公开(公告)号：US06603046B1

公开(公告)日：2003-08-05

申请号：US09085673

申请日：1998-05-27

申请人： Arsalan Kharazmi ,  Søren Brøgger Christensen ,  Chen Ming ,  Thor Grundtvig Theander

发明人： Arsalan Kharazmi ,  Søren Brøgger Christensen ,  Chen Ming ,  Thor Grundtvig Theander

IPC分类号： C07C4976

CPC分类号： C07D207/333 ,  A61K31/12 ,  A61K31/135 ,  A61K31/165 ,  A61K31/22 ,  A61K31/27 ,  A61K31/34 ,  C07C45/00 ,  C07C45/62 ,  C07C45/67 ,  C07C45/673 ,  C07C45/71 ,  C07C45/74 ,  C07C45/78 ,  C07C47/575 ,  C07C49/835 ,  C07C49/84 ,  C07C69/24 ,  C07C271/44 ,  C07C323/59 ,  C07D303/32 ,  C07D307/46 ,  C07D311/64 ,  C07K5/0215 ,  Y02A50/409 ,  Y02A50/411 ,  Y02A50/478 ,  Y02A50/481 ,  Y02A50/488 ,  Y10S977/775 ,  Y10S977/907 ,  C07C47/565

摘要： The invention is drawn to novel bis-aromatic a,&bgr;-unsaturated ketones. The compounds are useful in the treatment and prophylaxis of diseases caused by parasites or bacteria.

摘要翻译： 本发明涉及新颖的双芳族a，β-不饱和酮。 该化合物可用于治疗和预防由寄生虫或细菌引起的疾病。

公开(公告)号：US5985935A

公开(公告)日：1999-11-16

申请号：US302726

申请日：1994-11-01

申请人： Arsalan Kharazmi ,  S.o slashed.ren Br.o slashed.gger Christensen ,  Chen Ming ,  Thor Grundtvig Theander

发明人： Arsalan Kharazmi ,  S.o slashed.ren Br.o slashed.gger Christensen ,  Chen Ming ,  Thor Grundtvig Theander

IPC分类号： A61K31/12 ,  A61K31/135 ,  A61K31/165 ,  A61K31/22 ,  A61K31/27 ,  A61K31/34 ,  A61K36/48 ,  A61P31/04 ,  A61P33/02 ,  A61P37/00 ,  C07C45/00 ,  C07C45/45 ,  C07C45/62 ,  C07C45/67 ,  C07C45/71 ,  C07C45/74 ,  C07C45/78 ,  C07C47/575 ,  C07C49/835 ,  C07C49/84 ,  C07C67/14 ,  C07C69/007 ,  C07C69/24 ,  C07C225/22 ,  C07C271/44 ,  C07C323/22 ,  C07C323/59 ,  C07D207/32 ,  C07D207/333 ,  C07D301/12 ,  C07D303/32 ,  C07D307/46 ,  C07D311/64 ,  C07K5/02

CPC分类号： C07D207/333 ,  A61K31/12 ,  A61K31/135 ,  A61K31/165 ,  A61K31/22 ,  A61K31/27 ,  A61K31/34 ,  C07C271/44 ,  C07C323/59 ,  C07C45/00 ,  C07C45/62 ,  C07C45/67 ,  C07C45/673 ,  C07C45/71 ,  C07C45/74 ,  C07C45/78 ,  C07C47/575 ,  C07C49/835 ,  C07C49/84 ,  C07C69/24 ,  C07D303/32 ,  C07D307/46 ,  C07D311/64 ,  C07K5/0215 ,  Y10S977/775 ,  Y10S977/907

摘要： Aromatic compounds, or prodrugs thereof, which contain an alkylating site and which are capable of alkylating the thiol group in N-acetyl-L-cysteine, in particular bis-aromatic .alpha.,.beta.-unsaturated ketones, are used for the preparation of pharmaceutical compositions or medicated feed, food or drinking water for the treatment or prophylaxis of diseases caused by microorganisms or parasites, in particular protozoa such as Leishmannia, Trypanosoma, Toxoplasma, Plasmodium, Pneumocystis, Babesia and Theileria, intestinal protozoa such as Trichormionas and Ciardia; Coccidia such as Eimeria, Isospora, Cryptosporidium; Cappilaria, Microsporidium, Sarcocystis. Trichlodina, Trichoditella, Dacihylogurus, Pseudodacthylogurus, Acantocephalus, Ichthylophtherius, Botrecephalus; and intracellular bacteria, in particular Mycobacterium, Legionella species, Listeria and Salmonella. Preferred compounds have the formula (II): X.sub.m --Ph--C(O)--CH.dbd.CH--Ph--Y.sub.n, wherein each phenyl group (Ph) may be mono- or polysubstituted; X and Y designate AR.sub.H or AZ, wherein A is O, S, NH or N(C.sub.1-6 alkyl), R.sub.H designates aliphatic hydrocarbyl, and Z is H or a masking group which is decomposed to liberate AH; m is 0, 1 or 2, and n is 0, 1, 2 or 3, whereby, when m is 2, then the two X are the same or different, and when n is 2 or 3, then the two or three Y are the same or different, with the proviso that n and m are not both 0. As examples of such compounds, chalcones, e.g. licochalcone A (obtainable i.a. from batches of Chinese licorice root of Glycyrrhiza species, e.g. G. uralensis or G. inflata) as well as hydroxy, alk(en)yl, and/or alk(en)yloxy analogues thereof are active in vitro and/or in vivo against i.a. L. major and P. falciparum.

公开(公告)号：US07745580B2

公开(公告)日：2010-06-29

申请号：US10543312

申请日：2003-12-30

申请人： Thor Grundtvig Theander ,  Ali Salanti ,  Lars Hviid ,  Trine Staalsø ,  Anja Tatiana Ramstedt Jensen ,  Thomas Lavstsen ,  Madelaine Dahlbäck

发明人： Thor Grundtvig Theander ,  Ali Salanti ,  Lars Hviid ,  Trine Staalsø ,  Anja Tatiana Ramstedt Jensen ,  Thomas Lavstsen ,  Madelaine Dahlbäck

IPC分类号： A61K39/00 ,  C07K1/00 ,  C07K2/00

CPC分类号： C07K16/205 ,  A61K38/00 ,  Y10S435/975

摘要： The present invention relates to nucleic acid molecules related to the var2csa gene family as well as amino acid sequences encoded by such nucleic acid molecules with respect to their role in mediating adhesion of infected red blood cells to chondroitin sulphate A (CSA) in the placenta which is characteristic for the pathogenesis of pregnancy associated malaria (PAM). Accordingly, The invention provides the use compounds that are related to VAR2CSA polypeptides var2csa nucleic acid molecules as medicaments, as well as it provides pharmaceutical compositions, in particular immunological compositions and vaccines, hereunder nucleotide-based vaccines comprising these compounds. In addition, the invention provides the use of the compounds mentioned for the manufacture of compositions, such as immunogenic compositions. Other aspects of the invention relates to methods of treatment and prevention of pregnancy associated malaria wherein these methods are based on the nucleic acid molecules and polypeptides the invention. As these compounds can also be used as biotechnological tools the invention provides in vitro diagnostic methods and kits comprising reagents and IgGs/antibodies designated to the use in such methods. The invention also relates to methods of identifying agents capable of modulating the VAR2CSA dependent adhesion to CSA and agent capable of interacting with VAR2CSA. Finally, a method for identifying polypeptides, which will induce a specific IgG/antibody response upon administration to a subject is provided by the invention.

摘要翻译： 本发明涉及与var2csa基因家族有关的核酸分子，以及由这些核酸分子编码的氨基酸序列，涉及它们在介导感染的红细胞与胎盘中的硫酸软骨素A（CSA）的粘附中的作用， 是怀孕相关疟疾（PAM）发病机制的特征。 因此，本发明提供了与VAR2CSA多肽var2csa核酸分子作为药物相关的用途化合物，以及其提供药物组合物，特别是免疫组合物和疫苗，以下包含这些化合物的基于核苷酸的疫苗。 此外，本发明提供了所述化合物用于制备组合物如免疫原性组合物的用途。 本发明的其它方面涉及治疗和预防妊娠相关疟疾的方法，其中这些方法基于本发明的核酸分子和多肽。 由于这些化合物也可用作生物技术工具，本发明提供了体外诊断方法和试剂盒，其中包括用于此类方法的试剂和IgG /抗体。 本发明还涉及鉴定能够调节VAR2CSA对CSA的依赖性粘附和能够与VAR2CSA相互作用的试剂的鉴定试剂的方法。 最后，本发明提供了鉴定多肽的方法，所述多肽在给予受试者时将诱导特异性IgG /抗体应答。

公开(公告)号：US20090324628A1

公开(公告)日：2009-12-31

申请号：US10585027

申请日：2004-12-28

申请人： Thor Grundtvig Theander ,  Thomas Lavstsen ,  Lars Hviid ,  Morten A. Nielsen ,  Pamela A. Magistrado ,  Ali Salanti ,  Trine Staalso ,  Anja Tatiana Ramstedt Jensen ,  Louise Jorgensen

发明人： Thor Grundtvig Theander ,  Thomas Lavstsen ,  Lars Hviid ,  Morten A. Nielsen ,  Pamela A. Magistrado ,  Ali Salanti ,  Trine Staalso ,  Anja Tatiana Ramstedt Jensen ,  Louise Jorgensen

IPC分类号： A61K39/00 ,  A61P37/04

CPC分类号： C07K14/445 ,  A61K39/00 ,  Y02A50/412

摘要： The present invention relates to nucleic acid molecules related to the PFD1235w/MAL7P1.1, PF11_0008, and PF13_0003 gene families as well as amino acid sequences encoded by such nucleic acid molecules with respect to their role in mediating adhesion of infected red blood cells to endothelial cells, which is characteristic for the pathogenesis of severe malaria (SM). Accordingly, the invention provides pharmaceutical compositions and vaccines, hereunder nucleotide-based vaccines comprising compounds that are related to VAR4, VAR5, and/or VAR6 polypeptides and PFD1235w/MAL7P1.1 PF11_0008, and/or PF13_0003 nucleic acid molecules. The invention further relates to the use of these compounds as medicaments and for the manufacture of compositions, such as immunogenic compositions. In addition, the invention relates to methods of treatment and prevention of severe malaria wherein these methods are based on the nucleic acid molecules and polypeptides of the invention. As these compounds can also be used as biotechnological tools the invention provides in vitro diagnostic methods and kits comprising reagents and IgGs/antibodies designated to the use in such methods. The invention also relates to methods of identifying agents capable of modulating the VAR4, VAR5, and/or VAR6 dependent adhesion to endothelial cells and agent capable of interacting with VAR4, VAR5, and/or VAR6. Finally, a method for identifying polypeptides, which will induce a specific IgG/antibody response upon administration to a subject is provided by the invention.

摘要翻译： 本发明涉及与PFD1235w / MAL7P1.1，PF11_0008和PF13_0003基因家族相关的核酸分子以及由这些核酸分子编码的氨基酸序列，涉及它们介导感染的红细胞与内皮粘附的作用 细胞，这是严重疟疾（SM）发病机制的特征。 因此，本发明提供药物组合物和疫苗，以下基于核苷酸的疫苗包含与VAR4，VAR5和/或VAR6多肽和PFD1235w / MAL7P1.1 PF11_0008和/或PF13_0003核酸分子相关的化合物。 本发明还涉及这些化合物作为药物和制备组合物如免疫原性组合物的用途。 此外，本发明涉及治疗和预防严重疟疾的方法，其中这些方法基于本发明的核酸分子和多肽。 由于这些化合物也可用作生物技术工具，本发明提供了体外诊断方法和试剂盒，其中包括用于此类方法的试剂和IgG /抗体。 本发明还涉及鉴定能够调节VAR4，VAR5和/或VAR6对内皮细胞和能够与VAR4，VAR5和/或VAR6相互作用的试剂依赖性粘附的试剂的方法。 最后，本发明提供了鉴定多肽的方法，所述多肽在给予受试者时将诱导特异性IgG /抗体应答。

公开(公告)号：US20070053928A1

公开(公告)日：2007-03-08

申请号：US10543312

申请日：2003-12-30

申请人： Thor Grundtvig Theander ,  Ali Salanti ,  Lars Hviid ,  Trine Staalso ,  Anja Jensen ,  Thomas Lavstsen ,  Madelaine Dahlback

发明人： Thor Grundtvig Theander ,  Ali Salanti ,  Lars Hviid ,  Trine Staalso ,  Anja Jensen ,  Thomas Lavstsen ,  Madelaine Dahlback

IPC分类号： A61K48/00 ,  G01N33/569 ,  C07K16/18 ,  C07K14/445 ,  C12N15/74 ,  A61K39/002

CPC分类号： C07K16/205 ,  A61K38/00 ,  Y10S435/975

摘要： The present invention relates to nucleic acid molecules related to the var2csa gene family as well as amino acid sequences encoded by such nucleic acid molecules with respect to their role in mediating adhesion of infected red blood cells to chondroitin sulphate A (CSA) in the placenta which is characteristic for the pathogenesis of pregnancy associated malaria (PAM). Accordingly, The invention provides the use compounds that are related to VAR2CSA polypeptides var2csa nucleic acid molecules as medicaments, as well as it provides pharmaccutical compositions, in particular immunological compositions and vaccines, hereunder nucleotide-based vaccines comprising these compounds. In addition, the invention provides the use of the compounds mentioned for the manufacture of compositions, such as immunogenic compositions. Other aspects of the invention relates to methods of treatment and prevention of pregnancy associated malaria wherein these methods are based on the nucleic acid molecules and polypeptides the invention. As these compounds can also be used as biotechnological tools the invention provides in vitro diagnostic methods and kits comprising reagents and IgGs/antibodies designated to the use in such methods. The invention also relates to methods of identifying agents capable of modulating the VAR2CSA dependent adhesion to CSA and agent capable of interacting with VAR2CSA. Finally, a method for identifying polypeptides, which will induce a specific IgG/antibody response upon administration to a subject is provided by the invention.

摘要翻译： 本发明涉及与var2csa基因家族有关的核酸分子，以及由这些核酸分子编码的氨基酸序列，涉及它们在介导感染的红细胞与胎盘中的硫酸软骨素A（CSA）的粘附中的作用， 是怀孕相关疟疾（PAM）发病机制的特征。 因此，本发明提供了与VAR2CSA多肽var2csa核酸分子作为药物相关的用途化合物，以及其提供药物组合物，特别是免疫组合物和疫苗，以下包含这些化合物的基于核苷酸的疫苗。 此外，本发明提供了所述化合物用于制备组合物如免疫原性组合物的用途。 本发明的其它方面涉及治疗和预防妊娠相关疟疾的方法，其中这些方法基于本发明的核酸分子和多肽。 由于这些化合物也可用作生物技术工具，本发明提供了体外诊断方法和试剂盒，其中包括用于此类方法的试剂和IgG /抗体。 本发明还涉及鉴定能够调节VAR2CSA对CSA的依赖性粘附和能够与VAR2CSA相互作用的试剂的鉴定试剂的方法。 最后，本发明提供了鉴定多肽的方法，所述多肽在给予受试者时将诱导特异性IgG /抗体应答。