Conjugation reagents
View Patent ↗The invention provides compound of the general formula: in which each X independently represents a polymer chain; n represents an integer greater than 1; Q represents a linker; Y represents an amide group; and Z represents either —CH.(CH 2 L) 2 or —C(CH 2 L)(═CH 2 ), in which each L independently represents a leaving group. The compounds are useful reagents for the conjugation of polymers to proteins, the resulting conjugates being novel and also forming part of the invention.
1. A compound having the general formula:
in which Q is:
wherein each X independently represents a polymer chain;
A is CO or CHOH; and
Pr represents a single protein or peptide bonded via two sulfur atoms derived from a disulfide bond in said protein or peptide.
2. A compound as claimed in claim 1 , in which Pr represents an IgG Fab fragment, INF-α, IFN-β, or consensus IFN.
3. A compound as claimed in claim 1 , in which each X represents a poly(alkylene glycol), polyvinylpyrrolidone, polyacrylate, polymethacrylate, polyoxazoline, polyvinylalcohol, polyacrylamide, polymethacrylamide, HPMA copolymer, polyester, polyacetal, poly(ortho ester), polycarbonate, poly(imino carbonate), polyamide, or polysaccharide.
4. A compound as claimed in claim 3 , in which each X represent poly(ethylene glycol).
5. A compound as claimed in claim 4 , in which each X independently represents polyethylene glycol of the formula CH 3 O—(CH 2 CH 2 O) m — in which m is the number of ethylene oxide units in X.
6. A compound as claimed in claim 1 , having the formula
in which each X independently represents a polymer chain and Pr represents a single protein or peptide bonded at two separate points.
7. A compound as claimed in claim 6 , in which each X represents a poly(alkylene glycol), polyvinylpyrrolidone, polyacrylate, polymethacrylate, polyoxazoline, polyvinylalcohol, polyacrylamide, polymethacrylamide, HPMA copolymer, polyester, polyacetal, poly(ortho ester), polycarbonate, poly(imino carbonate), polyamide, or polysaccaride.
8. A pharmaceutical composition comprising a compound as claimed in claim 1 , together with a pharmaceutically acceptable carrier.
9. A pharmaceutical composition as claimed in claim 8 , which contains a further active ingredient.
10. A compound as claimed in claim 7 , in which each X represent poly(ethylene glycol).
11. A compound as claimed in claim 10 , in which each X independently represents polyethylene glycol of the formula CH 3 O—(CH 2 CH 2 O) m — in which m is the number of ethylene oxide units in X.