DOCSLIB.ORG

Antagonists of Il-6 to Prevent Or Treat

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Antagonists of Il-6 to Prevent Or Treat (19) TZZ ¥_ _T (11) EP 2 376 126 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 39/00 (2006.01) C07K 16/24 (2006.01) 20.12.2017 Bulletin 2017/51 (86) International application number: (21) Application number: 09830695.4 PCT/US2009/006266 (22) Date of filing: 24.11.2009 (87) International publication number: WO 2010/065077 (10.06.2010 Gazette 2010/23) (54) ANTAGONISTS OF IL-6 TO PREVENT OR TREAT THROMBOSIS ANTAGONISTEN VON IL-6 ZUR PRÄVENTION ODER BEHANDLUNG VON THROMBOSE ANTAGONISTES D IL-6 POUR PRÉVENIR OU TRAITER LA THROMBOSE (84) Designated Contracting States: • MATSUYAMA MASASHI ET AL: AT BE BG CH CY CZ DE DK EE ES FI FR GB GR "Anti-interleukin-6 receptor antibody HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL (tocilizumab) treatment of multicentric PT RO SE SI SK SM TR Castleman’s disease", INTERNAL MEDICINE, JAPANESE SOCIETY OF INTERNAL MEDICINE, (30) Priority: 05.02.2009 US 366567 TOKYO, JP; BIOSCIENCES INFORMATION 14.07.2009 US 502581 SERVICE, PHILADELPHIA, PA, US, vol. 46, 1 25.11.2008 US 117811 P January 2007 (2007-01-01), pages 771-774, 25.11.2008 US 117861 P XP002696891, ISSN: 0918-2918, DOI: 24.02.2009 US 391717 10.2169/INTERNALMEDICINE.46.6262 06.03.2009 US 399156 • EMILLE D ET AL: "ADMINISTRATION OF AN 25.11.2008 US 117839 P ANTI-INTERLEUKIN-6 MONOCLONAL 24.02.2009 US 391615 ANTIBODY TO PATIENTS WITH ACQUIRED IMUNODEFICIENCY SYNDROME AND (43) Date of publication of application: LYMPHOMA: EFFECT ON LYMPHOMA GROWTH 19.10.2011 Bulletin 2011/42 AND ON B CLINICAL SYMPTOMS", BLOOD, AMERICAN SOCIETY OFHEMATOLOGY, US, vol. (73) Proprietor: AlderBio Holdings LLC 84, no. 8, 15 October 1994 (1994-10-15), pages Las Vegas, NV 89109 (US) 2472-2479, XP001088120, ISSN: 0006-4971 • M. H. ZAKI ET AL: "Proc Am Soc Clin Oncol", 2003 (72) Inventor: SMITH, Jeffrey, T.L. ASCO ANNUAL MEETING - DEVELOPMENTAL Bellevue THERAPEUTICS - CLINICAL PHARMACOLOGY WA 98004 (US) AND IMMUNOTHERAPY , vol. 22, 697, 2003, XP055045899, Retrieved from the Internet: (74) Representative: Boult Wade Tennant URL:http://www.asco.org/ASCOv2/Meetings/Ab Verulam Gardens stracts?&vmview=abst_detail_view&confID=23 70 Gray’s Inn Road &abstractID=100701 [retrieved on 2012-11-27] London WC1X 8BT (GB) • BATAILLE R ET AL: "Biologic effects of anti-interleukin-6 murine monoclonal antibody in (56) References cited: advanced multiple myeloma", BLOOD, WO-A1-2004/039826 WO-A2-2008/065378 AMERICAN SOCIETY OFHEMATOLOGY, US, vol. WO-A2-2008/144763 US-A1- 2007 292 420 86, no. 2, 15 July 1995 (1995-07-15), pages US-B2- 7 169 573 685-691, XP002448659, ISSN: 0006-4971 Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 2 376 126 B1 Printed by Jouve, 75001 PARIS (FR) (Cont. next page) EP 2 376 126 B1 • G STRASSMANN ET AL: "Evidence for the • NISHIMOTOET AL.: ’Mechanismsand pathologic involvement of interleukin 6 in experimental significances in increase in serum interleukin-6 cancer cachexia.", JOURNAL OF CLINICAL (IL-6) and soluble IL-6 receptor after INVESTIGATION, vol. 89, no. 5, 1 May 1992 administration of an anti-IL-6 receptor antibody, (1992-05-01), pages 1681-1684, XP055045903, tocilizumab, in patients with rheumatoid arthritis ISSN: 0021-9738, DOI: 10.1172/JCI115767 and Castleman disease.’ BLOOD vol. 112, no. 10, • STRASSMANN G ET AL: "INHIBITION OF 15 November 2008, pages 3959 - 3964 EXPERIMENTAL CANCER CACHEXIA BY • ’LAB TESTS ONLINE. Hypercoagulable ANTI-CYTOKINE AND Disorders.’, [Online] 01 March 2008, Retrieved ANTI-CYTOKINE-RECEPTOR THERAPY", from the Internet: CYTOKINES AND MOLECULAR THERAPY, <URL:http://web.archive.org/web/20080301224 DUNITZ, LONDON, GB, vol. 1, no. 2, 1 January 129/http://www.labtestsonline.org/understan 1995 (1995-01-01) , pages 107-113, XP008043222, ding/conditions/hypercoagulable_disorders-6 .h ISSN: 1355-6568 tml> [retrieved on 2010-06-17] • KLEIN ET AL: "Murine anti-interleukin-6 • Thomson Reuters - Integrity: "Huamnized monoclonal antibody therapy for a patient with Anti-IL-6 monoclonal antibody - Heavy and light plasma cell leukemia.", BLOOD, vol. 78, no. 5, 1 chains", , 16 January 2008 (2008-01-16), September 1991 (1991-09-01), pages 1198-1204, XP055292638, Retrieved from the Internet: XP055045905, ISSN: 0006-4971 URL:https://integrity.thomson-pharma.com/i • KAORI FUJIMOTO-OUCHI ET AL: "Capecitabine ntegrity/xmlxsl/pk_prod_list.xml_prod_list improves cancer cachexia and normalizes IL-6 _card_pr?p_id=468410 [retrieved on 2016-08-01] and PTHrP levels in mouse cancer cachexia • Gerhard A Kalweit ET AL: "Markers of Activated models", CANCER CHEMOTHERAPY AND Hemostasis and Fibrinolysis in Patients with PHARMACOLOGY, SPRINGER, BERLIN, DE, vol. Pulmonary Malignancies", Thrombosis 59, no. 6, 29 September 2006 (2006-09-29), pages Research, vol. 97, no. 3, 1 February 2000 807-815, XP019490080, ISSN: 1432-0843 (2000-02-01), pages105-111, XP055199314, ISSN: • SUMIE TAMURA ET AL: "Involvement of human 0049-3848, DOI: 10.1016/S0049-3848(99)00161-9 interleukin6 in experimentalcachexia induced by • ZAKI M H ET AL: "CNTO 328, A monoclonal a human uterine cervical carcinoma xenograft.", antibody to IL-6, inhibits human tumor-induced CLINICAL CANCER RESEARCH, vol. 1, 1 January cachexia in nude mice", INTERNATIONAL 1995 (1995-01-01), pages 1353-1358, JOURNAL OF CANCER, JOHN WILEY & SONS, XP055045909, INC, US, vol. 111, 1 January 2004 (2004-01-01), • NISHIMOTO ET AL.: ’Improvement in pages 592-595, XP003012697, ISSN: 0020-7136, Castleman’s disease by humanized DOI: 10.1002/IJC.20270 anti-interleukin-6 receptor antibody therapy.’ • TRIKHA MOHIT ET AL: "Targeted BLOOD vol. 95, no. 1, 2000, pages 56 - 61 anti-interleukin-6 monoclonal antibody therapy • ’LAB TESTS ONLINE. D-Dimer: The Test.’, for cancer: a review of the rationale and clinical [Online] 20 October 2008, Retrieved from the evidence", CLINICAL CANCER RESEARCH, THE Internet: AMERICAN ASSOCIATION FOR CANCER <URL:http://web.archive.org/web/20071020065 RESEARCH, US, vol. 9, no. 13, 1 January 2003 024/http://www.labtestsonline.org/understan (2003-01-01), pages 4653-4665, XP002543280, ding/analytes/d_dimer/test.html> [retrieved on ISSN: 1078-0432 2010-06-17] • M.Oya: "High PreoperativePlasma D-dimer Level • BLAY ET AL.: ’Role of Interleukin-6 in the is Associated with Advanced Tumor Stage and Paraneoplastic inflammatory syndrome Short Survival After Curative Resection in associated with renal cell carcinoma.’ INT J Patients with Colorectal Cancer", JAPANESE CANCER vol. 72, no. 3, 1997, pages 424 - 430 JOURNALOF CLINICAL ONCOLOGY., vol.31, no. • CATA ET AL.: ’The effects of thalidomide and 8, 1 August 2001 (2001-08-01) , pages 388-394, minocycline on taxol-induced hyperalgesia in XP55293677, JP ISSN: 0368-2811, DOI: rats.’ BRAIN RES vol. 1229, 10 September 2008, 10.1093/jjco/hye075 pages 100 - 110 • RIDKER ET AL.: ’Rosuvastatin to prevent vascular events in men and women with elevated C- reactive protein.’ NEW ENG J MED vol. 359, no. 21, 20 November 2008, pages 2195 - 2207 2 EP 2 376 126 B1 Description BACKGROUND OF THE INVENTION 5 Field of the Invention [0001] This invention is an extension of Applicants’ prior invention relating to novel anti-IL-6 antibodies and novel therapies and therapeutic protocols using anti-IL-6 antibodies, preferably those described herein. In particular, this invention pertains to an anti-IL-6 antibody comprising a VL polypeptide of SEQ ID NO:709 and a light chain constant 10 region of SEQ ID NO: 586; and a VH polypeptide of SEQ ID NO:657 and a heavy chain constant region of SEQ ID NO: 588 for use in a method of treating a patient having an advanced cancer associated with hypercoagulation, wherein the anti-IL-6 antibody is aglycosylated. [0002] In another embodiment the invention provides novel combination therapies wherein the anti-IL-6 antibody of the invention is administered in combination with at least one other therapeutic compound e.g., a statin,including but 15 not limited to atorvastatin, cerivastatin, fluvastatin, lovastatin, mevastatin, pitavastatin, pravastatin, rosuvastatin, simv- astatin, or any combination thereof; a chemotherapeutic agent such as VEGF antagonists, EGFR antagonists, platins, taxols, irinotecan, 5-fluorouracil, gemcitabine, leucovorin, steroids, cyclophosphamide, melphalan, vinca alkaloids (e.g., vinblastine, vincristine, vindesine and vinorelbine), mustines, tyrosine kinase inhibitors, radiotherapy, sex hormone an- tagonists, selective androgen receptor modulators, selective estrogen receptor modulators, PDGF antagonists, TNF 20 antagonists, IL-1 antagonists, interleukins (e.g. IL-12 or IL-2), IL-12R antagonists, toxin conjugated monoclonal antibod- ies, tumor antigen specific monoclonal antibodies, Erbitux™ , Avastin™, Pertuzumab, anti-CD20 antibodies, RituxanTM, ocrelizumab, ofatumumab, DXL625, Herceptin.™, or any combination thereof; or an an anti-coagulant such as abciximab (ReoPro™), acenocoumarol, antithrombin, argatroban, aspirin, bivalirudin (Angiomax™), clopidogrel, dabigatran, da- bigatran, etexilate, (Pradaxa™/Pradax™), desirudin (Revasc™/Iprivask™), dipyridamole, eptifibatide (Integrilin™), fon- 25 daparinux, heparin, hirudin, idraparinux, lepirudin (Refludan™), low molecular weight heparin, Melagatran, phenindione, phenprocoumon, ticlopidine, tirofiban (Aggrastat™), warfarin, ximelagatran, ximelagatran (Exanta™/ Exarta™), or any combination thereof. Description of Related Art 30 [0003] Thrombosis is a significant cause of mortality in cancer patients. Bick, N Engl J Med 349:109-111 (2003). For example, serious, life-threatening thrombotic events occur in approximately 6% of lung cancer patients. Alguire et al., J Clin Oncol 2004 Vol 22 (July 15th Supplement) No. 14S: 8082. Cancer patients often exhibit hypercoagulation, in which the coagulation system has an increased clotting tendency. Rickles and Edwards, Blood 62:14-31 (1983).
Load more

Recommended publications
  • Prezentace Aplikace Powerpoint
    Analgesics - antipyretics = „weak“ analgesics = non-opioid analgesics Most of them also • non-steroidal anti-inflamatory drugs (NSAIDs) •antirheumatics Oldřich Farsa 2011 Metabolism of eicosanoids O O arachidonic O H acid = 2 C O R1 R2 OH R2 O OH CH C O P O + 3 H N CH 2 O 3 CH3 glucocorticoids inhibitors of phspholipase A2 prostaglandins sythesis = COOH = "weak" analgesics + lipoxygenase inhibitors + NSAIDs arachidonic acid cyclooxygenases (COX1 + COX2) lipoxygenase OOH O COOH COOH O PG 5-hydroperoxy-6-trans-8,11,14-cis-eikosatetraenoic acid G2 OOH (5-HPETE) cyklooxygenases tromboxan synthase prostacyklin synthase PG H2 PG I2 = prostacyklin TX A2 endothelium cells LT A4 trombocytes isomerases PG D2 PG E2 LT C4 LT B4 PG F2α all the cells LT D4 LT E4 Effects of prostaglandins ↓ Prostaglandin E, F2α : ache, fewer, inflammation, sekretion of HCl , stomach mucosa capilaries dilatation, contraction of + ↑ uterus, kidneys: excretion of Na and H2O Prostacyclin (prostaglandin I ): vasodilatation, platelets aggregation inhibition 2 Tromboxan: vasokonstriction, platelets aggregation activation Leukotriens: alergic reactions (e.g. asthma bronchiale) Cyklooxygenases (= prostaglandin G/H synthases) COX1 Constitutive: in all the tissues Functions: •protection of stomach mucosa (vasodilatation) •diuresis •platelets aggregation (TXA) COX2 Philipp Needlemann Constitutive: kidneys, brain (co-localized with cyclins D and E) inventor of COX 1 isoenzymes Inducible: macrophages, neutrophfils, fibroblasts, endothelium cells (1989) Functions: •vasodilatation
    [Show full text]
  • Expression of the P53 Inhibitors MDM2 and MDM4 As Outcome
    ANTICANCER RESEARCH 36 : 5205-5214 (2016) doi:10.21873/anticanres.11091 Expression of the p53 Inhibitors MDM2 and MDM4 as Outcome Predictor in Muscle-invasive Bladder Cancer MAXIMILIAN CHRISTIAN KRIEGMAIR 1* , MA TT HIAS BALK 1, RALPH WIRTZ 2* , ANNETTE STEIDLER 1, CLEO-ARON WEIS 3, JOHANNES BREYER 4* , ARNDT HARTMANN 5* , CHRISTIAN BOLENZ 6* and PHILIPP ERBEN 1* 1Department of Urology, University Medical Centre Mannheim, Mannheim, Germany; 2Stratifyer Molecular Pathology, Köln, Germany; 3Institute of Pathology, University Medical Centre Mannheim, Mannheim, Germany; 4Department of Urology, University of Regensburg, Regensburg, Germany; 5Institute of Pathology, University Erlangen-Nuernberg, Erlangen, Germany; 6Department of Urology, University of Ulm, Ulm, Germany Abstract. Aim: To evaluate the prognostic role of the p53- Urothelical cell carcinoma (UCC) of the bladder is the second upstream inhibitors MDM2, MDM4 and its splice variant most common urogenital neoplasm worldwide (1). Whereas MDM4-S in patients undergoing radical cystectomy (RC) for non-muscle invasive UCC can be well treated and controlled muscle-invasive bladder cancer (MIBC). Materials and by endoscopic resection, for MIBC, which represents 30% of Methods: mRNA Expression levels of MDM2, MDM4 and tumor incidence, radical cystectomy (RC) remains the only MDM4-S were assessed by quantitative real-time polymerase curative option. However, MIBC progresses frequently to a chain reaction (qRT-PCR) in 75 RC samples. Logistic life-threatening metastatic disease with limited therapeutic regression analyses identified predictors of recurrence-free options (2). Standard clinical prognosis parameters in bladder (RFS) and cancer-specific survival (CSS). Results: High cancer such as stage, grade or patient’s age, have limitations expression was found in 42% (MDM2), 27% (MDMD4) and in assessing individual patient’s prognosis and response to 91% (MDM4-S) of tumor specimens.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0156582 A1 Tsukamoto Et Al
    US 20090156582A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0156582 A1 Tsukamoto et al. (43) Pub. Date: Jun. 18, 2009 (54) PYRAZOLE COMPOUND Publication Classification (76) Inventors: Tetsuya Tsukamoto, Osaka-shi, (51) Int. Cl. Osaka (JP); Takeshi Yamamoto, A6II 3/55 (2006.01) Osaka-shi,Osaka (JP); Ryosuke A63L/454 (2006.01) Tokunoh, Osaka-shi, Osaka (JP); A63L/462 (2006.01) Tomohiro Kawamoto, Osaka-shi, C07D 403/02 (2006.01) Osaka (JP); Masahiro Okura, Osaka-shi, Osaka (JP); Masakumi (52) U.S. Cl. .................... 514/217.09: 514/406; 514/326; Kori, Osaka-shi, Osaka (JP); 548/364.1: 548/368.4: 546/211; 540/603 Katsuhito Murase, Osaka-shi, Osaka (JP) (57) ABSTRACT Correspondence Address: The present invention provides a pyrazole compound repre WENDEROTH, LIND & PONACK, L.L.P. sented by the formula (I): 1030 15th Street, N.W., Suite 400 East Washington, DC 20005-1503 (US) b (Io) (21) Appl. No.: 11/884,054 Ra R (22) PCT Filed: Feb. 9, 2006 (86). PCT No.: PCT/UP2006/302686 S371 (c)(1), wherein ring Ao is a pyrazole ring optionally further having 1 (2), (4) Date: Sep. 14, 2007 or 2 substituents; R is a substituted carbamoyl group; and R' (30) Foreign Application Priority Data is an optionally Substituted acylamino group, or a salt thereof or a prodrug thereof, which is useful as an agent for the Feb. 9, 2005 (JP) .................................. O333562005 prophylaxis or treatment of GSK-3? related pathology or Dec. 22, 2005 (JP) .................................. 3709622005 disease, and a GSK-3? inhibitor including same. US 2009/0156582 A1 Jun.
    [Show full text]
  • WO 2014/167554 A2 16 October 2014 (16.10.2014) P O P C T
    (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 WO 2014/167554 A2 16 October 2014 (16.10.2014) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 47/10 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, (21) International Application Number: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, PCT/IB20 14/060675 DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, 12 April 2014 (12.04.2014) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (25) Filing Language: English OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (26) Publication Language: English SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (30) Priority Data: zw. 1103/DEL/2013 12 April 2013 (12.04.2013) IN (84) Designated States (unless otherwise indicated, for every (71) Applicant: VYOME BIOSCIENCES PVT. LTD. kind of regional protection available): ARIPO (BW, GH, [IN/IN]; 459 F.I.E, First Floor, Patparganj Industrial Area, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, New Delhi 110092 (IN).
    [Show full text]
  • )&F1y3x PHARMACEUTICAL APPENDIX to THE
    )&f1y3X PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE )&f1y3X PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 3 Table 1. This table enumerates products described by International Non-proprietary Names (INN) which shall be entered free of duty under general note 13 to the tariff schedule. The Chemical Abstracts Service (CAS) registry numbers also set forth in this table are included to assist in the identification of the products concerned. For purposes of the tariff schedule, any references to a product enumerated in this table includes such product by whatever name known. Product CAS No. Product CAS No. ABAMECTIN 65195-55-3 ACTODIGIN 36983-69-4 ABANOQUIL 90402-40-7 ADAFENOXATE 82168-26-1 ABCIXIMAB 143653-53-6 ADAMEXINE 54785-02-3 ABECARNIL 111841-85-1 ADAPALENE 106685-40-9 ABITESARTAN 137882-98-5 ADAPROLOL 101479-70-3 ABLUKAST 96566-25-5 ADATANSERIN 127266-56-2 ABUNIDAZOLE 91017-58-2 ADEFOVIR 106941-25-7 ACADESINE 2627-69-2 ADELMIDROL 1675-66-7 ACAMPROSATE 77337-76-9 ADEMETIONINE 17176-17-9 ACAPRAZINE 55485-20-6 ADENOSINE PHOSPHATE 61-19-8 ACARBOSE 56180-94-0 ADIBENDAN 100510-33-6 ACEBROCHOL 514-50-1 ADICILLIN 525-94-0 ACEBURIC ACID 26976-72-7 ADIMOLOL 78459-19-5 ACEBUTOLOL 37517-30-9 ADINAZOLAM 37115-32-5 ACECAINIDE 32795-44-1 ADIPHENINE 64-95-9 ACECARBROMAL 77-66-7 ADIPIODONE 606-17-7 ACECLIDINE 827-61-2 ADITEREN 56066-19-4 ACECLOFENAC 89796-99-6 ADITOPRIM 56066-63-8 ACEDAPSONE 77-46-3 ADOSOPINE 88124-26-9 ACEDIASULFONE SODIUM 127-60-6 ADOZELESIN 110314-48-2 ACEDOBEN 556-08-1 ADRAFINIL 63547-13-7 ACEFLURANOL 80595-73-9 ADRENALONE
    [Show full text]
  • Sleason, Redwood City, CA (US), Juan W. W333. a 3. C
    USOO8288373B2 (12) United States Patent (10) Patent No.: US 8,288,373 B2 Chen et al. (45) Date of Patent: Oct. 16, 2012 (54) MODULATORS OF CXCR7 FOREIGN PATENT DOCUMENTS AU 2006-230674 A1 11, 2006 (75) Inventors: Xi Chen, Palo Alto, CA (US); Pingchen WO WOO2,08221 A2 1, 2002 Fan, Fremont, CA (US); Mark M. WO WOO3,O764OO A1 9, 2003 Sleason, Redwood City, CA (US), Juan W. W333. A 3. C. Jaen, Burlingame, CA (US). Lianfa WO WO 2007/126935 A2 11/2007 Li, Palo Alto, CA (US); Jeffrey P. WO WO 2008/008518 A1 1/2008 McMahon, Mountain View, CA (US); WO 2008, 11215.6 A1 9, 2008 Jay Powers, Pacifica, CA (US); Yibin Zeng, Foster City, CA (US); Penglie OTHER PUBLICATIONS Zhang, Foster City, CA (US) Konishi et al. (Yakugaku Zasshi (1973), 93(5), 684-7). Abstract.* r Miao et al., “CXCR7 (RDC1) promotes breast and lung tumor growth (73) Assignee: Chemocentryx, Inc., Mountain View, in vivo and is expressed on tumor-associated vasculature.” 2007. CA (US) PNAS, vol. 104. No. 40, pp. 15735-15740. c Zabel et al., “Elucidation of CXCR-7-Mediated Signaling Events and (*) Notice: Subject to any disclaimer the term of this Inhibition of CXCR4-Mediated Tumor Cell Transendothelial Migra patent is extended or adjusted under 35 tion by CXCR7 Ligands.” The Journal of Immunology, 2009, vol. U.S.C. 154(b) by 171 days. 183, Issue 5, pp. 3204-3211. International Search Reportmailed on Jan. 27, 2010, for International (21) Appl. No.: 12/612,638 Application No. PCT/US09/63298 filed on Nov.
    [Show full text]
  • Medsafe Sheet for Copaxone
    NEW ZEALAND DATA SHEET 1. PRODUCT NAME COPAXONE® 20 mg/mL PRE-FILLED SYRINGE COPAXONE® 40 mg/mL PRE-FILLED SYRINGE 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Copaxone 20 mg/mL contains 20 mg of glatiramer acetate. Copaxone 40 mg/mL contains 40 mg of glatiramer acetate. Glatiramer acetate, the active ingredient in both Copaxone 20 mg/mL and Copaxone 40 mg/mL, is the acetate salt of synthetic polypeptides, containing four naturally occurring amino acids: L-glutamic acid, L-alanine, L-tyrosine and L-lysine with an average molar fraction 0.141, 0.427, 0.095 and 0.338, respectively. The average molecular weight of glatiramer acetate is 5000 to 9000 Daltons. For a full list of excipients, see section 6.1 List of excipients. 3. PHARMACEUTICAL FORM Copaxone is a clear, colourless solution for injection, in a pre-filled syringe. The pH of a 0.5% solution in water is in the range of 5.5 to 7.0 and an osmolarity of about 265 mOsmol/L and 300 mOsmol/L for the 20 mg/mL and 40 mg/mL, respectively. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Reduction of the frequency of relapses in patients with Relapsing Remitting Multiple Sclerosis. Treatment of patients with a single clinical event suggestive of multiple sclerosis and at least two clinically silent MRI lesions characteristic of multiple sclerosis, if alternative diagnoses have been excluded. 4.2 Dose and method of administration The only recommended route of administration of Copaxone injection is by the subcutaneous route. Copaxone should not be administered by the intravenous or intramuscular routes.
    [Show full text]
  • United States Patent (10) Patent No.: US 9,724,354 B2 Brake Et Al
    USOO9724354B2 (12) United States Patent (10) Patent No.: US 9,724,354 B2 Brake et al. (45) Date of Patent: Aug. 8, 2017 (54) COMBINATION OF CATALYTIC MTORC1/2 6,727.251 B2 4/2004 Bebbington et al. INHIBITORS AND SELECTIVE INHIBITORS g: R 1939: Shano et al. O OF AURORAAKNASE 7,049,116 B2 5, 2006 Shokat 7,148,228 B2 12/2006 Kasibhatla et al. (71) Applicant: Millennium Pharmaceuticals, Inc., 7,271,262 B2 9, 2007 tty al Cambridge, MA (US) 7,572,784 B2 8/2009 Claiborne et al. 8,026,246 B2 9, 2011 Claiborne et al. (72) Inventors: Rachael L. Brake, Natick, MA (US); 8,399.659 B2 3/2013 Claiborne et al. Huifeng Niu, Cambridge, MA (US) 9,102,678 B2 8, 2015 Claiborne et al. g Nu, 2C, 2001/0024.833 A1 9, 2001 Laborde et al. 2002fOO16976 A1 2/2002 Shokat (73) Assignee: Millennium Pharmaceuticals, Inc., 2002fO156081 A1 10, 2002 Hirst et al. Cambridge, MA (US) 2003/0022885 A1 1/2003 Bebbington et al. 2003/0055068 A1 3/2003 Bebbington et al. c - r 2003. O180924 A1 9, 2003 DeSimone (*) Notice: Sibi tO E. site th still 2003/0187001 A1 10, 2003 Calderwood et al. patent 1s extended or adjusted under 2005/0085472 A1 4/2005 Tanaka et al. U.S.C. 154(b) by 0 days. 2005. O197340 A1 9, 2005 Arora et al. 2006,0074074 A1 4/2006 Ohtsuka et al. (21) Appl. No.: 14/777,888 2006/0235031 A1 10, 2006 Arnold et al. 2006/0246551 A1 11/2006 Stack et al.
    [Show full text]
  • Human Anatomy As Related to Tumor Formation Book Four
    SEER Program Self Instructional Manual for Cancer Registrars Human Anatomy as Related to Tumor Formation Book Four Second Edition U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service National Institutesof Health SEER PROGRAM SELF-INSTRUCTIONAL MANUAL FOR CANCER REGISTRARS Book 4 - Human Anatomy as Related to Tumor Formation Second Edition Prepared by: SEER Program Cancer Statistics Branch National Cancer Institute Editor in Chief: Evelyn M. Shambaugh, M.A., CTR Cancer Statistics Branch National Cancer Institute Assisted by Self-Instructional Manual Committee: Dr. Robert F. Ryan, Emeritus Professor of Surgery Tulane University School of Medicine New Orleans, Louisiana Mildred A. Weiss Los Angeles, California Mary A. Kruse Bethesda, Maryland Jean Cicero, ART, CTR Health Data Systems Professional Services Riverdale, Maryland Pat Kenny Medical Illustrator for Division of Research Services National Institutes of Health CONTENTS BOOK 4: HUMAN ANATOMY AS RELATED TO TUMOR FORMATION Page Section A--Objectives and Content of Book 4 ............................... 1 Section B--Terms Used to Indicate Body Location and Position .................. 5 Section C--The Integumentary System ..................................... 19 Section D--The Lymphatic System ....................................... 51 Section E--The Cardiovascular System ..................................... 97 Section F--The Respiratory System ....................................... 129 Section G--The Digestive System ......................................... 163 Section
    [Show full text]
  • Etats Rapides
    List of European Pharmacopoeia Reference Standards Effective from 2015/12/24 Order Reference Standard Batch n° Quantity Sale Information Monograph Leaflet Storage Price Code per vial Unit Y0001756 Exemestane for system suitability 1 10 mg 1 2766 Yes +5°C ± 3°C 79 ! Y0001561 Abacavir sulfate 1 20 mg 1 2589 Yes +5°C ± 3°C 79 ! Y0001552 Abacavir for peak identification 1 10 mg 1 2589 Yes +5°C ± 3°C 79 ! Y0001551 Abacavir for system suitability 1 10 mg 1 2589 Yes +5°C ± 3°C 79 ! Y0000055 Acamprosate calcium - reference spectrum 1 n/a 1 1585 79 ! Y0000116 Acamprosate impurity A 1 50 mg 1 3-aminopropane-1-sulphonic acid 1585 Yes +5°C ± 3°C 79 ! Y0000500 Acarbose 3 100 mg 1 See leaflet ; Batch 2 is valid until 31 August 2015 2089 Yes +5°C ± 3°C 79 ! Y0000354 Acarbose for identification 1 10 mg 1 2089 Yes +5°C ± 3°C 79 ! Y0000427 Acarbose for peak identification 3 20 mg 1 Batch 2 is valid until 31 January 2015 2089 Yes +5°C ± 3°C 79 ! A0040000 Acebutolol hydrochloride 1 50 mg 1 0871 Yes +5°C ± 3°C 79 ! Y0000359 Acebutolol impurity B 2 10 mg 1 -[3-acetyl-4-[(2RS)-2-hydroxy-3-[(1-methylethyl)amino] propoxy]phenyl] 0871 Yes +5°C ± 3°C 79 ! acetamide (diacetolol) Y0000127 Acebutolol impurity C 1 20 mg 1 N-(3-acetyl-4-hydroxyphenyl)butanamide 0871 Yes +5°C ± 3°C 79 ! Y0000128 Acebutolol impurity I 2 0.004 mg 1 N-[3-acetyl-4-[(2RS)-3-(ethylamino)-2-hydroxypropoxy]phenyl] 0871 Yes +5°C ± 3°C 79 ! butanamide Y0000056 Aceclofenac - reference spectrum 1 n/a 1 1281 79 ! Y0000085 Aceclofenac impurity F 2 15 mg 1 benzyl[[[2-[(2,6-dichlorophenyl)amino]phenyl]acetyl]oxy]acetate
    [Show full text]
  • Information for Authors / Submission Process New
    INFORMATION FOR AUTHORS / SUBMISSION PROCESS NEW Electronic Submission Uniform Requirements for Manuscripts Submitted to Biomedical Journals: Writing and Editing for As of December 1, 2007, the Canadian Journal of Neurological Biomedical Publication International Committee of Sciences went to an Electronic Submission process. ALL manuscript submissions will be handled by an On-Line tracking system. Go to Medical Journal Editors www.cjns.org and click on SUBMIT YOUR MANUSCRIPT and For detailed instructions regarding style and layout refer to "Uniform follow the instructions. requirements for manuscripts submitted to biomedical journals". Copies of this document may be obtained on the website (we will no longer accept paper/disc submissions) http://www.icmje.org. Articles should be submitted under The manuscript submission process is broken into a series of five conventional headings of introduction, methods and materials, screens that gather detailed information about your manuscript and results, discussion, but other headings will be considered if more allow you to upload the pertinent files. The sequence of screens are as suitable. For Uniform Requirements for Sample References go to follows: http://www.nlm.nih.gov/bsd/uniform_requirements.html. After the manuscript is submitted, you will be asked to select the order you would like the files to be displayed in a merged PDF file 1. A long form asking for author information, title, abstract, and file that the system will create for you. Next, you will be directed to a quantities. page that will allow you to review your converted manuscript. If the 2. A screen asking for the actual file locations on your computer (via conversion is not correct, you can replace or delete your manuscript an open file dialog).
    [Show full text]
  • The Use of Stems in the Selection of International Nonproprietary Names (INN) for Pharmaceutical Substances
    WHO/PSM/QSM/2006.3 The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances 2006 Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Medicines Policy and Standards The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 © World Health Organization 2006 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.
    [Show full text]