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Protein-excipient Interactions and Protein-Protein Interactions in formulation

Deliverables

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

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.

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

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Publications

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

Author(s): Matja Zalar, Hristo Svilenov, Alexander Golovanov
Published in: European Journal of Pharmaceutics and Biopharmaceutics, 2020, Page(s) 127-136, ISSN 0939-6411
Publisher: Elsevier BV
DOI: 10.1016/j.ejpb.2020.04.002

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

Author(s): Sujata Mahapatra, Marco Polimeni, Lorenzo Gentiluomo , Dierk Roessner , Wolfgang Frieß , Günther H J Peters , Werner W Streicher , Mikael Lund , Pernille Harris
Published in: Molecular Pharmaceutics, 2022, ISSN 1543-8384
Publisher: American Chemical Society
DOI: 10.1021/acs.molpharmaceut.1c00627

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

Author(s): Lorenzo Gentiluomo; Dierk Roessner, Wolfgan Frieß
Published in: International Journal of Pharmaceutics, 2020, ISSN 0378-5173
Publisher: Elsevier BV
DOI: 10.1016/j.ijpharm.2020.119039

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

Author(s): Roche, A., Gentiluomo, L., Sibanda, N., Roessner, D., Friess, W., Trainoff, S. P., & Curtis, R.
Published in: Journal of Colloid and Interface Science, 2022, ISSN 0021-9797
Publisher: 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

Author(s): Hristo Svilenov, Uroš Markoja, Gerhard Winter
Published in: European Journal of Pharmaceutics and Biopharmaceutics, 125, 2018, Page(s) 106-113, ISSN 0939-6411
Publisher: 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

Author(s): Hristo Svilenov, Lorenzo Gentiluomo, Wolfgang Friess, Dierk Roessner, Gerhard Winter
Published in: Journal of Pharmaceutical Sciences, 107/12, 2018, Page(s) 3007-3013, ISSN 0022-3549
Publisher: 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

Author(s): Matja Zalar, Alexander P. Golovanov
Published in: ACS Omega, 4/19, 2019, Page(s) 18248-18256, ISSN 2470-1343
Publisher: Americal Chemical Society
DOI: 10.1021/acsomega.9b02269

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

Author(s): Roberto Fernandez-Alvarez, Žiga Medoš, Zdeněk Tošner, Alexander Zhigunov, Mariusz Uchman, Stefan Hervø-Hansen, Mikael Lund, Marija Bešter-Rogač, Pavel Matějíček
Published in: Langmuir, 34/47, 2018, Page(s) 14448-14457, ISSN 0743-7463
Publisher: 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

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

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

Author(s): Matja Zalar, Sowmya Indrakumar, Colin W. Levy, Richard B. Tunnicliffe, Günther H. J. Peters, Alexander P. Golovanov
Published in: Scientific Reports, 9/1, 2019, ISSN 2045-2322
Publisher: 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

Author(s): Dillen Augustijn, Sujata Mahapatra, Werner Streicher, Hristo Svilenov, Alina Kulakova, Christin Pohl, Åsmund Rinnan
Published in: European Journal of Pharmaceutics and Biopharmaceutics, 142, 2019, Page(s) 506-517, ISSN 0939-6411
Publisher: Elsevier BV
DOI: 10.1016/j.ejpb.2019.06.001

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

Author(s): Marcello Martinez Morales, Matja Zalar, Silvia Sonzini, Alexander P. Golovanov, Christopher F. van der Walle, Jeremy P. Derrick
Published in: Molecular Pharmaceutics, 16/7, 2019, Page(s) 3100-3108, ISSN 1543-8384
Publisher: 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

Author(s): Hristo Svilenov, Gerhard Winter
Published in: European Journal of Pharmaceutics and Biopharmaceutics, 137, 2019, Page(s) 131-139, ISSN 0939-6411
Publisher: Elsevier BV
DOI: 10.1016/j.ejpb.2019.02.018

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

Author(s): Silvia Sonzini, Maria Laura Greco, Thais Cailleau, Lauren Adams, Luke Masterson, Balakumar Vijayakrishnan, Conor Barry, Phillip Howard, Peter Ravn, Christopher F. van der Walle
Published in: Bioconjugate Chemistry, 2019, ISSN 1043-1802
Publisher: 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?

Author(s): Hristo Svilenov, Gerhard Winter
Published in: International Journal of Pharmaceutics, 562, 2019, Page(s) 42-50, ISSN 0378-5173
Publisher: 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

Author(s): Lorenzo Gentiluomo, Vanessa Schneider, Dierk Roessner, Wolfgang Frieß
Published in: Scientific Reports, 9/1, 2019, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-019-51233-6

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

Author(s): Andreas Tosstorff, Tim Menzen, Gerhard Winter
Published in: Journal of Pharmaceutical Sciences, 109/1, 2020, Page(s) 301-307, ISSN 0022-3549
Publisher: 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

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

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

Author(s): 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
Published in: Molecular Pharmaceutics, 2020, ISSN 1543-8384
Publisher: American Chemical Society
DOI: 10.1021/acs.molpharmaceut.9b00852

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

Author(s): Max Hebditch, Aisling Roche, Robin A. Curtis, Jim Warwicker
Published in: Journal of Pharmaceutical Sciences, 108/4, 2019, Page(s) 1434-1441, ISSN 0022-3549
Publisher: 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

Author(s): Lorenzo Gentiluomo, Dierk Roessner, Werner Streicher, Sujata Mahapatra, Pernille Harris, Wolfgang Frieß
Published in: Journal of Pharmaceutical Sciences, 109/1, 2020, Page(s) 443-451, ISSN 0022-3549
Publisher: John Wiley & Sons Inc.
DOI: 10.1016/j.xphs.2019.09.021

Application of interpretable artificial neural networks to early monoclonal antibodies development

Author(s): 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
Published in: European Journal of Pharmaceutics and Biopharmaceutics, 141, 2019, Page(s) 81-89, ISSN 0939-6411
Publisher: 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

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

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

Author(s): Andreas Tosstorff, Hristo Svilenov, Günther H.J. Peters, Pernille Harris, Gerhard Winter
Published in: European Journal of Pharmaceutics and Biopharmaceutics, 144, 2019, Page(s) 207-216, ISSN 0939-6411
Publisher: Elsevier BV
DOI: 10.1016/j.ejpb.2019.09.010

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

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

Modulated_Scanning_Fluorimetry_Can_Quickly_Assess_Thermal_Protein_Unfolding_Reversibility_in_Microvolume_Samples

Author(s): Hristo Svilenov, Tim Menzen, Klaus Richter, Gerhard Winter
Published in: Molecular Pharmaceutics, 2020, Page(s) 2638-2647, ISSN 1543-8392
Publisher: American Chemical Association
DOI: 10.1021/acs.molpharmaceut.0c00330

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

Author(s): Pernille Harris
Published in: Impact, 2017/8, 2017, Page(s) 75-77, ISSN 2398-7073
Publisher: Science Impact Ltd
DOI: 10.21820/23987073.2017.8.75

Structural-stability studies on recombinant human transferrin

Author(s): A. Kulakova, S. Indrakumar, P. Sønderby, L. Gentiluomo, W. Streicher, D. Roessner, W. Frieß, G. H.J. Peters, P. Harris
Published in: bioRxiv, 2019
Publisher: Cold Spring Harbor Laborator
DOI: 10.1101/742957