DOCSLIB.ORG

United States Patent (10) Patent No.: US 9,624,276 B2 Young Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
United States Patent (10) Patent No.: US 9,624,276 B2 Young Et Al USOO9624276B2 (12) United States Patent (10) Patent No.: US 9,624,276 B2 Young et al. (45) Date of Patent: Apr. 18, 2017 (54) PEPTIDIC CHIMERIC ANTIGEN RECEPTOR 7,258,986 B2 8/2007 Maur et al. T CELL, SWITCHES AND USES THEREOF 7,446,190 B2 11/2008 Sadelain et al. 7,514,537 B2 4/2009 Jensen 8,802.374 B2 8, 2014 Jensen (71) Applicant: The California Institute for 8,916,381 B1 12/2014 June et al. Biomedical Research, La Jolla, CA 2004/0044177 A1 3/2004 Macke et al. (US) 2004f0072299 A1* 4, 2004 Gillies ................. A61K 38, 193 435/695 (72) Inventors: Travis Young, La Jolla, CA (US); 2839; ;: A. 258 at al. Chanhyuk Kim, San Diego, CA (US); ck ooper et al. Peter G. Schultz, La Jolla, CA (US) 2006/0083683 A1* 4/2006 HSei ................... Aikip3. 2007/01725.04 A1 7/2007 Shirwan et al. (73) Assignee: The California Institute for 2008/0260731 A1* 10, 2008 Bernett .............. CO7K 16,2803 Biomedical Research, La Jolla, CA 424,133.1 (US) 2009/0117108 A1 5/2009 Wang et al. 2010/0178276 A1* 7, 2010 Sadelain ............ A61K 39.0011 (*)c Notice:- r Subject to any site- the still 2010/0278830 A1 11/2010 Shoemaker et al. 424,93.7 patent is extended or adjusted under 35 2010, O297076 A1* 11, 2010 Morrison ............. A61K 38,212 U.S.C. 154(b) by 0 days. 424,856 2010/0324008 A1 12/2010 Low et al. (21) Appl. No.: 14/688,894 2012.0034223 A1 2/2012 Hall et al. 2012fO213783 A1 8/2012 Rosenberg et al. 1-1. 2014f0065171 A1 3/2014 Geierstanger et al. (22) Filed: Apr. 16, 2015 2014/0234348 A1 8/2014 Scholler et al. (65) Prior Publication Data FOREIGN PATENT DOCUMENTS US 2015/0307564 A1 Oct. 29, 2015 DE WO 2008O25558 A2 * 3, 2008 ...... CO7K 14.f4702 WO WO 97.15669 A1 5, 1997 Related U.S. Application Data WO WO 2004/10638O 12, 2004 WO WO 2007/059312 5/2007 (63) Continuation of application No. WO WO 2007/07O659 6, 2007 PCT/US2014/060684, filed on Oct. 15, 2014. WO WO 2007/079 130 7/2007 WO WO 2007/094916 8, 2007 WO WO 2008/O77O79 6, 2008 (60) gril applier Neil S.S. WO WO 2008.083346 T 2008 s provisional application No. 04/u3U,340, WO WO 2010/037062 4/2010 filed on Jul. 29, 2014, provisional application No. (Continued) 62/009,054, filed on Jun. 6, 2014, provisional application No. 61/895,704, filed on Oct. 25, 2013, provisional application No. 61/891.347, filed on Oct. OTHER PUBLICATIONS 15, 2013. Murphy et al., Proc. Amer. Assoc. Cancer Res., 2005, 46, abstract 51) Int. C No. 1495. (51) Int. Cl. U.S. Appl. No. 14/432,065 Restriction Requirement Mailed Nov. 6, C07K I4/395 (2006.01) 2015. C07K I4/00 (2006.01) U.S. Appl. No. 14/432,065, Travis Young. C07K 6/00 (2006.01) AXup, J. et al., Synthesis of site-specific antibody-drug conjugates A6 IK 39/00 (2006.01) using unnatural amino acids. PNAS. 2012, pp. 16101-16106, vol. CI2N 5/10 (2006.01) 109, No. 40. C07K 9/00 (2006.01) Baeuerle, P.A., P. Kufer, and R. Bargou, BiTE: Teaching antibodies CI2N 5/0783 (2010.01) to engage T-cells for cancer therapy. Curr Opin Mol Ther, 2009. pp. 22-30, vol. 11, Issue No. 1. A61 K 38/00 (2006.01) Beers, S.A., et al., Antigenic modulation limits the efficacy of (52) U.S. Cl. anti-CD20 antibodies: implications for antibody selection. Blood, CPC .......... C07K 14/395 (2013.01); C12N5/0636 Jun. 24, 2010. pp. 5191-5201, vol. 115, Issue No. 25. (2013.01); A6 IK 38/00 (2013.01); C07K Bibl. M., et al., Stability of amyloid-beta peptides in plasma and 2319/01 (2013.01); C07K 2319/30 (2013.01) serum. Electrophoresis, 2012. pp. 445-450, vol. 33, Issue No. 3. (58) Field of Classification Search (Continued) NoneSee application file for complete search history. Pririmary ExaminerE iner — Hong9. San9. (57) ABSTRACT (56) References Cited Disclosed herein are chimeric antigen receptor effector cells U.S. PATENT DOCUMENTS (CAR-ECs) and CAR-EC switches. The switchable CAR ECs are generally T cells. The one or more chimeric antigen 5,372,930 A 12/1994 Colton et al. receptors may recognize a peptidic antigen on the CAR-EC 5,861,156 A 1/1999 George et al. switch. The CAR-ECs and switches may be used for the 5,906,936 A 5, 1999 Eshhar et al. treatment of a condition in a Subject in need thereof. 5,912, 172 A 6, 1999 Eshhar et al. 6,083,751 A 7/2000 Feldhaus et al. 25 Claims, 8 Drawing Sheets US 9,624,276 B2 Page 2 (56) References Cited Cole, D.K., et al. The molecular determinants of CD8 co-receptor function. Immunology, Oct. 2012. pp. 139-148, vol. 137, No. 2. Cui et al. Chemically programmed bispecific antibodies that recruit FOREIGN PATENT DOCUMENTS and activate T cells. Journal of Biological Chemistry, 2012, pp. WO WO 2011/028195 3, 2011 28206-28214, vol. 287, No. 34. WO WO 2012/031744 3, 2012 Davila, M.L., et al., CD19 CAR-targeted T cells induce long-term WO WO 2012/079000 6, 2012 remission and B Cell Aplasia in an immunocompetent mouse model WO WO 2012/082841 6, 2012 of B cell acute lymphoblastic leukemia. PLoS One, 2013. p. e61338, WO WO 2012082841 A2 * 6, 2012 ......... CO7K 16,2863 vol. 8 No. 4. WO WO 2012,166.559 12/2012 WO WO 2012, 166560 12/2012 Davis, T.A., et al., Therapy of B-cell lymphoma with anti-CD20 WO WO 2013/O19615 2, 2013 antibodies can result in the loss of CD20 antigen expression. Clin WO WO 2013/044225 3, 2013 Cancer Res, 1999. pp. 611-615, vol. 5, No. 3. WO WO 2013/093809 6, 2013 Dubrovska, A., et al. A chemically induced vaccine strategy for WO WO 2013/123061 8, 2013 prostate cancer. ACS Chem Biol. 2011. pp. 1223-1231, vol. 6, No. WO WO 2014/100615 6, 2014 11. WO WO 2014/1530O2 9, 2014 Gavrilyuk, et al. B-Lactam-based Approach for the Chemical Pro WO WO 2014/153164 9, 2014 gramming of Aldolase Antibody 38C2. Bioorg Med Chem Lett. Mar. 1, 2009, pp. 1421-1424, vol. 19, No. 5, e-pub Jan. 15, 2009. OTHER PUBLICATIONS GenBank Accession No. AB064051: Homo sapiens IGK mRNA for Bluemel, C., et al., Epitope distance to the target cell membrane and immunoglobulin kappa light chain VLJ region, partial cods, clone: antigen size determine the potency of T cell-mediated lysis by BiTE K10. Jul. 2, 2002. antibodies specific for a large melanoma Surface antigen. Cancer Gilham et al., CAR-T cells and solid tumors: tuning T cells to Immunol Immunother, 2010. pp. 1197-1209, vol. 59, Issue No. 8. challenge an inveterate foe, Trends in Molecular Medicine, 2012, Boder, E.T., K.S. Midelfort, and K.D. Wittrup, Directed evolution of pp. 377-384, vol. 18, No. 7. antibody fragments with monovalent femtomolar antigen-binding Grada et al., TanCAR: a novel bispecific chimeric antigen receptor affinity. Proc Natl Acad Sci USA, 2000, pp. 10701-10705, vol. 97. for cancer immunotherapy, Molecular Therapy-Nucleic Acids, No. 20. 2013, pp. 1-11, vol. 2, No. 7. Bonini, C., et al., The Suicide gene therapy challenge: how to Griffioen, M., et al., Retroviral transfer of human CD20 as a suicide improve a Successful gene therapy approach. Mol Ther, 2007. pp. gene for adoptive T-cell therapy. Haematologica, 2009. pp. 1316 1248-1252, vol. 15, No. 7. 1320, vol. 94, No. 9. Boulassel, M.R. and A. Galal, Immunotherapy for B-Cell Neo Gross, G., T. Waks, and Z. Eshhar, Expression of immunoglobulin plasms using T Cells expressing Chimeric Antigen Receptors: From T-cell receptor chimeric molecules as functional receptors with antigen choice to clinical implementation. Sultan Qaboos Univ Med antibody-type specificity. Proc Natl Acad Sci U S A. 1989. 86(24): J, 2012. p. 273-85, vol. 12, No. 3. p. 10024-8. Brentjens, R., et al., Treatment of chronic lymphocytic leukemia Grupp, S.A., et al., Chimeric antigen receptor-modified T cells for with genetically targeted autologous T cells: case report of an acute lymphoid leukemia. NEngl J Med, 2013. pp. 1509-1518, vol. unforeseen adverse event in a phase I clinical trial. Mol Ther, 2010. 68, No. 16. pp. 666-668, vol. 18, No. 4. Hanes, J., et al., Ribosome display efficiently selects and evolves Bridgeman, J.S., et al., Structural and biophysical determinants of high-affinity antibodies in vitro from immune libraries. Proc Natl alphabeta T-cell antigen recognition. Immunology, 2011. pp. 9-18, Acad Sci U S A, 1998. pp. 14130-1435, vol. 95, No. 24. vol. 135, No. 1. Herron, J.N., et al., High resolution structures of the 4-4-20 Fab Cairo, M.S., et al., NCI first International Workshop on the biology, fluorescein complex in two solvent systems: effects of solvent on prevention, and treatment of relapse after allogeneic hematopoietic structure and antigen-binding affinity. Biophys J, 1994. pp. 2167 stem cell transplantation: report from the committee on the biologi cal considerations of hematological relapse following allogeneic 2183, vol. 67, No. 6. stem cell transplantation unrelated to graft-versus-tumor effects: Heslop, H.E., Safer CARS. Mol Ther, Apr. 2010. pp. 661-662, vol. state of the science. Biol Blood Marrow Transplant, 2010. pp. 18, No. 4. 709-728, vol. 16, No. 6. Hollatz, G., et al., T cells for Suicide gene therapy: activation, Cameron, B.J., et al., Identification of a Titin-Derived HLA-Al functionality and clinical relevance.
Load more

Recommended publications
  • Correlation of Cytokine Level with the Severity of Severe Fever With
    Liu et al. Virology Journal (2017) 14:6 DOI 10.1186/s12985-016-0677-1 RESEARCH Open Access Correlation of cytokine level with the severity of severe fever with thrombocytopenia syndrome Miao-Miao Liu1, Xiao-Ying Lei1, Hao Yu2, Jian-zhi Zhang3 and Xue-jie Yu1,4* Abstract Background: Severe fever with thrombocytopenia syndrome (SFTS) was an emerging hemorrhagic fever that was caused by a tick-borne bunyavirus, SFTSV. Although SFTSV nonstructural protein can inhibit type I interferon (IFN-I) production Ex Vivo and IFN-I played key role in resistance SFTSV infection in animal model, the role of IFN-I in patients is not investigated. Methods: We have assayed the concentration of IFN-α, a subtype of IFN-I as well as other cytokines in the sera of SFTS patients and the healthy population with CBA (Cytometric bead array) assay. Results: The results showed that IFN-α, tumor necrosis factor (TNF-α), granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), macrophage inflammatory protein (MIP-1α), interleukin-6 (IL-6), IL-10, interferon-inducible protein (IP-10), monocyte chemoattractant protein (MCP-1) were significantly higher in SFTS patients than in healthy persons (p < 0.05); the concentrations of IFN-α, IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10 were significant higher in severe SFTS patients than in mild SFTS patients (p < 0.05). Conclusion: The concentration of IFN-α as well as other cytokines (IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10) is correlated with the severity of SFTS, suggesting that type I interferon may not be significant in resistance SFTSV infection in humans and it may play an import role in cytokine storm.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0367695A1 Wilson Et Al
    US 20160367695A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0367695A1 Wilson et al. (43) Pub. Date: Dec. 22, 2016 (54) POLYPEPTIDE CONSTRUCTS AND USES (30) Foreign Application Priority Data THEREOF Oct. 28, 2011 (AU) ................................ 2011 9045O2 (71) Applicant: Teva Pharmaceuticals Australia Pty Ltd, Macquarie Park (AU) Publication Classification (72) Inventors: David S. Wilson, Freemont, CA (US); Sarah L. Pogue, Freemont, CA (US); (51) Int. Cl. Glen E. Mikesell, Pacifica, CA (US); A6II 47/48 (2006.01) Tetsuya Taura, Palo Alto, CA (US); C07K 6/28 (2006.01) Wouter Korver, Mountain View, CA (52) U.S. Cl. (US); Anthony G. Doyle, Drummoyne CPC ..... A61K 47/48269 (2013.01); C07K 16/2896 (AU); Adam Clarke, Five Dock (AU); (2013.01); C07K 231 7/565 (2013.01); C07K Matthew Pollard, Dural (AU): 2317/55 (2013.01); C07K 2317/92 (2013.01) Stephen Tran, Strathfield South (AU); Jack Tzu Chiao Lin, Redwood City, (57) ABSTRACT CA (US) (21) Appl. No.: 15/194,926 The present invention provides a polypeptide construct (22) Filed: Jun. 28, 2016 comprising a peptide or polypeptide signaling ligand linked to an antibody or antigen binding portion thereof which Related U.S. Application Data binds to a cell Surface-associated antigen, wherein the ligand (63) Continuation of application No. 14/262,841, filed on comprises at least one amino acid Substitution or deletion Apr. 28, 2014, which is a continuation of application which reduces its potency on cells lacking expression of said No. PCT/AU2012/001323, filed on Oct. 29, 2012. antigen. Patent Application Publication Dec.
    [Show full text]
  • WO 2010/142017 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 2010/142017 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 48/00 (2006.01) A61P 37/04 (2006.01) kind of national protection available): AE, AG, AL, AM, A61P 31/00 (2006.01) A61K 38/21 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) Number: International Application DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/CA20 10/000844 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 8 June 2010 (08.06.2010) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (26) Publication Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/185,261 9 June 2009 (09.06.2009) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, (71) Applicant (for all designated States except US): DE- ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, FYRUS, INC .
    [Show full text]
  • ( 12 ) Patent Application Publication ( 10 ) Pub . No .: US 2020/0331966 A1 STOVER Et Al
    US 20200331966A1 IN ( 19 ) United States ( 12 ) Patent Application Publication ( 10 ) Pub . No .: US 2020/0331966 A1 STOVER et al . ( 43 ) Pub . Date : Oct. 22 , 2020 ( 54 ) FUSION PROTEIN COMPOSITION ( S ) Related U.S. Application Data COMPRISING MASKED TYPE I INTERFERONS ( IFNA AND IFNB ) FOR USE ( 60 ) Provisional application No. 62 / 920,140 , filed on Apr. IN THE TREATMENT OF CANCER AND 15 , 2019 . METHODS THEREOF Publication Classification ( 71 ) Applicant: Qwixel Therapeutics, Los Angeles, CA ( 51 ) Int. Ci . ( US ) CO7K 7/08 ( 2006.01 ) A61K 47/65 ( 2006.01 ) ( 72 ) Inventors : David STOVER , Encino, CA (US ) ; A61P 35/00 ( 2006.01 ) Sherie MORRISON , Los Angeles, CA ( 52 ) U.S. CI . ( US ) ; Alex VASUTHASAWAT , Los CPC CO7K 7/08 ( 2013.01 ) ; A61K 38/00 Angeles , CA ( US ) ; Kham TRINH , ( 2013.01 ) ; A61P 35/00 ( 2018.01 ) ; A61K 47/65 Porter Ranch , CA ( US ) ; George ( 2017.08 ) AYOUB , Los Angeles, CA ( US ) ( 57 ) ABSTRACT Fusion Protein compositions comprising masked IFNs and ( 73 ) Assignee : Qwixel Therapeutics, Los Angeles, CA methods of making masked IFNs are disclosed herein . ( US ) Consequently, the masked IFNs can be fused to a Mab or binding fragment thereof and be administered to patients as ( 21 ) Appl. No .: 16 /849,889 a therapeutic modality and provide a method of treating cancer, immunological disorders and other disease . ( 22 ) Filed : Apr. 15 , 2020 Specification includes a Sequence Listing . Matripase ST 14 Cleaves an IFN Mask from the Heavy Chain of an anti CD138 Fusion Ab . 1 2 3 1. ant - CD138 / Na 2. anti - C0138 IFNa mask 3. anti - C0138 FNa mask w / MST14 Patent Application Publication Oct.
    [Show full text]
  • United States Patent (10) Patent No.: US 9,464,124 B2 Bancel Et Al
    USOO9464124B2 (12) United States Patent (10) Patent No.: US 9,464,124 B2 Bancel et al. (45) Date of Patent: Oct. 11, 2016 (54) ENGINEERED NUCLEIC ACIDS AND 4,500,707 A 2f1985 Caruthers et al. METHODS OF USE THEREOF 4,579,849 A 4, 1986 MacCoSS et al. 4,588,585 A 5/1986 Mark et al. 4,668,777 A 5, 1987 Caruthers et al. (71) Applicant: Moderna Therapeutics, Inc., 4,737.462 A 4, 1988 Mark et al. Cambridge, MA (US) 4,816,567 A 3/1989 Cabilly et al. 4,879, 111 A 11/1989 Chong (72) Inventors: Stephane Bancel, Cambridge, MA 4,957,735 A 9/1990 Huang (US); Jason P. Schrum, Philadelphia, 4.959,314 A 9, 1990 Mark et al. 4,973,679 A 11/1990 Caruthers et al. PA (US); Alexander Aristarkhov, 5.012.818 A 5/1991 Joishy Chestnut Hill, MA (US) 5,017,691 A 5/1991 Lee et al. 5,021,335 A 6, 1991 Tecott et al. (73) Assignee: Moderna Therapeutics, Inc., 5,036,006 A 7, 1991 Sanford et al. Cambridge, MA (US) 9. A 228 at al. J. J. W. OS a 5,130,238 A 7, 1992 Malek et al. (*) Notice: Subject to any disclaimer, the term of this 5,132,418 A 7, 1992 °N, al. patent is extended or adjusted under 35 5,153,319 A 10, 1992 Caruthers et al. U.S.C. 154(b) by 0 days. 5,168,038 A 12/1992 Tecott et al. 5,169,766 A 12/1992 Schuster et al.
    [Show full text]
  • W O 2014/151535 a L 2 5 September 2014 (25.09.2014) 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 W O 2014/151535 A l 2 5 September 2014 (25.09.2014) P O P C T (51) International Patent Classification: HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, C07K 14/705 (2006.01) KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, (21) International Application Number: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, PCT/US20 14/025940 SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (22) International Filing Date: TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, 13 March 2014 (13.03.2014) ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (30) Priority Data: UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 61/791,537 15 March 2013 (15.03.2013) TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 61/787,753 15 March 2013 (15.03.2013) EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, (71) Applicant: BAYER HEALTHCARE LLC [US/US]; 555 TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, White Plains Rd., Tarrytown, NY 10591 (US).
    [Show full text]
  • Severe Sepsis Epidemiology and Sex-Related Differences in Inflammatory Markers
    UMEÅ UNIVERSITY MEDICAL DISSERTATIONS NEW SERIES NO. 1680 ISSN 0346-6612 ISBN: 978-91-7601-149-2 From the Department of Surgical and Perioperative Sciences Anesthesiology and Intensive Care Medicine Umeå University, Sweden Severe sepsis Epidemiology and sex-related differences in inflammatory markers. Sofie Jacobson Fakultetsopponent: Professor Else Tönnesen Dept. of Clinical Medicine - Anaesthesiology Århus, Danmark Umeå 2014 Cover illustration: "First line of defence" Anders Jacobsson Copyright © 2014 Sofie Jacobson ISBN: 978-91-7601-149-2 NEW SERIES NO. 1680 ISSN 0346-6612 Layout and printed by: Print & Media Umeå, Sweden 2014 To my family A goal is a dream with a deadline. ~ Napolean Hill Contents CONTENTS ABSTRACT......................................................................................................................... iv Svensk sammanfattning .........................................................................................................v Abbreviations..................................................................................................................... viii ORIGINAL PAPERS............................................................................................................x PROLOGUE ........................................................................................................................xi INTRODUCTION..................................................................................................................1 Epidemiology ....................................................................................................................2
    [Show full text]
  • Hepatitis C Virus and Interferon Type
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector REVIEW 10.1111/1469-0691.12797 Hepatitis C virus and interferon type III (interferon-k3/interleukin-28B and interferon-k4): genetic basis of susceptibility to infection and response to antiviral treatment E. Riva1, C. Scagnolari2, O. Turriziani2 and G. Antonelli2 1) Department of Integrated Research, Virology Section, University Campus Bio-Medico of Rome and 2) Department of Molecular Medicine, Virology Section, Sapienza University of Rome, Rome, Italy Abstract There has been a significant increase in our understanding of the host genetic determinants of susceptibility to viral infections in recent years. Recently, two single-nucleotide polymorphisms (SNPs), rs12979860 T/C and rs8099917 T/G, upstream of the interleukin (IL)-28B/interferon (IFN)-k3 gene have been clearly associated with spontaneous and treatment-induced viral clearance in hepatitis C virus (HCV) infection. Because of their power in predicting the response to IFN/ribavirin therapy, the above SNPs have been used as a diagnostic tool, even though their relevance in the management of HCV infection will be blunt in the era of IFN-free regimens. The recent discovery of a new genetic variant, ss469415590 TT/DG, upstream of the IL-28B gene, which generates the novel IFN-k4 protein, has opened up a new and alternative scenario to understand the functional architecture of type III IFN genomic regions and to improve our knowledge of the pathogenetic mechanism of HCV infection. A role of ss469415590 in predicting responsiveness to antiviral therapy has also been observed in HCV-infected patients receiving direct antiviral agents.
    [Show full text]
  • Patent Application Publication Oo) Pub. No.: US 2013/0260367 Al Lowery, JR
    US 20130260367A1 (19) United States (12) Patent Application Publication oo) Pub. No.: US 2013/0260367 Al Lowery, JR. et al. (43) Pub. Date: Oct. 3,2013 (54) NMR SYSTEMS AND METHODS FOR THE (86) PCTNo.: PCT/US11/56936 RAPID DETECTION OF ANALYTES § 371 (c)(1), (2), (4) Date: Jun. 20, 2013 Related U.S. Application Data (75) Inventors: Thomas Jay Lowery, JR., Belmont, MA (US); Mark John Audeh, Brighton, (60) Provisional application No. 61/414,141, filed onNov. 16, 2010, provisional application No. 61/418,465, MA (US); Matthew Blanco, Boston, filed on Dec. I, 2010, provisional application No. MA (US); James Franklin Chepin, 61/497,374, filed on Jun. 15,2011. Arlington, MA (US); Vasiliki Demas, Arlington, MA (US); Rahul Dhanda, (30) Foreign Application Priority Data Needham, MA (US); Marilyn Lee Fritzemeier, Lexington, MA (US); Isaac Oct. 22, 2010 (US) .................................... 12/910594 Koh, Arlington, MA (US); Sonia Publication Classification Kumar, Cambridge, MA (US); Lori (51) Int. Cl. Anne Neely, Reading, MA (US); Brian GOlN 33/543 (2006.01) Mozeleski, Knox, ME (US); Daniella C12Q1/70 (2006.01) Lynn Plourde, Arlington, MA (US); GOlN 33/94 (2006.01) Charles William Rittershaus, Malden, C12Q1/68 (2006.01) MA (US); Parris Wellman, Reading, (52) U.S. Cl. MA (US) CPC ........ GOlN33/54326 (2013.01); C12Q1/6825 (2013.01); C12Q1/70 (2013.01); GOlN 33/9493 (2013.01); C12Q1/6895 (2013.01) USPC . 435/5; 436/501; 435/7.1; 435/6.11; 435/7.4; (73) Assignee: T2 Biosystems, Inc., Lexington, MA 435/287.2; 422/69; 422/554 (US) (57) ABSTRACT (21) Appl.
    [Show full text]
  • WO 2013/126803 Al 29 August 2013 (29.08.2013) 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 2013/126803 Al 29 August 2013 (29.08.2013) P O P C T (51) International Patent Classification: DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, C07C 271/20 (2006.01) C07C 229/12 (2006.01) HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, C07C 217/08 (2006.01) KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (21) International Application Number: NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, PCT/US20 13/027469 RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (22) International Filing Date: TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, 22 February 2013 (22.02.2013) ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (30) Priority Data: UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 61/602,990 24 February 2012 (24.02.2012) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (71) Applicant: PROTIVA BIOTHERAPEUTICS INC. MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, [CA/CA]; 100-8900 Glenlyon Parkway, Burnaby, British TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Columbia V5 5J8 (CA).
    [Show full text]
  • WO 2013/179143 A2 5 December 2013 (05.12.2013) 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 2013/179143 A2 5 December 2013 (05.12.2013) P O P C T (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61M 1/36 (2006.01) A61K 38/19 (2006.01) kind of national protection available): AE, AG, AL, AM, C07K 16/28 (2006.01) A61M 1/34 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61P 35/00 (2006.01) BZ, 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, KN, KP, KR, PCT/IB2013/001583 KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (22) International Filing Date: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 3 1 May 2013 (3 1.05.2013) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (25) Filing Language: English TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (26) Publication Language: English (84) Designated States (unless otherwise indicated, for every (30) Priority Data: kind of regional protection available): ARIPO (BW, GH, PCT/EP20 12/002340 1 June 2012 (01 .06.2012) EP GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 12196527.
    [Show full text]
  • The Interactions Between Cancer Stem Cells and the Innate Interferon Signaling Pathway
    REVIEW published: 31 March 2020 doi: 10.3389/fimmu.2020.00526 The Interactions Between Cancer Stem Cells and the Innate Interferon Signaling Pathway Laura Martin-Hijano 1,2,3 and Bruno Sainz Jr. 1,2,3* 1 Cancer Stem Cell and Tumor Microenvironment Group, Department of Biochemistry, Universidad Autónoma de Madrid (UAM), Madrid, Spain, 2 Cancer Stem Cell and Tumor Microenvironment Group, Department of Cancer Biology, Instituto de Investigaciones Biomédicas “Alberto Sols” (IIBM), CSIC-UAM, Madrid, Spain, 3 Cancer Stem Cell and Tumor Microenvironment Group, Chronic Diseases and Cancer—Area 3, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain Interferons (IFNs) form a family of cytokines with pleiotropic effects that modulate the immune response against multiple challenges like viral infections, autoimmune diseases, and cancer. While numerous anti-tumor activities have been described for IFNs, IFNs have also been associated with tumor growth and progression. The effect of IFNs on apoptosis, angiogenesis, tumor cell immunogenicity, and modulation of immune cells have been largely studied; however, less is known about their specific effects on cancer stem cells (CSCs). CSCs constitute a subpopulation of tumor cells endowed with Edited by: Cristina Maccalli, stem-like properties including self-renewal, chemoresistance, tumorigenic capacity, and Sidra Medicine, Qatar quiescence. This rare and unique subpopulation of cells is believed to be responsible for Reviewed by: tumor maintenance, metastatic spread, and relapse. Thus, this review aims to summarize Carlo Catapano, Institute of Oncology Research and discuss the current knowledge of the anti- and pro-CSCs effects of IFNs and also (IOR), Switzerland to highlight the need for further research on the interplay between IFNs and CSCs.
    [Show full text]