EP2550365 - PREDICTING HUMAN DEVELOPMENTAL TOXICITY OF PHARMACEUTICALS USING HUMAN STEM-LIKE CELLS AND METABOLOMICS [Right-click to bookmark this link] | Status | No opposition filed within time limit Status updated on 10.05.2019 Database last updated on 03.10.2024 | |
Former | The patent has been granted Status updated on 01.06.2018 | ||
Former | Grant of patent is intended Status updated on 17.01.2018 | ||
Former | Examination is in progress Status updated on 04.12.2017 | ||
Former | Grant of patent is intended Status updated on 18.07.2017 | ||
Former | Examination is in progress Status updated on 21.02.2017 | Most recent event Tooltip | 01.07.2022 | Lapse of the patent in a contracting state New state(s): MK | published on 03.08.2022 [2022/31] | Applicant(s) | For all designated states Stemina Biomarker Discovery, Inc. 504 S. Rosa Road Suite 150 Madison, WI 53719 / US | [2013/05] | Inventor(s) | 01 /
WEST, Paul, R. 7540 US Highway 14 Arena, WI 53503 / US | 02 /
WEIR, April, M. 6405 Woodington Way Madison, WI 53711 / US | 03 /
SMITH, Alan, M. 1146 Erin Street Madison, WI 53715 / US | 04 /
DONLEY, Elizabeth, L.R. 9201 Bear Claw Way Madison, WI 53717 / US | 05 /
CEZAR, Gabriela, G. 110 Vaughn Court Madison, WI 53705 / US | [2013/05] | Representative(s) | Vossius & Partner Patentanwälte Rechtsanwälte mbB Siebertstrasse 3 81675 München / DE | [2018/27] |
Former [2013/05] | Vossius & Partner Siebertstrasse 4 81675 München / DE | Application number, filing date | 11760090.8 | 22.03.2011 | [2018/27] | WO2011US29471 | Priority number, date | US20100316165P | 22.03.2010 Original published format: US 316165 P | US20100394426P | 19.10.2010 Original published format: US 394426 P | [2013/05] | Filing language | EN | Procedural language | EN | Publication | Type: | A1 Application with search report | No.: | WO2011119637 | Date: | 29.09.2011 | Language: | EN | [2011/39] | Type: | A1 Application with search report | No.: | EP2550365 | Date: | 30.01.2013 | Language: | EN | The application published by WIPO in one of the EPO official languages on 29.09.2011 takes the place of the publication of the European patent application. | [2013/05] | Type: | B1 Patent specification | No.: | EP2550365 | Date: | 04.07.2018 | Language: | EN | [2018/27] | Search report(s) | International search report - published on: | US | 29.09.2011 | (Supplementary) European search report - dispatched on: | EP | 06.08.2013 | Classification | IPC: | C12Q1/00 | [2013/05] | CPC: |
G01N33/5073 (EP,US);
G01N33/5014 (US);
G01N33/6848 (EP,US)
| Designated contracting states | AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LI, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR [2013/05] | Extension states | BA | Not yet paid | ME | Not yet paid | Title | German: | VORHERSAGE DER ENTWICKLUNG DER TOXIZITÄT VON PHARMAZEUTIKA FÜR MENSCHEN MITHILFE MENSCHLICHER STAMMZELLEN UND METABOLOME | [2013/05] | English: | PREDICTING HUMAN DEVELOPMENTAL TOXICITY OF PHARMACEUTICALS USING HUMAN STEM-LIKE CELLS AND METABOLOMICS | [2013/05] | French: | PRÉDICTION DE LA TOXICITÉ SUR LE DÉVELOPPEMENT HUMAIN D'AGENTS PHARMACEUTIQUES AU MOYEN DE CELLULES DE TYPE CELLULES SOUCHES HUMAINES ET DE LA MÉTABOLOMIQUE | [2013/05] | Entry into regional phase | 22.10.2012 | National basic fee paid | 22.10.2012 | Search fee paid | 22.10.2012 | Designation fee(s) paid | 22.10.2012 | Examination fee paid | Examination procedure | 22.10.2012 | Examination requested [2013/05] | 06.06.2014 | Amendment by applicant (claims and/or description) | 13.11.2015 | Despatch of a communication from the examining division (Time limit: M06) | 17.06.2016 | Despatch of communication that the application is deemed to be withdrawn, reason: reply to the communication from the examining division not received in time | 27.06.2016 | Reply to a communication from the examining division | 20.07.2016 | Despatch of a communication from the examining division (Time limit: M02) | 06.09.2016 | Reply to a communication from the examining division | 10.02.2017 | Despatch of a communication from the examining division (Time limit: M04) | 31.05.2017 | Reply to a communication from the examining division | 19.07.2017 | Communication of intention to grant the patent | 28.11.2017 | Disapproval of the communication of intention to grant the patent by the applicant or resumption of examination proceedings by the EPO | 18.01.2018 | Communication of intention to grant the patent | 24.05.2018 | Fee for grant paid | 24.05.2018 | Fee for publishing/printing paid | 24.05.2018 | Receipt of the translation of the claim(s) | Divisional application(s) | The date of the Examining Division's first communication in respect of the earliest application for which a communication has been issued is 13.11.2015 | Opposition(s) | 05.04.2019 | No opposition filed within time limit [2019/24] | Request for further processing for: | The application is deemed to be withdrawn due to failure to reply to the examination report | 27.06.2016 | Request for further processing filed | 27.06.2016 | Full payment received (date of receipt of payment) Request granted | 13.07.2016 | Decision despatched | The application is deemed to be withdrawn due to failure to reply to the Extended European Search Report/Written Opinion of the International Searching Authority/International Preliminary Examination Report/Supplementary international search report/Supplementary European search report | 06.06.2014 | Request for further processing filed | 06.06.2014 | Full payment received (date of receipt of payment) Request granted | 20.06.2014 | Decision despatched | Fees paid | Renewal fee | 27.03.2013 | Renewal fee patent year 03 | 27.03.2014 | Renewal fee patent year 04 | 27.03.2015 | Renewal fee patent year 05 | 31.03.2016 | Renewal fee patent year 06 | 27.03.2017 | Renewal fee patent year 07 | 27.03.2018 | Renewal fee patent year 08 |
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Responsibility for the accuracy, completeness or quality of the data displayed under the link provided lies entirely with the Unified Patent Court. | Lapses during opposition Tooltip | AL | 04.07.2018 | AT | 04.07.2018 | CY | 04.07.2018 | CZ | 04.07.2018 | EE | 04.07.2018 | ES | 04.07.2018 | FI | 04.07.2018 | HR | 04.07.2018 | IT | 04.07.2018 | LT | 04.07.2018 | LV | 04.07.2018 | MC | 04.07.2018 | MK | 04.07.2018 | PL | 04.07.2018 | RO | 04.07.2018 | RS | 04.07.2018 | SI | 04.07.2018 | SK | 04.07.2018 | SM | 04.07.2018 | TR | 04.07.2018 | BG | 04.10.2018 | NO | 04.10.2018 | GR | 05.10.2018 | IS | 04.11.2018 | PT | 05.11.2018 | LU | 22.03.2019 | MT | 22.03.2019 | [2022/31] |
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LU | 22.03.2019 | ||
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Former [2019/07] | LT | 04.07.2018 | Documents cited: | Search | [A]US2002081626 (KADDURAH-DAOUK RIMA [US], et al) [A] 1-25 * para 0011 *; | [XI]US2007248947 (CEZAR GABRIELA G [US]) [X] 16-18 * claims 17, 31,-33 45, para's 0046, 0053, 0060 ff,0075,0078,0079 * [I] 1-15,20-25; | [A] - TIBONI ET AL., "Production of Axial Skeletal Malformations with the Nitric Oxide Synthesis Inhibitor NG-Nitro-L-Arginine Methyl Ester (L-NAME) in the Mouse.", BIRTH DEFECTS RESEARCH PART B: DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY, (200702), vol. 80, no. IS.1, pages 28 - 33, XP002705233 [A] 1-25 * abstract * DOI: http://dx.doi.org/10.1002/bdrb.20100 | [IP] - WEST P R ET AL, "Predicting human developmental toxicity of pharmaceuticals using human embryonic stem cells and metabolomics", TOXICOLOGY AND APPLIED PHARMACOLOGY, ACADEMIC PRESS, AMSTERDAM, NL, vol. 247, no. 1, ISSN 0041-008X, (20100815), pages 18 - 27, (20100521), XP027142153 [IP] 1-25 * abstract * | [T] - WEST P R ET AL, "A High Throughput Metabolite-Based Biomarker Approach to Predict Developmental Toxicity Using Human Embryonic Stem Cells", INTERNATIONAL JOURNAL OF TOXICOLOGY, & 33RD ANNUAL MEETING OF THE AMERICAN-COLLEGE-OF-TOXICOLOGY; , FL, USA; NOVEMBER 04 -07, 2012, (201301), vol. 32, no. 1, page 70, XP009171379 [T] * the whole document * | [T] - KLEINSTREUER N C ET AL, "Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics", TOXICOLOGY AND APPLIED PHARMACOLOGY, ACADEMIC PRESS, AMSTERDAM, NL, vol. 257, no. 1, doi:10.1016/J.TAAP.2011.08.025, ISSN 0041-008X, (20110828), pages 111 - 121, (20110903), XP028112545 [T] * the whole document * DOI: http://dx.doi.org/10.1016/j.taap.2011.08.025 | International search | [Y]US2002081626 (KADDURAH-DAOUK RIMA [US], et al); | [Y]US2004086982 (HERMANN THERON [US], et al); | [Y]US2007166707 (SCHADT ERIC E [US], et al); | [X]US2007248947 (CEZAR GABRIELA G [US]) | [Y] - CEZAR ET AL., "Identification of Small Molecules from Human Embryonic Stem Cells Using Metabolomics.", STEM CELLS AND DEVELOPMENT, (2007), vol. 16, pages 869 - 882 | by applicant | US6200806 | - BRENT; BECKMAN, BULL NY ACAD MED, (1990), vol. 66, pages 123 - 63 | - ROSANO ET AL., J. EPIDEMIOLOGY COMMUNITY HEALTH, (2000), vol. 54, pages 660 - 66 | - BECKMAN; BRENT, ANNU REV PHARMACOL, (1984), vol. 24, pages 483 - 500 | - CLAUDIO ET AL., ENVIRONM HEALTH PERSPECT, (2001), vol. 109, pages A254 - A261 | - PIERSMA, TOXICOLOGY LETTERS, (2004), vol. 149, pages 147 - 53 | - GREAVES ET AL., NAT REV DRUG DISCOV, (2004), vol. 3, pages 226 - 36 | - HUUSKONEN, TOXICOLOGY & APPLIED PHARM, (2005), vol. 207, pages S495 - S500 | - HUUSKONEN, TOXICOLOGY & APPLIED PHARM, (2005), vol. 207, page 495 | - SOGA ET AL., J BIOL CHEM, (2006), vol. 281, pages 16768 - 78 | - ZHAO ET AL., BIRTH DEFECTS RES A CLIN MOL TERATOL, (2006), vol. 76, pages 230 - 6 | - LEVENSTEIN ET AL., STEM CELLS, (2005), vol. 24, pages 568 - 574 | - LI ET AL., BIOTECHNOL BIOENG, (2005), vol. 91, pages 688 - 698 | - LUDWIG ET AL., "Feeder-independent culture of human embryonic stem cells", NAT METHODS, (2006), vol. 3, pages 637 - 46 | - KIRK-OTHMER, Encyclopedia of Chemical Technology, JOHN WILEY & SONS, (1995), vol. 15, pages 1071 - 1094 | - LU ET AL., MOL. TERATOLOGY, (2008), vol. 82, pages 670 - 675 | - ROCK ET AL., J. BIOL. CHEM., (2000), vol. 275, pages 1377 - 1383 | - NELSON ET AL., J. NUTR., (1957), vol. 62, pages 395 - 405 | - BAKER ET AL., AM. J. CLIN. NUTR., (1975), vol. 28, pages 56 - 65 | - SIMONIAN ET AL., ANN REV PHARM. TOX., (1996), vol. 36, pages 83 - 106 | - REPINE ET AL., AM. J. RESP. CRITICAL CARE MED., (1997), vol. 156, pages 341 - 357 | - WALSH ET AL., SEMIN. REPROD. MED., (1998), vol. 16, pages 93 - 104 | - ISIBASHI ET AL., FREE RAD. BIOL. MED., (1997), vol. 22, pages 447 - 454 | - ZHAO ET AL., BIRTH DEFECTS RESEARCH PART A: CLINICAL AND MOLECULAR TERATOLOGY, (2006), vol. 76, pages 230 - 236 | - NACHMANY ET AL., J. NEUROCHEM., (2006), vol. 96, pages 247 - 253 | - ABRAMOVICI, A.; SHAKLAI, M.; PINKHAS, J., "Myeloschisis in a six weeks embryo of a leukemic woman treated with busulfan", TERATOLOGY, (2005), vol. 18, pages 241 - 245 | - ADLER, S.; PELLIZZER, C.; HARENG, L.; HARTUNG, T.; BREMER, S., "First steps in establishing a developmental toxicity test method based on human embryonic stem cells", TOXICOLOGY IN VITRO, (2008), vol. 22, pages 200 - 211 | - ALEXANDER, P.; CHAU, L.; TUAN, R., "Role of nitric oxide in chick embryonic organogenesis and dysmorphogenesis", BIRTH DEFECTS RESEARCH PART A: CLINICAL AND MOLECULAR TERATOLOGY, (2007), vol. 79, pages 581 - 594 | - ALPERT, A., "Hydrophilic-interaction chromatography for the separation of peptides, nucleic acids, and other polar compounds", JOURNAL OF CHROMATOGRAPHY, (1990), vol. 499, pages 177 - 196 | - ANDERSON, D.; KIETH, J.; NOVAK, P.; ELLIOT, M., "teratogen", MOSBY'S MEDICAL, NURSING & ALLIED HEALTH DICTIONARY, (2002), page 1690 | - BAKER H; FRAN O; THOMSON A; LANGER A; MUNVES E; DEANGELIS B ET AL., "Vitamin profile of 174 mothers and newborns at parturition", AM J CLIN NUTR., (1975), vol. 28, pages 56 - 65 | - BARR, D.; SILVA, M.; KATO, K. ET AL., "Assessing human exposure to phthalates using monoesters and their oxidized metabolites as biomarkers", ENVIRONMENTAL HEALTH PERSPECTIVE, (2003), vol. 11, pages 1148 - 1151 | - BAUMAN, K.A., "Neuropathology of infantile autism", JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, (1998), vol. 57, pages 645 - 652 | - BOGDANOV, M.; MATSON, W.R.; WANG, L. ET AL., "Metabolomic profiling to develop blood biomarkers for Parkinson's disease", BRAIN, (2008), vol. 131, pages 389 - 396 | - BRENT, R.; HOLMES, L., "Clinical and basic science from the thalidomide tragedy: what have we learned about the causes of limb defects?", TERATOLOGY, (1988), vol. 38, pages 241 - 251 | - BRIEMAN, L., "Random Forests", MACHINE LEARNING, (2001), vol. 45, pages 5 - 32 | - CEZAR, G.; QUAM, J.; SMITH, A. ET AL., "Identification of small molecules from human embryonic stem cells using metabolomics", STEM CELLS AND DEVELOPMENT, (2007), vol. 16, pages 869 - 882 | - CHAPIN, R.; AUGUSTIN-RAUCH, K.; BEYER, B. ET AL., "State of the art in developmental toxicity screening methods and a way forward: a meeting report addressing embryonic stem cells, whole embryo culture, and zebrafish", BIRTH DEFECTS RESEARCH PART B: DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY, (2008), vol. 83, pages 446 - 456 | - DILIBERTI, J.; FARNDON, P.; DENNIS, N.; CURRY, C., "The fetal valproate syndrome", AM. J. MED. GENETIC., (1984), vol. 19, pages 473 - 481 | - GENSCHOW, E.; SCHOLZ, G.; BROWN, N. ET AL., "Development of prediction models for three in vitro embryotoxicity tests in an ECVAM validation study", IN VITRO MOLECULAR TOXICOLOGY, (2000), vol. 13, pages 51 - 66 | - GENSCHOW, E.; SPIELMANN, H.; SCHOLZ, G. ET AL., "The ECVAM international validation study on in vitro embryotoxicity tests: results of the definitive phase and evaluation of prediction models", EUROPEAN CENTRE FOR THE VALIDATION OF ALTERNATIVE METHODS. ALTERNATIVES TO LABORATORY ANIMALS, (2002), vol. 30, pages 151 - 176 | - GOODACRE, R.; VAIDYANATHAN, S.; DUNN, W.B.; HARRIGAN, G.G.; KELL, D.B., "Metabolomics by numbers: acquiring and understanding global metabolite data", TRENDS IN BIOTECHNOLOGY, (2004), vol. 22, pages 245 - 252 | - ISIBASHI M; AKAZAWA S; SAKAMAKE H, "Oxygen-induced embryopathy and the significance of glutathione-dependent antioxidant system in the rate embryo during early organogenesis", FREE RAID BIOL MED., (1997), vol. 22, pages 447 - 54 | - KIND, T.; TOLSTIKOV, V.; FIEHN, O.; WEISS, R., "A comprehensive urinary metabolomic approach for identifying kidney cancer", ANALYTICAL BIOCHEMISTRY, (2007), vol. 363, pages 185 - 195 | - LEE, Q.; JUCHAU, M., "Dysmorphogenic effects of nitric oxide (NO) and NO-synthase inhibition: studies with intra-amniotic injections of sodium nitroprusside and N-monmethyl-L-arginine", TERATOLOGY, (2005), vol. 49, pages 452 - 464 | - LIAW, A.; WIENER, M., "Classification and regression by random forest", R NEWS: THE NEWSLETTER OF THE R PROJECT, (2002), vol. 2, pages 18 - 22 | - LU W; ZHU H; WEN S; YANG W; SHAW G; LAMMER E ET AL., "Nicotinamide N-methyl transferase (NNMT) gene polymorphisms and risk for spina bifida", BIRTH DEFECTS RESEARCH PART A: CLINICAL AND MOLECULAR TERATOLOGY, (2008), vol. 82, no. 10, pages 670 - 5 | - LUJAN, R.; SHIGEMOTO, R.; LOPEZ-BENDITO, G., "Glutamate and GABA receptor signaling in the developing brain", NEUROSCIENCE, (2005), vol. 130, pages 567 - 580 | - MARX-STOELTING, P.; ADRIAENS, E.; AHR, H. ET AL., "A review of the implementation of the embryonic stem cell test (EST). The report and recommendations of an ECVAM/ReProTect Workshop", ALTERNATIVES TO LABORATORY ANIMALS, (2009), vol. 37, pages 313 - 328 | - MILLER, M.; STROMLAND, K., "Teratogen update: Thalidomide: a review, with a focus on ocular findings and new potential uses", TERATOLOGY, (1999), vol. 60, pages 306 - 321 | - NACHMANY, A.; GOLD, V.; TSUR, A.; ARAD, D.; WEIL, D., "Neural tube closure depends on nitric oxidase synthase activity", J. NEUROCHEM., (2006), vol. 96, pages 247 - 253 | - NELSON M; WRIGHT H; BARID C; EVANS M, "Teratogenic effects of pantothenic acid deficiency in the rat", J NUTR., (1957), vol. 62, pages 395 - 405 | - NIEDEN, N.Z.; RUF, L.; KEMPKA, G.; HILDEBRAND, H.; AHR, H., "Molecular markers in embryonic stem cells", TOXICOLOGY IN VITRO, (2001), vol. 15, pages 455 - 461 | - PAQUETTE, J.; KUMPF, S.; STRECK, R.; THOMSON, J.; CHAPIN, R.; STEDMAN, D., "Assessment of the embryonic stem cell test and application and use in the pharmaceutical industry", BIRTH DEFECTS RESEARCH PART B: DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY, (2008), vol. 83, pages 104 - 111 | - PEARL, P.; BIGSON, K., "Clinical aspects of the disorder of GABA metabolism in children", CURRENT OPINION IN NEUROLOGY, (2004), vol. 17, pages 107 - 113 | - PEARL, P.; TAYLOR, J.; TRZCINSKI, S.; SOKOHL, A., "The Pediatric neurotransmitter disorders", JOURNAL OF CHILD NEUROLOGY, (2007), vol. 22, pages 606 - 616 | - QU, Q.; MELIKIAN, A.A.; LI, G. ET AL., "Validation of biomarkers in humans exposed to benzene: Urine metabolites", AMERICAN JOURNAL OF INDUSTRIAL MEDICINE, (2000), vol. 37, pages 522 - 531 | - REPINE J; BAST A; LANKHORST I; GROUP OSS, "Oxidative stress in chronic obstructive pulmonary disease", AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, (1997), vol. 156, no. 2, pages 341 - 57 | - ROCK C; CALDER R; KARIM M; JACKOWSKI S, "Pantothenate kinase regulation of the intracellular concentration of coenzyme A", THE JOURNAL OF BIOLOGICAL CHEMISTRY, (2000), vol. 275, pages 1377 - 83 | - SABATINE, M.; LIU, E.; MORROW, D. ET AL., "Metabolomic identification of novel biomarkers of myocardial ischemia", CIRCULATION, (2005), vol. 112, pages 3868 - 3875 | - SELDERSLAGHS, I.; ROMPAY, A.; DE COEN, W.; WITTERS, H., "Development of a screening assay to identify teratogenic and embryotoxic chemicals using the zebrafish embryo", REPRODUCTIVE TOXICOLOGY, (2009), vol. 28, pages 308 - 320 | - SERKOVA, N.; ZHANG, Y.; COATNEY, J. ET AL., "Early detection of graft failure using the blood metabolic profile of a liver recipient", TRANSPLANTATION, (2007), vol. 83, pages 517 - 521 | - SHANKS, N.; GREEK, R.; GREEK, J., "Are animal models predictive for humans?", PHILOSOPHY, ETHICS, AND HUMANITIES IN MEDICINE, (2009), vol. 4, page 2 | - SHINKA, T.; OHFU, M.; HIROSE, S.; KUHARA, T., "Effect of valproic acid on the urinary metabolic profile of a patient with succinic semialdehyde dehydrogenase deficiency", JOURNAL OF CHROMATOGRAPHY B, (2003), vol. 792, pages 99 - 106 | - SIMONIAN N; COYLE J, "Oxidative stress in neurodegenerative diseases", ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, (1996), vol. 36, pages 83 - 106 | - SREEKUMAR, A.; POISSON, L.; RAJENDIRAN, T. ET AL., "Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression", NATURE, (2009), vol. 457, pages 910 - 914 | - SUMMAR, M, "Current strategies for the management of neonatal urea cycle disorders", J PEDIATR, (2001), vol. 131, pages S30 - S39 | - TAN, D.; MANCHESTER, L.; REITER, R. ET AL., "A novel melatonin metabolite, cyclic 3-hydroxymelatonin: a biomarker of in vitro hydroxyl radical generation", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, (1998), vol. 253, pages 614 - 620 | - TASHIRO, A.; SANDLER, V.; TONI, N.; ZHAO, C.; GAGE, F., "NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus", NATURE, (2006), vol. 442, pages 929 - 933 | - THOMSON, J.; ITSKOVITZ-ELDOR, J.; SHAPIRO, S. ET AL., "Embryonic stem cell lines derived from human blastocysts", SCIENCE, (1998), vol. 282, pages 1145 - 1147 | - TOMS, D., "Thalidomide and congenital abnormalities", LANCET, (1962), vol. 2, page 400 | - VRIEND, J.; ALEXIUK, N., "Effects of valproate on amino acid and monoamine concentration in striatum of audiogenic seizure-prone balb/c mice", MOLECULAR AND CHEMICAL NERUOPATHOLOGY, (1996), vol. 27, pages 307 - 324 | - WALSH S, "Maternal-placental interactions of oxidative stress and antioxidants in preeclampsia", SEMIN REPROD MED., (1998), vol. 16, no. 1, pages 93 - 104 | - ZHAO W; MOSLEY B; CLEVES M; MELNYK S; JAMES S; HOBBS C, "Neural tube defects and maternal biomarkers of folate, homocysteine, and glutathione metabolism", BIRTH DEFECTS RESEARCH PART A: CLINICAL AND MOLECULAR TERATOLOGY, (2006), vol. 76, no. 4, pages 230 - 6 |