Naresh Chennamsetty - Cambridge MA, US Stefan Ewert - Allschwil, CH Bernard Helk - Riehen, CH Bernhardt Trout - Lexington MA, US Philipp Wechner - Schwaz, AT
An scFv peptide comprising a Vdomain and a Vdomain linked by an amino acid spacer is disclosed. The Vdomain comprises a sequence with at least 80% sequence identity to the sequence of SEQ ID NO. 64. The Vdomain comprises a sequence with at least 80% sequence identity to the sequence of SEQ ID NO. 66. The scFv peptide comprises an additional feature selected from (a) to (e) and combinations thereof. (a) A substitution or deletion of an amino acid in the Vdomain at a position corresponding to that selected from the group consisting of: I, H, N, Cand combinations thereof. (b) A substitution or deletion of an amino acid in the Vdomain at a position corresponding to that selected from the group consisting of: V, V, F, F, A, Nand combinations thereof. (c) The amino acid spacer comprises the sequence (GGGGS)wherein n is between 4 and 6. (d) The Vdomain further comprises an N-terminal pelB signal sequence comprising the sequence of SEQ ID NO. 68 or a sequence having at least 80% sequence identity thereto. (e) The Vdomain is located at the N-terminal end of the Vdomain. (f) The substitution of the cysteine residue in the Vdomain corresponding to position 28 with a serine residue.
Methods To Identify Macromolecule Binding And Aggregation Prone Regions In Proteins And Uses Therefor
Naresh Chennamsetty - Cambridge MA, US Bernhard Helk - Basel, CH Bernhardt Trout - Cambridge MA, US Veysel Kayser - Cambridge MA, US Vladimir Voynov - Cambridge MA, US
Assignee:
MASSACHUSETTS INSTITUTE OF TECHNOLOGY - Cambridge MA NOVARTIS AG - Basel
International Classification:
A61K 38/16 A61P 37/00 G06F 19/00 C07K 14/00
US Classification:
514 212, 530402, 702 19
Abstract:
The present invention provides methods and computational tools based, at least in part, on computer simulations that identify macromolecule binding regions and aggregation prone regions of a protein. Substitutions may then be made in these aggregation prone regions to engineer proteins with enhanced stability and/or a reduced propensity for aggregation. Similarly, substitutions may then be made in these macromolecule binding regions to engineer proteins with altered binding affinity for the macromolecule.
Naresh Chennamsetty - Cambridge MA, US Bernhard Helk - Basel, CH Veysel Kayser - Cambridge MA, US Bernhardt Trout - Cambridge MA, US Vladimir Voynov - Cambridge MA, US
Assignee:
MASSACHUSETTS INSTITUTE OF TECHNOLOGY - Cambridge MA NOVARTIS AG - Base;
The present disclosure relates to immunoglobulins with reduced aggregation and compositions, methods of generating such immunoglobulins with computational tools and methods of using such immunoglobulins particularly in the treatment and prevention of disease.
Compositions, Methods, And Systems Relating To Controlled Crystallization And/Or Nucleation Of Molecular Species
Bernhardt Levy Trout - Lexington MA, US Patrick S. Doyle - Boston MA, US Trevor Alan Hatton - Sudbury MA, US Allan Stuart Myerson - Boston MA, US Ying Diao - Palo Alto CA, US Matthew E. Helgeson - Somerville MA, US
Assignee:
Massachusetts Institute of Technology - Cambridge MA
International Classification:
A61K 9/14 C30B 19/12
US Classification:
424489, 117 64
Abstract:
The present invention generally relates to compositions, methods, and systems relating to controlled crystallization and/or nucleation of a molecular species. In some embodiments, the crystallization and/or nucleation of the molecular species may be controlled by tuning the surface chemistry and/or the morphology of a crystallization substrate. In some embodiments, the molecular species is a small organic molecule (e.g., pharmaceutically active agent).
Methods For Identification Of Sites For Igg Conjugation
The present disclosure relates to immunoglobulins and immunoglobulin conjugates with reduced oligomerization and efficient labeling and compositions, methods of generating such immunoglobulins and immunoglobulin conjugates and methods of using such immunoglobulin conjugates particularly in the treatment and prevention of disease.
Bernhardt Levy Trout - Lexington MA, US Trevor Alan Hatton - Sudbury MA, US Emily Chang - Edison NJ, US James MB Evans - Sudbury MA, US Salvatore Mascia - Boston MA, US Won Kim - Gyeonggi-Do, KR Ryan Richard Slaughter - Riverside CA, US Yi Du - Union Township NJ, US Himanshu Hemant Dhamankar - Cambridge MA, US Keith M. Forward - Somerville MA, US Gregory C. Rutledge - Newton MA, US Mao Wang - Belmont MA, US Allan Stuart Myerson - Boston MA, US Blair Kathryn Brettmann - Cambridge MA, US Nikhil Padhye - Cambridge MA, US Jung-Hoon Chun - Sudbury MA, US
Assignee:
Massachusetts Institute of Technology - Cambridge MA
International Classification:
A61K 9/70 B29C 59/16 B29C 39/00
US Classification:
156227, 264299, 264447
Abstract:
Layer processing for pharmaceuticals, and related systems, methods, and articles are generally described. In some embodiments, ingestible pharmaceutical products (e.g., tablets) can be formed by processing one or more layers containing a pharmaceutically active composition. For example, at least one layer containing a pharmaceutically active composition can be manipulated (e.g., folded, rolled, stacked, etc.) such that the average thickness of the product formed by the manipulation is at least about two times the average thickness of the portions of the layer(s) used to form the product. In some embodiments, after the layer is manipulated, it can be processed (e.g., cut, coated, etc.) to form a final product such as, for example, a tablet.
Methods And Systems Relating To The Selection Of Substrates Comprising Crystalline Templates For The Controlled Crystallization Of Molecular Species
The present invention generally relates to methods and systems relating to the selection of substrates comprising crystalline templates for the controlled crystallization of molecular species. In some embodiments, the methods and systems allow for the controlled crystallization of a molecular species in a selected polymorphic form. In some embodiments, the molecular species is a small organic molecule (e.g., pharmaceutically active agent).
Solution Additives For The Attenuation Of Protein Aggregation
In part, the present invention relates to a compound or polymer comprising a non-protein-binding moiety and at least one protein-binding group. The present invention relates to a method of screening compounds or polymers for the property of inhibiting protein aggregation in solution, a method of preparing a compound or polymer having the property of protein aggregation inhibition in solution, a method of classifying a compound or polymer as either inhibitory of protein aggregation in solution or not inhibitory of protein aggregation in solution, and to a method of determining the preferential binding coefficient, Γ, of an additive in a protein solution. The present invention also relates to a method of suppressing or preventing aggregation of a protein in solution, a method of decreasing the toxicological risk associated with administering a protein to a mammal in need thereof, and a method of facilitating native folding of a recombinant protein in solution.
Name / Title
Company / Classification
Phones & Addresses
Bernhardt Trout President
BERNANA, INC Business Services at Non-Commercial Site
Hedgeness
Raymond F Baddour, Scd, Professor of Chemical Engineering, Mit and Member of the Advisory Board
Massachusetts Institute of Technology (Mit)
Associate Professor Department of Chemical Engineering
Education:
University of California, Berkeley 1991 - 1996
Massachusetts Institute of Technology 1986 - 1990
Skills:
Chemical Engineering Formulation R&D Chemistry Crystallization Technology Transfer Nanotechnology Hplc Life Sciences Organic Chemistry Materials Science Science Spectroscopy Protein Chemistry Drug Delivery Characterization Uv/Vis Lifesciences Uv/Vis Spectroscopy Physical Chemistry Nmr
Languages:
French German Italian
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Speech 01 | Bernhardt L. Trout | Can't stop t...
"Continuous manufacturing: state of the art, challenges, and future pr...
Duration:
43m 56s
Why Future Scientists, Physicians and Enginee...
Dr Richard Harper, Dr Bernhardt Trout, Dr Hans Mark October 18, 2010.
Duration:
1h 6m 24s
Thermodynamics, Atoms, and Citizenship - A Le...
About the Lecture: This lecture features a discussion about the way in...
Duration:
1h 28m 14s
Leisurely Conversations with Rob Jackson - Fe...
Bernhardt L. Trout is the Raymond F. Baddour, ScD, (1949) Professor of...
Duration:
11m 2s
Bernhardt Trout on "Of the Education in Bacon...
A lecture at the Montesquieu Forum on November 16, 2016. Professor Tro...
Duration:
1h 27m 36s
Franz Schubert - Quintet in A Major, op. 1...
The 15th Annual Donald Bernhardt Memorial Chamber Music Concert Novemb...