公开(公告)号：WO2012156920A1

公开(公告)日：2012-11-22

申请号：PCT/IB2012/052447

申请日：2012-05-16

Applicant: KONINKLIJKE PHILIPS ELECTRONICS N.V. ,  ROBILLARD, Marc, Stefan ,  TEN HOEVE, Wolter ,  VERSTEEGEN, Ronny, Mathieu ,  ROSSIN, Raffaella ,  HOEBEN, Freek, Johannes, Maria

Inventor： ROBILLARD, Marc, Stefan ,  TEN HOEVE, Wolter ,  VERSTEEGEN, Ronny, Mathieu ,  ROSSIN, Raffaella ,  HOEBEN, Freek, Johannes, Maria

IPC: A61K47/48

CPC classification number: 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

Abstract: 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.

Abstract translation: 本发明涉及用于治疗的前药活化方法，其中使用由彼此表现出生物正交反应性的非生物反应性化学基团组成。 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药盒，其中前药包含药物和第一生物正交反应性基团（触发剂），并且其中活化剂包含第二生物正交反应性基团 。 本发明还涉及在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 - 药物偶联物和双和三特异性抗体衍生物。

公开(公告)号：WO2012049624A1

公开(公告)日：2012-04-19

申请号：PCT/IB2011/054481

申请日：2011-10-11

Applicant: KONINKLIJKE PHILIPS ELECTRONICS N.V. ,  LUB, Johan ,  TEN HOEVE, Wolter ,  ROSSIN, Raffaella ,  VAN DEN BOSCH, Sandra Martina ,  ROBILLARD, Marc Stefan

Inventor： LUB, Johan ,  TEN HOEVE, Wolter ,  ROSSIN, Raffaella ,  VAN DEN BOSCH, Sandra Martina ,  ROBILLARD, Marc Stefan

IPC: A61K47/48 ,  A61K51/04

CPC classification number: A61K51/1093 ,  A61K47/4813 ,  A61K47/48215 ,  A61K47/48723 ,  A61K47/6889 ,  A61K47/6891 ,  A61K49/16 ,  A61K51/0495 ,  A61K51/10 ,  B82Y5/00

Abstract: 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 chemistryin 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 one or more axial substituents.

Abstract translation: 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，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，另一个是具有一个或多个轴取代基的E-环辛烯。

公开(公告)号：WO2012156918A1

公开(公告)日：2012-11-22

申请号：PCT/IB2012/052445

申请日：2012-05-16

Applicant: KONINKLIJKE PHILIPS ELECTRONICS N.V. ,  ROBILLARD, Marc, Stefan ,  JANSSEN, Henricus, Marie ,  TEN HOEVE, Wolter ,  VERSTEEGEN, Ronny, Mathieu

Inventor： ROBILLARD, Marc, Stefan ,  JANSSEN, Henricus, Marie ,  TEN HOEVE, Wolter ,  VERSTEEGEN, Ronny, Mathieu

IPC: A61K47/48

CPC classification number: 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

Abstract: 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.

Abstract translation: 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：WO2012156919A1

公开(公告)日：2012-11-22

申请号：PCT/IB2012/052446

申请日：2012-05-16

Applicant: KONINKLIJKE PHILIPS ELECTRONICS N.V. ,  ROBILLARD, Marc, Stefan ,  JANSSEN, Henricus, Marie ,  TEN HOEVE, Wolter ,  VERSTEEGEN, Ronny, Mathieu ,  ROSSIN, Raffaella

Inventor： ROBILLARD, Marc, Stefan ,  JANSSEN, Henricus, Marie ,  TEN HOEVE, Wolter ,  VERSTEEGEN, Ronny, Mathieu ,  ROSSIN, Raffaella

IPC: A61K47/48

CPC classification number: 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

Abstract: 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.

Abstract translation: 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 - 药物偶联物和双和三特异性抗体衍生物。

公开(公告)号：WO2004083160A1

公开(公告)日：2004-09-30

申请号：PCT/IB2004/050264

申请日：2004-03-17

Applicant: KONINKLIJKE PHILIPS ELECTRONICS N.V. ,  TEN HOEVE, Wolter ,  HUISMAN, Bart-Hendrik

Inventor： TEN HOEVE, Wolter ,  HUISMAN, Bart-Hendrik

IPC: C07C43/305

CPC classification number: C07C49/697 ,  C07C13/62 ,  C07C17/16 ,  C07C17/361 ,  C07C43/313 ,  C07C2603/54 ,  C07C22/02 ,  C07C23/18

Abstract: The synthesis of a precursor oligocene, particularly pentacene, is a two-step process. In the fist step the Diels-Alder adduct of the a,b-dihydro-a,b-etheno-oligocene with a 1,1-dialkoxy-cyclopentadiene is formed. In the second step this Diels-Alder adduct is converted into the precursor oligocene, in that first the corresponding keto-compound is formed, which may be eliminated thereafter. The resulting precursor oligocene can be converted to the oligocene with a heat treatment, particularly after providing a solution hereof on a substrate. It is suitable for use as semiconductor material in a thin-film transistor. Formula (I).

Abstract translation: 前体寡烯，特别是并五苯的合成是两步法。 在第一步骤中，形成a，b-二氢-α，b-亚乙基 - 低聚烯烃与1,1-二烷氧基 - 环戊二烯的Diels-Alder加合物。 在第二步中，该狄尔斯 - 阿尔德加合物被转化为前体寡烯，因为首先形成相应的酮基化合物，此后可以除去它们。 所得到的前体寡烯可以通过热处理转化为寡烯，特别是在将其溶液提供在基材上之后。 它适用于薄膜晶体管中的半导体材料。 式（I）。

公开(公告)号：WO1993017030A1

公开(公告)日：1993-09-02

申请号：PCT/NZ1993000010

申请日：1993-02-26

Applicant: THE HORTICULTURE AND FOOD RESEARCH INSTITUTE OF ... ,  JONES, William, Thomas ,  WYNBERG, Hans ,  TEN HOEVE, Wolter

Inventor： THE HORTICULTURE AND FOOD RESEARCH INSTITUTE OF ...

IPC: C07F09/6571

CPC classification number: A62D3/02 ,  A61K47/643 ,  A62D2101/02 ,  A62D2101/26 ,  C07D319/06 ,  C07F9/657118 ,  C07F9/657154 ,  C07F9/65742 ,  C07K16/44 ,  G01N33/5308 ,  G01N33/6857 ,  Y10S436/815 ,  Y10S530/807

Abstract: The invention provides novel organophosphate compounds of formula (I), wherein X is selected from the group consisting of R-O-, R-S- and R-NH-, where R is an optionally substituted aromatic or heterocyclic group, or an optionally substituted alkyl or alkenyl group; Y is O or S; R is H or alkyl; and R is a group of the formula -(CH2)n- wherein n is an integer of from 0 to 10, or branched chain alkylene, or a group of the formula R -O-R wherein R and R are both straight or branched chain alkylene, and salts and esters thereof. These compounds are structurally similar to organophosphate pesticides, but may be conjugated to antigenic macromolecules. The invention therefore also provides immunoconjugates for use in preparing antibodies or fragments thereof which are capable of binding to ''parent'' organophosphate compounds and also the antibodies thus prepared. Such antibodies can be polyclonal or monoclonal with monoclonal antibodies being preferred. A method for detecting the presence of an organophosphate in a sample, and assay kits therefor are also provided, the method comprising the step of assaying the sample with an antibody or fragment thereof as provided by the invention. For such methods, the antibody can optionally be labelled or bound to a support or both. The methods of the invention are applicable to all classes of organophosphates.

Abstract translation: 本发明提供新的式（I）有机磷酸酯化合物，其中X选自RO-，RS-和R-NH-，其中R是任选取代的芳族或杂环基，或任选取代的烷基或烯基 组; Y为O或S; R 1是H或烷基; 并且R 2是式 - （CH 2）n - 其中n是0至10的整数的基团，或支链亚烷基或式R 3 -OR 4的基团，其中R 3和R 4都是直链或支链亚烷基，及其盐和酯。 这些化合物在结构上类似于有机磷农药，但可以与抗原性大分子缀合。 因此，本发明还提供了用于制备能够结合“母体”有机磷酸酯化合物的抗体或其片段的免疫偶联物，以及由此制备的抗体。 这样的抗体可以是多克隆或单克隆抗体，优选单克隆抗体。 还提供了用于检测样品中有机磷酸盐存在的方法及其测定试剂盒，该方法包括用本发明提供的抗体或其片段测定样品的步骤。 对于这样的方法，抗体可以任选地被标记或结合到载体或两者。 本发明的方法适用于所有类型的有机磷酸盐。