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Dejong Autman
King’s Research Portal Document Version Peer reviewed version Link to publication record in King's Research Portal Citation for published version (APA): De Jong, S., Vidler, L., Mokrab, Y., Collier, D. A., & Breen, G. D. (Accepted/In press). Gene-set analysis based on the pharmacological profiles of drugs to identify repurposing opportunities in schizophrenia. Journal of Psychopharmacology. Citing this paper Please note that where the full-text provided on King's Research Portal is the Author Accepted Manuscript or Post-Print version this may differ from the final Published version. If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections. General rights Copyright and moral rights for the publications made accessible in the Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognize and abide by the legal requirements associated with these rights. •Users may download and print one copy of any publication from the Research Portal for the purpose of private study or research. •You may not further distribute the material or use it for any profit-making activity or commercial gain •You may freely distribute the URL identifying the publication in the Research Portal Take down policy If you believe that this document breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. -
Fig. L COMPOSITIONS and METHODS to INHIBIT STEM CELL and PROGENITOR CELL BINDING to LYMPHOID TISSUE and for REGENERATING GERMINAL CENTERS in LYMPHATIC TISSUES
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date Χ 23 February 2012 (23.02.2012) WO 2U12/U24519ft ft A2 (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, A61K 31/00 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (21) International Application Number: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, PCT/US201 1/048297 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 18 August 201 1 (18.08.201 1) NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (25) Filing Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (26) Publication Language: English ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/374,943 18 August 2010 (18.08.2010) US kind of regional protection available): ARIPO (BW, GH, 61/441,485 10 February 201 1 (10.02.201 1) US GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, 61/449,372 4 March 201 1 (04.03.201 1) US ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (72) Inventor; and EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, (71) Applicant : DEISHER, Theresa [US/US]; 1420 Fifth LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, Avenue, Seattle, WA 98101 (US). -
E30 SEM. O.C. Disclosed Is a Compound Represented by the Formula (1) (51) Int
USOO9453000B2 (12) United States Patent (10) Patent No.: US 9.453,000 B2 Kimura et al. (45) Date of Patent: *Sep. 27, 2016 (54) POLYCYCLIC COMPOUND (56) References Cited (75) Inventors: Teiji Kimura, Tsukuba (JP); Noritaka U.S. PATENT DOCUMENTS Kitazawa, Tsukuba (JP); Toshihiko 3,470,167 A 9, 1969 Sarkar Kaneko, Tsukuba (JP); Nobuaki Sato, 3,989,816 A 1 1/1976 Rajadhyaksha Tsukuba (JP); Koki Kawano, Tsukuba 4,910,200 A 3, 1990 Curtze et al. (JP): Koichi Ito, Tsukuba (JP); 5,281,626 A 1/1994 Oinuma et al. M s Tak ishi Tsukub JP 5,563,162 A 10, 1996 Oku et al. amoru Takaishi Tsukuba (JP); 5,804,577 A 9, 1998 Hebeisen et al. Takeo Sasaki, Tsukuba (JP); Yu 5,985,856 A 11/1999 Stella et al. Yoshida, Tsukuba (JP); Toshiyuki 6,235,728 B1 5, 2001 Golik et al. Uemura, Tsukuba (JP); Takashi Doko, g R 1939. E. al. Its SE E. Shinmyo, 7,138.414 B2 11/2006 Schoenafingereatch et al. et al. sukuba (JP); Daiju Hasegawa, 7,300,936 B2 11/2007 Parker et al. Tsukuba (JP); Takehiko Miyagawa, 7,314,940 B2 1/2008 Graczyk et al. Hatfield (GB); Hiroaki Hagiwara, 7,618,960 B2 11/2009 Kimura et al. Tsukuba (JP) 7,667,041 B2 2/2010 Kimura et al. 7,687,640 B2 3/2010 Kimura et al. 7,713,993 B2 5/2010 Kimura et al. (73) Assignee: EISAI R&D MANAGEMENT CO., 7,737,141 B2 6/2010 Kimura et al. LTD., Tokyo (JP) 7,880,009 B2 2/2011 Kimura et al. -
9 the Present and Future of Tocolysis
Best Practice & Research Clinical Obstetrics and Gynaecology Vol. 21, No. 5, pp. 857–868, 2007 doi:10.1016/j.bpobgyn.2007.03.011 available online at http://www.sciencedirect.com 9 The present and future of tocolysis Warwick Giles* MBBS, FRANZCOG, PhD, CMFM Conjoint Professor Reproductive Medicine and Director Maternal Fetal Medicine Andrew Bisits MBMS, FRANZCOG, Dip Clin Epidemiol Conjoint Senior Lecture and Director of Obstetrics Faculty of Health, University of Newcastle, Australia This chapter discusses the tocolytic agents currently in use for the treatment of preterm labour and considers them in light of the evidence base. These agents are the b2 sympathomimetic ag- onists, magnesium sulphate (MgSO4), indomethacin, nifedipine and atosiban. The available evidence for these agents shows that the b2 agents are effective but have sig- nificant maternal side effects and no effect on perinatal outcome. MgSO4 and glyceryl trinitrate are clearly ineffective. Nifedipine is effective with a low maternal side effect profile and is asso- ciated with improved perinatal outcomes. Meta-analyses of the several randomized controlled trials of atosiban show that it is no more effective than other tocolytic therapies. Possible direc- tions for the future will be discussed. Key words: tocolysis; preterm delivery. It has long been the desire of clinicians to have therapies that can interrupt premature labour and allow the delivery of more mature infants with lower morbidity and mor- tality, time to use antenatal corticosteroids and transfer to tertiary care centres for delivery. The promising therapies of each recent generation have often been tried and found wanting. Observations from the 1990s have described preterm labour (PTL) as a syndrome rather than a distinct entity (as the causes are varied) reflecting the possible causes of a breakdown in the normal functional uterine quiescence with a short-circuiting or overwhelming of the normal parturition cascade. -
Malignant B Lymphocyte Survival in Vivo CD22 Ligand Binding Regulates Normal
The Journal of Immunology CD22 Ligand Binding Regulates Normal and Malignant B Lymphocyte Survival In Vivo1 Karen M. Haas, Suman Sen, Isaac G. Sanford, Ann S. Miller, Jonathan C. Poe, and Thomas F. Tedder2 The CD22 extracellular domain regulates B lymphocyte function by interacting with ␣2,6-linked sialic acid-bearing ligands. To understand how CD22 ligand interactions affect B cell function in vivo, mouse anti-mouse CD22 mAbs were generated that inhibit CD22 ligand binding to varying degrees. Remarkably, mAbs which blocked CD22 ligand binding accelerated mature B cell turnover by 2- to 4-fold in blood, spleen, and lymph nodes. CD22 ligand-blocking mAbs also inhibited the survival of adoptively transferred normal (73–88%) and malignant (90%) B cells in vivo. Moreover, mAbs that bound CD22 ligand binding domains induced significant CD22 internalization, depleted marginal zone B cells (82–99%), and reduced mature recirculating B cell numbers by 75–85%. The CD22 mAb effects were independent of complement and FcRs, and the CD22 mAbs had minimal effects in CD22AA mice that express mutated CD22 that is not capable of ligand binding. These data demonstrate that inhibition of CD22 ligand binding can disrupt normal and malignant B cell survival in vivo and suggest a novel mechanism of action for therapeutics targeting CD22 ligand binding domains. The Journal of Immunology, 2006, 177: 3063–3073. D22 is a B cell-specific glycoprotein of the Ig superfam- cell surface CD22, IgM, and MHC class II expression on mature B ily expressed on the surface of maturing B cells coinci- cells, whereas normal BCR signaling and Ca2ϩ mobilization are dent with IgD expression (1, 2). -
(12) Patent Application Publication (10) Pub. No.: US 2017/0209462 A1 Bilotti Et Al
US 20170209462A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0209462 A1 Bilotti et al. (43) Pub. Date: Jul. 27, 2017 (54) BTK INHIBITOR COMBINATIONS FOR Publication Classification TREATING MULTIPLE MYELOMA (51) Int. Cl. (71) Applicant: Pharmacyclics LLC, Sunnyvale, CA A 6LX 3/573 (2006.01) A69/20 (2006.01) (US) A6IR 9/00 (2006.01) (72) Inventors: Elizabeth Bilotti, Sunnyvale, CA (US); A69/48 (2006.01) Thorsten Graef, Los Altos Hills, CA A 6LX 3/59 (2006.01) (US) A63L/454 (2006.01) (52) U.S. Cl. CPC .......... A61 K3I/573 (2013.01); A61K 3 1/519 (21) Appl. No.: 15/252,385 (2013.01); A61 K3I/454 (2013.01); A61 K 9/0053 (2013.01); A61K 9/48 (2013.01); A61 K (22) Filed: Aug. 31, 2016 9/20 (2013.01) (57) ABSTRACT Disclosed herein are pharmaceutical combinations, dosing Related U.S. Application Data regimen, and methods of administering a combination of a (60) Provisional application No. 62/212.518, filed on Aug. BTK inhibitor (e.g., ibrutinib), an immunomodulatory agent, 31, 2015. and a steroid for the treatment of a hematologic malignancy. US 2017/0209462 A1 Jul. 27, 2017 BTK INHIBITOR COMBINATIONS FOR Subject in need thereof comprising administering pomalido TREATING MULTIPLE MYELOMA mide, ibrutinib, and dexamethasone, wherein pomalido mide, ibrutinib, and dexamethasone are administered con CROSS-REFERENCE TO RELATED currently, simulataneously, and/or co-administered. APPLICATION 0008. In some aspects, provided herein is a method of treating a hematologic malignancy in a subject in need 0001. This application claims the benefit of U.S. -
Nicotinic Receptors in Neurodegeneration
Send Orders of Reprints at [email protected] 298 Current Neuropharmacology, 2013, 11, 298-314 Nicotinic Receptors in Neurodegeneration Inmaculada Posadas, Beatriz López-Hernández and Valentín Ceña* Unidad Asociada Neurodeath. CSIC-Universidad de Castilla-La Mancha, Departamento de Ciencias Médicas. Albacete, Spain and CIBERNED, Instituto de Salud Carlos III, Spain Abstract: Many studies have focused on expanding our knowledge of the structure and diversity of peripheral and central nicotinic receptors. Nicotinic acetylcholine receptors (nAChRs) are members of the Cys-loop superfamily of pentameric ligand-gated ion channels, which include GABA (A and C), serotonin, and glycine receptors. Currently, 9 alpha (2-10) and 3 beta (2-4) subunits have been identified in the central nervous system (CNS), and these subunits assemble to form a variety of functional nAChRs. The pentameric combination of several alpha and beta subunits leads to a great number of nicotinic receptors that vary in their properties, including their sensitivity to nicotine, permeability to calcium and propensity to desensitize. In the CNS, nAChRs play crucial roles in modulating presynaptic, postsynaptic, and extrasynaptic signaling, and have been found to be involved in a complex range of CNS disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, Tourette´s syndrome, anxiety, depression and epilepsy. Therefore, there is growing interest in the development of drugs that modulate nAChR functions with optimal benefits and minimal adverse effects. The present review describes the main characteristics of nAChRs in the CNS and focuses on the various compounds that have been tested and are currently in phase I and phase II trials for the treatment of neurodegenerative diseases including PD, AD and age-associated memory and mild cognitive impairment. -
(19) United States (12) Patent Application Publication (10) Pub
US 20130289061A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0289061 A1 Bhide et al. (43) Pub. Date: Oct. 31, 2013 (54) METHODS AND COMPOSITIONS TO Publication Classi?cation PREVENT ADDICTION (51) Int. Cl. (71) Applicant: The General Hospital Corporation, A61K 31/485 (2006-01) Boston’ MA (Us) A61K 31/4458 (2006.01) (52) U.S. Cl. (72) Inventors: Pradeep G. Bhide; Peabody, MA (US); CPC """"" " A61K31/485 (201301); ‘4161223011? Jmm‘“ Zhu’ Ansm’ MA. (Us); USPC ......... .. 514/282; 514/317; 514/654; 514/618; Thomas J. Spencer; Carhsle; MA (US); 514/279 Joseph Biederman; Brookline; MA (Us) (57) ABSTRACT Disclosed herein is a method of reducing or preventing the development of aversion to a CNS stimulant in a subject (21) App1_ NO_; 13/924,815 comprising; administering a therapeutic amount of the neu rological stimulant and administering an antagonist of the kappa opioid receptor; to thereby reduce or prevent the devel - . opment of aversion to the CNS stimulant in the subject. Also (22) Flled' Jun‘ 24’ 2013 disclosed is a method of reducing or preventing the develop ment of addiction to a CNS stimulant in a subj ect; comprising; _ _ administering the CNS stimulant and administering a mu Related U‘s‘ Apphcatlon Data opioid receptor antagonist to thereby reduce or prevent the (63) Continuation of application NO 13/389,959, ?led on development of addiction to the CNS stimulant in the subject. Apt 27’ 2012’ ?led as application NO_ PCT/US2010/ Also disclosed are pharmaceutical compositions comprising 045486 on Aug' 13 2010' a central nervous system stimulant and an opioid receptor ’ antagonist. -
WO 2010/142752 Al
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 16 December 2010 (16.12.2010) WO 2010/142752 Al (51) International Patent Classification: nia 94568 (US). ROBARGE, Kirk D. [US/US]; 1679 C07D 213/75 (2006.01) Λ61K 31/4439 (2006.01) 27th Avenue, San Francisco, California 94122 (US). C07D 401/12 (2006.01) A61K 31/444 (2006.01) STANLEY, Mark S. [US/US]; 284 Lauren Avenue, A61K 31/506 (2006.01) A61P 37/04 (2006.01) Pacifica, California 94044 (US). TSUI, Vickie Hsiao- A61K 31/495 (2006.01) Wei [US/US]; 2626 Martinez Avenue, Burlingame, Cali fornia 94010 (US). WILLIAMS, Karen [GB/GB]; 8/9 (21) International Application Number: Spire Green Centre, Flex Meadow, Harlow, Essex CM 19 PCT/EP2010/058128 5TR (GB). ZHANG, Birong [US/US]; 3060 San Andreas (22) International Filing Date: Drive, Union City, California 94587 (US). ZHOU, Aihe 10 June 2010 (10.06.2010) [US/US]; 1361 Stephen Way, San Jose, California 95129 (US). (25) Filing Language: English (74) Agent: KLOSTERMEYER-RAUBER, Doerte; Gren- (26) Publication Language: English zacherstrasse 124, CH-4070 Basel (CH). (30) Priority Data: (81) Designated States (unless otherwise indicated, for every 61/186,322 11 June 2009 ( 11.06.2009) US kind of national protection available): AE, AG, AL, AM, (71) Applicant (for all designated States except US): F. AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, HOFFMANN-LA ROCHE AG [CWCH]; Grenzacher- CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, strasse 124, CH-4070 Basel (CH). -
(12) United States Patent (10) Patent No.: US 9.498,544 B2 Ennis Et Al
USOO949854.4B2 (12) United States Patent (10) Patent No.: US 9.498,544 B2 Ennis et al. (45) Date of Patent: Nov. 22, 2016 (54) GENETICALLY MODIFIED HUMAN (56) References Cited UMIBILICAL CORD PERVASCULAR CELLS FOR PROPHYLAXIS AGAINST OR U.S. PATENT DOCUMENTS TREATMENT OF BIOLOGICAL, OR 5,158,867 A 10/1992 McNally et al. CHEMICAL AGENTS 5,919,702 A 7/1999 Purchio et al. 6,132,724 A 10/2000 Blum (71) Applicant: Tissue Regeneration Therapeutics 7,122,178 B1 10/2006 Simmons et al. 7,547,546 B2 6/2009 Davies et al. Inc., Toronto (CA) 2003.0161818 A1 8, 2003 Weiss et al. 2004/O136967 A1 7/2004 Weiss et al. 2004/O137612 A1 7/2004 Baksh et al. (72) Inventors: Jane Elizabeth Ennis, Oakville (CA); 2005/OO 19911 A1 1/2005 Gronthos et al. Jeffrey Donald Turner, 2005, 0148074 A1 7/2005 Davies et al. Chute-a-Blondeau (CA); John Edward 2005/O158289 A1 7/2005 Simmons et al. Davies, Toronto (CA) 2005/0281790 A1 12/2005 Simmons et al. 2006, OOO8452 A1 1/2006 Simmons et al. 2006, O193840 A1 8, 2006 Gronthos et al. (73) Assignee: Tissue Regeneration Therapeutics 2006, O199263 A1 9/2006 Auger et al. Inc., Toronto (CA) 2006/0286O77 A1 12/2006 Gronthos et al. 2007/0134205 A1 6/2007 Rosenberg 2008.0020459 A1 1/2008 Baksh et al. (*) Notice: Subject to any disclaimer, the term of this 2008.0113434 A1 5/2008 Davies et al. patent is extended or adjusted under 35 2009/0047277 A1 2/2009 Reed et al. -
As a Registered E-Materials Service User of the EBMT Annual Meeting in Marseille March 26-29Th 2017, You Have Been Granted Permi
Copyright Statement As a registered E-materials Service user of the EBMT Annual Meeting in Marseille March 26-29th 2017, you have been granted permission to access a copy of the presentation in the following pages for the purpose of scientific education. This presentation is copyrighted material and must not be copied, reproduced, transferred, distributed, leased, licensed, placed in a storage retrieval system, publicly performed or used in any way, except as specifically permitted in writing by the presenter or, as allowed under the terms and conditions under which it was received or as permitted by applicable copyright law or rules of proper citation. Any unauthorised distribution or use of this presentation, a subset of it or graphics taken from the presentation may be a direct infringement of the presenter’s rights. RACE DM training session: Immunusuppressive treatment for aplastic anemia Antonio M. Risitano, M.D., Ph.D. Head of Bone Marrow Transplantation Unit Federico II University of Naples Aplastic anemia Neutrophils for Incidence, age for SCT . Opha disease. Iidee ates peset geogaphi aiatios. to ‐fold highe ates i Asia tha Euope ad the Uited States . Gloal iidee ates age .‐. ases pe illio ihaitats. Aplasti aeia: AA • AA: hat does it ea? • Ho e do the diagosis? • Whe should e teat? • Ho e teat? Aplasti aeia: AA • AA: hat does it ea? • Ho e do the diagosis? • Whe should e teat? • Ho e teat? Aplastic anemia Normal Aplastic anemia CML AA Normal Marrow aplasia Takaku et al, Blood 2010 Takaku et al, Blood 2010 Contraction of stem cell pool Cytopenia AA: hat does it ea? (Oligo) clonal CD8+ T cells Auto-immunity = immune disorder = idiopathic AA AA: hat does it ea? Constitutionnal = inherited disorder (FA, dyskeratosis congenita) Hematopoietic stem cells in AA Hematopoietic progenitor cultures T-cell clonality in aplastic anemia A surrogate marker for Ag-driven immune response Experimental Hematology 23 (1995): 433 Establishment of a CD4+ T cell clone recognizing autologous hematopoietic progenitor cells from a patient with immune-mediated aplastic anemia. -
Tanibirumab (CUI C3490677) Add to Cart
5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor