公开(公告)号：US09913921B2

公开(公告)日：2018-03-13

申请号：US14115455

申请日：2012-05-07

申请人： Marc Stefan Robillard ,  Johan Lub ,  Raffaella Rossin ,  Sandra Martina Van Ben Bosch ,  Ronny Mathieu Versteegen

发明人： Marc Stefan Robillard ,  Johan Lub ,  Raffaella Rossin ,  Sandra Martina Van Ben Bosch ,  Ronny Mathieu Versteegen

IPC分类号： A61K51/10 ,  A61K51/04 ,  B82Y5/00 ,  C07D207/46 ,  C07D235/02 ,  C07D245/02 ,  C07D249/16 ,  A61K47/68 ,  A61K49/10

CPC分类号： A61K51/1093 ,  A61K47/6897 ,  A61K49/106 ,  A61K51/041 ,  A61K51/0495 ,  A61K51/0497 ,  B82Y5/00 ,  C07D207/46 ,  C07D235/02 ,  C07D245/02 ,  C07D249/16

摘要： 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.

公开(公告)号：US09421274B2

公开(公告)日：2016-08-23

申请号：US14117246

申请日：2012-05-16

申请人： Marc Stefan Robillard ,  Hendricus Marie Janssen ,  Wolter Ten Hoeve ,  Ronny Mathieu Versteegen

发明人： Marc Stefan Robillard ,  Hendricus Marie Janssen ,  Wolter Ten Hoeve ,  Ronny Mathieu Versteegen

IPC分类号： C07D257/08 ,  C07D237/26 ,  C07C13/263 ,  C07C33/16 ,  A61K31/435 ,  A61K31/502 ,  A61K31/045 ,  A61K47/48 ,  B82Y5/00

CPC分类号： A61K47/6803 ,  A61K31/435 ,  A61K31/444 ,  A61K31/704 ,  A61K38/05 ,  A61K39/3955 ,  A61K39/39558 ,  A61K47/22 ,  A61K47/545 ,  A61K47/555 ,  A61K47/558 ,  A61K47/6897 ,  B82Y5/00 ,  C07C33/16 ,  C07D237/26 ,  C07D257/08 ,  Y02A50/471

摘要： 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.

摘要翻译： 本发明涉及用于治疗剂的前药活化方法，其中使用对彼此具有生物正交反应性的非生物活性化学基团。 本发明还涉及包含至少一种前药和至少一种活化剂的前药盒，其中所述前药包含药物和第一生物正交反应性组（所述触发剂），并且其中所述活化剂包含第二生物正交反应性组 。 本发明还涉及上述方法和试剂盒中使用的靶向治疗剂。 本发明特别涉及抗体 - 药物偶联物和双特异性和三特异性抗体衍生物。

公开(公告)号：US20130272959A1

公开(公告)日：2013-10-17

申请号：US13994783

申请日：2011-12-16

申请人： Raffaella Rossin ,  Tilman Laeppchen ,  Sandra Martina Van Den Bosch ,  Marc Stefan Robillard ,  Ronny Mathieu Versteegen

发明人： Raffaella Rossin ,  Tilman Laeppchen ,  Sandra Martina Van Den Bosch ,  Marc Stefan Robillard ,  Ronny Mathieu Versteegen

IPC分类号： A61K51/04 ,  A61K45/06

CPC分类号： A61K51/044 ,  A61K31/495 ,  A61K45/06 ,  A61K47/4873 ,  A61K47/48746 ,  A61K47/6893 ,  A61K47/6897 ,  A61K51/0495 ,  A61K51/1027 ,  A61K51/1045 ,  A61K51/1093 ,  B82Y5/00

摘要： 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.

摘要翻译： 描述了一种方法，以及其中使用的试剂的组合，通过其可以将施用于受试者的药剂迅速地从循环中清除。 这通过提供与反应性基团的给药剂（例如用于预靶向的探针）并向澄清剂提供另一反应性基团来实现，所述反应性基团形成生物正交反应性对。 优选地，反应性对包括作为一种反应物的环辛烯或环辛烯，和作为其它反应物的二烯。 该方法和组合可用于从循环中除去任何可结合的分子，例如在预靶向法，靶向或成像剂递送过程中过量的预靶向探针，或去除任何生物分子 已经流通。

公开(公告)号：US20110039958A1

公开(公告)日：2011-02-17

申请号：US12865067

申请日：2009-01-30

申请人： Jakob Doetze Sikkema ,  Ronny Mathieu Versteegen ,  Maarten Jozef Pouderoijen

发明人： Jakob Doetze Sikkema ,  Ronny Mathieu Versteegen ,  Maarten Jozef Pouderoijen

IPC分类号： C08G65/38

CPC分类号： C07D401/10 ,  C08G65/44

摘要： The present invention relates to A phenol compound according to Formula (I): wherein: R1 is selected from the group consisting of, optionally substituted, 2-pyridyl, 3-pyridiyl and 4-pyridyl groups, wherein R1 is at position 2 or 3 of the phenol ring; R2 is selected from the group consisting of, optionally substituted, 2-pyridyl, 3-pyridiyl, 4-pyridyl and phenyl groups, wherein R2 is 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 C6-C12 aryl group or an optionally substituted C1-C10 alkyl 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.

摘要翻译： 本发明涉及式（I）的酚化合物：其中：R 1选自任选取代的2-吡啶基，3-吡啶基和4-吡啶基，其中R 1在2或3位 的酚环; R2选自任选取代的2-吡啶基，3-吡啶基，4-吡啶基和苯基，其中R2在酚环的5或6位; 酚环任选在一个或两个位置上独立地选自位置2,3,5和6与卤素原子或具有任选取代的C 6 -C 12芳基或任选取代的C 1 -C 10烷基取代。 本发明还涉及包含根据式（I）的酚化合物和包含所述（共））聚合物的膜和离子性树脂的（共）聚合物。

公开(公告)号：US09427482B2

公开(公告)日：2016-08-30

申请号：US13994783

申请日：2011-12-16

申请人： Raffaella Rossin ,  Tilman Laeppchen ,  Sandra Martina Van Den Bosch ,  Marc Stefan Robillard ,  Ronny Mathieu Versteegen

发明人： Raffaella Rossin ,  Tilman Laeppchen ,  Sandra Martina Van Den Bosch ,  Marc Stefan Robillard ,  Ronny Mathieu Versteegen

IPC分类号： A61K51/00 ,  A61M36/14 ,  A61K51/04 ,  A61K47/48 ,  A61K51/10 ,  B82Y5/00 ,  A61K45/06 ,  A61K31/495

CPC分类号： A61K51/044 ,  A61K31/495 ,  A61K45/06 ,  A61K47/4873 ,  A61K47/48746 ,  A61K47/6893 ,  A61K47/6897 ,  A61K51/0495 ,  A61K51/1027 ,  A61K51/1045 ,  A61K51/1093 ,  B82Y5/00

摘要： 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.

摘要翻译： 描述了一种方法，以及其中使用的试剂的组合，通过其可以将施用于受试者的药剂迅速地从循环中清除。 这通过提供与反应性基团的给药剂（例如用于预靶向的探针）并向澄清剂提供另一反应性基团来实现，所述反应性基团形成生物正交反应性对。 优选地，反应性对包括作为一种反应物的环辛烯或环辛烯，和作为其它反应物的二烯。 该方法和组合可用于从循环中除去任何可结合的分子，例如在预靶向法，靶向或成像剂递送过程中过量的预靶向探针，或去除任何生物分子 已经流通。

公开(公告)号：US20140093450A1

公开(公告)日：2014-04-03

申请号：US14115455

申请日：2012-05-07

申请人： Marc Stefan Robillard ,  Johan Lub ,  Raffaella Rossin ,  Sandra Martina Van Ben Bosch ,  Ronny Mathieu Versteegen

发明人： Marc Stefan Robillard ,  Johan Lub ,  Raffaella Rossin ,  Sandra Martina Van Ben Bosch ,  Ronny Mathieu Versteegen

IPC分类号： A61K51/04 ,  A61K51/10 ,  C07D245/02 ,  C07D235/02 ,  C07D207/46 ,  C07D249/16

CPC分类号： A61K51/1093 ,  A61K47/6897 ,  A61K49/106 ,  A61K51/041 ,  A61K51/0495 ,  A61K51/0497 ,  B82Y5/00 ,  C07D207/46 ,  C07D235/02 ,  C07D245/02 ,  C07D249/16

摘要： 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.

摘要翻译： 描述了用于靶向医学成像和/或治疗剂的预靶向方法和相关试剂盒，其中使用对彼此显示出生物正交反应性的非生物反应性化学基团。 本发明涉及使用[4 + 2]反电子需求（复古）Diels-Alder化学来提供预瞄准探针和效应探针之间的耦合。 为此目的，这些探针中的一个包括电子缺乏四嗪或其它合适的二烯，另一个是由于至少两个环外键的位置而具有扁平结构的E-环辛烯。

公开(公告)号：US07622131B2

公开(公告)日：2009-11-24

申请号：US11148552

申请日：2005-06-09

申请人： Anton Willem Bosman ,  Hendricus Marie Janssen ,  Gaby Maria Leonarda Van Gemert ,  Ronny Mathieu Versteegen ,  Egbert Willem Meijer ,  Rintje Pieter Sijbesma

发明人： Anton Willem Bosman ,  Hendricus Marie Janssen ,  Gaby Maria Leonarda Van Gemert ,  Ronny Mathieu Versteegen ,  Egbert Willem Meijer ,  Rintje Pieter Sijbesma

IPC分类号： A61K8/89 ,  A61K31/74 ,  A61Q15/00 ,  C08G77/00 ,  C08G77/26 ,  C08G77/388

CPC分类号： A61K8/898 ,  A61K8/0229 ,  A61K8/042 ,  A61Q15/00 ,  C08G77/26 ,  C08G77/388 ,  C08G77/54 ,  C08G83/008

摘要： 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.

摘要翻译： 本发明涉及含有自互补四氢键合基团（4H-单元）的硅氧烷聚合物的合成。 所得到的聚合物显示由基于4H单元之间的（超分子）相互作用的聚硅氧烷链之间的可逆的物理相互作用产生的独特的新特征。 本发明中的聚硅氧烷显示出前所未有的散装材料性能，并且用作有机硅流体的胶凝剂。 所得凝胶是透明的并且显示出良好的材料性质，同时具有无与伦比的高硅液体含量。

公开(公告)号：US09931408B2

公开(公告)日：2018-04-03

申请号：US14117655

申请日：2012-05-16

申请人： Marc Stefan Robillard ,  Hendricus Marie Janssen ,  Wolter Ten Hoeve ,  Ronny Mathieu Versteegen ,  Raffaella Rossin

发明人： Marc Stefan Robillard ,  Hendricus Marie Janssen ,  Wolter Ten Hoeve ,  Ronny Mathieu Versteegen ,  Raffaella Rossin

IPC分类号： C07D257/08 ,  C07D237/26 ,  A61K31/435 ,  A61K31/502 ,  C07C13/263 ,  C07C33/16 ,  A61K31/045 ,  A61K47/48 ,  B82Y5/00 ,  A61K31/704 ,  A61K38/05 ,  A61K39/395 ,  A61K47/22

CPC分类号： A61K47/6803 ,  A61K31/435 ,  A61K31/444 ,  A61K31/704 ,  A61K38/05 ,  A61K39/3955 ,  A61K39/39558 ,  A61K47/22 ,  A61K47/545 ,  A61K47/555 ,  A61K47/558 ,  A61K47/6897 ,  B82Y5/00 ,  C07C33/16 ,  C07D237/26 ,  C07D257/08 ,  Y02A50/471

摘要： 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.

公开(公告)号：US20140199331A1

公开(公告)日：2014-07-17

申请号：US14117246

申请日：2012-05-16

申请人： Marc Stefan Robillard ,  Hendricus Marie Janssen ,  Wolter Ten Hoeve ,  Ronny Mathieu Versteegen

发明人： Marc Stefan Robillard ,  Hendricus Marie Janssen ,  Wolter Ten Hoeve ,  Ronny Mathieu Versteegen

IPC分类号： A61K47/48

CPC分类号： A61K47/6803 ,  A61K31/435 ,  A61K31/444 ,  A61K31/704 ,  A61K38/05 ,  A61K39/3955 ,  A61K39/39558 ,  A61K47/22 ,  A61K47/545 ,  A61K47/555 ,  A61K47/558 ,  A61K47/6897 ,  B82Y5/00 ,  C07C33/16 ,  C07D237/26 ,  C07D257/08 ,  Y02A50/471

摘要： 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.

公开(公告)号：US20110301288A1

公开(公告)日：2011-12-08

申请号：US13133217

申请日：2009-12-18

申请人： Mark Johannes Boerakker ,  Aylvin Jorge Angelo Dias ,  Ronny Mathieu Versteegen

发明人： Mark Johannes Boerakker ,  Aylvin Jorge Angelo Dias ,  Ronny Mathieu Versteegen

IPC分类号： C09D181/00 ,  C08G75/26 ,  C07C327/06 ,  B82Y30/00

CPC分类号： C07C327/06 ,  C07C327/22 ,  C08G75/26

摘要： The present invention relates to thioic acids according to formula (II) suitable as building block for polythioesters; Wherein X is O, N or S and whereby R1 is chosen from (—CH2—)2, —CH2—O—CH2— or (—CH2—)3, R2 is preferably chosen from a biodegradable oligomer or polymer chosen from poly(lactide) (PLLA), polyglycolide (PGA), co-oligomers or copolymers of PLA and PGA (PLGA), poly(anhydrides), poly(trimethylenecarbonates), poly(orthoesters), poly(dioxanones), poly(ε-caprolactones) (PCL) or polyesteramides and n>1.

摘要翻译： 本发明涉及适合作为聚硫酯的结构单元的式（II）的硫酸; 其中X是O，N或S，其中R 1选自（-CH 2 - ）2，-CH 2 -O-CH 2 - 或（-CH 2 - ）3，R 2优选选自可生物降解的低聚物或聚合物， 丙交酯）（PLLA），聚乙交酯（PGA），PLA和PGA（PLGA）的共低聚物或共聚物，聚（酸酐），聚（三亚甲基碳酸酯），聚（原酸酯），聚（二氧杂环戊烯酮），聚（ε-己内酯 ）（PCL）或聚酯酰胺，n> 1。