Syntarga Bv

Synthon Biopharmaceuticals B.v.

Byondis B.v.

Georg-August-Universitat Gottingen Stiftung Offentlichen Rechts

Patrick Henry Beusker

Franciscus Marinus Hendrikus De Groot

Henri Johannes Spijker

Johannes Albertus Frederikus Joosten

Rudy Gerardus Elisabeth Coumans

Ronald Christiaan Elgersma

Gijsbertus Franciscus Maria Verheijden

Peter Johannes Goedings

Tijl Huijbregts

Wiro Michael Petrus Bernardus Menge

Willem Dokter

Johannes Albertus Joosten

Franciscus Marinus De Groot

Johannes Wilhelm Scheeren

Rudy Gerardus Coumans

Wiro Michael Menge

Dick De Vos

Lutz F Tietze

Felix Major

Leonardus Wilhelmus Adriaan Van Berkom

Guuske Frederike Busscher

Antoinette Eugenie Seelen

Ralph Koekkoek

Carsten Albrecht

Wiro Menge

Wiro Michaël Petrus Bernardus Menge

Leonardus Wilhelmus Van Berkom

Franciscus Marinus Hendrikus Groot De

Tijl Huijbrgts

Franciscus Mariuns Hendrikus De Groot

The present invention relates to duocarmycin-containing antibody-drug conjugates (ADCs) for use in the treatment of human solid tumours and haematological malignancies expressing HER2, in particular breast cancer, gastric cancer, bladder cancer, ovarian cancer, lung cancer, prostate cancer, pancreatic cancer, colorectal cancer, head and neck squamous cell cancer or osteosarcoma, and acute lymphoblastic leukaemia. In particular, the present invention relates to duocarmycin-containing ADCs for use in the treatment of human solid tumours with HER2 IHC 2+ or 1+ and HER2 FISH negative tissue status. Advantageously, the present invention relates to duocarmycin-containing ADCs for use in the treatment of triple negative breast cancer (TNBC).

Duocarmycin ADCs showing improved in vivo antitumor activity

This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Conjugates of CC-1065 analogs and bifunctional linkers

This invention relates to novel agents that are analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and their conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Substituted CC-1065 analogs and their conjugates

The present invention relates to a process comprising converting a compound of formula (I) into a compound of formula (II) by reaction with an organolithium reagent, which compound can be further converted into duocarmycin analogs consisting of a DNA-alkylating and a DNA-binding part, and still further into corresponding antibody-drug conjugates. 

Process for making duocarmycin prodrugs

CC-1065 analogs and their conjugates

The present invention relates to duocarmycin-containing antibody-drug conjugates (ADCs) for use in the treatment of human solid tumors and haematological malignancies expressing HER2, in particular breast cancer, gastric cancer, bladder cancer, ovarian cancer, lung cancer, prostate cancer, pancreatic cancer, colorectal cancer, head and neck squamous cell cancer or osteosarcoma, and acute lymphoblastic leukaemia. In particular, the present invention relates to duocarmycin-containing ADCs for use in the treatment of human solid tumors with HER2 IHC 2+ or 1+ and HER2 FISH negative tissue status. Advantageously, the present invention relates to duocarmycin-containing ADCs for use in the treatment of triple negative breast cancer (TNBC).

Duocarmycin ADCS showing improved in vivo antitumor activity

This invention relates to novel analogs of the DNA-binding alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and their conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

Water-soluble CC-1065 analogs and their conjugates

This invention relates to compounds comprising one or more therapeutic and/or diagnostic moieties and one or more functional moieties linked together via one or more triazole-containing linkers and to their intermediates and methods of their preparation. The triazole-containing linker may optionally contain one or more conditionally-cleavable or conditionally-transformable moieties and one or more spacer systems in between said moiety/moieties and the one or more therapeutic and/or diagnostic moieties.

Triazole-containing releasable linkers, conjugates thereof, and methods of preparation

This invention concerns multiple release spacers and spacer systems, which release multiple leaving groups following a single activation. It concerns compounds comprising a specifier linked to two or more of the same or different leaving groups (L in the figure) via a self-eliminating multiple release spacer or spacer system, which compounds upon a single activation step, in particular removal or transformation of the specifier, release at least two leaving groups. 

Prodrugs built as multiple self-elimination-release spacers

This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V&#x2014;(W)&#x2014;(X)&#x2014;A&#x2014;Z, wherein: V is a specifier; (W)&#x2014;(X)&#x2014;A is an elongated self-elimination spacer system; W and X are each a 1,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y)wherein: Y is a 1,(4+2n) electronic cascade spacer, or a group of formula U being a cyclization elimination spacer; Z is a therapeutic drug; k, l and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that: &#x2014;when A is (Y): k+l+m&#x2267;1, and if k+l+m=1; &#x2014;when A is U: k+l&#x2267;1.

Elongated and multiple spacers in activatible prodrugs

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Nijmegen, Netherlands

Patrick Henry Beusker