DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2007/0258889 A1 Douglas Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2007/0258889 A1 Douglas Et Al US 20070258889A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0258889 A1 Douglas et al. (43) Pub. Date: Nov. 8, 2007 (54) NOVEL NANOPARTICLES AND USE Related U.S. Application Data THEREOF (60) Provisional application No. 60/736,041, filed on Nov. 9, 2005. Provisional application No. 60/831,109, filed (75) Inventors: Trevor Douglas, Bozeman, MT (US); on Jul. 14, 2006. Peter Suci, Bozeman, MT (US); Mark J. Young, Bozeman, MT (US) Publication Classification (51) Int. Cl. A6IR 9/14 (2006.01) Correspondence Address: A61R 49/14 (2006.01) DORSEY & WHITNEY LLP A6II 5L/08 (2006.01) 555 CALIFORNIA STREET, SUITE 1000 (52) U.S. Cl. ....................... 424/1.37: 424/499: 424/9.34; SUTE 1 OOO 977/773 SAN FRANCISCO, CA 94104 (US) (57) ABSTRACT Assignee: Montana State University, Bozman, MT The present invention is directed to novel compositions and (73) methods utilizing delivery agents or nanoparticles that include protein cages with modified and/or unmodified (21) Appl. No.: 11/558,393 Subunits and various agents, such as therapeutic and/or imaging agents located on the interior and/or exterior Sur (22) Filed: Nov. 9, 2006 face of the protein cages. sHsp Loop Insert N-TerminuS > s C-Terminus CCMV C-Terminus--> * Patent Application Publication Nov. 8, 2007 Sheet 1 of 29 US 2007/0258889 A1 sHsp Loop Insert N-Terminus > * D & C-Terminus CCMV C-Terminus--> y Loop Insert.) N-Terminus os FIG. 1 on 3... O O OH O O DMF. disopropyleyamine --O Horsa X = M OMO 1 M. HO s o O NH, N/Yssn1 HN-Jo. O FIG. 3 T2 relaxitvity from 7.0 Telsa MRI 400 2OO Magnevist CCMW hand (100 uM) (56 uM) COOH HOO C3" COOH C. COOH Patent Application Publication Nov. 8, 2007 Sheet 2 of 29 US 2007/0258889 A1 w er CN CD Patent Application Publication Nov. 8, 2007 Sheet 3 of 29 US 2007/0258889 A1 T2 relaxitvity at 7 Telsa 15uM Gd 15uMHSP-DPTA sv. W. Sw & 8 ity was Ciss FIG. 7 Patent Application Publication Nov. 8, 2007 Sheet 4 of 29 US 2007/0258889 A1 Patent Application Publication Nov. 8, 2007 Sheet 5 of 29 US 2007/0258889 A1 Disassemble Subunits,Y A Patent Application Publication Nov. 8, 2007 Sheet 6 of 29 US 2007/0258889 A1 FIG. 13 Patent Application Publication Nov. 8, 2007 Sheet 7 of 29 US 2007/0258889 A1 Closed Open Pore (1) Soluble Pores (4) O o-/Material (3) SP O O O O pH > 6.5 O O Closed Form (2) Open Form (5) FIG. 14A He pH < 6.5 Crystallization FIG. 14B Patent Application Publication Nov. 8, 2007 Sheet 8 of 29 US 2007/0258889 A1 FIG. 15A FIG. 15B FIG. 15C Patent Application Publication Nov. 8, 2007 Sheet 9 of 29 US 2007/0258889 A1 O AISueu Patent Application Publication Nov. 8, 2007 Sheet 10 of 29 US 2007/0258889 A1 500 HspG41CRGD-4C 34 OO OO H Abs 280 nm 2 O O O 5 10 15 2O 25 30 Elution Volume (mL) FIG. 17A 468 OOO 2 O O 2O 45 60 8O 1 OO Diameter (nm) FIG. 17B FIG. 17C Patent Application Publication Nov. 8, 2007 Sheet 11 of 29 US 2007/0258889 A1 - - c d C C C C - - Fluorescent Fluorescent Image Image Protein Protein Image Image FIG. 18A FIG. 18B US 2007/0258889 A1 (suo][eo])sseW Patent Application Publication Nov. 8, 2007 Sheet 13 of 29 US 2007/0258889 A1 Patent Application Publication Nov. 8, 2007 Sheet 14 of 29 US 2007/0258889 A1 s8 & 9 1O 11 10 10 10 160 101 162 13 164 Fluorescence Intensity (a.u.) Fluorescein FIG 21B FIG 21D Patent Application Publication Nov. 8, 2007 Sheet 15 of 29 US 2007/0258889 A1 160 11 12 10 164 Fluorescein FIG. 22 e 2 103 2 108 10 FIG. 23A FIG. 23C e e FITC Fluorescence intensity (a.u.) FIG. 23B FIG. 23C Patent Application Publication Nov. 8, 2007 Sheet 16 of 29 US 2007/0258889 A1 HspG41CRGD4C-Fluorescein to Hsp Protein (280 nm) 4 O S&N 8 Fluorescein (495 nm) 30 CD 2 20 O s & 3 10 C O Y, m YYYYYYY w YYYYYYYYYYYYY WYYYYYY WW O 5 10 15 20 2 Elution Volume (mL) HspG41CRGD4C-Doxorubicin o Hsp Protein (280 nm) es 888 & Doxorubicin (495 nm) 300 s 3 200 t O 5 3 1OO C O S&R's S w NilsSSS swysw O 5 1O 15 20 Elution Volume (mL) FIG. 25 Patent Application Publication Nov. 8, 2007 Sheet 17 of 29 US 2007/0258889 A1 Z ##### SS AISueu Patent Application Publication Nov. 8, 2007 Sheet 18 of 29 US 2007/0258889 A1 100 80 ge 60 g 40 d Y O O 2O 45 60 80 100 Diameter (nm) FIG. 27 Patent Application Publication Nov. 8, 2007 Sheet 19 of 29 US 2007/0258889 A1 TEM DLS 20 40 60 80 Diameter 1 nm 100 O 20 4 O 60 80 Diameter 1 nm FIG. 28 Patent Application Publication Nov. 8, 2007 Sheet 20 of 29 US 2007/0258889 A1 246 3.8 + O.7 mm FIG. 29A OOOO O 2 4 6 8 10 12 Diameter 1 nm 246 5.5 + 0.9 nm FIG. 29B OOOO O 2 4 6 8 10 12 Diameter 1 nm 246 6.O. O.9 nm. FIG. 29C OOOO O 2 4 6 8 10 12 Diameter 1 nm 246 5.6 + O.9 mm FIG. 29D OOOO O 2 4 6 8 10 12 Diameter 1 nm 246 5.9 + 1.3 nm OOOO O 2 4 6 8 10 12 FIG. 29E Diameter 1 nm Patent Application Publication Nov. 8, 2007 Sheet 21 of 29 US 2007/0258889 A1 650 700 750 Energy loss 1 eV FIG. 3OA FIG. 3OB Before Mineralization After Mineralization -280nm -41 Onm hears O 10 20 30 O 10 20 30 Elution Volume I ml Elution Volume I ml FIG. 31A FIG. 31B Patent Application Publication Nov. 8, 2007 Sheet 22 of 29 US 2007/0258889 A1 1.0 - 1000Fe?cage - 3000Fe?cage 0.8 -5000Felcage 5000Fe?cage 9 A 0.6 3000Felcage Se 3. * 0.4 ig 1000Felcage t 0.2 0.0 20 40 60 80 100 O 20 40 60 80 100 120 140 Blocking temperature (T) IK Particle Volume 1 nm. S c s O E O 1000Felcage 3000Felcage A 5000Felcage O.050 0.075 O. 100 (1IT) 1 K g 4 1000Fe?cage 2 S o O -2 Savingg-4x10 -80x108 -40 O 40 80 Field G o 10 3000Fellcage o 15 5000Fe?cage s S 10 5 s 5 S o O o O E E -5 -5 2 -10 g -10x10 S-15x108 -80x108 -40 O 40 80 -80x108 -40 O 40 80 Field G Field G FIG. 34 Patent Application Publication Nov. 8, 2007 Sheet 23 of 29 US 2007/0258889 A1 100 101 102 103 104 Fluorescence Intensity FIG. 36 Patent Application Publication Nov. 8, 2007 Sheet 24 of 29 US 2007/0258889 A1 Differentially modify Š Disassemble, isolate SS Subunits SSS II) Detection (Western blot) i) Binding to Mix, reassemble Streptavidin agarose Subunit ratio FIG. 39 FIG 38 Patent Application Publication Nov. 8, 2007 Sheet 25 of 29 US 2007/0258889 A1 Monomers 1 2 Unmodified: MSTVGTGELTEAOEEAAAEE CCMV-CALMSTDKDGDGW LEEEEGGGEE 28nM FIG. 43 Protein Cage (1) input anti-dig anti-biotin 6 O 4. O 2 O O O 10 20 30 digibio (input) .N. N. N N.N.Yo-YS) SS; SS)R.W. SS-SSSSS Patent Application Publication Nov. 8, 2007 Sheet 26 of 29 US 2007/0258889 A1 A B 1OO 200 a 80 s g 150 S. 60 5 100 S 40 3 a 50 20 Y O : O 5 10 15 20 25 3O 35 O 1 O 20 30 40 50 60 Elution Volume 1 mL. Diameter 1 nm 18 20 22 24 26 2830x108 Mass 1 Daltons Experiment 1,550mm Experiment 2,550mm Experiment 3, 550mm Experiment 3, 340mm Fit to Eq. (12) OO 0.4 O4 12 Free Tb | uM FIG. 46 Patent Application Publication Nov. 8, 2007 Sheet 27 of 29 US 2007/0258889 A1 O Experiment 1 A Experiment 2 O.O 0.2 0.4 0.6 0.8 1.0 Tb) * (Subunit FIG. 47 20021 0000 3222 20285 OOOO 2587 21362 0000 204 21902 0000 651 20239 0000 biggs 0000 3 100 20000 OOOO is 0055 19000 195OO 20000 20500 21OOO 21500 22000 22500 23OOO FIG. 48 Patent Application Publication Nov. 8, 2007 Sheet 28 of 29 US 2007/0258889 A1 H CCMV-CAL-Gd A WtCCMV-Gd 3OO 4OO 350 250 3OO 200 N250 2OO 150 150 1OO 1 OO 1O 20 30 40 50 60 1O 20 30 40 50 60 MHZ MHZ FIG. 5OA FIG. 5OB Patent Application Publication Nov. 8, 2007 Sheet 29 of 29 US 2007/0258889 A1 -- CCMV-DOTA-Gd -O- DOTA-Gd 60 120 40 V GN 80 20 40 O O O O 10 20 30 40 50 60 10 20 30 40 50 60 MHz MHz FIG 51A FIG. 51B US 2007/0258889 A1 Nov. 8, 2007 NOVEL NANOPARTICLES AND USE THEREOF an apoferritin shell and an inorganic core, and are thought to be useful in the production of ultrafine particles for high CROSS-REFERENCE TO RELATED performance ceramics, drug delivery, and other uses. APPLICATIONS 0006. A general review of systems employing the apof 0001) This application claims the benefit under 35 U.S.C. erritin/core nanoscale particle production system is provided S 119(e) of U.S.
Load more

Recommended publications
  • Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy
    cancers Review Primary and Acquired Resistance to Immunotherapy in Lung Cancer: Unveiling the Mechanisms Underlying of Immune Checkpoint Blockade Therapy Laura Boyero 1 , Amparo Sánchez-Gastaldo 2, Miriam Alonso 2, 1 1,2,3, , 1,2, , José Francisco Noguera-Uclés , Sonia Molina-Pinelo * y and Reyes Bernabé-Caro * y 1 Institute of Biomedicine of Seville (IBiS) (HUVR, CSIC, Universidad de Sevilla), 41013 Seville, Spain; [email protected] (L.B.); [email protected] (J.F.N.-U.) 2 Medical Oncology Department, Hospital Universitario Virgen del Rocio, 41013 Seville, Spain; [email protected] (A.S.-G.); [email protected] (M.A.) 3 Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), 28029 Madrid, Spain * Correspondence: [email protected] (S.M.-P.); [email protected] (R.B.-C.) These authors contributed equally to this work. y Received: 16 November 2020; Accepted: 9 December 2020; Published: 11 December 2020 Simple Summary: Immuno-oncology has redefined the treatment of lung cancer, with the ultimate goal being the reactivation of the anti-tumor immune response. This has led to the development of several therapeutic strategies focused in this direction. However, a high percentage of lung cancer patients do not respond to these therapies or their responses are transient. Here, we summarized the impact of immunotherapy on lung cancer patients in the latest clinical trials conducted on this disease. As well as the mechanisms of primary and acquired resistance to immunotherapy in this disease. Abstract: After several decades without maintained responses or long-term survival of patients with lung cancer, novel therapies have emerged as a hopeful milestone in this research field.
    [Show full text]
  • WO 2015/123595 Al 20 August 2015 (20.08.2015) 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 2015/123595 Al 20 August 2015 (20.08.2015) P O P C T (51) International Patent Classification: nut Creek, California 94597 (US). SPANGLER, Ben¬ A61K 31/4025 (2006.01) A61P 33/06 (2006.01) jamin B.; 525 Nelson Rising Lane, Apt. 509, San Fran C07D 407/12 (2006.01) cisco, California 94158 (US). WELLS, James A.; 1341, Columbus Ave., Burlingame, California 94010 (US). (21) International Application Number: PCT/US2015/015948 (74) Agents: NOMURA, Anson M. et al; Mintz Levin Cohn Ferris Glovsky and Popeo PC, 3580 Carmel Mountain (22) International Filing Date: Road, Suite 300, San Diego, CA 92130 (US). 13 February 2015 (13.02.2015) (81) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of national protection available): AE, AG, AL, AM, (26) Publication Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (30) Priority Data: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 61/940,295 14 February 2014 (14.02.2014) US HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (71) Applicant: THE REGENTS OF THE UNIVERSITY KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, OF CALIFORNIA [US/US]; 1111 Franklin Street, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, Twelfth Floor, Oakland, California 94607-5200 (US).
    [Show full text]
  • The Two Tontti Tudiul Lui Hi Ha Unit
    THETWO TONTTI USTUDIUL 20170267753A1 LUI HI HA UNIT ( 19) United States (12 ) Patent Application Publication (10 ) Pub. No. : US 2017 /0267753 A1 Ehrenpreis (43 ) Pub . Date : Sep . 21 , 2017 ( 54 ) COMBINATION THERAPY FOR (52 ) U .S . CI. CO - ADMINISTRATION OF MONOCLONAL CPC .. .. CO7K 16 / 241 ( 2013 .01 ) ; A61K 39 / 3955 ANTIBODIES ( 2013 .01 ) ; A61K 31 /4706 ( 2013 .01 ) ; A61K 31 / 165 ( 2013 .01 ) ; CO7K 2317 /21 (2013 . 01 ) ; (71 ) Applicant: Eli D Ehrenpreis , Skokie , IL (US ) CO7K 2317/ 24 ( 2013. 01 ) ; A61K 2039/ 505 ( 2013 .01 ) (72 ) Inventor : Eli D Ehrenpreis, Skokie , IL (US ) (57 ) ABSTRACT Disclosed are methods for enhancing the efficacy of mono (21 ) Appl. No. : 15 /605 ,212 clonal antibody therapy , which entails co - administering a therapeutic monoclonal antibody , or a functional fragment (22 ) Filed : May 25 , 2017 thereof, and an effective amount of colchicine or hydroxy chloroquine , or a combination thereof, to a patient in need Related U . S . Application Data thereof . Also disclosed are methods of prolonging or increasing the time a monoclonal antibody remains in the (63 ) Continuation - in - part of application No . 14 / 947 , 193 , circulation of a patient, which entails co - administering a filed on Nov. 20 , 2015 . therapeutic monoclonal antibody , or a functional fragment ( 60 ) Provisional application No . 62/ 082, 682 , filed on Nov . of the monoclonal antibody , and an effective amount of 21 , 2014 . colchicine or hydroxychloroquine , or a combination thereof, to a patient in need thereof, wherein the time themonoclonal antibody remains in the circulation ( e . g . , blood serum ) of the Publication Classification patient is increased relative to the same regimen of admin (51 ) Int .
    [Show full text]
  • W W W .Bio Visio N .Co M
    Biosimilar Monoclonal Antibodies Human IgG based monoclonal antibodies (mAbs) are the fastest-growing category of therapeutics for cancer therapy. Several mechanisms of tumor cell killing by antibodies (mAbs) can be summarized as: direct action through receptor blockade or induction of apoptosis; immune-mediated cell killing by complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) or regulation of T cell function. Several monoclonal antibodies have received FDA approval for the treatment of a variety of solid tumors and hematological malignancies. BioVision is pleased to offer research grade biosimilars in human IgG format for your research needs. Our monoclonal antibodies are manufactured using recombinant technology with variable regions from the therapeutic antibody to achieve similar safety and efficacy. These antibodies can be used as controls for preclinical lead identification and potency assays for the development of novel therapeutics. Antibody Name Cat. No. Trade Name Isotype Size Anti-alpha 5 beta 1 Integrin (Volociximab), Human IgG4 Ab A1092 - IgG4 200 µg Anti-Beta-galactosidase, Human IgG1 Ab A1104 - IgG1 200 µg Anti-C5 (Eculizumab), Humanized Ab A2138 - IgG2/4 100 μg Anti-Carcinoembryonic antigen (Arcitumomab), Human IgG1 Ab A1096 - IgG1 200 µg Anti-CCR4 (Mogamulizumab), Human IgG1, kappa Ab A2005 - IgG1 200 μg Anti-CD11a (Efalizumab), Human IgG1 Ab A1089 Raptiva IgG1 200 µg Anti-CD20 (Rituximab), Chimeric Ab A1049 Mabthera IgG1 100 µg Anti-CD22 (Epratuzumab), Human IgG1 Ab A1445 LymphoCide IgG1 200 µg Anti-CD3 epsilon (Muromonab), Mouse IgG2a, kappa Ab A2008 - IgG2a 200 μg Anti-CD33 (Gemtuzumab), Human IgG4 Ab A1443 Mylotarg IgG4 200 µg Anti-CD38 (Daratumumab), Human IgG1 Ab A2151 Darzalex IgG1 100 μg www.biovision.com 155 S.
    [Show full text]
  • The Constituents and Potential Targets Of
    genesi ino s & rc a M C u t f a o g Weber, J Carcinogene Mutagene 2013, S13 l Journal of Carcinogenesis & e a n n e DOI: 4172/2157-2518.S13-006 r s u i s o J Mutagenesis ISSN: 2157-2518 ReviewResearch Article Article OpenOpen Access Access The Constituents and Potential Targets of the Extracellular Matrix: Implications for Carcinogenesis and Cancer Treatment Weber CE, Driver J, Franzen CA, Mascarenhas JB, Mi Z, Gupta GN, Wai PY and Kuo PC* Department of Surgery, Loyola University, Maywood, Ireland Abstract The dense extracellular matrix consists of a multitude of proteins with important implications in tumorogenesis that extend beyond the maintenance of tissue integrity. Several of the main macromolecular constituents- proteoglycans, collagens, integrins, and syndecans will be discussed in this review, with particular attention to their roles in tumor initiation, invasion, angiogenesis, and metastasis. In addition, a brief synopsis of the role of enzymes that remodel the extracellular matrix will be provided. Finally, specific examples of targeted molecular therapies: anti-integrin agents, MMP inhibitors, and hyaluronidase will be discussed. Keywords: Extracellular matrix; Proteoglycans; Integrins; Syndecans; and mechanical signaling in the Tumor Microenvironment (TME). Matrix metalloproteinases; Hyaluronidase These cues modulate many aspects of carcinogenesis, from tumor formation to tumor migration and invasion to distant metastasis [1,2]. Abbreviations: ECM- Extracellular Matrix; BM- Basement Communication between the ECM and cancer cells occurs directly Membrane; PG- Proteoglycan; HSPG- Heparan Sulfate Proteoglycan; through cell-ECM adhesion molecules such as integrins and syndecans GAG- Glycosaminoglycan; MMP- Matrix Metalloproteinase; ADAM- and also indirectly through ECM bound growth factors and transmitted A Disintegrin And Metalloproteinase; TIMP- Tissue Inhibitor of mechanical forces.
    [Show full text]
  • Integrins As Therapeutic Targets: Successes and Cancers
    cancers Review Integrins as Therapeutic Targets: Successes and Cancers Sabine Raab-Westphal 1, John F. Marshall 2 and Simon L. Goodman 3,* 1 Translational In Vivo Pharmacology, Translational Innovation Platform Oncology, Merck KGaA, Frankfurter Str. 250, 64293 Darmstadt, Germany; [email protected] 2 Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK; [email protected] 3 Translational and Biomarkers Research, Translational Innovation Platform Oncology, Merck KGaA, 64293 Darmstadt, Germany * Correspondence: [email protected]; Tel.: +49-6155-831931 Academic Editor: Helen M. Sheldrake Received: 22 July 2017; Accepted: 14 August 2017; Published: 23 August 2017 Abstract: Integrins are transmembrane receptors that are central to the biology of many human pathologies. Classically mediating cell-extracellular matrix and cell-cell interaction, and with an emerging role as local activators of TGFβ, they influence cancer, fibrosis, thrombosis and inflammation. Their ligand binding and some regulatory sites are extracellular and sensitive to pharmacological intervention, as proven by the clinical success of seven drugs targeting them. The six drugs on the market in 2016 generated revenues of some US$3.5 billion, mainly from inhibitors of α4-series integrins. In this review we examine the current developments in integrin therapeutics, especially in cancer, and comment on the health economic implications of these developments. Keywords: integrin; therapy; clinical trial; efficacy; health care economics 1. Introduction Integrins are heterodimeric cell-surface adhesion molecules found on all nucleated cells. They integrate processes in the intracellular compartment with the extracellular environment. The 18 α- and 8 β-subunits form 24 different heterodimers each having functional and tissue specificity (reviewed in [1,2]).
    [Show full text]
  • Ep 3321281 A1
    (19) TZZ¥¥ _ __T (11) EP 3 321 281 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 16.05.2018 Bulletin 2018/20 C07K 14/79 (2006.01) A61K 38/40 (2006.01) A61K 38/00 (2006.01) A61K 38/17 (2006.01) (2006.01) (2006.01) (21) Application number: 17192980.5 A61K 39/395 A61K 39/44 C07K 16/18 (2006.01) (22) Date of filing: 03.08.2012 (84) Designated Contracting States: • TIAN, Mei Mei AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Coquitlam, BC V3J 7E6 (CA) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • VITALIS, Timothy PL PT RO RS SE SI SK SM TR Vancouver, BC V6Z 2N1 (CA) (30) Priority: 05.08.2011 US 201161515792 P (74) Representative: Gowshall, Jonathan Vallance Forresters IP LLP (62) Document number(s) of the earlier application(s) in Skygarden accordance with Art. 76 EPC: Erika-Mann-Strasse 11 12746240.6 / 2 739 649 80636 München (DE) (71) Applicant: biOasis Technologies Inc Remarks: Richmond BC V6X 2W8 (CA) •This application was filed on 25.09.2017 as a divisional application to the application mentioned (72) Inventors: under INID code 62. • JEFFERIES, Wilfred •Claims filed after the date of receipt of the divisional South Surrey, BC V4A 2V5 (CA) application (Rule 68(4) EPC). (54) P97 FRAGMENTS WITH TRANSFER ACTIVITY (57) The present invention is related to fragments of duction of the melanotransferrin fragment conjugated to human melanotransferrin (p97). In particular, this inven- a therapeutic or diagnostic agent to a subject.
    [Show full text]
  • Integrin Alpha5 in Human Breast Cancer Is a Mediator of Bone Metastasis and a Therapeutic Target for the Treatment of Osteolytic Lesions
    Oncogene (2021) 40:1284–1299 https://doi.org/10.1038/s41388-020-01603-6 ARTICLE Integrin alpha5 in human breast cancer is a mediator of bone metastasis and a therapeutic target for the treatment of osteolytic lesions 1,2,3 1,2 4 5,6 3 Francesco Pantano ● Martine Croset ● Keltouma Driouch ● Natalia Bednarz-Knoll ● Michele Iuliani ● 3 1,2 5 1,2 4 3 Giulia Ribelli ● Edith Bonnelye ● Harriet Wikman ● Sandra Geraci ● Florian Bonin ● Sonia Simonetti ● 3 2,7 1,2 5 3 3 Bruno Vincenzi ● Saw See Hong ● Sofia Sousa ● Klaus Pantel ● Giuseppe Tonini ● Daniele Santini ● Philippe Clézardin 1,2,8 Received: 10 May 2020 / Revised: 26 November 2020 / Accepted: 3 December 2020 / Published online: 8 January 2021 © The Author(s) 2021. This article is published with open access Abstract Bone metastasis remains a major cause of mortality and morbidity in breast cancer. Therefore, there is an urgent need to better select high-risk patients in order to adapt patient’s treatment and prevent bone recurrence. Here, we found that integrin alpha5 (ITGA5) was highly expressed in bone metastases, compared to lung, liver, or brain metastases. High ITGA5 1234567890();,: 1234567890();,: expression in primary tumors correlated with the presence of disseminated tumor cells in bone marrow aspirates from early stage breast cancer patients (n = 268; p = 0.039). ITGA5 was also predictive of poor bone metastasis-free survival in two separate clinical data sets (n = 855, HR = 1.36, p = 0.018 and n = 427, HR = 1.62, p = 0.024). This prognostic value remained significant in multivariate analysis (p = 0.028).
    [Show full text]
  • INN Working Document 05.179 Update 2011
    INN Working Document 05.179 Update 2011 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) INN Working Document 05.179 Distr.: GENERAL ENGLISH ONLY 2011 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) Programme on International Nonproprietary Names (INN) Quality Assurance and Safety: Medicines Essential Medicines and Pharmaceutical Policies (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) © World Health Organization 2011 All rights reserved. Publications of the World Health Organization are available on the WHO web site (www.who.int) or can be purchased from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; email: [email protected]). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press through the WHO web site (http://www.who.int/about/licensing/copyright_form/en/index.html). 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.
    [Show full text]
  • (INN) for Biological and Biotechnological Substances
    WHO/EMP/RHT/TSN/2019.1 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) 2019 WHO/EMP/RHT/TSN/2019.1 International Nonproprietary Names (INN) for biological and biotechnological substances (a review) 2019 International Nonproprietary Names (INN) Programme Technologies Standards and Norms (TSN) Regulation of Medicines and other Health Technologies (RHT) Essential Medicines and Health Products (EMP) International Nonproprietary Names (INN) for biological and biotechnological substances (a review) FORMER DOCUMENT NUMBER: INN Working Document 05.179 © World Health Organization 2019 All rights reserved. Publications of the World Health Organization are available on the WHO website (www.who.int) or can be purchased 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 non-commercial distribution– should be addressed to WHO Press through the WHO website (www.who.int/about/licensing/copyright_form/en/index.html). 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 and dashed 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.
    [Show full text]
  • Biosimilar Antibodies & ELISA Kits
    Biosimilar Antibodies & ELISA Kits Tech Help: Email: [email protected] | Toll Free: 800.891.9699 (US Only) | Human IgG based monoclonal antibodies (mAbs) are the fastest-growing category of therapeutics for cancer therapy. With various degree of humanization of the antibody developed from murine, large foreign biologic antibodies are able to detect and kill tumor cells. Several mechanisms of tumor cell killing by antibodies (mAbs) can be sumarized as: direct action through receptor blockade or induction of apoptosis; immune-mediated cell killing by complement-dependent cytotoxicty (CDC), antibody-dependent cellular cytotoxicity (ADCC) or regulation of T cell function. Several monoclonal antibodies have received FDA approval for the treatment of a variety of solid tumors and hematological malignancies. BioVision is pleased to offer research-grade biosimilar antibodies and ELISA kits for your research needs. These antibodies can be used as controls for preclinical lead identification and potency assays for the development of novel therapeutics; ELISA kits can be used to identify biomarkers for (non-)response and risk factors for adverse drug reactions. Granulocyte Monocyte Complement Tumor antigen Tumor cell MAC ITAM NK Cell Figure A: Immune-mediated effects of tumour-specific IgG Figure B: Direct effects of tumour-specific IgG 2 Biosimilar Antibodies Research grade biosimilars-monoclonal antibodies are manufactured using recombinant technology. These antibodies are ideal research tools for preclinical lead identification and potency assays for the development of novel therapeutics. Key Features: • No additives: Supplied in PBS buffer with preservative (0.02% Proclin™ 300) • High purity: >98% purity as determined by SDS-PAGE • Low endotoxin: <1 EU/µg as determined by the LAL-method • Versatile: Can be used for various applications; ELISA, Neutralization, Flow Cytometry, IHC, IF A B C D Figure: Immunofluorescent and Immunohistochemical staining using Anti-Carcinoembryonic antigen (Arcitumomab), Human IgG1 Antibody (Cat.
    [Show full text]
  • SN12C Xenograft Model for Renal Cancer
    ASCO Oncology Roundtable June 3, 2007 ASCO 2007 Oncology Roundtable Overview of PDL’s oncology pipeline – Update on volociximab development program – Summary of early stage programs focused on novel new targets Roundtable discussion/Q&A with PDL oncology experts Biogen Idec presence demonstrates commitment to volociximab collaboration A solid oncology team in place Mark McCamish, MD, PhD Senior Vice President & Chief Medical Officer Isagani (Gani) Chico, MD Therapeutic Area Head, Oncology Lamia Mounedji-Boudiaf, MD Head, European Clinical Development Vanitha Ramakrishnan, PhD Senior Director, Translational Research Focused mAb discovery efforts Tracking to 1 new mAb IND per year in oncology or AID Created 4 oncology mAb candidates since April 2003 – Outlicensed 1 to Genentech in ’05 – Two currently in clinical development – 4th expected to file IND in late ‘07 Building our oncology franchise with PDL192 – Our newest novel humanized oncology mAb, targeting Q4’07 IND Creating a flow of oncology programs PDL192 program 2007 IND candidate DiscoveryDiscovery eefffortsforts toto createcreate averageaverage 11 INDIND perper yearyear HuLuc63 – phase 1 In multiple myeloma Volociximab – multiple phase 2 studies Volociximab: preclinical summary Potent activity in preclinical models of angiogenesis Development of a surrogate antibody targeting murine α5β1 permits biological and therapeutic profiling: – Dissecting mechanisms of tumorigenesis vs angiogenesis – Dose, schedule, pharmacodynamic characterization – Comparisons, synergies and contrast
    [Show full text]