Protein-excipient Interactions and Protein-Protein Interactions in formulation

Información del proyecto

PIPPI

Identificador del acuerdo de subvención: 675074

DOI

10.3030/675074

Proyecto cerrado

Fecha de la firma de la CE 31 Julio 2015

Fecha de inicio 1 Enero 2016

Fecha de finalización 31 Diciembre 2019

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 4 067 745,48

Aportación de la UE

€ 4 067 745,48

Coordinado por

DANMARKS TEKNISKE UNIVERSITET
Denmark

CORDIS proporciona enlaces a los documentos públicos y las publicaciones de los proyectos de los programas marco HORIZONTE.

Los enlaces a los documentos y las publicaciones de los proyectos del Séptimo Programa Marco, así como los enlaces a algunos tipos de resultados específicos, como conjuntos de datos y «software», se obtienen dinámicamente de OpenAIRE .

Resultado final

Other (8)

Society outreach including scientific publications

Publication results in Scientific journals and at international conferences and workshops. Easy-to-read information material for the society at large.

Aggregation propensity assessed for all proteins

Aggregation propensity - including surface induced aggregation propensity - assessed for all proteins.

Weak and strong protein-protein and protein-excipient interactions are identified.

For all proteins in the library the relevant weak and strong protein-protein and protein-excipient interactions are identified.

Structures based on measurements and modeling

For all soluble proteins, there will be at least 1 but preferable 2 or more solution structures based on SAXS measurements and in-silico modeling

Tagg and Tgel are determined for each protein

For each protein the determination of the temperature of aggregation, Tagg, and gelation, Tgel, using light scattering experiments, differential scanning calorimetry and temperature ramp rheology Measurements.

Protocols for the making of screens 1 and 2 established

A general protocol for the making of the screens 1 and 2 that are used for all proteins should be ready

International conference

International conferences with contribution from all ESRs as well as external contributions.

Model for the prediction of protein aggregation and stability

A general model for the prediction of protein aggregation and stability of all proteins

Websites, patent fillings, videos etc. (2)

Database made public accessible

Database with web-based graphical interface will be made public accessible

Project website

Establishment of a PIPPI website with a password protected area and a publically accessible area.

Documents, reports (3)

Personal Carrier Development Plans

For all ESRs a personal carrier Development plan will be ready.

Periodic, financial and final reports to the EC

Reports will be delivered to the EC periodically. This covers also the Financial reports. A report will be given in when the project finishes.

Evaluation report on training activities

For all training activities an evaluation report will be ready

Publicaciones

Peer reviewed articles (27)

Binding of excipients is a poor predictor for aggregation kinetics of biopharmaceutical proteins

Autores: Matja Zalar, Hristo Svilenov, Alexander Golovanov
Publicado en: European Journal of Pharmaceutics and Biopharmaceutics, 2020, Página(s) 127-136, ISSN 0939-6411
Editor: Elsevier BV
DOI: 10.1016/j.ejpb.2020.04.002

The Effect of Point Mutations on the Biophysical Properties of an Antimicrobial Peptide: Development of a Screening Protocol for Peptide Stability Screening

Autores: Christin Pohl, Matja Zalar, Inas El Bialy, Sowmya Indrakumar, Günther H. J. Peters, Wolfgang Friess, Alexander P. Golovanov, Werner W. Streicher, Allan Noergaard, and Pernille Harris
Publicado en: Molecular Pharmaceutics, 2020, ISSN 1543-8384
Editor: American Chemical Society
DOI: 10.1021/acs.molpharmaceut.0c00406

Self-Interactions of Two Monoclonal Antibodies: Small-Angle X-ray Scattering, Light Scattering, and Coarse-Grained Modeling

Autores: Sujata Mahapatra, Marco Polimeni, Lorenzo Gentiluomo , Dierk Roessner , Wolfgang Frieß , Günther H J Peters , Werner W Streicher , Mikael Lund , Pernille Harris
Publicado en: Molecular Pharmaceutics, 2022, ISSN 1543-8384
Editor: American Chemical Society
DOI: 10.1021/acs.molpharmaceut.1c00627

Application of machine learning to predict monomer retention of therapeutic proteins after long term storage

Autores: Lorenzo Gentiluomo; Dierk Roessner, Wolfgan Frieß
Publicado en: International Journal of Pharmaceutics, 2020, ISSN 0378-5173
Editor: Elsevier BV
DOI: 10.1016/j.ijpharm.2020.119039

Towards an improved prediction of concentrated antibody solution viscosity using the Huggins coefficient

Autores: Roche, A., Gentiluomo, L., Sibanda, N., Roessner, D., Friess, W., Trainoff, S. P., & Curtis, R.
Publicado en: Journal of Colloid and Interface Science, 2022, ISSN 0021-9797
Editor: Academic Press
DOI: 10.1016/j.jcis.2021.08.191

Isothermal chemical denaturation as a complementary tool to overcome limitations of thermal differential scanning fluorimetry in predicting physical stability of protein formulations

Autores: Hristo Svilenov, Uroš Markoja, Gerhard Winter
Publicado en: European Journal of Pharmaceutics and Biopharmaceutics, Edición 125, 2018, Página(s) 106-113, ISSN 0939-6411
Editor: Elsevier BV
DOI: 10.1016/j.ejpb.2018.01.004

A New Approach to Study the Physical Stability of Monoclonal Antibody Formulations—Dilution From a Denaturant

Autores: Hristo Svilenov, Lorenzo Gentiluomo, Wolfgang Friess, Dierk Roessner, Gerhard Winter
Publicado en: Journal of Pharmaceutical Sciences, Edición 107/12, 2018, Página(s) 3007-3013, ISSN 0022-3549
Editor: John Wiley & Sons Inc.
DOI: 10.1016/j.xphs.2018.08.004

New Disulphide Bond in Cystatin-Based Protein Scaffold Prevents Domain-Swap-Mediated Oligomerization and Stabilizes the Functionally Active Form

Autores: Matja Zalar, Alexander P. Golovanov
Publicado en: ACS Omega, Edición 4/19, 2019, Página(s) 18248-18256, ISSN 2470-1343
Editor: Americal Chemical Society
DOI: 10.1021/acsomega.9b02269

Total Description of Intrinsic Amphiphile Aggregation: Calorimetry Study and Molecular Probing

Autores: Roberto Fernandez-Alvarez, Žiga Medoš, Zdeněk Tošner, Alexander Zhigunov, Mariusz Uchman, Stefan Hervø-Hansen, Mikael Lund, Marija Bešter-Rogač, Pavel Matějíček
Publicado en: Langmuir, Edición 34/47, 2018, Página(s) 14448-14457, ISSN 0743-7463
Editor: American Chemical Society
DOI: 10.1021/acs.langmuir.8b03462

Conformational Stability Study of a Therapeutic Peptide Plectasin Using Molecular Dynamics Simulations in Combination with NMR

Autores: Sowmya Indrakumar, Matja Zalar, Christin Pohl, Allan Nørgaard, Werner Streicher, Pernille Harris, Alexander P. Golovanov, Günther H.J. Peters
Publicado en: The Journal of Physical Chemistry B, Edición 123/23, 2019, Página(s) 4867-4877, ISSN 1520-6106
Editor: American Chemical Society
DOI: 10.1021/acs.jpcb.9b02370

Studies of the oligomerisation mechanism of a cystatin-based engineered protein scaffold

Autores: Matja Zalar, Sowmya Indrakumar, Colin W. Levy, Richard B. Tunnicliffe, Günther H. J. Peters, Alexander P. Golovanov
Publicado en: Scientific Reports, Edición 9/1, 2019, ISSN 2045-2322
Editor: Nature Publishing Group
DOI: 10.1038/s41598-019-45565-6

Novel non-linear curve fitting to resolve protein unfolding transitions in intrinsic fluorescence differential scanning fluorimetry

Autores: Dillen Augustijn, Sujata Mahapatra, Werner Streicher, Hristo Svilenov, Alina Kulakova, Christin Pohl, Åsmund Rinnan
Publicado en: European Journal of Pharmaceutics and Biopharmaceutics, Edición 142, 2019, Página(s) 506-517, ISSN 0939-6411
Editor: Elsevier BV
DOI: 10.1016/j.ejpb.2019.06.001

Interaction of a Macrocycle with an Aggregation-Prone Region of a Monoclonal Antibody

Autores: Marcello Martinez Morales, Matja Zalar, Silvia Sonzini, Alexander P. Golovanov, Christopher F. van der Walle, Jeremy P. Derrick
Publicado en: Molecular Pharmaceutics, Edición 16/7, 2019, Página(s) 3100-3108, ISSN 1543-8384
Editor: American Chemical Society
DOI: 10.1021/acs.molpharmaceut.9b00338

The ReFOLD assay for protein formulation studies and prediction of protein aggregation during long-term storage

Autores: Hristo Svilenov, Gerhard Winter
Publicado en: European Journal of Pharmaceutics and Biopharmaceutics, Edición 137, 2019, Página(s) 131-139, ISSN 0939-6411
Editor: Elsevier BV
DOI: 10.1016/j.ejpb.2019.02.018

Improved Physical Stability of an Antibody–Drug Conjugate Using Host–Guest Chemistry

Autores: Silvia Sonzini, Maria Laura Greco, Thais Cailleau, Lauren Adams, Luke Masterson, Balakumar Vijayakrishnan, Conor Barry, Phillip Howard, Peter Ravn, Christopher F. van der Walle
Publicado en: Bioconjugate Chemistry, 2019, ISSN 1043-1802
Editor: American Chemical Society
DOI: 10.1021/acs.bioconjchem.9b00809

Rapid sample-saving biophysical characterisation and long-term storage stability of liquid interferon alpha2a formulations: Is there a correlation?

Autores: Hristo Svilenov, Gerhard Winter
Publicado en: International Journal of Pharmaceutics, Edición 562, 2019, Página(s) 42-50, ISSN 0378-5173
Editor: Elsevier BV
DOI: 10.1016/j.ijpharm.2019.03.025

Coupling Multi-Angle Light Scattering to Reverse-Phase Ultra-High-Pressure Chromatography (RP-UPLC-MALS) for the characterization monoclonal antibodies

Autores: Lorenzo Gentiluomo, Vanessa Schneider, Dierk Roessner, Wolfgang Frieß
Publicado en: Scientific Reports, Edición 9/1, 2019, ISSN 2045-2322
Editor: Nature Publishing Group
DOI: 10.1038/s41598-019-51233-6

Exploring Chemical Space for New Substances to Stabilize a Therapeutic Monoclonal Antibody

Autores: Andreas Tosstorff, Tim Menzen, Gerhard Winter
Publicado en: Journal of Pharmaceutical Sciences, Edición 109/1, 2020, Página(s) 301-307, ISSN 0022-3549
Editor: John Wiley & Sons Inc.
DOI: 10.1016/j.xphs.2019.10.057

Small angle X-ray scattering and molecular dynamic simulations provide molecular insight for stability of recombinant human transferrin

Autores: Alina Kulakova, Sowmya Indrakumar, Pernille Sønderby, Lorenzo Gentiluomo, Werner Streicher, Dierk Roessner, Wolfgang Frieß, Günther H.J. Peters, Pernille Harris
Publicado en: Journal of Structural Biology: X, Edición 4, 2020, Página(s) 100017, ISSN 2590-1524
Editor: Elsevier
DOI: 10.1016/j.yjsbx.2019.100017

Advancing Therapeutic Protein Discovery and Development through Comprehensive Computational and Biophysical Characterization

Autores: Lorenzo Gentiluomo, Hristo L. Svilenov, Dillen Augustijn, Inas El Bialy, Maria Laura Greco, Alina Kulakova, Sowmya Indrakumar, Sujata Mahapatra, Marcello Martinez Morales, Christin Pohl, Aisling Roche, Andreas Tosstorff, Robin Curtis, Jeremy P. Derrick, Allan Nørgaard, Tarik A. Khan, Günther H. J. Peters, Alain Pluen, Åsmund Rinnan, Werner W. Streicher, Christopher F. van der Walle, Shahid Uddi
Publicado en: Molecular Pharmaceutics, 2020, ISSN 1543-8384
Editor: American Chemical Society
DOI: 10.1021/acs.molpharmaceut.9b00852

Models for Antibody Behavior in Hydrophobic Interaction Chromatography and in Self-Association

Autores: Max Hebditch, Aisling Roche, Robin A. Curtis, Jim Warwicker
Publicado en: Journal of Pharmaceutical Sciences, Edición 108/4, 2019, Página(s) 1434-1441, ISSN 0022-3549
Editor: John Wiley & Sons Inc.
DOI: 10.1016/j.xphs.2018.11.035

Characterization of Native Reversible Self-Association of a Monoclonal Antibody Mediated by Fab-Fab Interaction

Autores: Lorenzo Gentiluomo, Dierk Roessner, Werner Streicher, Sujata Mahapatra, Pernille Harris, Wolfgang Frieß
Publicado en: Journal of Pharmaceutical Sciences, Edición 109/1, 2020, Página(s) 443-451, ISSN 0022-3549
Editor: John Wiley & Sons Inc.
DOI: 10.1016/j.xphs.2019.09.021

Application of interpretable artificial neural networks to early monoclonal antibodies development

Autores: Lorenzo Gentiluomo, Dierk Roessner, Dillen Augustijn, Hristo Svilenov, Alina Kulakova, Sujata Mahapatra, Gerhard Winter, Werner Streicher, Åsmund Rinnan, Günther H.J. Peters, Pernille Harris, Wolfgang Frieß
Publicado en: European Journal of Pharmaceutics and Biopharmaceutics, Edición 141, 2019, Página(s) 81-89, ISSN 0939-6411
Editor: Elsevier BV
DOI: 10.1016/j.ejpb.2019.05.017

Orthogonal Techniques to Study the Effect of pH, Sucrose, and Arginine Salts on Monoclonal Antibody Physical Stability and Aggregation During Long-Term Storage

Autores: Hristo L. Svilenov, Alina Kulakova, Matja Zalar, Alexander P. Golovanov, Pernille Harris, Gerhard Winter
Publicado en: Journal of Pharmaceutical Sciences, Edición 109/1, 2020, Página(s) 584-594, ISSN 0022-3549
Editor: John Wiley & Sons Inc.
DOI: 10.1016/j.xphs.2019.10.065

Structure-based discovery of a new protein-aggregation breaking excipient

Autores: Andreas Tosstorff, Hristo Svilenov, Günther H.J. Peters, Pernille Harris, Gerhard Winter
Publicado en: European Journal of Pharmaceutics and Biopharmaceutics, Edición 144, 2019, Página(s) 207-216, ISSN 0939-6411
Editor: Elsevier BV
DOI: 10.1016/j.ejpb.2019.09.010

Determination of Protein–Protein Interactions in a Mixture of Two Monoclonal Antibodies

Autores: Priyanka Singh, Aisling Roche, Christopher F. van der Walle, Shahid Uddin, Jiali Du, Jim Warwicker, Alain Pluen, Robin Curtis
Publicado en: Molecular Pharmaceutics, Edición 16/12, 2019, Página(s) 4775-4786, ISSN 1543-8384
Editor: American Chemical Society
DOI: 10.1021/acs.molpharmaceut.9b00430

Modulated_Scanning_Fluorimetry_Can_Quickly_Assess_Thermal_Protein_Unfolding_Reversibility_in_Microvolume_Samples

Autores: Hristo Svilenov, Tim Menzen, Klaus Richter, Gerhard Winter
Publicado en: Molecular Pharmaceutics, 2020, Página(s) 2638-2647, ISSN 1543-8392
Editor: American Chemical Association
DOI: 10.1021/acs.molpharmaceut.0c00330

Non-peer reviewed articles (1)

PIPPI – Protein-excipient Interactions and Protein-Protein Interactions in formulation – ERC

Autores: Pernille Harris
Publicado en: Impact, Edición 2017/8, 2017, Página(s) 75-77, ISSN 2398-7073
Editor: Science Impact Ltd
DOI: 10.21820/23987073.2017.8.75

Other (1)

Structural-stability studies on recombinant human transferrin

Autores: A. Kulakova, S. Indrakumar, P. Sønderby, L. Gentiluomo, W. Streicher, D. Roessner, W. Frieß, G. H.J. Peters, P. Harris
Publicado en: bioRxiv, 2019
Editor: Cold Spring Harbor Laborator
DOI: 10.1101/742957