamoto

Yoshiki Nagatomo

Osamu Nanba

Katsuji Yoshida

Takashi Ohsako

Shoji Yo

Yoshirou Tsurugida

Masamichi Tsuji

Akihiko Ohara

Joseph C Glorioso Iii

The present invention provides a novel antibody-pyrrolodiazepine derivative and a novel antibody-pyrrolodiazepine derivative conjugate using the same, and a novel CLDN6 and/or CLDN9 antibody.

Methods of treating a tumor by administering a claudin-6 (CLDN6) or CLDN9 antibody-pyrrolobenzodiazepine derivative conjugate

It is an object of the present invention to develop a virus preparation comprising an oncolytic HSV having, in vivo, more effective cancer cell-killing activity than the antitumor effects of existing oncolytic HSVs. Specifically, the present invention relates to a virus preparation for the treatment of a cancer, comprising an HSV (herpes simplex virus) having a receptor-retargeted gD mutation and at least one membrane fusion activity-promoting region on the genome, and a method for treating cancer using the aforementioned virus preparation.

Oncolytic virus for cancer therapy

Provided are novel antibody-pyrrolodiazepine derivative and novel antibody-pyrrolodiazepine derivative conjugates, as well as methods of using the same, and a novel CLDN6 and/or CLDN9 antibody. The disclosed compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics, and include substituted benzo[e]pyrrolo[1,2-α][1,4]diazepine.

Antibody-drug conjugates comprising substituted benzo[e]pyrrolo[1,2-a][1,4]diazepines

A nozzle includes a slit-shaped discharge port at tip ends of a pair of nozzle walls arranged to face each other at a predetermined interval and a plurality of protrusions protruding toward the facing nozzle walls at tip end sides of the nozzle walls.

Nozzle, drying device, and method for producing can body

The present invention provides a recombinant oncolytic Herpes Simplex Virus (oHSV) comprising a non-HSV ligand specific for a molecule (protein, lipid, or carbohydrate determinant) present on the surface of a cell (such as a cancer cell) and one or more copies of one or more microRNA target sequences inserted into one or more HSV gene loci, preferably one or more HSV gene(s) required for replication of HSV in normal (i.e., non-cancerous) cells. The invention further provides stocks and pharmaceutical compositions comprising the inventive oHSV and methods for killing tumor cells employing the inventive oHSV.

Oncolytic HSV vector

A novel antibody-pyrrolodiazepine derivative and a novel antibody-pyrrolodiazepine derivative conjugate using the same, comprising substituted benzo[e]pyrrolo[1,2-a][1,4]diazepines represented by the [Formula 24], [Formula 25], [Formula 26], and/or [Formula 27].

Antibody-drug conjugates comprising substituted benzo[e]pyrrolo[1,2-&#x3b1;][1,4]diazepines

Antibody-pyrrolobenzodiazepine derivative conjugate and method of use thereof for treating a tumor

In one embodiment, the invention provides an HSV vector comprising a mutant gB and/or a mutant gH glycoprotein, where the viral envelope further comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type. In another embodiment, the invention provides an HSV vector comprising (a) a mutant gC and/or gD envelope glycoprotein which comprises a non-native ligand specific for a protein present on the surface of a predetermined cell type; and (b) a mutant envelope glycoprotein other than gD.

Identification of mutations in herpes simplex virus envelope glycoproteins that enable or enhance vector retargeting to novel non-HSV receptors

The present invention provides a recombinant herpes simplex virus (HSV), comprising (a) a mutation of the glycoprotein B (gB) at position 285 or 549, (b) a plurality of copies of one or more microRNA target sequences inserted into a locus of an HSV gene required for HSV replication, wherein said target sequence is the reverse complement of microRNA miR-124 and wherein said target sequence is present in the ICP4 gene, and (c) a transgene encoding a matrix metalloproteinase. The present invention also provides a method of killing a cancerous cell using a recombinant HSV according to the invention and a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a recombinant HSV according to the invention.

The present invention provides a recombinant oncolytic Herpes Simplex Virus (oHSV) comprising a non-HSV ligand specific for a molecule (protein, lipid, or carbohydrate determinant) present on the surface of a cell (such as a cancer cell) and a plurality of copies of one or more microRNA target sequences inserted into one or more HSV gene loci, preferably one or more HSV gene(s) required for replication of HSV in normal (i.e., non-cancerous) cells, and a deletion of the internal repeat (joint) region in the HSV genome comprising one copy of the ICP0, ICP34.5, LAT, and ICP4 genes and the ICP47 promoter. The invention further provides stocks and pharmaceutical compositions comprising the inventive oHSV and methods for killing tumor cells employing the inventive oHSV.

The invention provides modified HSV vectors that exhibit enhanced entry of cells, either through direct infection and/or lateral spread. In one aspect, HSV vectors of the present invention can directly infect cells through interaction with cell proteins other than typical mediators of HSV infection. In another aspect, the invention provides an HSV vector, which exhibits lateral spread in cells typically resistant to HSV lateral spread, such as cells lacking gD receptors. The invention further provides DNA encoding mutant forms of the HSV gB and gH glycoproteins, stocks of the inventive virus, and methods for effecting viral targeting and efficient entry of cells. The invention also pertains to the use of the inventive vectors for treating cancers.

The present invention provides a semiconductor wafer comprising an insulated board of sapphire or the like having translucency, which is provided with a positioning orientation flat at a peripheral portion thereof, and a silicon thin film formed over the entire one surface of the insulated board. In the semiconductor wafer, ions are implanted in an area containing the orientation flat at a peripheral portion of the silicon thin film to amorphize silicon. Thus, the translucency at the amorphized spot is eliminated and accurate positioning using the conventional optical sensor can be performed.

Semiconductor wafer and manufacturing method thereof

Growing community of inventors

Tokyo, Japan

Hiroaki Uchida