DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 9,161,992 B2 Jefferies Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

US009 161992B2 (12) United States Patent (10) Patent No.: US 9,161,992 B2 Jefferies et al. (45) Date of Patent: Oct. 20, 2015 (54) P97 FRAGMENTS WITH TRANSFER 4,683.202 A 7, 1987 Mullis ACTIVITY 4,704,362 A 11/1987 Itakura et al. 4,766,075 A 8, 1988 Goeddeletal. (71) Applicant: biosis Technologies, Inc., Richmond 4,800,1594,784.950 A 11/19881/1989 MullisHagen et al. (CA) 4,801,542 A 1/1989 Murray et al. 4.866,042 A 9, 1989 Neuwelt (72) Inventors: Wilfred Jefferies, South Surrey (CA); 4,935,349 A 6/1990 McKnight et al. Mei Mei Tian, Coquitlam (CA): 4.946,778 A 8, 1990 Ladner et al. Timothy Vitalis, Vancouver (CA) 5,091,513 A 2f1992 Huston et al. 5,132,405 A 7, 1992 Huston et al. (73) Assignee: biOasis Technologies, Inc., British 5, 186,941 A 2f1993 Callahan et al. Columbia (CA) 5,672,683 A 9, 1997 Friden et al. 5,677,171 A 10, 1997 Hudziak et al. c - r 5,720,937 A 2f1998 Hudziak et al. (*) Notice: Subject to any disclaimer, the term of this 5,720,954. A 2f1998 Hudziak et al. patent is extended or adjusted under 35 5,725,856 A 3, 1998 Hudziak et al. U.S.C. 154(b) by 0 days. 5,770,195 A 6/1998 Hudziak et al. 5,772,997 A 6/1998 Hudziak et al. (21) Appl. No.: 14/226,506 5,844,093 A 12/1998 Kettleborough et al. 5,962,012 A 10, 1999 Lin et al. (22) Filed: Mar. 26, 2014 5,981, 194 A 11/1999 Jefferies et al. 6,015,557 A 1/2000 Tobinicket al. (65) Prior Publication Data 6,165,464 A 12/2000 Hudziak et al. 6,177,077 B1 1/2001 Tobinick US 2015/0056218 A1 Feb. 26, 2015 6.261,595 B1 7/2001 Stanley et al. 6,387,371 B1 5, 2002 Hudziak et al. 6,399,063 B1 6/2002 Hudziak et al. Related U.S. Application Data 6,419,934 B1 7/2002 Tobinick (63) Continuation of application No. 13/566,260, filed on 6,419,944 B2 7/2002 Tobinick Aug 3, 2012, now Pat. No. 8,722,019 6,455,494 B1 9, 2002 Jefferies et al. • - 9 s • v Y Y’s a 4-3 W J - 6,537,549 B2 3/2003 Tobinick (60) Provisional application No. 61/515,792, filed on Aug. 6,596,541 B2 7/2003 Murphy et al. 5, 2011. 6,765,087 B1 7/2004 Casterman et al. 6,838,254 B1 1/2005 Hamers et al. (51) Int. Cl. 6,982,089 B2 1/2006 Tobinick A6 IK 47/48 (2006.01) (Continued) A6 IK38/17 (2006.01) C07K 4/705 (2006.01) FOREIGN PATENT DOCUMENTS C07K I4/79 (2006.01) C07K 6/8 (2006.01) GB 2188637 10, 1987 A6 IK39/44 (2006.01) WO WO 89,04663 6, 1989 A 6LX39/395 (2006.01) (Continued) A6 IK38/40 (2006.01) A61 K38/00 (2006.01) OTHER PUBLICATIONS (52) U.S. Cl. CPC ....... A61 K47748276 (2013.01); A61K 38/1793 International Search Report for International Application No. PCT/ (2013.01); A61 K38/40 (2013.01); A61 K US2003/00894, mailed Sep. 10, 2003, 3 pages. 39/3955 (2013.01); A61K.39/39533 (2013.01); (Continued) A61K 39/44 (2013.01); C07K 14/70575 (2013.01); C07K 16/18 (2013.01); A61 K38/00 (2013.01); C07K 14/79 (2013.01); C07K 2319/00 (2013.01); C07K 2319/55 (2013.01); Primary Examiner — Amber D Steele C07K 2319/60 (2013.01); C07K 2319/70 Assistant Examiner — Schuyler Milton (2013.01); Y10S 977/773 (2013.01); Y10S (74) Attorney, Agent, or Firm — Cooley LLP 977/92 (2013.01); Y10S 977/927 (2013.01) (58) Field of Classification Search None (57) ABSTRACT See application file for complete search history. The present invention is related to fragments of human mel (56) References Cited anotransferrin (p97). In particular, this invention relates to treatment of diseases through the introduction of the melan U.S. PATENT DOCUMENTS otransferrin fragment conjugated to a therapeutic or diagnos 4,391904. A 7, 1983 Litman et al. tic agent to a Subject. 4,394,448 A 7/1983 Szoka, Jr. et al. 4,399.216 A 8, 1983 Axel et al. 4,683, 195 A 7, 1987 Mullis et al. 16 Claims, 11 Drawing Sheets US 9,161,992 B2 Page 2 (56) References Cited Bickel, U. et al., “In vivo demonstration of subcellular localization of anti-transferrin receptor monoclonal antibody-colloidal gold conju U.S. PATENT DOCUMENTS gate in brain capillary endothelium.” Journal of Histochemistry and Cytochemistry, 42(11): 1493-1497 (1994). 7,132,511 B2 11/2006 Carr et al. 7,138,371 B2 11/2006 DeFrees et al. Bickel, U. et al., “In vivo cleavability of a disulfide-based chimeric 7,179,617 B2 2/2007 DeFrees et al. opioid peptide in rat brain.” Bioconjugate Chem, 6(2):211-218 7,214,658 B2 5, 2007 Tobinick (1995). 7,244,592 B2 7/2007 Hoogenboom et al. Bickel, U. et al., “Delivery of peptides and proteins through the 7,247,301 B2 7/2007 van de Winkel et al. blood-brain barrier.” Advanced Drug Delivery Review, 46(1-3):247 7.462,697 B2 12/2008 Couto et al. 279 (2001). 7,595,378 B2 9, 2009 van de Winkel et al. Blattler, W. A. et al., “New heterobifunctional protein cross-linking 7,700,554 B2 4/2010 Beliveau et al. 7,723,484 B2 5, 2010 Beidler et al. reagent that forms an acid-labile link.” Biochem. 24:1517-1524 7,939,072 B2 5, 2011 Yarden et al. (1985). 7,960,516 B2 6/2011 Matheus et al. Boado, R. J. et al., “Cloning and expression in Pichia pastoris of a 8,546,319 B2 10/2013 Starret al. genetically engineered single chain antibody against the rat transfer 8,722,019 B2 5, 2014 Jeffries et al. rin receptor.” Journal of Drug Targeting, 8(6):403-412 (2000). 2002/01 19095 A1 8, 2002 Gabathuler et al. Broadwell, R. D. et al., “Transcytosis of protein through the mam 2003/OO72761 A1 4/2003 LeBowitz malian cerebral epithelium and endothelium. III. Receptor-mediated 2004/0055022 A1 3/2004 Cheng et al. 2004/O137557 A1 7/2004 DeFrees et al. transcytosis through the blood-brain barrier of blood-borne transfer 2005, 0026823 A1 2/2005 Zankel et al. rin and antibody against the transferrin receptor.” Experimental Neu 2005/O158296 A1 7/2005 Starret al. rology, 142(1):47-65 (1996). 2007/0167365 A1 7/2007 Beliveau et al. Carter, P. et al., “Humanization of an anti-p185' antibody for 2008, OO14188 A1 1/2008 Zankel et al. human cancer therapy.” Proc. Natl. Acad. Sci. USA, 89:4285-4289 2009, 0226421 A1 9, 2009 Parren et al. (1992). 2010/03O3797 A1 12/2010 Starr et al. Cerletti, A. et al., “Endocytosis and transcytosis of an immunolipo 2011/0093.962 A1 4/2011 Heidbrink et al. Some-based brain drug delivery system.” Journal of Drug Targeting, 2012/0107302 A1 5/2012 Berry et al. 8(6):435-446 (2000). 2013,0058873 A1 3/2013 Jefferies et al. Chen, Q. et al., “Efficient Synthesis of Doxorubicin Melanotransfer 2013,0183368 A1 7, 2013 Hutchison et al. rin p97 Conjugates Through SMCC Linker.” Synthetic Communica 2014/0322132 A1 10/2014 Vitalis et al. tions, 34(13) (2004). CO. M. S. et al., “Humanized antibodies for antiviral therapy.” Proc. FOREIGN PATENT DOCUMENTS Natl. Acad. Sci. Usa, 88(7):2869-2873 (1991). WO WO93, 11161 6, 1993 Co., M.S. etal. "Chimeric and humanized antibodies with specificity WO WO94/O1463 1, 1994 for the CD33 antigen.” J. Immunol., 148(4): 1149-1154 (1992). WO WO94f13804 6, 1994 Deguchi.Y. et al., “Retention of biologic activity of human epidermal WO WO98,23646 6, 1998 growth factor following conjugation to a blood-brain barrier drug WO WOO1,59459 8, 2001 delivery vector via an extended poly (ethylene glycol) linker.” WO WO O2, 13843 2, 2002 Bioconjugate Chem., 10(1):32-37 (1999). WO WO O2/13873 2, 2002 Delabarre, B. et al., “Central Pore Residues Mediate the p97/VCP WO WOO3,OO9815 2, 2003 activity required for ERAD. Molecular Cell, 19(22):451-462 WO WOO3/O57179 T 2003 (2006). WO WO 2004/078215 9, 2004 Demeule, M. et al., “High transcytosis of melanotransferrin (P97) WO WO 2006/079372 8, 2006 WO WO 2013, OO67O6 1, 2013 across the blood-brain barrier.” Journal of Neurochemistry, 83:924 WO WO 2013,022.738 2, 2013 933 (2002). WO WO 2014/0225.15 2, 2014 Demeule, M. et al., “Regulation of plasminogen activation: A role for WO WO 2014, 160438 10/2014 melantransferrin (p97) in cell migration.” Blood, 102(5):1723-1731 (2003). OTHER PUBLICATIONS Dorr, R. T. et al., “In vitro rat myocyte cardiotoxicity model for antitumor antibiotics using adenosine triphosphate/protein ratios.” International Preliminary Examination Report for International Cancer Research, 48:5222-5227 (1988). Application No. PCT/US2003/00894, dated Feb. 14, 2005, 5 pages. Endo, N. et al., “In-Vitro Cytotoxicity of a Human Serum Albumin International Search Report and Written Opinion for International mediated Conjugate of Methotrexate with Anti-MM46 Monoclonal Antibody.” Cancer Research, 47(4): 1076-1080 (1987). Application No. PCT/US2012/045568, mailed on Sep. 27, 2012, 9 Enzyme: L-iduronidase. EC 3.2.1.76. http://www.chem.qmul.ac.uk/ pageS. iubmb/enzyme/EC3/2/1/76.html, 2 pages.
Recommended publications
  • CD74 Targeted Nanoparticles As Dexamethasone Delivery System for B Lymphoid Malignancies

    CD74 Targeted Nanoparticles As Dexamethasone Delivery System for B Lymphoid Malignancies

    CD74 targeted nanoparticles as Dexamethasone Delivery System for B lymphoid malignancies DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Georgia Triantafillou, MPH Integrated Biomedical Sciences Graduate Program The Ohio State University 2011 Dissertation Committee John C. Byrd, MD, advisor Natarajan Muthusamy, PhD co-advisor Robert J.Lee, PhD, co-advisor Mitch A.Phelps, PhD, co-advisor Guido Marcucci, MD committee member Susheela Tridandapani, PhD committee member Copyright page Georgia Triantafillou 2011 ABSTRACT Chronic Lymphocytic Leukemia (CLL) is the most common adult leukemia and is not curable with standard therapy. In CLL the B lymphocytes appear morphologically mature but immunologically express less mature B cell makers. Specifically, the CLL B cells co-express surface antigens including CD19, CD20, CD5, CD23. Due to nonspecific delivery of the drugs to malignant as well as normal cells, patients experience numerous side effects. Targeted drug delivery to cancer cells is a desirable goal for all anti cancer strategies. Corticosteroids have been proven to be a beneficial and well established part of CLL treatment. Dexamethasone(DEX) is frequently used in CLL therapies as well as other malignancies and antiinflammatory diseases. However, DEX nonspecifically enters all tissues inducing various toxicities to patients. Therefore, DEX treatment is often discontinued or not administered to certain patients. We aimed to deliver this efficient clinical agent via a targeted delivery vehicle and examine its effect on its target B-CLL cells. The main scope of the work presented is the creation of a sterically stable nanoparticle, an ii immunoliposome (ILP), that has DEX encapsulated in its interior and a monoclonal antibody(Mab) in its exterior targeting CLL B cells expressing the surface antigen that is recognized by the Mab.
  • Predictive QSAR Tools to Aid in Early Process Development of Monoclonal Antibodies

    Predictive QSAR Tools to Aid in Early Process Development of Monoclonal Antibodies

    Predictive QSAR tools to aid in early process development of monoclonal antibodies John Micael Andreas Karlberg Published work submitted to Newcastle University for the degree of Doctor of Philosophy in the School of Engineering November 2019 Abstract Monoclonal antibodies (mAbs) have become one of the fastest growing markets for diagnostic and therapeutic treatments over the last 30 years with a global sales revenue around $89 billion reported in 2017. A popular framework widely used in pharmaceutical industries for designing manufacturing processes for mAbs is Quality by Design (QbD) due to providing a structured and systematic approach in investigation and screening process parameters that might influence the product quality. However, due to the large number of product quality attributes (CQAs) and process parameters that exist in an mAb process platform, extensive investigation is needed to characterise their impact on the product quality which makes the process development costly and time consuming. There is thus an urgent need for methods and tools that can be used for early risk-based selection of critical product properties and process factors to reduce the number of potential factors that have to be investigated, thereby aiding in speeding up the process development and reduce costs. In this study, a framework for predictive model development based on Quantitative Structure- Activity Relationship (QSAR) modelling was developed to link structural features and properties of mAbs to Hydrophobic Interaction Chromatography (HIC) retention times and expressed mAb yield from HEK cells. Model development was based on a structured approach for incremental model refinement and evaluation that aided in increasing model performance until becoming acceptable in accordance to the OECD guidelines for QSAR models.
  • International Nonproprietary Names for Pharmaceutical Substances (INN)

    International Nonproprietary Names for Pharmaceutical Substances (INN)

    WHO Drug Information, Vol. 23, No. 2, 2009 Proposed INN: List 101 International Nonproprietary Names for Pharmaceutical Substances (INN) Notice is hereby given that, in accordance with article 3 of the Procedure for the Selection of Recommended International Nonproprietary Names for Pharmaceutical Substances, the names given in the list on the following pages are under consideration by the World Health Organization as Proposed International Nonproprietary Names. The inclusion of a name in the lists of Proposed International Nonproprietary Names does not imply any recommendation of the use of the substance in medicine or pharmacy. Lists of Proposed (1–96) and Recommended (1–57) International Nonproprietary Names can be found in Cumulative List No. 12, 2007 (available in CD-ROM only). The statements indicating action and use are based largely on information supplied by the manufacturer. This information is merely meant to provide an indication of the potential use of new substances at the time they are accorded Proposed International Nonproprietary Names. WHO is not in a position either to uphold these statements or to comment on the efficacy of the action claimed. Because of their provisional nature, these descriptors will neither be revised nor included in the Cumulative Lists of INNs. Dénominations communes internationales des Substances pharmaceutiques (DCI) Il est notifié que, conformément aux dispositions de l'article 3 de la Procédure à suivre en vue du choix de Dénominations communes internationales recommandées pour les Substances pharmaceutiques les dénominations ci-dessous sont mises à l'étude par l'Organisation mondiale de la Santé en tant que dénominations communes internationales proposées.
  • Advances in Anticancer Antibody-Drug Conjugates and Immunotoxins

    Advances in Anticancer Antibody-Drug Conjugates and Immunotoxins

    Send Orders for Reprints to [email protected] Recent Patents on Anti-Cancer Drug Discovery, 2014, 9, 35-65 35 Advances in Anticancer Antibody-Drug Conjugates and Immunotoxins Franco Dosio1,*, Barbara Stella1, Sofia Cerioni1, Daniela Gastaldi2 and Silvia Arpicco1 1Dipartimento di Scienza e Tecnologia del Farmaco, University of Torino, Torino, I-10125, Italy; 2Dipartimento di Bio- tecnologie Molecolari e Scienze per la Salute, University of Torino, Torino, I-10125, Italy Received: December 13, 2012; Accepted: February 21, 2013; Revised: March 7, 2013 Abstract: Antibody-delivered drugs and toxins are poised to become important classes of cancer therapeutics. These bio- pharmaceuticals have potential in this field, as they can selectively direct highly potent cytotoxic agents to cancer cells that present tumor-associated surface markers, thereby minimizing systemic toxicity. The activity of some conjugates is of particular interest receiving increasing attention, thanks to very promising clinical trial results in hematologic cancers. Over twenty antibody-drug conjugates and eight immunotoxins in clinical trials as well as some recently approved drugs, support the maturity of this approach. This review focuses on recent advances in the development of these two classes of biopharmaceuticals: conventional toxins and anticancer drugs, together with their mechanisms of action. The processes of conjugation and purification, as reported in the literature and in several patents, are discussed and the most relevant results in clinical trials are listed. Innovative technologies and preliminary results on novel drugs and toxins, as reported in the literature and in recently-published patents (up to February 2013) are lastly examined. Keywords: Antibody drug conjugate, anticancer agents, auristatins immunotoxin, calicheamicins, cross-linkers, duocarmycins, maytansinoids.
  • Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix

    Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix

    United States International Trade Commission Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix USITC Publication 4208 December 2010 U.S. International Trade Commission COMMISSIONERS Deanna Tanner Okun, Chairman Irving A. Williamson, Vice Chairman Charlotte R. Lane Daniel R. Pearson Shara L. Aranoff Dean A. Pinkert Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436 U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Modifications to the Harmonized Tariff Schedule of the United States to Implement Changes to the Pharmaceutical Appendix Publication 4208 December 2010 (This page is intentionally blank) Pursuant to the letter of request from the United States Trade Representative of December 15, 2010, set forth at the end of this publication, and pursuant to section 1207(a) of the Omnibus Trade and Competitiveness Act, the United States International Trade Commission is publishing the following modifications to the Harmonized Tariff Schedule of the United States (HTS) to implement changes to the Pharmaceutical Appendix, effective on January 1, 2011. Table 1 International Nonproprietary Name (INN) products proposed for addition to the Pharmaceutical Appendix to the Harmonized Tariff Schedule INN CAS Number Abagovomab 792921-10-9 Aclidinium Bromide 320345-99-1 Aderbasib 791828-58-5 Adipiplon 840486-93-3 Adoprazine 222551-17-9 Afimoxifene 68392-35-8 Aflibercept 862111-32-8 Agatolimod
  • New Biological Therapies: Introduction to the Basis of the Risk of Infection

    New Biological Therapies: Introduction to the Basis of the Risk of Infection

    New biological therapies: introduction to the basis of the risk of infection Mario FERNÁNDEZ RUIZ, MD, PhD Unit of Infectious Diseases Hospital Universitario “12 de Octubre”, Madrid ESCMIDInstituto de Investigación eLibraryHospital “12 de Octubre” (i+12) © by author Transparency Declaration Over the last 24 months I have received honoraria for talks on behalf of • Astellas Pharma • Gillead Sciences • Roche • Sanofi • Qiagen Infections and biologicals: a real concern? (two-hour symposium): New biological therapies: introduction to the ESCMIDbasis of the risk of infection eLibrary © by author Paul Ehrlich (1854-1915) • “side-chain” theory (1897) • receptor-ligand concept (1900) • “magic bullet” theory • foundation for specific chemotherapy (1906) • Nobel Prize in Physiology and Medicine (1908) (together with Metchnikoff) Infections and biologicals: a real concern? (two-hour symposium): New biological therapies: introduction to the ESCMIDbasis of the risk of infection eLibrary © by author 1981: B-1 antibody (tositumomab) anti-CD20 monoclonal antibody 1997: FDA approval of rituximab for the treatment of relapsed or refractory CD20-positive NHL 2001: FDA approval of imatinib for the treatment of chronic myelogenous leukemia Infections and biologicals: a real concern? (two-hour symposium): New biological therapies: introduction to the ESCMIDbasis of the risk of infection eLibrary © by author Functional classification of targeted (biological) agents • Agents targeting soluble immune effector molecules • Agents targeting cell surface receptors
  • Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011

    Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011

    CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products.
  • Tanibirumab (CUI C3490677) Add to Cart

    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
  • Antibody Drug Conjugates in Lymphoma

    Antibody Drug Conjugates in Lymphoma

    Review: Clinical Trial Outcomes Nathwani & Chen Antibody drug conjugates in lymphoma 6 Review: Clinical Trial Outcomes Antibody drug conjugates in lymphoma Clin. Investig. (Lond.) Antibody drug conjugates (ADCs) are comprised of monoclonal antibodies physically Nitya Nathwani1 & Robert linked to cytotoxic molecules. They expressly target cancer cells by delivering cytotoxic Chen*,1 agents to cells displaying specific antigens, and minimize damage to normal tissue. The 1Department of Hematology & Hematopoietic Cell Transplantation, City efficacy and tolerability of these agents are primarily determined by the target antigen, of Hope, Duarte, CA, USA the cytotoxic agent and the linker connecting the cytotoxic agent to the monoclonal *Author for correspondence: antibody. Following advances in technology, clinical trials have demonstrated greater Tel.: +626 256 4673 (ext. 65298) efficacy for ADCs compared with the corresponding naked monoclonal antibodies. Fax: +626 301 8116 This review summarizes the features of current clinically active ADCs in lymphoma and [email protected] emphasizes recent clinical data elucidating the benefit of antibody-directed delivery of cytotoxic agents to tumor cells. Keywords: antibody drug conjugates • lymphoma • monoclonal antibodies Lymphoma is the most common hematologic concentration and poor performance status malignancy, and is subdivided into two main are adverse prognostic factors. SEER (Sur- types: Hodgkin lymphoma (HL) and non- veillance, Epidemiology and End Results) Hodgkin lymphoma (NHL). In the United data from the National Cancer Institute, States, there are an estimated 731,277 people 2013 has revealed a significant improvement 10.4155/CLI.14.73 living with or in remission from lymphoma. in survival rates in this group of diseases in In 2013, there were an estimated 79,030 new the last four decades.
  • B-Cell Targets to Treat Antibody-Mediated Rejection In

    B-Cell Targets to Treat Antibody-Mediated Rejection In

    Muro et al. Int J Transplant Res Med 2016, 2:023 Volume 2 | Issue 2 International Journal of Transplantation Research and Medicine Commentary: Open Access B-Cell Targets to Treat Antibody-Mediated Rejection in Transplantation Manuel Muro1*, Santiago Llorente2, Jose A Galian1, Francisco Boix1, Jorge Eguia1, Gema Gonzalez-Martinez1, Maria R Moya-Quiles1 and Alfredo Minguela1 1Immunology Service, University Clinic Hospital Virgen de la Arrixaca, Spain 2Nephrology Service, University Clinic Hospital Virgen de la Arrixaca, Spain *Corresponding author: Manuel Muro, PhD, Immunology Service, University Clinic Hospital “Virgen de la Arrixaca”, Biomedical Research Institute of Murcia (IMIB), Murcia, Spain, Tel: 34-968-369599, E-mail: [email protected] Antibody-mediated rejection (AMR) in allograft transplantation APRIL (a proliferation-inducing ligand). These co-activation signals can be defined with a rapid increase in the levels of specific are required for B-cell differentiation into plasma cell and enhancing serological parameters after organ transplantation, presence of donor their posterior survival and are a key determinant of whether specific antibodies (DSAs) against human leukocyte antigen (HLA) developing B-cells will survive or die during the establishment molecules, blood group (ABO) antigens and/or endothelial cell of immuno-tolerance [5,6]. Important used agents commercially antigens (e.g. MICA, ECA, Vimentin, or ETAR) and also particular available are Tocilizumab (anti-IL6R) and Belimumab (BAFF). histological parameters [1,2]. If the AMR persists or progresses, the The receptors of BAFF and APRIL could also be important as treatment to eliminate the humoral component of acute rejection eventual targets, for example BAFF-R, TACI (transmembrane include three sequential steps: (a) steroid pulses, antibody removal activator and calcium modulator and cyclophyllin ligand interactor) (plasma exchange or immuno-adsorption) and high doses of and BCMA (B-cell maturation antigen).
  • 2017 Immuno-Oncology Medicines in Development

    2017 Immuno-Oncology Medicines in Development

    2017 Immuno-Oncology Medicines in Development Adoptive Cell Therapies Drug Name Organization Indication Development Phase ACTR087 + rituximab Unum Therapeutics B-cell lymphoma Phase I (antibody-coupled T-cell receptor Cambridge, MA www.unumrx.com immunotherapy + rituximab) AFP TCR Adaptimmune liver Phase I (T-cell receptor cell therapy) Philadelphia, PA www.adaptimmune.com anti-BCMA CAR-T cell therapy Juno Therapeutics multiple myeloma Phase I Seattle, WA www.junotherapeutics.com Memorial Sloan Kettering New York, NY anti-CD19 "armored" CAR-T Juno Therapeutics recurrent/relapsed chronic Phase I cell therapy Seattle, WA lymphocytic leukemia (CLL) www.junotherapeutics.com Memorial Sloan Kettering New York, NY anti-CD19 CAR-T cell therapy Intrexon B-cell malignancies Phase I Germantown, MD www.dna.com ZIOPHARM Oncology www.ziopharm.com Boston, MA anti-CD19 CAR-T cell therapy Kite Pharma hematological malignancies Phase I (second generation) Santa Monica, CA www.kitepharma.com National Cancer Institute Bethesda, MD Medicines in Development: Immuno-Oncology 1 Adoptive Cell Therapies Drug Name Organization Indication Development Phase anti-CEA CAR-T therapy Sorrento Therapeutics liver metastases Phase I San Diego, CA www.sorrentotherapeutics.com TNK Therapeutics San Diego, CA anti-PSMA CAR-T cell therapy TNK Therapeutics cancer Phase I San Diego, CA www.sorrentotherapeutics.com Sorrento Therapeutics San Diego, CA ATA520 Atara Biotherapeutics multiple myeloma, Phase I (WT1-specific T lymphocyte South San Francisco, CA plasma cell leukemia www.atarabio.com
  • Looking for Therapeutic Antibodies in Next Generation Sequencing Repositories

    Looking for Therapeutic Antibodies in Next Generation Sequencing Repositories

    bioRxiv preprint doi: https://doi.org/10.1101/572958; this version posted March 10, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Title: Looking for Therapeutic Antibodies in Next Generation Sequencing Repositories. Authors: Konrad Krawczyk1*, Matthew Raybould2, Aleksandr Kovaltsuk2, Charlotte M. Deane2 1 NaturalAntibody, Hamburg, Germany 2 Oxford University Department of Statistics, Oxford, UK *Correspondence to [email protected] Abstract: Recently it has become possible to query the great diversity of natural antibody repertoires using Next Generation Sequencing (NGS). These methods are capable of producing millions of sequences in a single experiment. Here we compare Clinical Stage Therapeutic antibodies to the ~1b sequences from 60 independent sequencing studies in the Observed Antibody Space Database. Of the 242 post Phase I antibodies, we find 16 with sequence identity matches of 95% or better for both heavy and light chains. There are also 54 perfect matches to therapeutic CDR-H3 regions in the NGS outputs, suggesting a nontrivial amount of convergence between naturally observed sequences and those developed artificially. This has potential implications for both the discovery of antibody therapeutics and the legal protection of commercial antibodies. Introduction Antibodies are proteins in jawed vertebrates that recognize noxious molecules (antigens) for elimination. An organism expresses millions of diverse antibodies to increase the chances that some of them will be able to bind the foreign antigen, initiating the adaptive immune response.