Biosimilar Antibodies & ELISA Kits
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Fig. L COMPOSITIONS and METHODS to INHIBIT STEM CELL and PROGENITOR CELL BINDING to LYMPHOID TISSUE and for REGENERATING GERMINAL CENTERS in LYMPHATIC TISSUES
(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 Χ 23 February 2012 (23.02.2012) WO 2U12/U24519ft ft A2 (51) International Patent Classification: AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, A61K 31/00 (2006.01) 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, KM, KN, KP, PCT/US201 1/048297 KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, (22) International Filing Date: ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, 18 August 201 1 (18.08.201 1) NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, 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 61/374,943 18 August 2010 (18.08.2010) US kind of regional protection available): ARIPO (BW, GH, 61/441,485 10 February 201 1 (10.02.201 1) US GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, 61/449,372 4 March 201 1 (04.03.201 1) US ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, (72) Inventor; and EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, (71) Applicant : DEISHER, Theresa [US/US]; 1420 Fifth LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, Avenue, Seattle, WA 98101 (US). -
(PDCO) Minutes of the Meeting on 29 January - 01 February 2019
1 March 2019 EMA/PDCO/56017/2019 Inspections, Human Medicines Pharmacovigilance and Committees Division Paediatric Committee (PDCO) Minutes of the meeting on 29 January - 01 February 2019 Chair: Dirk Mentzer – Vice-Chair: Koenraad Norga 29 January 2019, 14:00- 19:00, room 3A 30 January 2019, 08:30- 19:00, room 3A 31 January 2019, 08:30- 19:00, room 3A 01 February 2019, 08:30- 13:00, room 3A Disclaimers Some of the information contained in this set of minutes is considered commercially confidential or sensitive and therefore not disclosed. With regard to intended therapeutic indications or procedure scopes listed against products, it must be noted that these may not reflect the full wording proposed by applicants and may also vary during the course of the review. Additional details on some of these procedures will be published in the PDCO Committee meeting reports (after the PDCO Opinion is adopted), and on the Opinions and decisions on paediatric investigation plans webpage (after the EMA Decision is issued). Of note, this set of minutes is a working document primarily designed for PDCO members and the work the Committee undertakes. Further information with relevant explanatory notes can be found at the end of this document. Note on access to documents Some documents mentioned in the minutes cannot be released at present following a request for access to documents within the framework of Regulation (EC) No 1049/2001 as they are subject to on-going procedures for which a final decision has not yet been adopted. They will become public when adopted or considered public according to the principles stated in the Agency policy on access to documents (EMA/127362/2006). -
Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients
antibodies Review Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients Andrew T. Lucas 1,2,3,*, Ryan Robinson 3, Allison N. Schorzman 2, Joseph A. Piscitelli 1, Juan F. Razo 1 and William C. Zamboni 1,2,3 1 University of North Carolina (UNC), Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA; [email protected] (J.A.P.); [email protected] (J.F.R.); [email protected] (W.C.Z.) 2 Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; [email protected] 3 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-919-966-5242; Fax: +1-919-966-5863 Received: 30 November 2018; Accepted: 22 December 2018; Published: 1 January 2019 Abstract: The rapid advancement in the development of therapeutic proteins, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), has created a novel mechanism to selectively deliver highly potent cytotoxic agents in the treatment of cancer. These agents provide numerous benefits compared to traditional small molecule drugs, though their clinical use still requires optimization. The pharmacology of mAbs/ADCs is complex and because ADCs are comprised of multiple components, individual agent characteristics and patient variables can affect their disposition. To further improve the clinical use and rational development of these agents, it is imperative to comprehend the complex mechanisms employed by antibody-based agents in traversing numerous biological barriers and how agent/patient factors affect tumor delivery, toxicities, efficacy, and ultimately, biodistribution. -
Chemokine Receptors in Allergic Diseases Laure Castan, A
Chemokine receptors in allergic diseases Laure Castan, A. Magnan, Grégory Bouchaud To cite this version: Laure Castan, A. Magnan, Grégory Bouchaud. Chemokine receptors in allergic diseases. Allergy, Wiley, 2017, 72 (5), pp.682-690. 10.1111/all.13089. hal-01602523 HAL Id: hal-01602523 https://hal.archives-ouvertes.fr/hal-01602523 Submitted on 11 Jul 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution - ShareAlike| 4.0 International License Allergy REVIEW ARTICLE Chemokine receptors in allergic diseases L. Castan1,2,3,4, A. Magnan2,3,5 & G. Bouchaud1 1INRA, UR1268 BIA; 2INSERM, UMR1087, lnstitut du thorax; 3CNRS, UMR6291; 4Universite de Nantes; 5CHU de Nantes, Service de Pneumologie, Institut du thorax, Nantes, France To cite this article: Castan L, Magnan A, Bouchaud G. Chemokine receptors in allergic diseases. Allergy 2017; 72: 682–690. Keywords Abstract asthma; atopic dermatitis; chemokine; Under homeostatic conditions, as well as in various diseases, leukocyte migration chemokine receptor; food allergy. is a crucial issue for the immune system that is mainly organized through the acti- Correspondence vation of bone marrow-derived cells in various tissues. Immune cell trafficking is Gregory Bouchaud, INRA, UR1268 BIA, rue orchestrated by a family of small proteins called chemokines. -
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. -
Cutaneous Adverse Effects of Biologic Medications
REVIEW CME MOC Selena R. Pasadyn, BA Daniel Knabel, MD Anthony P. Fernandez, MD, PhD Christine B. Warren, MD, MS Cleveland Clinic Lerner College Department of Pathology Co-Medical Director of Continuing Medical Education; Department of Dermatology, Cleveland Clinic; of Medicine of Case Western and Department of Dermatology, W.D. Steck Chair of Clinical Dermatology; Director of Clinical Assistant Professor, Cleveland Clinic Reserve University, Cleveland, OH Cleveland Clinic Medical and Inpatient Dermatology; Departments of Lerner College of Medicine of Case Western Dermatology and Pathology, Cleveland Clinic; Assistant Reserve University, Cleveland, OH Clinical Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH Cutaneous adverse effects of biologic medications ABSTRACT iologic therapy encompasses an expo- B nentially expanding arena of medicine. Biologic therapies have become widely used but often As the name implies, biologic therapies are de- cause cutaneous adverse effects. The authors discuss the rived from living organisms and consist largely cutaneous adverse effects of tumor necrosis factor (TNF) of proteins, sugars, and nucleic acids. A clas- alpha inhibitors, epidermal growth factor receptor (EGFR) sic example of an early biologic medication is inhibitors, small-molecule tyrosine kinase inhibitors insulin. These therapies have revolutionized (TKIs), and cell surface-targeted monoclonal antibodies, medicine and offer targeted therapy for an including how to manage these reactions -
Comparative Safety and Efficacy of Anti-PD-1 Monotherapy, Chemotherapy
Lv et al. Journal for ImmunoTherapy of Cancer (2019) 7:159 https://doi.org/10.1186/s40425-019-0636-7 COMMENTARY Open Access Comparative safety and efficacy of anti-PD- 1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials Jia-Wei Lv1†, Jun-Yan Li1†, Lin-Na Luo2†, Zi-Xian Wang2* and Yu-Pei Chen1* Abstract Recent phase 1–2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking. We aimed to comprehensively compare the efficacy and safety of different anti-PD-1 drugs, standard chemotherapy, and their combination therapy in RM-NPC. Adverse event (AE) and objective response rate (ORR) were assessed. The pooled incidence rates of grade 1–5/3–5 AEs were 74.1%/29.6, 54.2%/17.4, 92.3%/24.5, 96.8%/16.1, 91.2%/42.8, and 100%/87.9% for pembrolizumab, nivolumab, JS001, camrelizumab, chemotherapy and camrelizumab+chemotherapy, respectively, which suggested that nivolumab and pembrolizumab exhibited the optimal safety regarding grade 1–5 AEs whereas camrelizumab and nivolumab regarding grade 3–5 AEs. As second- or later-line therapy, ORR was higher with camrelizumab (34.1%), followed by pembrolizumab (26.3%), JS001 (23.3%), and nivolumab (19.0%); whereas ORR with first-line nivolumab reached 40%. Additionally, first-line camrelizumab+chemotherapy achieved a dramatically higher ORR than that with chemotherapy alone (90.9% vs. -
Challenges and Approaches for the Development of Safer Immunomodulatory Biologics
REVIEWS Challenges and approaches for the development of safer immunomodulatory biologics Jean G. Sathish1*, Swaminathan Sethu1*, Marie-Christine Bielsky2, Lolke de Haan3, Neil S. French1, Karthik Govindappa1, James Green4, Christopher E. M. Griffiths5, Stephen Holgate6, David Jones2, Ian Kimber7, Jonathan Moggs8, Dean J. Naisbitt1, Munir Pirmohamed1, Gabriele Reichmann9, Jennifer Sims10, Meena Subramanyam11, Marque D. Todd12, Jan Willem Van Der Laan13, Richard J. Weaver14 and B. Kevin Park1 Abstract | Immunomodulatory biologics, which render their therapeutic effects by modulating or harnessing immune responses, have proven their therapeutic utility in several complex conditions including cancer and autoimmune diseases. However, unwanted adverse reactions — including serious infections, malignancy, cytokine release syndrome, anaphylaxis and hypersensitivity as well as immunogenicity — pose a challenge to the development of new (and safer) immunomodulatory biologics. In this article, we assess the safety issues associated with immunomodulatory biologics and discuss the current approaches for predicting and mitigating adverse reactions associated with their use. We also outline how these approaches can inform the development of safer immunomodulatory biologics. Immunomodulatory Biologics currently represent more than 30% of licensed The high specificity of the interactions of immu- biologics pharmaceutical products and have expanded the thera- nomodulatory biologics with their relevant immune Biotechnology-derived peutic options available -
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 -
Avelumab (Bavencio®) Prior Authorization Drug Coverage Policy
1 Avelumab (Bavencio®) Prior Authorization Drug Coverage Policy Effective Date: 9/1/2020 Revision Date: n/a Review Date: 3/6/2020 Lines of Business: Commercial Policy type: Prior Authorization This Drug Coverage Policy provides parameters for the coverage of avelumab (Bavencio®). Consideration of medically necessary indications are based upon U.S. Food and Drug Administration (FDA) indications, recommended uses within the Centers of Medicare & Medicaid Services (CMS) five recognized compendia, including the National Comprehensive Cancer Network (NCCN) Drugs & Biologics Compendium (Category 1 or 2A recommendations), and peer-reviewed scientific literature eligible for coverage according to the CMS, Medicare Benefit Policy Manual, Chapter 15, section 50.4.5 titled, “Off-Label Use of Anti-Cancer Drugs and Biologics.” This policy evaluates whether the drug therapy is proven to be effective based on published evidence-based medicine. Drug Description 1-2 Avelumab is a fully human IgG1 monoclonal antibody that specifically binds to PD-L1. This binding blocks the interaction between PD-L1 and its receptors, PD-1 and B7.1. Blocking PD-1 and B7.1 interaction restores anti-tumor T-cell function. FDA Indications 1 Avelumab is FDA indicated for the following: Treatment of metastatic Merkel Cell carcinoma (MCC) in adults and children ≥ 12 years of age. Treatment of locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. First-line treatment of advanced renal cell carcinoma (RCC) in combination with axitinib Coverage Determinations 1,3 Avelumab will require prior authorization. -
LAG-3: from Molecular Functions to Clinical Applications
Open access Review J Immunother Cancer: first published as 10.1136/jitc-2020-001014 on 13 September 2020. Downloaded from LAG-3: from molecular functions to clinical applications Takumi Maruhashi , Daisuke Sugiura , Il- mi Okazaki , Taku Okazaki To cite: Maruhashi T, Sugiura D, ABSTRACT (PD-1) and cytotoxic T lymphocyte antigen Okazaki I, et al. LAG-3: from To prevent the destruction of tissues owing to excessive 4 (CTLA-4) significantly improved the molecular functions to clinical and/or inappropriate immune responses, immune outcomes of patients with diverse cancer applications. Journal for cells are under strict check by various regulatory ImmunoTherapy of Cancer types, revolutionizing cancer treatment. The mechanisms at multiple points. Inhibitory coreceptors, 2020;8:e001014. doi:10.1136/ success of these therapies verified that inhib- including programmed cell death 1 (PD-1) and cytotoxic jitc-2020-001014 itory coreceptors serve as critical checkpoints T lymphocyte antigen 4 (CTLA-4), serve as critical checkpoints in restricting immune responses against for immune cells to not attack the tumor Accepted 29 July 2020 self- tissues and tumor cells. Immune checkpoint inhibitors cells as well as self-tissues. However, response that block PD-1 and CTLA-4 pathways significantly rates are typically lower and immune-related improved the outcomes of patients with diverse cancer adverse events (irAEs) are also observed in types and have revolutionized cancer treatment. However, patients administered with immune check- response rates to such therapies are rather limited, and point inhibitors. This is indicative of the immune-rela ted adverse events are also observed in a continued need to decipher the complex substantial patient population, leading to the urgent need biology of inhibitory coreceptors to increase for novel therapeutics with higher efficacy and lower response rates and prevent such unwanted toxicity. -
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.