公开(公告)号：US11969459B2

公开(公告)日：2024-04-30

申请号：US16477878

申请日：2018-01-26

Applicant: StemRIM Inc. ,  OSAKA UNIVERSITY

Inventor： Katsuto Tamai ,  Yoshiki Sawa ,  Shigeru Miyagawa ,  Takashi Kido ,  Takasumi Goto ,  Takehiko Yamazaki

IPC: A61K38/00 ,  A61K38/19 ,  A61P9/10 ,  C07K14/00

CPC classification number: A61K38/19 ,  A61P9/10

Abstract: The present inventors have found that HMGB1 fragment peptides having a particular amino acid sequence exhibit the effects of improvement of cardiac function, inhibition of cardiomyocyte hypertrophy, inhibition of myocardial fibrosis, and promotion of angiogenesis in an animal model of dilated cardiomyopathy, that the particular HMGB1 fragment peptides also exhibit the effects of improvement of cardiac function, inhibition of cardiomegaly, inhibition of cardiomyocyte hypertrophy, inhibition of myocardial fibrosis, and promotion of angiogenesis in an animal model of ischemic cardiomyopathy caused by old myocardial infarction, and that the particular HMGB1 fragment peptides exhibit the effects of inhibition of cardiomyocyte hypertrophy and inhibition of myocardial fibrosis in an animal model of hypertensive cardiomyopathy. Based on these findings, pharmaceutical compositions are provided for the prevention and/or treatment of cardiomyopathy and old myocardial infarction and chronic heart failure resulting therefrom, which comprise an HMGB1 fragment peptide having a particular amino acid sequence.

公开(公告)号：US20240050481A1

公开(公告)日：2024-02-15

申请号：US18017149

申请日：2021-07-21

Applicant: OSAKA UNIVERSITY ,  STEMRIM INC.

Inventor： Katsuto TAMAI ,  Yasushi KIKUCHI ,  Tomoki TAMAKOSHI ,  Takehiko YAMAZAKI

IPC: A61K35/28 ,  C12N5/0775 ,  C07K14/78 ,  A61P17/00

CPC classification number: A61K35/28 ,  C12N5/0668 ,  C07K14/78 ,  A61P17/00

Abstract: The present disclosure includes a composition for use in the treatment of dystrophic epidermolysis bullosa, comprising a blister-derived cell of a patient with dystrophic epidermolysis bullosa that is genetically modified to produce type VII collagen.

公开(公告)号：US11298403B2

公开(公告)日：2022-04-12

申请号：US16768654

申请日：2018-11-30

Applicant: StemRIM Inc. ,  OSAKA UNIVERSITY

Inventor： Katsuto Tamai ,  Takashi Shimbo ,  Takehiko Yamazaki

IPC: A61K38/19 ,  A61K38/17 ,  A61P1/00 ,  A61P1/04 ,  A61P43/00 ,  C07K14/47

Abstract: The present inventors discovered that an HMGB1 fragment peptide having a specific amino acid sequence exhibits an effect of suppressing weight loss and an effect of suppressing shortening of the large intestine and mucosal damage in an animal model of inflammatory bowel diseases. Based on these findings, pharmaceutical compositions for the prevention and/or treatment of inflammatory bowel diseases, which comprise the HMGB1 fragment peptide having the specific amino acid sequence are provided.

公开(公告)号：US20200291359A1

公开(公告)日：2020-09-17

申请号：US16768203

申请日：2018-11-30

Applicant: STEMRIM INC. ,  OSAKA UNIVERSITY

Inventor： Katsuto TAMAI ,  Takashi SHIMBO ,  Eiji SASAKI ,  Takehiko YAMAZAKI

IPC: C12N5/0775 ,  A61K35/28 ,  G01N33/50 ,  C07K14/47

Abstract: The inventors discovered that ectodermal mesenchymal stem cells circulating in peripheral blood that are induced by necrotic tissue damage contribute to the regeneration of damaged tissue. On the basis of this discovery, provided are ectodermal mesenchymal stem cells, a method for producing the same, and a screening method for a substance having pluripotent stem cell inductive activity, the screening method using cells induced by necrotic tissue damage in peripheral blood as an index.

公开(公告)号：US20220009976A1

公开(公告)日：2022-01-13

申请号：US17281862

申请日：2019-10-04

Applicant: StemRIM Inc. ,  OSAKA UNIVERSITY

Inventor： Katsuto TAMAI ,  Takashi SHIMBO ,  Takehiko YAMAZAKI ,  Koichi YOKOTA

IPC: C07K14/47 ,  A61P1/00 ,  A61P17/00 ,  A61P9/10

Abstract: The present inventors designed an artificial sequence peptide based on the results of original research conducted so far, and found that the peptide exhibits an activity of mobilizing mesenchymal stem cells into peripheral blood. The present inventors also found that the artificial sequence peptide has a therapeutic effect on inflammatory bowel disease, atopic dermatitis, and cerebral infarction. Based on these findings, a new regenerative medicine technology that can overcome the problems of cell transplantation therapy is provided.

公开(公告)号：US20210386823A1

公开(公告)日：2021-12-16

申请号：US17287636

申请日：2019-10-25

Applicant: OSAKA UNIVERSITY ,  STEMRIM INC.

Inventor： Katsuto TAMAI ,  Takashi SHIMBO ,  Eiji SASAKI ,  Takahiro TSUSHIMA ,  Takehiko YAMAZAKI

IPC: A61K38/17 ,  A61P19/02

Abstract: The inventors of the present invention searched for a substance that is effective in treating a cartilage disorder, and as a result, found that, in an animal model of joint cartilage deficiency, an HMGB1 fragment peptide having a specific amino acid sequence exhibits the effect of reproducing a healthy cartilage tissue including a hyaline cartilage. Based on this finding, the present invention provides a pharmaceutical composition that contains the specific HMGB1 fragment peptide and that is for preventing and/or treating a cartilage disorder.

公开(公告)号：US20210347839A1

公开(公告)日：2021-11-11

申请号：US17282872

申请日：2019-10-04

Applicant: StemRIM Inc. ,  OSAKA UNIVERSITY

Inventor： Katsuto TAMAI ,  Takashi SHIMBO ,  Takehiko YAMAZAKI

IPC: C07K14/47 ,  A61P1/00 ,  A61P37/06 ,  A61P17/06

Abstract: The present inventors identified many nuclear proteins contained in the extract of skin tissue by mass spectrometry, randomly selected multiple partial amino acid sequences of the nuclear proteins, chemically synthesized peptides consisting of the partial amino acid sequences, and examined their activity of mobilizing mesenchymal stem cells. As a result, it was found that these multiple peptides show the activity of mobilizing mesenchymal stem cells into peripheral blood, even though their amino acid sequences are completely different from each other. The inventors also found that fragment peptides of the nuclear proteins have therapeutic effects on diseases characterized by inflammation and abnormalities of the immune system (e.g., inflammatory bowel disease and psoriasis). Based on these findings, a new regenerative medicine technology that can overcome the problems of cell transplantation therapy is provided.

公开(公告)号：US20200038486A1

公开(公告)日：2020-02-06

申请号：US16499604

申请日：2018-04-06

Applicant: StemRIM Inc. ,  OSAKA UNIVERSITY

Inventor： Katsuto TAMAI ,  Takahiro AOTO ,  Sho YAMAZAKI ,  Takehiko YAMAZAKI

IPC: A61K38/19 ,  A61P17/02 ,  A61P1/00

Abstract: The present inventors discovered that an HMGB1 fragment peptide having a particular amino acid sequence exhibits effects of inhibiting finger adhesion and digestive tract scarring and prolonging survival in the dystrophic epidermolysis bullosa model mice. Also in the skin ulcer model, administration of the specific HMGB1 fragment peptide was found to inhibit the fibrosing of skin during the healing process of the ulcer. Based on these findings, the present application provides pharmaceutical compositions for the treatment of fibrotic diseases, which comprise the specific HMGB1 fragment peptide.

公开(公告)号：US20240050460A1

公开(公告)日：2024-02-15

申请号：US18152249

申请日：2023-01-10

Applicant: StemRIM Inc. ,  Osaka University

Inventor： Katsuto TAMAI ,  Takehiko YAMAZAKI ,  Yasufumi KANEDA

IPC: A61K31/711 ,  G01N33/68 ,  C07K14/52 ,  G01N33/50

CPC classification number: A61K31/711 ,  G01N33/6863 ,  C07K14/52 ,  G01N33/5073 ,  A61K38/00

Abstract: The present inventors revealed the following for the first time in the world:



1) a large amount of bone marrow-derived cells are mobilized to grafted skin;
2) the mobilized bone marrow-derived cells are differentiated into any of dermal fibroblasts, adipocytes, muscle cells, vascular endothelial cells, and epidermal keratinocytes in the grafted skin, and the mobilized bone marrow-derived cells include bone marrow-derived mesenchymal stem cells;
3) the factors which mobilize bone marrow-derived mesenchymal stem cells from peripheral blood to the grafted skin are HMGB1, HMGB2, and HMGB3 released from the necrosed tissue of recipient skin;
4) purified HMGB1, HMGB2, and HMGB3 promote the migration of mesenchymal stem cells isolated and cultured from bone marrow;
5) activators containing HMGB1 which allows the migration of bone marrow mesenchymal stem cells can be conveniently purified from several organ extracts including skin, brain, and heart;
6) activators which allow the migration of bone marrow mesenchymal stem cells can be conveniently extracted from cultured cells; and
7) a heparin-column purified fraction of skin extract mobilizes a large amount of bone marrow-derived cells in case of brain injury.

公开(公告)号：US20230241159A1

公开(公告)日：2023-08-03

申请号：US17995017

申请日：2021-04-02

Applicant: StemRIM Inc. ,  OSAKA UNIVERSITY

Inventor： Katsuto TAMAI ,  Takashi SHIMBO ,  Takehiko YAMAZAKI

IPC: A61K38/16 ,  A61P9/10 ,  A61P17/00 ,  A61P29/00 ,  C07K14/00

CPC classification number: A61K38/16 ,  A61P9/10 ,  A61P17/00 ,  A61P29/00 ,  C07K14/001

Abstract: The present inventors synthesized a plurality of peptides each consisting of a partial sequence of the artificial sequence peptide “1r10” (1r10 fragment peptides), which was discovered from their own research conducted to date, investigated whether they have an activity of mobilizing mesenchymal stem cells into peripheral blood, and as a result, discovered that a 1r10 fragment peptide having a specific amino acid sequence shows the activity. Based on such finding, a peptide is provided which is considered to show therapeutic effects on various diseases through mobilization of mesenchymal stem cells into peripheral blood.