Method and device to detect therapeutic protein immunogenicity
First Claim
1. A time-temperature indicator device for monitoring a therapeutic protein drug;
- said indicator being associated with said drug throughout the majority of the drug'"'"'s storage life;
said indicator having at least one time-temperature indication parameter selected by;
monitoring chemical and structural changes in the therapeutic protein as a function of time and storage temperature;
determining which time and temperature conditions cause a certain percentage of said protein to undergo structural or chemical alterations;
said percentage being set at a predetermined immunological risk threshold wherein amounts above said threshold have an unacceptable risk of provoking an immunological reaction;
said structural alterations being selected from the group consisting of protein aggregation, denaturation, dimerization, oxidation, deamidation, disulfide exchange, proteolysis, peptide map change, creation of antigenic activity, creation of antibody epitopes, or destruction of antibody epitopes;
Said immunological risk threshold being set at or below ten percent of the total quantity of said therapeutic protein.
0 Assignments
0 Petitions
Accused Products
Abstract
The present invention consists of a time-temperature indicator device that has at least one parameter set to warn when a therapeutic protein drug has had a thermal history associated with increased risk of unwanted immunological activity. The indicator device is designed to remain with the drug as the drug travels throughout different links of the cold chain. In a preferred embodiment, the indicator device remains associated with the therapeutic protein from the time of manufacture up until the final few minutes before the drug is used. In alternate forms of the invention, additional parameters, including motion, light, and turbidity may also be monitored. Novel methods for determining therapeutic protein time-temperature immunological risk parameters, and programming or adjusting the indicator device, are also disclosed.
24 Citations
19 Claims
-
1. A time-temperature indicator device for monitoring a therapeutic protein drug;
-
said indicator being associated with said drug throughout the majority of the drug'"'"'s storage life;
said indicator having at least one time-temperature indication parameter selected by;
monitoring chemical and structural changes in the therapeutic protein as a function of time and storage temperature;
determining which time and temperature conditions cause a certain percentage of said protein to undergo structural or chemical alterations;
said percentage being set at a predetermined immunological risk threshold wherein amounts above said threshold have an unacceptable risk of provoking an immunological reaction;
said structural alterations being selected from the group consisting of protein aggregation, denaturation, dimerization, oxidation, deamidation, disulfide exchange, proteolysis, peptide map change, creation of antigenic activity, creation of antibody epitopes, or destruction of antibody epitopes;
Said immunological risk threshold being set at or below ten percent of the total quantity of said therapeutic protein. - View Dependent Claims (2, 3, 4, 5, 6)
-
-
7. An electronic time-temperature indicator device for monitoring a non-vaccine therapeutic protein drug;
-
said indicator being associated with said drug throughout the majority of the drug'"'"'s storage life;
said indicator having at least one time-temperature indication parameter selected by;
monitoring chemical and structural changes in the therapeutic protein as a function of time and storage temperature;
determining which time and temperature conditions cause a certain percentage of said protein to undergo structural or chemical alterations;
said percentage being set at a predetermined immunological risk threshold wherein amounts above said threshold have an unacceptable risk of provoking an immunological reaction;
said structural alterations being selected from the group consisting of protein aggregation, denaturation, dimerization, oxidation, deamidation, disulfide exchange, proteolysis, peptide map change, creation of antigenic activity, creation of antibody epitopes, or destruction of antibody epitopes;
said immunological risk threshold being set at or below ten percent of the total quantity of said therapeutic protein;
said indicator producing an output signal when said time-temperature indication parameters exceeds a preset limit. - View Dependent Claims (8, 9, 10, 11, 12, 13)
-
-
14. :
- A method to determine the potential immunological risk of a therapeutic protein, said method comprising;
Constructing a pool of antibody or immune response genes representative of the genetic diversity of a target population;
Using said genetic pool to produce a panel of antibodies or immune response proteins directed against one or more representative samples of said therapeutic protein, Using said panel to determine which epitopes are expressed on various preparations of said therapeutic proteins under various storage conditions;
said storage conditions representing at least different combinations of time and temperature storage parameters;
and determining what combinations of time and temperature storage parameters are associated with the formation of epitopes representative of immunogenic risk. - View Dependent Claims (15, 16, 17, 18, 19)
- A method to determine the potential immunological risk of a therapeutic protein, said method comprising;
Specification