Polypeptide derivatives
AssigneeNovartis AG
InventorsRainer Albert, Wilfried Bauer, Janos Pless
Life of this patent
Estimating the term…
Abstract
A biologically active peptide selected from growth factors, peptide hormones, interferons and cytokines and analogues and derivatives thereof, and bearing at least one chelating group linked to an amino group of said peptide, the chelating group being capable of complexing a detectable element and such amino group having no significant binding affinity to target receptors, are complexed with a detectable element and are useful as a pharmaceutical, e.g. a radiopharmaceutical for in vivo imaging of target tissues or for therapy.
Claims17
A peptide in free base or salt form consisting of EGF having a chelating group capable of complexing with a detectable element covalently linked either directly or indirectly by means of a divalent bridging group to the N-terminal amino group or a lysine N.sup..epsilon. -amino group of said EGF, the chelating group being selected from the group consisting of
- Diethylenetriamine pentaacetic acid;
- N-hydroxyethyl-N,N',N'-ethylenediamine triacetic acid;
- Ethylene glycol-O,O'-bis(2-aminoethyl)-N,N,N',N'-tetraacetic acid;
- N,N'-bis(hydroxybenzyl)ethylenediamine-N,N'-diacetic acid;
- Triethylenetetramine hexaacetic acid;
- 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid;
- 1,4,8,11-tetraazacyclotetradecane-N,N',N",N'"-tetraacetic acid;
- N'-p-isothiocyanatobenzyl-diethylenetriamine-N,N,N",N"-tetraacetic acid;
- N'-p-isothiocyanatophenethyl-diethylenetriamine-N,N,N", N'"-tetraacetic acid;
- N-{2-bis(carboxymethyl)amino!ethyl}-N'-{2-bis(carboxymethyl)amino!-2-(p-i sothiocyanatobenzyl)-ethyl}-glycine;
- a compound of formula Ia, Ib or Ic, ##STR22## wherein R.sub.10 is --CH.sub.2 COOH, and
- R.sub.11 is --(CH.sub.2).sub.1-6 --NCS, p-isothiocyanatobenzyl, or p-isothiocyanatophenethyl;
- and a compound of formula v ##STR23## wherein each of
- R.sub.24, R.sub.25, R.sub.26, R.sub.27, R.sub.28 and R.sub.29 is independently hydrogen or C.sub.1-4 alkyl,
- m' is 2 or 3, and
- X.sub.2 is p-isothiocyanatobenzyl or p-isothiocyanatophenethyl.
A chelate in free base or pharmaceutically acceptable acid addition salt form consisting of an EGF peptide having a chelating group complexed with a detectable element covalently linked either directly or indirectly by means of a divalent bddging group to the N-terminal amino group or a lysine N.sup..epsilon. -amino group of said EGF peptide, the chelating group being selected from the group consisting of
- Diethylenetriaminepentaacetic acid;
- N-hydroxyethyl-N,N',N'-ethylenediaminetriacetic acid;
- Ethylene glycol-)O,O'-bis(2-aminoethyl)-N,N,N',N'-tetraacetic acid;
- N,N'-bis(hydroxybenzyl)ethylenediamine-N,N'-diacetic acid;
- Triethylenetetraminehexaacetic acid;
- 1,4,7,10-tetraazacyclododecane-N,N',N",N'"-tetraacetic acid;
- 1,4,8,11-tetraazacyclotetradecane-N,N',N",N'"-tetraacetic acid;
- N'-p-isothiocyanatobenzyl-diethylenetriamine-N,N,N",N"-tetraacetic acid;
- N'-p-isothiocyanatophenethyl-diethylenetriamine-N,N',N",N'"-tetraacetic acid;
- N-{2-bis(carboxymethyl)amino!ethyl}-N'-{2-bis(carboxymethyl)amino!-2-(p-i sothiocyanatobenzyl)ethyl}-glysine;
- a compound of formula Ia, Ib or Ic ##STR26## wherein R.sub.10 is --CH.sub.2 COOH, and
- R.sub.11 is --(CH.sub.2).sub.1-6 --NCS, p-isothiocyanatobenzyl, or p-isothiocyanatophenethyl;
- and a compound of formula V ##STR27## wherein each of
- R.sub.24, R.sub.25, R.sub.26, R.sub.27, R.sub.28 and R.sub.29 is independently hydrogen or C.sub.1-4 alkyl,
- m' is 2 or 3, and
- X.sub.2 is p-isothiocyanatobenzyl or p-isothiocyanatophenethyl.
Dependencies are inferred from the claim text.