Gemcitabine immunoassay
Inventors
Salamone, Salvatore J. • Courtney, Jodi Blake • Sard, Howard • Spedaliere, Christopher
Assignees
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Publication Number
US-8946392-B2
Publication Date
2015-02-03
Expiration Date
Abstract
The present invention comprises novel conjugates and immunogens derived from gemcitabine and unique antibodies generated by using gemcitabine linked immunogens, which conjugates immunogens and antibodies, are useful in immunoassays for the quantification and monitoring of gemcitabine in biological fluids.
Core Innovation
The invention relates to gemcitabine immunoassay technology using antibodies and gemcitabine-derived immunogens and conjugates. It provides antibodies that bind selectively to gemcitabine while minimizing substantially cross reactivity to 2',2'-difluoro-2'-deoxyuridine (dFdU) and tetrahydrouridine (THU). The antibody binding behavior is described in terms of cross-reactivity relative to gemcitabine, supporting competitive immunoassay quantification.
A central aspect is the design of gemcitabine immunogens and conjugates, including gemcitabine derivatives of formula IV conjugated to immunogenic carriers. The immunogenic carriers include structures such as polyamine polymers bearing reactive amino or thiol groups for conjugation, with the patent describing linker and spacer components X, Y, B and p.
The antibodies generated and screened in the described work are characterized in competitive ELISA format, including reported cross-reactivity results based on IC50 measurements. The document frames the approach as enabling accurate competitive immunoassay quantification in blood and plasma for therapeutic drug management, by reducing cross-reactivity toward inactive metabolite and preservative-related interferents.
Claims Coverage
The independent claim covers an antibody that binds selectively to gemcitabine with substantially no cross reactivity to dFdU and tetrahydrouridine. The claim set includes at least five refinements covering quantitative cross-reactivity limits, specified source species, monoclonal format, and derivation from defined immunogenic carrier/conjugate structures.
Selective gemcitabine binding without substantially cross reactivity
An antibody which binds selectively to gemcitabine and does not have any substantially cross reactivity to 2',2'-difluoro-2'-deoxyuridine and tetrahydrouridine.
Quantitative low cross-reactivity
An antibody having less than 20% cross-reactivity with 2',2'-difluoro-2'-deoxyuridine and tetrahydrouridine, determined by its reactivity with gemcitabine.
Tight cross-reactivity threshold below 10%
An antibody in which the antibody's cross reactivity is less than 10%.
Specified antibody source species
An antibody derived from mice, sheep, rabbits, or rats.
Monoclonal antibody format
The antibody is a monoclonal antibody.
Derived from defined immunogenic carrier/conjugate structure
The antibody is derived from an immunogenic carrier bearing a reactive amino or thiol group that is polymer conjugated to a compound defined by formula IV or a salt thereof, where B is defined as —CH2— or a specified acylamide-containing substituent, and X is a carrier-binding functional group, Y is an organic spacing group, and p is an integer from 0 to 1.
Overall, the claim set is directed to antibodies with selective gemcitabine binding and constrained cross-reactivity versus dFdU and tetrahydrouridine, with additional limitations covering quantified cross-reactivity thresholds, source species, monoclonal status, and specific immunogenic carrier/conjugate derivation based on formula IV linker and spacer components.
Stated Advantages
Enables accurate competitive immunoassay quantification in blood and plasma for therapeutic drug management by minimizing cross-reactivity to dFdU and THU.
Documented Applications
Competitive immunoassay quantification in blood and plasma for therapeutic drug management.
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