Selection of an Artificial Binding Protein Against the Ectodomain of PTH1R
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Wo2015188839a2
Downloaded from orbit.dtu.dk on: Oct 08, 2021 General detection and isolation of specific cells by binding of labeled molecules Pedersen, Henrik; Jakobsen, Søren; Hadrup, Sine Reker; Bentzen, Amalie Kai; Johansen, Kristoffer Haurum Publication date: 2015 Document Version Publisher's PDF, also known as Version of record Link back to DTU Orbit Citation (APA): Pedersen, H., Jakobsen, S., Hadrup, S. R., Bentzen, A. K., & Johansen, K. H. (2015). General detection and isolation of specific cells by binding of labeled molecules. (Patent No. WO2015188839). General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. Users may download and print one copy of any publication from the public portal for the purpose of private study or research. You may not further distribute the material or use it for any profit-making activity or commercial gain You may freely distribute the URL identifying the publication in the public portal If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2015/188839 -
Fig. 1C Combination Therapy of Tumor Targeted ICOS Agonists with T-Cell Bispecific Molecules
( (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C07K 16/30 (2006.01) A61P 35/00 (2006.01) kind of national protection av ailable) . AE, AG, AL, AM, C07K 16/28 (2006.01) A 6IK 39/00 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, C07K 16/40 (2006.01) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (21) International Application Number: HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, PCT/EP20 18/086046 KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (22) International Filing Date: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 20 December 2018 (20. 12.2018) 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, 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, 17209444.3 2 1 December 2017 (21. 12.2017) EP GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (71) Applicant (for all designated States except US): F. HOFF- TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, MANN-LA ROCHE AG [CH/CH]; Grenzacherstrasse EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, 124, 4070 Basel (CH). -
Design and Screening of Degenerate-Codon-Based Protein Ensembles with M13 Bacteriophage
Design and Screening of Degenerate-Codon-Based Protein Ensembles with M13 Bacteriophage by Griffin James Clausen B.S. Biomedical Engineering University of Minnesota – Twin Cities, 2012 Submitted to the Department of Biological Engineering in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy in Biological Engineering at the Massachusetts Institute of Technology February 2019 © 2019 Massachusetts Institute of Technology. All rights reserved. Signature of Author: ____________________________________________________________ Griffin Clausen Department of Biological Engineering January 14, 2019 Certified by: ___________________________________________________________________ Angela Belcher James Mason Crafts Professor of Biological Engineering and Materials Science Thesis Supervisor Accepted by: ___________________________________________________________________ Forest White Professor of Biological Engineering Graduate Program Committee Chair This doctoral thesis has been examined by the following committee: Amy Keating Thesis Committee Chair Professor of Biology and Biological Engineering Massachusetts Institute of Technology Angela Belcher Thesis Supervisor James Mason Crafts Professor of Biological Engineering and Materials Science Massachusetts Institute of Technology Paul Blainey Core Member, Broad Institute Associate Professor of Biological Engineering Massachusetts Institute of Technology 2 Design and Screening of Degenerate-Codon-Based Protein Ensembles with M13 Bacteriophage by Griffin James Clausen Submitted -
Strategies and Challenges for the Next Generation of Therapeutic Antibodies
FOCUS ON THERAPEUTIC ANTIBODIES PERSPECTIVES ‘validated targets’, either because prior anti- TIMELINE bodies have clearly shown proof of activity in humans (first-generation approved anti- Strategies and challenges for the bodies on the market for clinically validated targets) or because a vast literature exists next generation of therapeutic on the importance of these targets for the disease mechanism in both in vitro and in vivo pharmacological models (experi- antibodies mental validation; although this does not necessarily equate to clinical validation). Alain Beck, Thierry Wurch, Christian Bailly and Nathalie Corvaia Basically, the strategy consists of develop- ing new generations of antibodies specific Abstract | Antibodies and related products are the fastest growing class of for the same antigens but targeting other therapeutic agents. By analysing the regulatory approvals of IgG-based epitopes and/or triggering different mecha- biotherapeutic agents in the past 10 years, we can gain insights into the successful nisms of action (second- or third-generation strategies used by pharmaceutical companies so far to bring innovative drugs to antibodies, as discussed below) or even the market. Many challenges will have to be faced in the next decade to bring specific for the same epitopes but with only one improved property (‘me better’ antibod- more efficient and affordable antibody-based drugs to the clinic. Here, we ies). This validated approach has a high discuss strategies to select the best therapeutic antigen targets, to optimize the probability of success, but there are many structure of IgG antibodies and to design related or new structures with groups working on this class of target pro- additional functions. -
International Patent Classification: KR, KW, KZ, LA, LC, LK, LR, LS, LU
( 2 (51) International Patent Classification: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, A61K 39/42 (2006.01) C07K 16/10 (2006.01) HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, C07K 16/08 (2006.01) KR, KW, KZ, LA, LC, LK, LR, LS, 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 19/033 995 SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, (22) International Filing Date: TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. 24 May 2019 (24.05.2019) (84) Designated States (unless otherwise indicated, for every (25) Filing Language: English kind of regional protection available) . ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (26) Publication Language: English UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, (30) Priority Data: TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, 62/676,045 24 May 2018 (24.05.2018) US 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: LANKENAU INSTITUTE FOR MEDICAL TR), OAPI (BF, BJ, CF, CG, Cl, CM, GA, GN, GQ, GW, RESEARCH [US/US]; 100 Lancaster Avenue, Wyn- KM, ML, MR, NE, SN, TD, TG). -
WO 2018/144999 Al 09 August 2018 (09.08.2018) W ! P O PCT
(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 2018/144999 Al 09 August 2018 (09.08.2018) W ! P O PCT (51) International Patent Classification: Lennart; c/o Orionis Biosciences NV, Rijvisschestraat 120, A61K 38/00 (2006.01) C07K 14/555 (2006.01) Zwijnaarde, B-9052 (BE). TAVERNIER, Jan; c/o Orionis A61K 38/21 (2006.01) C12N 15/09 (2006.01) Biosciences NV, Rijvisschestraat 120, Zwijnaarde, B-9052 C07K 14/52 (2006.01) (BE). (21) International Application Number: (74) Agent: ALTIERI, Stephen, L. et al; Morgan, Lewis & PCT/US2018/016857 Bockius LLP, 1111 Pennsylvania Avenue, NW, Washing ton, D.C. 20004 (US). (22) International Filing Date: 05 February 2018 (05.02.2018) (81) Designated States (unless otherwise indicated, for every kind of national protection available): AE, AG, AL, AM, (25) Filing Language: English AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (26) Publication Language: English CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, (30) Priority Data: HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, 62/454,992 06 February 2017 (06.02.2017) US KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (71) Applicants: ORIONIS BIOSCIENCES, INC. [US/US]; MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, 275 Grove Street, Newton, MA 02466 (US). -
Affinity Chromatography (AC)
Affinity Chromatography (AC) 1 Affinity Chromatography (AC) • Principles of AC • Main stages in Chromatography • How to prepare Affinity gel - Ligand Immobilization - Spacer arms – Coupling methods – Coupling tips • Types of AC • Elution Conditions • Binding equilibrium, competitive elution, kinetics • Industrial Examples: Protein A/G for Therapeutic proteins • Future Considerations 2 What is affinity chromatography? Affinity chromatography is a technique of liquid chromatography which separates molecules through biospecific interactions. The molecule to be purified is specifically and reversibly adsorbed to a specific ligand The ligand is immobilized to an insoluble support (“matrix”): resin, “chip”, Elisa plate, membrane, Western, IP (immuneprecipitation), etc Introduction of a “spacer arm” between the ligand and the matrix to improve binding Elution of the bound target molecule a) non specific or b) specific elution method 3 What is it used for? Monoclonal and polyclonal antibodies Fusion proteins Enzymes DNA-binding proteins . ANY protein where we have a binding partner!! 4 Designing and preparing an affinity gel Choosing the matrix Designing the ligand - Spacer arms Coupling methods 5 Ligand Immobilization Ligand + Activating agent + Matrix Activated Immobilised matrix ligand 6 Designing the ligand Essential ligand properties: interacts selectively and reversibly with the target Carries groups which can couple it to the matrix without losing its binding activity Available in a pure form 7 Steric considerations & spacer arms Small ligand (<1,000) Risk of steric interference with binding between matrix and target molecule Often need spacer arm but watch out for Spacer arm adsorption to the spacer! 8 Design of spacer arms Alkyl chain Real risk of unspecific interactions between H H spacer and target molecule O O Hydrophilic chain Risk of unspecific interactions greatly O H reduced No coupling reaction will use 100% of the available binding sites. -
EURL ECVAM Recommendation on Non-Animal-Derived Antibodies
EURL ECVAM Recommendation on Non-Animal-Derived Antibodies EUR 30185 EN Joint Research Centre This publication is a Science for Policy report by the Joint Research Centre (JRC), the European Commission’s science and knowledge service. It aims to provide evidence-based scientific support to the European policymaking process. The scientific output expressed does not imply a policy position of the European Commission. Neither the European Commission nor any person acting on behalf of the Commission is responsible for the use that might be made of this publication. For information on the methodology and quality underlying the data used in this publication for which the source is neither Eurostat nor other Commission services, users should contact the referenced source. EURL ECVAM Recommendations The aim of a EURL ECVAM Recommendation is to provide the views of the EU Reference Laboratory for alternatives to animal testing (EURL ECVAM) on the scientific validity of alternative test methods, to advise on possible applications and implications, and to suggest follow-up activities to promote alternative methods and address knowledge gaps. During the development of its Recommendation, EURL ECVAM typically mandates the EURL ECVAM Scientific Advisory Committee (ESAC) to carry out an independent scientific peer review which is communicated as an ESAC Opinion and Working Group report. In addition, EURL ECVAM consults with other Commission services, EURL ECVAM’s advisory body for Preliminary Assessment of Regulatory Relevance (PARERE), the EURL ECVAM Stakeholder Forum (ESTAF) and with partner organisations of the International Collaboration on Alternative Test Methods (ICATM). Contact information European Commission, Joint Research Centre (JRC), Chemical Safety and Alternative Methods Unit (F3) Address: via E. -
Generation of Novel Intracellular Binding Reagents Based on the Human Γb-Crystallin Scaffold
Generation of novel intracellular binding reagents based on the human γB-crystallin scaffold Dissertation zur Erlangung des akademischen Grades doctor rerum naturalium (Dr. rer. nat.) vorgelegt der Naturwissenschaftlichen Fakultät I-Biowissenschaften der Martin-Luther-Universität Halle-Wittenberg Institut für Biochemie und Biotechnologie von Ewa Mirecka geboren am 17. Dezember 1976 in Gdynia, Polen Table of contents Table of contents 1. INTRODUCTION.........................................................................................................1 1.1 Monoclonal antibodies as a biomolecular scaffold..........................................................1 1.2 Binding molecules derived from non-immunoglobulin scaffolds.....................................3 1.2.1 Alternative protein scaffolds – general considerations............................................................ 3 1.2.2 Application of alternative binding molecules ........................................................................... 6 1.3 Affilin – novel binding molecules based on the human γB-crystallin scaffold................... 6 1.3.1 Human γB-crystallin as a molecular scaffold........................................................................... 6 1.3.2 Generation of a human γB-crystallin library and selection of first-generation Affilin molecules ................................................................................................................................ 8 1.4 Selection of binding proteins by phage display ................................................................... -
WO 2018/098356 Al 31 May 2018 (31.05.2018) W !P O PCT
(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 2018/098356 Al 31 May 2018 (31.05.2018) W !P O PCT (51) International Patent Classification: co, California 94124 (US). DUBRIDGE, Robert B.; 825 A61K 39/395 (2006.01) C07K 16/28 (2006.01) Holly Road, Belmont, California 94002 (US). LEMON, A61P 35/00 (2006.01) C07K 16/46 (2006.01) Bryan D.; 2493 Dell Avenue, Mountain View, California 94043 (US). AUSTIN, Richard J.; 1169 Guerrero Street, (21) International Application Number: San Francisco, California 941 10 (US). PCT/US20 17/063 126 (74) Agent: LIN, Clark Y.; WILSON SONSINI GOODRICH (22) International Filing Date: & ROSATI, 650 Page Mill Road, Palo Alto, California 22 November 201 7 (22. 11.201 7) 94304 (US). (25) Filing Language: English (81) Designated States (unless otherwise indicated, for every (26) Publication Langi English kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, (30) Priority Data: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, 62/426,069 23 November 2016 (23. 11.2016) US DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, 62/426,077 23 November 2016 (23. 11.2016) US HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, (71) Applicant: HARPOON THERAPEUTICS, INC. KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, [US/US]; 4000 Shoreline Court, Suite 250, South San Fran MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, cisco, California 94080 (US). -
Understanding Ubiquitin Recognition and Generating Affinity Reagents
Ubiquitin Engineering: Understanding Ubiquitin Recognition and Generating Affinity Reagents by Isabel Leung A thesis submitted in conformity with the requirements for the degree of Doctor of Philosophy Department of Molecular Genetics University of Toronto © Copyright by Isabel Leung 2017 Abstract Ubiquitin Engineering: Understanding Ubiquitin Recognition and Generating Affinity Reagents Isabel Leung Doctor of Philosophy Department of Molecular Genetics University of Toronto 2016 Protein-protein interactions are necessary for virtually all biological processes. There have been tremendous efforts to document the diversity of molecular recognition, and to understand how molecular recognition occurs. The understanding of molecular interaction has also served as the foundation for designing novel protein interactions for use in therapeutics, diagnostics and basic sciences. An attractive system for studying protein-protein interactions is the ubiquitin (Ub) system. Ub is a protein modifier that is combinatorially ligated onto substrate proteins to influence substrate turnover and function. Ub uses a common surface to interact with more than 1000 proteins and plays pivotal roles in cell physiology. Despite the substantial structural information on Ub mediated interactions, there is no clear understanding of how individual Ub residues contribute to Ub’s broad scope of interactions. To address this question, I used affinity enhanced Ub variants (Ubvs) as proxies of native Ub in saturation scanning. Using saturation scanning, I studied the interactions between Ubvs and two Ub specific proteases (USP), USP2 and USP21, and elucidated a common functional epitope that is critical for USP recognition. The functional epitope recognizes USP residues that are conserved among the human USP family, suggesting it may make functional contributions in many other USP interactions. -
WO 2018/218207 Al 29 November 2018 (29.11.2018) W !P O PCT
(t) include a VL chain of SEQ ID NO: 24 and a VH chain of SEQ ID NO: 25; (u) include a VL chain of SEQ ID NO: 84 and a VH chain of SEQ ID NO: 83; (v) include a VL chain of SEQ ID NO: 154 and a VH chain of SEQ ID NO: 155; (w) include CDRs including SEQ ID NO: 85; SEQ ID NO: 86; SEQ ID NO: 87; SEQ ID NO: 88; SEQ ID NO: 89; and SEQ ID NO: 90; (x) include CDRs including SEQ ID NO: 130; SEQ ID NO: 13 1; SEQ ID NO: 132; SEQ ID NO: 133; SEQ ID NO: 134; and SEQ ID NO: 135; (y) include CDRs including SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110 , and SEQ ID NO: 111; (z) include CDRs including SEQ ID NO: 112 , SEQ ID NO: 113 , SEQ ID NO: 114 , SEQ ID NO: 115 , SEQ ID NO: 116 , and SEQ ID NO: 117 ; (aa) include CDRs including SEQ ID NO: 118 , SEQ ID NO: 119 , SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, and SEQ ID NO: 123; (bb) include CDRs including SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, and SEQ ID NO: 129; (cc) include CDRs including SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, and SEQ ID NO: 14 1; (dd) include CDRs including SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, and SEQ ID NO: 147 (ee) include CDRs including SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, and SEQ ID NO: 99; (ff) include CDRs including SEQ ID NO: 100, SEQ ID NO: 10 1, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, and SEQ ID NO: 105; (gg) include CDRs including SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 15 1, SEQ ID NO: 152, and SEQ ID NO: 153; (hh) includes a humanized sequence of an antibody disclosed herein; and/or (ii) binds to endogenous human CD33 with a KD of less than 10 nM.