Fibrillation resistant proteins
US8343914B2 · kind B2 · utility
Assignee
Inventor
Key dates
| Filing date | Jan 8, 2007 |
| Grant date | Jan 1, 2013 |
| Priority date | — |
| Expiry date | Jan 13, 2029 |
Classification
- Technology area (CPC A)Human Necessities
- CPC primaryA61K38/00
- WIPO fieldPharmaceuticals
- WIPO sectorChemistry
Abstract
Protection of proteins against fibrillation may be afforded by introduction of certain histidine substitutions into the protein, such that a pair of histidines are present with sufficient spacing as to allow the histidines to coordinate with zinc. In the case of insulin, introduction of histidine residue substitutions at residues A4 and A8 together or a histidine residue substitution at residue B1, provides increased resistance to fibrillation while maintaining at least a majority of the activity of the insulin analogue. Introduction of a histidine residue substitution at residue A8 restores at least a portion of fibrillation resistance that may have been harmed by substitutions present on the B-chain such as those present in fast-acting insulins. Proteins protected by such histidine substitutions may be used to provide a pharmaceutical composition. A method of treating a patient includes administering a physiologically effective amount of the pharmaceutical composition to the patient.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.