Patents by Inventor Yoshito Kishi

Yoshito Kishi has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Patent number: 11155562
    Abstract: The present invention provides halichondrin analogs, such as compounds of Formula (I). The compounds may bind to microtubule sites, thereby inhibiting microtubule dynamics. Also provided are methods of synthesis, pharmaceutical compositions, kits, methods of treatment, and uses that involve the compounds for treatment of a proliferative disease (e.g., cancer). Compounds of the present invention are particularly useful for the treatment of metastatic breast cancer, non-small cell lung cancer, prostate cancer, and sarcoma. The included methods of synthesis are useful for the preparation of compounds of Formula (I)-(III) along with naturally occurring halicondrins (e.g., halichondrin B & C, norhalichondrin A, B, & C, and homohalichondrin A, B, & C). Also included are methods for interconverting between the halichondrins, norhalichondrins, and homohalichondrins and their unnatural epimers at the C38 ketal stereocenter through the use of an acid-mediated equilibration.
    Type: Grant
    Filed: January 17, 2020
    Date of Patent: October 26, 2021
    Assignee: President and Fellows of Harvard College
    Inventors: Yoshito Kishi, Atsushi Ueda, Akihiko Yamamoto, Daisuke Kato
  • Publication number: 20210261566
    Abstract: The present invention provides novel Compound (1) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, and medical uses thereof.
    Type: Application
    Filed: February 4, 2021
    Publication date: August 26, 2021
    Applicants: President and Fellows of Harvard College, Eisai R&D Management Co., LTD.
    Inventors: Yoshito Kishi, Kazunobu Kira, Ken Ito
  • Publication number: 20210230177
    Abstract: The present invention provides methods for the synthesis of ketones involving a Ni/Zr-mediated coupling reaction. The Ni/Zr-mediated ketolization reactions can be used in the synthesis of halichondrins (e.g., halichondrin A, B, C; homohalichondrin A, B, C; norhalichondrin A, B, C), and analogs thereof. Therefore, the present invention also provides synthetic methods useful for the synthesis of halichondrins, and analogs thereof. Also provided herein are compounds (i.e., intermediates) useful in the synthesis of halichondrins, and analogs thereof.
    Type: Application
    Filed: July 6, 2018
    Publication date: July 29, 2021
    Applicants: President and Fellows of Harvard College, Eisai R&D Management Co., LTD.
    Inventors: Yoshito Kishi, Yanran Ai, Ning Ye, Qiaoyi Wang, Kenzo Yahata, Kentaro Iso, Santhosh Reddy Naini, Shuji Yamashita, Jihoon Lee, Isao Ohashi, Takashi Fukuyama
  • Publication number: 20210179522
    Abstract: Provided herein are methods for preparing ketone-containing organic molecules. The methods are based on novel iron/copper-mediated (“Fe/Cu-mediated”) coupling reactions. The Fe/Cu-mediated coupling reaction can be used in the preparation of complex molecules, such as halichondrins and analogs thereof. In particular, the Fe/Cu-mediated ketolization reactions described herein are useful in the preparation of intermediates en route to halichondrins.
    Type: Application
    Filed: May 9, 2018
    Publication date: June 17, 2021
    Applicant: President and Fellows of Harvard College
    Inventors: Yoshito Kishi, Kenzo Yahata, Vemula Praveen Kumar, Sudheer Babu Vaddela
  • Patent number: 10954249
    Abstract: The present invention provides novel Compound (1) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable and medical uses thereof.
    Type: Grant
    Filed: April 3, 2018
    Date of Patent: March 23, 2021
    Assignees: President and Fellows of Harvard College, Eisai R&D Management Co., Ltd.
    Inventors: Yoshito Kishi, Kazunobu Kira, Ken Ito
  • Publication number: 20210009605
    Abstract: The present invention provides unified synthesis of the C1-C19 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hybridized carbon. The provided efficient selective coupling reactions can allow easy access to the C1-C19 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.
    Type: Application
    Filed: April 27, 2020
    Publication date: January 14, 2021
    Applicant: President and Fellows of Harvard College
    Inventors: Yoshito Kishi, Wuming Yan, Jingwei Li, Zhanjie Li, Kenzo Yahata
  • Patent number: 10844073
    Abstract: Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer).
    Type: Grant
    Filed: July 1, 2019
    Date of Patent: November 24, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: Jung Hwa Lee, Yoshito Kishi, Ayumi Osawa, Zhanjie Li
  • Publication number: 20200325152
    Abstract: The present invention provides novel compounds (e.g., compounds of Formulae (I), (II), (III), (IV)) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or pharmaceutically acceptable salts thereof, optionally in a pharmaceutically acceptable carrier, and a medical uses thereof.
    Type: Application
    Filed: November 15, 2018
    Publication date: October 15, 2020
    Applicants: President and Fellows of Harvard College, Eisai R&D Management Co., LTD.
    Inventors: Yoshito Kishi, Kazunobu Kira, Ken Ito
  • Publication number: 20200223863
    Abstract: The present invention provides halichondrin analogs, such as compounds of Formula (I). The compounds may bind to microtubule sites, thereby inhibiting microtubule dynamics. Also provided are methods of synthesis, pharmaceutical compositions, kits, methods of treatment, and uses that involve the compounds for treatment of a proliferative disease (e.g., cancer). Compounds of the present invention are particularly useful for the treatment of metastatic breast cancer, non-small cell lung cancer, prostate cancer, and sarcoma. The included methods of synthesis are useful for the preparation of compounds of Formula (I)-(III) along with naturally occurring halicondrins (e.g., halichondrin B & C, norhalichondrin A, B, & C, and homohalichondrin A, B, & C). Also included are methods for interconverting between the halichondrins, norhalichondrins, and homohalichondrins and their unnatural epimers at the C38 ketal stereocenter through the use of an acid-mediated equilibration.
    Type: Application
    Filed: January 17, 2020
    Publication date: July 16, 2020
    Applicant: President and Fellows of Harvard College
    Inventors: Yoshito Kishi, Atsushi Ueda, Akihiko Yamamoto, Daisuke Kato
  • Publication number: 20200165183
    Abstract: Provided herein are methods for preparing ketone-containing organic molecules. The methods are based on novel iron/copper-mediated (“Fe/Cu-mediated”) coupling reactions. The Fe/Cu-mediated coupling reaction can be used in the preparation of complex molecules, such as halichondrins and analogs thereof. In particular, the Fe/Cu-mediated ketolization reactions described herein are useful in the preparation of intermediates en route to halichondrins.
    Type: Application
    Filed: May 9, 2018
    Publication date: May 28, 2020
    Applicant: President and Fellows of Flarvard College
    Inventors: Yoshito Kishi, Kenzo Yahata, Vemula Praveen Kumar, Sudheer Babu Vaddela
  • Publication number: 20200148698
    Abstract: The present invention provides novel Compound (1) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable and medical uses thereof.
    Type: Application
    Filed: April 3, 2018
    Publication date: May 14, 2020
    Applicants: President and Fellows of Harvard College, Eisai R&D Management Co., LTD
    Inventors: Yoshito Kishi, Kazunobu Kira, Ken Ito
  • Patent number: 10633392
    Abstract: The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.
    Type: Grant
    Filed: June 14, 2019
    Date of Patent: April 28, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: Yoshito Kishi, Wuming Yan, Jingwei Li, Zhanjie Li, Kenzo Yahata
  • Patent number: 10556910
    Abstract: The present invention provides halichondrin analogs, such as compounds of Formula (I). The compounds may bind to microtubule sites, thereby inhibiting microtubule dynamics. Also provided are methods of synthesis, pharmaceutical compositions, kits, methods of treatment, and uses that involve the compounds for treatment of a proliferative disease (e.g., cancer). Compounds of the present invention are particularly useful for the treatment of metastatic breast cancer, non-small cell lung cancer, prostate cancer, and sarcoma. The included methods of synthesis are useful for the preparation of compounds of Formula (I)-(III) along with naturally occurring halicondrins (e.g., halichondrin B & C, norhalichondrin A, B, & C, and homohalichondrin A, B, & C). Also included are methods for interconverting between the halichondrins, norhalichondrins, and homohalichondrins and their unnatural epimers at the C38 ketal stereocenter through the use of an acid-mediated equilibration.
    Type: Grant
    Filed: June 30, 2015
    Date of Patent: February 11, 2020
    Assignee: President and Fellows of Harvard College
    Inventors: Yoshito Kishi, Atsushi Ueda, Akihiko Yamamoto, Daisuke Kato
  • Publication number: 20200031843
    Abstract: The present invention provides unified synthesis of the C1-C19 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hybridized carbon. The provided efficient selective coupling reactions can allow easy access to the C1-C19 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.
    Type: Application
    Filed: June 14, 2019
    Publication date: January 30, 2020
    Applicant: President and Fellows of Harvard College
    Inventors: Yoshito Kishi, Wuming Yan, Jingwei Li, Zhanjie Li, Kenzo Yahata
  • Publication number: 20200002352
    Abstract: Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer).
    Type: Application
    Filed: July 1, 2019
    Publication date: January 2, 2020
    Applicant: President and Fellows of Harvard College
    Inventors: Jung Hwa Lee, Yoshito Kishi, Ayumi Osawa, Zhanjie Li
  • Patent number: 10392400
    Abstract: Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer).
    Type: Grant
    Filed: November 10, 2017
    Date of Patent: August 27, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Jung Hwa Lee, Yoshito Kishi, Ayumi Osawa, Zhanjie Li
  • Patent number: 10344038
    Abstract: The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs thereof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.
    Type: Grant
    Filed: April 29, 2016
    Date of Patent: July 9, 2019
    Assignee: President and Fellows of Harvard College
    Inventors: Yoshito Kishi, Wuming Yan, Jingwei Li, Zhanjie Li, Kenzo Yahata
  • Publication number: 20180230164
    Abstract: The present invention provides unified synthesis of the CI-CI 9 building blocks of halichondrins and analogs theoreof using selective coupling of poly-halogenated nucleophiles in chromium-mediated coupling reactions. The present invention also provides a practical and efficient synthesis of C20-C38 building blocks of halichondrins and analogs thereof. Also provided herein are general methods of selective activation and coupling of poly-halogenated analogs with an aldehyde. The provided coupling reactions are selective for halo-enone and halo-acetylenic ketal over vinyl halide and halide attached to a sp hydridized carbon. The provided efficient selective coupling reactions can allow easy access to the CI-CI 9 building blocks and C20-C38 building blocks of halichondrins and analogs thereof with limited or no purification or separation of the intermediates.
    Type: Application
    Filed: April 29, 2016
    Publication date: August 16, 2018
    Applicant: President and Fellows of Harvard College
    Inventors: Yoshito Kishi, Wuming Yan, Jingwei Li, Jhanjie Li, Kenzo Yahata
  • Publication number: 20180155361
    Abstract: Provided herein are palladium-mediated coupling reactions useful in the preparation of ketone-containing organic molecules. The provided methods can be used for the preparation of natural products and pharmaceutical agents, including Eribulin, halichondrins, and analogs thereof. The present invention also provides novel halichondrin analogs which can be prepared via the palladium-mediated coupling reactions. The novel halichondrin analogs can be used in the prevention and/or treatment of diseases or conditions (e.g., proliferative diseases such as cancer).
    Type: Application
    Filed: November 10, 2017
    Publication date: June 7, 2018
    Inventors: Jung Hwa Lee, Yoshito Kishi
  • Patent number: 9938288
    Abstract: The present invention provides novel Compound (1) having tumor vascular remodeling effect and/or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, and a medical uses thereof.
    Type: Grant
    Filed: November 15, 2017
    Date of Patent: April 10, 2018
    Assignees: President and Fellows of Harvard College, Eisai R&D Management Co., LTD.
    Inventors: Yoshito Kishi, Kazunobu Kira, Ken Ito