WO 2014/144600 A2 18 September 2014 (18.09.2014) P O P CT

Total Page:16

File Type:pdf, Size:1020Kb

WO 2014/144600 A2 18 September 2014 (18.09.2014) P O P CT (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 2014/144600 A2 18 September 2014 (18.09.2014) P O P CT (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, A61K 39/395 (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, IR, IS, JP, KE, KG, KN, KP, KR, PCT/US20 14/029077 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, 14 March 2014 (14.03.2014) OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, (25) Filing Language: English TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, (26) Publication Language: English ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/802,343 15 March 2013 (15.03.2013) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, (72) Inventors; and UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (71) Applicants : ROSCHKE, Viktor [US/US]; 4702 West TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, Virginia Avenue, Bethesda, MD 20814 (US). LAFLEUR, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, David [US/US]; 3142 Quesada Street, N.w., Washington, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, DC 20015 (US). HILBERT, David, M. [US/US]; 5801 TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Meadowlark Lane, Bethesda, MD 20817 (US). KIENER, KM, ML, MR, NE, SN, TD, TG). Peter [US/US]; 14017 Gorky Drive, Potomac, MD 20854 Published: (US). without international search report and to be republished (74) Agents: HOOVER, Kenley, K. et al; Sterne, Kessler, upon receipt of that report (Rule 48.2(g)) Goldstein & Fox PLLC, 1100 New York Avenue, N.W., Washington, DC 20005-3934 (US). with sequence listing part of description (Rule 5.2(a)) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, < o© (54) Title: MULTIVALENT AND MONOVALENT MULTISPECIFIC COMPLEXES AND THEIR USES (57) Abstract: Compositions containing multivalent and monovalent multispecific complexes having scaffolds such as antibodies that support such binding functionalities are described. The use of and methods of compositions containing multivalent and mono - S valent multispecific complexes having scaffolds, such as antibodies, that support such binding functionalities are also described. MULTIVALENTAND MONOVALENTMULTISPECIFIC COMPLEXES AND THEIR USES BACKGROUND OF THE INVENTION Field of the Invention [0001] This invention relates generally to compositions containing multivalent multispecific complexes and to compositions containing multivalent and monovalent multispecific complexes having scaffolds, such as antibodies, that support such binding functionalities. The invention also generally relates to methods of making these multispecific compositions and the diagnostic and therapeutic uses of these compositions. Background [0002] In recent years, drug discovery efforts have primarily focused on identifying agents that modulate preselected individual targets. However, agents directed to individual targets frequently show limited efficacies and poor safety and resistance profiles, as a result of the robustness, redundancy, crosstalk, compensatory signaling networks and anti- or counter- signaling network activities associated with the therapeutic target. Consequently, drug discovery efforts have increasingly been directed toward the discovery of new multicomponent based therapies. [0003] The development of bispecific or multi-specific molecules that target two or more targets simultaneously offers a novel and promising solution for discovering new systems-oriented multitargeted agents demonstrating improved efficacy and pharmacological properties over conventional monotherapies. Numerous attempts to develop multispecific molecules have been based on immunoglobulin-like domains or subdomains. For example, traditionally, bispecific antibodies have been prepared by chemically linking two different monoclonal antibodies or by fusing two hybridoma cell lines to produce a hybrid-hybridoma. Other immunoglobulin-like domain-based technologies that have created multispecific, and/or multivalent molecules include dAbs, diabodies, TandAbs, nanobodies, BiTEs, SMIPs, DNLs, Affibodies, Fynomers, unitz Domains, Albu-dabs, DARTs, DVD-IG, Covx-bodies, peptibodies, scFv-Igs, SVD-Igs, dAb-Igs, Knobs-in-Holes, DuoBodies™ and triomAbs. Although each of these molecules may bind one or more targets, they each present challenges with respect to retention of typical Ig function (e.g., half-life, effector function), production (e.g., yield, purity), valency, simultaneous target recognition, and bioavailability. [0004] Other attempts to generate multispecific and multivalent molecules have relied on alternative scaffolds, based VASP polypeptides, Avian pancreatic polypeptide (aPP), Tetranectin (based on CTLD3), Affilin (based on γ Β -crystallin/ubiquitin), knottins, SH3 domains, PDZ domains, Tendamistat, Transferrin, an ankyrin consensus repeat domain (e.g., DARPins), lipocalin protein folds (e.g., Duocalins), fibronectin (see for example, US Application Publ. Nos. 2003/0170753 and 20090155275 which are herein incorporated by reference), a domain of protein A (e.g., Affibodies), thioredoxin. Other attempts have relied on alternative scaffolds fuse or associate polypeptides of interest with albumin (e.g., ALBUdAb (Domantis/GSK) and ALB-Kunitz (Dyax)), unstructured repeat sequences of 3 or 6 amino acids (e.g., PASylation® technology and XTEN® technology), and sequences containing elastin-like repeat domains (see for example, U.S. Pat. Appl. No. 61/442,106, which is herein incorporated by reference). To date, these technologies have demonstrated limited clinical potential as robust platforms for developing diverse multispecific and multivalent therapeutic compositions. [0005] The genetic complexity of most human malignancies and other disorders strongly suggest that interfering with a single target or pathway associated with these disorders is unlikely to produce optimal or sustained therapeutic benefit. There is, therefore, a great need for developing multispecific and multivalent therapeutics such as multispecific antibodies that are capable of interfering with the activity of multiple targets and/or signaling mechanisms in or to optimize the therapeutic benefits of treatments directed towards these disorders. BRIEF SUMMARY OF THE INVENTION [0006] The invention relates to compositions containing multivalent as well as multivalent and monovalent, multispecific complexes having scaffolds, such as antibodies, that support such binding functionalities. The invention is based in part on the surprising discovery that multispecific and multivalent binding compositions, such as those generated using the ZYBODY™ platform (Zyngenia, Inc.; see, e.g., Intl. Pub. No. W0 2009/088805 which is herein incorporated by reference) demonstrate dramatic synergistic biological activity compared to conventional monotherapy combinations. This synergistic activity is expected to extend to novel therapies, for treating or preventing cancer, diseases or disorders of the immune system (e.g., autoimmune diseases such as, rheumatoid arthritis, and IBD), skeletal system (e.g., osteoporosis), cardiovascular system (e.g., stroke, heart disease), nervous system (e.g., Alzheimer's), infectious disease (e.g., HIV), and other diseases or disorders described herein or otherwise known in the art. 10007] In one embodiment, the invention is directed to treating a disease or disorder by administering a therapeutically effective amount of a multivalent and monovalent multispecific composition to a patient in need thereof. In a further embodiment, the invention is directed to treating a disease or disorder by administering a therapeutically effective amount of a multivalent and multispecific MRD-containing antibody to a patient in need thereof. [0008] In one embodiment, the multivalent and monovalent multispecific composition contains 2 binding sites for three or more targets. In an additional embodiment, the multivalent and monovalent multispecific composition contains 2 binding sites for four or more targets. In another embodiment, the multivalent and monovalent multispecific composition contains 2 binding sites for five or more targets. According to some embodiments, at least 1, 2, 3, 4 or more of the targets are located on a cell surface. According to some embodiments, at least 1, 2, 3, 4 or more of the targets are soluble targets (e.g., chemokines, cytokines, and growth factors). In additional embodiments, the multivalent and monovalent multispecific composition binds 1, 2, 3, 4 or more of the targets described herein. [0009] In additional embodiments, the targets bound by the multivalent and monovalent multispecific composition are associated with cancer. In a further embodiment the targets bound by the multivalent and monovalent multispecific composition are associated with 1, 2, 3, 4 or more different signaling pathways or modes of action associated with cancer. [0010] In additional embodiments, the targets bound by the multivalent and monovalent multispecific composition are associated with
Recommended publications
  • Print PDF Opens in a New Window
    CADTH ISSUES IN EMERGING HEALTH TECHNOLOGIES Informing Decisions About New Health Technologies Issue July 173 2018 Monoclonal Antibodies for Osteoarthritis of the Hip or Knee Image courtesy of iStock CADTH ISSUES IN EMERGING HEALTH TECHNOLOGIES 1 Authors: Sirjana Pant, Ke Xin Li, Melissa Severn Cite As: Monoclonal Antibodies for Osteoarthritis of the Hip or Knee. Ottawa: CADTH; 2018. (CADTH issues in emerging health technologies; issue 173). Acknowledgments: CADTH would like to acknowledge the contribution of Dr. Tom Appleton, MD, PhD, FRCPC, Assistant Professor, Rheumatologist; Department of Medicine, Department of Physiology and Pharmacology, The University of Western Ontario; Clinician Scientist, Lawson Health Research Institute; The Rheumatology Centre, St. Joseph’s Health Care London; for his review of the draft version of this bulletin. ISSN: 1488-6324 (online) Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy- makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services.
    [Show full text]
  • Malignant B Lymphocyte Survival in Vivo CD22 Ligand Binding Regulates Normal
    The Journal of Immunology CD22 Ligand Binding Regulates Normal and Malignant B Lymphocyte Survival In Vivo1 Karen M. Haas, Suman Sen, Isaac G. Sanford, Ann S. Miller, Jonathan C. Poe, and Thomas F. Tedder2 The CD22 extracellular domain regulates B lymphocyte function by interacting with ␣2,6-linked sialic acid-bearing ligands. To understand how CD22 ligand interactions affect B cell function in vivo, mouse anti-mouse CD22 mAbs were generated that inhibit CD22 ligand binding to varying degrees. Remarkably, mAbs which blocked CD22 ligand binding accelerated mature B cell turnover by 2- to 4-fold in blood, spleen, and lymph nodes. CD22 ligand-blocking mAbs also inhibited the survival of adoptively transferred normal (73–88%) and malignant (90%) B cells in vivo. Moreover, mAbs that bound CD22 ligand binding domains induced significant CD22 internalization, depleted marginal zone B cells (82–99%), and reduced mature recirculating B cell numbers by 75–85%. The CD22 mAb effects were independent of complement and FcRs, and the CD22 mAbs had minimal effects in CD22AA mice that express mutated CD22 that is not capable of ligand binding. These data demonstrate that inhibition of CD22 ligand binding can disrupt normal and malignant B cell survival in vivo and suggest a novel mechanism of action for therapeutics targeting CD22 ligand binding domains. The Journal of Immunology, 2006, 177: 3063–3073. D22 is a B cell-specific glycoprotein of the Ig superfam- cell surface CD22, IgM, and MHC class II expression on mature B ily expressed on the surface of maturing B cells coinci- cells, whereas normal BCR signaling and Ca2ϩ mobilization are dent with IgD expression (1, 2).
    [Show full text]
  • Anticuerpos Monoclonales: Desarrollo Físico Y Perspectivas Terapéuticas
    NINA PATRICIA MACHADO ET. AL ARTÍCULO DE REVISIÓN Anticuerpos monoclonales: desarrollo físico y perspectivas terapéuticas Monoclonal antibodies: physical development and therapeutic perspectives NINA PATRICIA MACHADO1, GERMÁN ALBERTO TÉLLEZ2, JOHN CARLOS CASTAÑO2 Resumen Los anticuerpos monoclonales son glucoproteínas Abstract especializadas que hacen parte del sistema inmune, Monoclonal antibodies are specialized glucopro- producidas por las células B, con la capacidad de re- teins that belong to the immune system, produced conocer moléculas específicas (antígenos). Los anti- by the B cells which have the ability to recognize cuerpos monoclonales son herramientas esenciales other molecules (antigens). They are important en el ámbito clínico y biotecnológico, y han probado tools in clinical practice and biotechnology and have ser útiles en el diagnóstico y tratamiento de enfer- been useful in the diagnosis and treatment of medades infecciosas, inmunológicas y neoplá-sicas, infectious, inflammatory, immunological and así como también en el estudio de las interacciones neoplasic diseases, as well as in the study of the patógeno-hospedero y la marcación, detección y cuan- host/patogen interaction, and in the detection and tificación de diversas moléculas. quantification of diverse molecules. Actualmente, la incorporación de las técnicas The incorporation of molecular biology, de biología molecular e ingeniería genética y proteica proteic and genetic engineering have extended the han permitido ampliar el horizonte de la generación production
    [Show full text]
  • As a Registered E-Materials Service User of the EBMT Annual Meeting in Marseille March 26-29Th 2017, You Have Been Granted Permi
    Copyright Statement As a registered E-materials Service user of the EBMT Annual Meeting in Marseille March 26-29th 2017, you have been granted permission to access a copy of the presentation in the following pages for the purpose of scientific education. This presentation is copyrighted material and must not be copied, reproduced, transferred, distributed, leased, licensed, placed in a storage retrieval system, publicly performed or used in any way, except as specifically permitted in writing by the presenter or, as allowed under the terms and conditions under which it was received or as permitted by applicable copyright law or rules of proper citation. Any unauthorised distribution or use of this presentation, a subset of it or graphics taken from the presentation may be a direct infringement of the presenter’s rights. RACE DM training session: Immunusuppressive treatment for aplastic anemia Antonio M. Risitano, M.D., Ph.D. Head of Bone Marrow Transplantation Unit Federico II University of Naples Aplastic anemia Neutrophils for Incidence, age for SCT . Opha disease. Iidee ates peset geogaphi aiatios. to ‐fold highe ates i Asia tha Euope ad the Uited States . Gloal iidee ates age .‐. ases pe illio ihaitats. Aplasti aeia: AA • AA: hat does it ea? • Ho e do the diagosis? • Whe should e teat? • Ho e teat? Aplasti aeia: AA • AA: hat does it ea? • Ho e do the diagosis? • Whe should e teat? • Ho e teat? Aplastic anemia Normal Aplastic anemia CML AA Normal Marrow aplasia Takaku et al, Blood 2010 Takaku et al, Blood 2010 Contraction of stem cell pool Cytopenia AA: hat does it ea? (Oligo) clonal CD8+ T cells Auto-immunity = immune disorder = idiopathic AA AA: hat does it ea? Constitutionnal = inherited disorder (FA, dyskeratosis congenita) Hematopoietic stem cells in AA Hematopoietic progenitor cultures T-cell clonality in aplastic anemia A surrogate marker for Ag-driven immune response Experimental Hematology 23 (1995): 433 Establishment of a CD4+ T cell clone recognizing autologous hematopoietic progenitor cells from a patient with immune-mediated aplastic anemia.
    [Show full text]
  • 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.
    [Show full text]
  • PHARMACEUTICAL APPENDIX to the TARIFF SCHEDULE 2 Table 1
    Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE HARMONIZED TARIFF SCHEDULE Harmonized Tariff Schedule of the United States (2020) Revision 19 Annotated for Statistical Reporting Purposes PHARMACEUTICAL APPENDIX TO THE TARIFF SCHEDULE 2 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.
    [Show full text]
  • Ectrims Meeting November 2015
    SUPPLEMENT TO HIGHLIGHTS FROM THE ECTRIMS MEETING NOVEMBER 2015 Ocrelizumab May Reduce Disability Progression in People With Primary Progressive MS Data support the hypothesis that B cells are central to the underlying biology of MS. BARCELONA—In people with primary progressive Overall, the incidence of adverse events associated multiple sclerosis (MS), treatment with ocrelizumab may with ocrelizumab was similar to that of placebo. The most significantly reduce the progression of clinical disability common adverse events were mild-to-moderate infusion- sustained for at least 12 weeks, compared with placebo, related reactions. The incidence of serious adverse events according to results from a pivotal phase III study presented associated with ocrelizumab, including serious infections, at the 31st Congress of the European Committee for Treat- was also similar to that of placebo. ment and Research in Multiple Sclerosis (ECTRIMS). In the “People with the primary progressive form of MS typi- study, which is called ORATORIO, clinical disability was cally experience symptoms that continuously worsen after measured by the Expanded Disability Status Scale (EDSS). the onset of their disease, and there are no approved treat- Ocrelizumab is an investigational, humanized mono- ments for this debilitating condition,” said Sandra Horn- clonal antibody designed to selectively target CD20-posi- ing, MD, Chief Medical Officer and Head of Global Product tive B cells. CD20-positive B cells are a type of immune cell Development for Genentech, the developer
    [Show full text]
  • Nuevos Medicamentos De Origen Biotecnológico
    mismo. el en contenida TRABAJO DE FIN DE GRADO GRADO EN FARMACIA información la de responsable NUEVOS MEDICAMENTOS DE hace se ORIGEN BIOTECNOLÓGICO no Farmacia de Facultad La docente. finalidad una tiene Tutor: Ángeles Heras Caballero trabajo Realizado por: Javier Martínez Tejedor Este Facultad de Farmacia Universidad Complutense de Madrid 1 Nuevos medicamentos de origen biotecnológico Javier Martínez Tejedor Contenido 1.- Resumen……………………………………………………………………………………………………pág 3 2.- Introducción y antecedentes………………………………………………………………………pág 4 mismo. el - 2.1 La industria farmacéutica y el desarrollo de la biotecnología ………pág 5 en -2.2 Principales características de los medicamentos biotecnológicos..…pág 6 contenida 3.- El desarrollo de nuevos medicamentos biotecnológicos………………………………pág 9 - 3.1.- Puesta en marcha información la - 3.2.- Validación de - 3.3.- Cribado 4.- Material y métodos……………………………………………………………………………………pág 12 responsable hace 5.- Resultados y discusión……………………………………………………………………………….pág 13 se no - 5.1.- El futuro de la biotecnología y la industria farmacéutica - Terapia Génica………………………………………………………………………pág 14 Farmacia de - Células Madre……………………………………………………………………….pág 14 - Nanomedicina………………………………………………………………………pág 14 Facultad La - Biosimilares………………………………………………………………………….pág 15 docente. - Nuevos sistemas de administración………………………………………pág 16 - MAB en desarrollo………………………………………………………………..pág 17 finalidad una 6.- Conclusión………………………………………………………………………………………………pág 19 tiene 7.- Agradecimientos. ……………………………………………………………………………………pág 20
    [Show full text]
  • Targeting Costimulatory Molecules in Autoimmune Disease
    Targeting costimulatory molecules in autoimmune disease Natalie M. Edner1, Gianluca Carlesso2, James S. Rush3 and Lucy S.K. Walker1 1Institute of Immunity & Transplantation, Division of Infection & Immunity, University College London, Royal Free Campus, London, UK NW3 2PF 2Early Oncology Discovery, Early Oncology R&D, AstraZeneca, Gaithersburg, MD, USA 3Autoimmunity, Transplantation and Inflammation Disease Area, Novartis Institutes for Biomedical Research, Basel, Switzerland *Correspondence: Professor Lucy S.K. Walker. Institute of Immunity & Transplantation, Division of Infection & Immunity, University College London, Royal Free Campus, London, UK NW3 2PF. Tel: +44 (0)20 7794 0500 ext 22468. Email: [email protected]. 1 Abstract Therapeutic targeting of immune checkpoints has garnered significant attention in the area of cancer immunotherapy, and efforts have focused in particular on the CD28 family members CTLA-4 and PD-1. In autoimmunity, these same pathways can be targeted to opposite effect, to curb the over- exuberant immune response. The CTLA-4 checkpoint serves as an exemplar, whereby CTLA-4 activity is blocked by antibodies in cancer immunotherapy and augmented by the provision of soluble CTLA-4 in autoimmunity. Here we review the targeting of costimulatory molecules in autoimmune disease, focusing in particular on the CD28 family and TNFR family members. We present the state-of-the-art in costimulatory blockade approaches, including rational combinations of immune inhibitory agents, and discuss the future opportunities and challenges in this field. 2 The risk of autoimmune disease is an inescapable consequence of the manner in which the adaptive immune system operates. To ensure effective immunity against a diverse array of unknown pathogens, antigen recognition systems based on random gene rearrangement and mutagenesis have evolved to anticipate the antigenic universe.
    [Show full text]
  • Immunfarmakológia Immunfarmakológia
    Gergely: Immunfarmakológia Immunfarmakológia Prof Gergely Péter Az immunpatológiai betegségek döntő többsége gyulladásos, és ennek következtében általában szövetpusztulással járó betegség, melyben – jelenleg – a terápia alapvetően a gyulladás csökkentésére és/vagy megszűntetésére irányul. Vannak kizárólag gyulladásgátló gyógyszereink és vannak olyanok, amelyek az immunreakció(k) bénításával (=immunszuppresszió révén) vagy emellett vezetnek a gyulladás mérsékléséhez. Mind szerkezetileg, mind hatástanilag igen sokféle csoportba oszthatók, az alábbi felosztás elsősorban didaktikus célokat szolgál. 1. Nem-szteroid gyulladásgátlók (‘nonsteroidal antiinflammatory drugs’ NSAID) 2. Kortikoszteroidok 3. Allergia-elleni szerek (antiallergikumok) 4. Sejtoszlás-gátlók (citosztatikumok) 5. Nem citosztatikus hatású immunszuppresszív szerek 6. Egyéb gyulladásgátlók és immunmoduláns szerek 7. Biológiai terápia 1. Nem-szteroid gyulladásgátlók (NSAID) Ezeket a vegyületeket, melyek őse a szalicilsav (jelenleg, mint acetilszalicilsav ‘aszpirin’ használatos), igen kiterjedten alkalmazzák a reumatológiában, az onkológiában és az orvostudomány szinte minden ágában, ahol fájdalom- és lázcsillapításra van szükség. Egyes felmérések szerint a betegek egy ötöde szed valamilyen NSAID készítményt. Szerkezetük alapján a készítményeket több csoportba sorolhatjuk: szalicilátok (pl. acetilszalicilsav) pyrazolidinek (pl. fenilbutazon) ecetsav származékok (pl. indometacin) fenoxiecetsav származékok (pl. diclofenac, aceclofenac)) oxicamok (pl. piroxicam, meloxicam) propionsav
    [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]
  • (12) Patent Application Publication (10) Pub. No.: US 2017/0172932 A1 Peyman (43) Pub
    US 20170172932A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0172932 A1 Peyman (43) Pub. Date: Jun. 22, 2017 (54) EARLY CANCER DETECTION AND A 6LX 39/395 (2006.01) ENHANCED IMMUNOTHERAPY A61R 4I/00 (2006.01) (52) U.S. Cl. (71) Applicant: Gholam A. Peyman, Sun City, AZ CPC .......... A61K 9/50 (2013.01); A61K 39/39558 (US) (2013.01); A61K 4I/0052 (2013.01); A61 K 48/00 (2013.01); A61K 35/17 (2013.01); A61 K (72) Inventor: sham A. Peyman, Sun City, AZ 35/15 (2013.01); A61K 2035/124 (2013.01) (21) Appl. No.: 15/143,981 (57) ABSTRACT (22) Filed: May 2, 2016 A method of therapy for a tumor or other pathology by administering a combination of thermotherapy and immu Related U.S. Application Data notherapy optionally combined with gene delivery. The combination therapy beneficially treats the tumor and pre (63) Continuation-in-part of application No. 14/976,321, vents tumor recurrence, either locally or at a different site, by filed on Dec. 21, 2015. boosting the patient’s immune response both at the time or original therapy and/or for later therapy. With respect to Publication Classification gene delivery, the inventive method may be used in cancer (51) Int. Cl. therapy, but is not limited to such use; it will be appreciated A 6LX 9/50 (2006.01) that the inventive method may be used for gene delivery in A6 IK 35/5 (2006.01) general. The controlled and precise application of thermal A6 IK 4.8/00 (2006.01) energy enhances gene transfer to any cell, whether the cell A 6LX 35/7 (2006.01) is a neoplastic cell, a pre-neoplastic cell, or a normal cell.
    [Show full text]