Tagworks Pharmaceuticals B.v.

Koninklijke Philips Corporation N.v.

Suprapolix B.v.

Other

Syncom B.v.

Ronny Mathieu Versteegen

Marc Stefan Robillard

Wolter Ten Hoeve

Raffaella Rossin

Hendricus Marie Janssen

Egbert Willem Meijer

Anton Willem Bosman

Henricus Marie Janssen

Gaby Maria Leonarda Van Gemert

Johan Lub

Doetze Jakob Sikkema

Sandra Martina Van Den Bosch

Rintje Pieter Sijbesma

Freek Johannes Maria Hoeben

Arthur Henry Antoon Marie Van Onzen

Sandra Martina Van Ben Bosch

Tilman Laeppchen

Maarten Jozef Pouderoijen

Laurens Henri Johan Kleijn

Martijn Hendrikus Martinus Gerardus Maria Den Brok

Lieke Willemijn Maria Wouters

Kim Elisa De Roode

Lucas Hendricus Maria Zijlmans

Disclosed is an advancement in provoked chemical cleavage. Thereby the invention provides the use of a diene as a chemically cleavable group attached to a Construct, and the use of a dienophile to provoke the release of the Construct by allowing the diene to react with a dienophile capable of undergoing an inverse electron demand Diels Alder reaction with the diene. The invention includes a kit for releasing a Construct Cbound to a Trigger T, the kit having a tetrazine and a dienophile, wherein the Trigger is the tetrazine. The invention also includes the use of the formation of a pyridazine by reacting a tetrazine having a Construct Cbound thereto and a dienophile, as a chemical tool for the release, in a chemical, biological or physiological environment, of the Construct.

Cleavable tetrazine used in bio-orthogonal drug activation

The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

Bio-orthogonal drug activation

Disclosed is the use of the reactive components of the inverse electron-demand Diels Alder reaction for chemical masking and unmasking in vitro. This can be applied in complex chemical reactions and, particularly in the synthesis of biomolecules, e.g. on solid supports. The reactive components are a dienophile, particularly a trans-cyclooctene, and a diene, particularly a tetrazine.

Chemically cleavable group

Described is a pretargeting method, and related kits, for targeted medical imaging and/or therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention involves the use of [4+2] inverse electron demand (retro) Diels-Alder chemistry in providing the coupling between a Pre-targeting Probe and an Effector Probe. To this end one of these probes comprises an electron-deficient tetrazine or other suitable diene, and the other an E-cyclooctene which has a flattened structure as a result of the position of at least two exocyclic bonds.

Pretargeting kit for imaging or therapy comprising a trans-cyclooctene dienophile and a diene

Described is a method, and a combination of agents for used therein, by which an agent administered to a subject can be rapidly cleared from circulation. This is achieved by providing an Administration Agent (e.g. a probe for pretargeting) with a reactive group and providing a Clearing Agent with another reactive group, said reactive groups forming a bio-orthogonally reactive pair. Preferably, the reactive pair comprises a cyclooctene or cyclooctyn as one reactant, and a diene as the other reactant. The method and combination can be used for the removal of any bindable molecule from circulation, such as an excess of a pre-targeting probe in the course of a pre-targeting method, a targeting or imaging agent delivered, or the removal of any biomolecule already present in circulation.

Agents for clearing biomolecules from circulation

The present invention relates to A phenol compound according to Formula (I): wherein: Ris selected from the group consisting of, optionally substituted, 2-pyridyl, 3-pyridiyl and 4-pyridyl groups, wherein Ris at position 2 or 3 of the phenol ring; Ris selected from the group consisting of, optionally substituted, 2-pyridyl, 3-pyridiyl, 4-pyridyl and phenyl groups, wherein Ris at position 5 or 6 of the phenol ring; and the phenol ring is optionally substituted at one or two positions, independently selected from positions 2, 3, 5 and 6, with a halogen atom or a with an optionally substituted C-Caryl group or an optionally substituted C-Calkyl group. The present invention relates also to (co)polymers comprising the phenol compound according to Formula (I) and membranes and ionic resins comprising said (co)polymers. 

Phenol compounds and (co)polymers thereof

The invention relates to supramolecular ionomers. i.e. polymers having quadruple hydrogen bonding units (4H-units) and ionic groups or ionogenic groups within their structure. The supramolecular ionomers can be dispersed or solubilized in water at high solids contents while maintaining low viscosities, facilitating easy use and processing of the resulting aqueous formulations. The aqueous supramolecular ionomer compositions have excellent film-forming properties. Moreover, the polymer materials have good mechanical properties after drying, as they are not tacky, show high elasticity and low or no creep.

Supramolecular ionomers

The invention relates to the synthesis of siloxane polymers containing self-complementary quadruple hydrogen bonding groups (4H-units). The resulting polymers show unique new characteristics that result from the reversible, physical interactions between the polysiloxane chains that are based on the (supramolecular) interactions between the 4H-units. The polysiloxanes in this invention show unprecedented bulk material properties and are used as gelling agents for silicone fluids. The resulting gels are clear and display good material properties, while having unparalleled high silicone fluid contents.

Siloxane polymers with quadruple hydrogen bonding units

Growing community of inventors

Hegelsom, Netherlands

Ronny Mathieu Versteegen