Radio-pharmaceutical complexes
AssigneeAlgeta ASA
InventorsHanne Therese Bonge-Hanssen, Olav Benjamin Ryan
Life of this patent
Estimating the term…
Abstract
A tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand comprising four HOPO moieties and the ion of an alpha-emitting thorium radionuclide, where at least one of the four HOPO moieties is substituted at the N-position with a hydroxyalkyi solubilising group and wherein the tissue targeting moiety has binding affinity for the CD33 receptor. A corresponding pharmaceutical formulation and method and use in treatment, as well as methods of manufacture are provided.
Claims28
A tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand comprising four HOPO moieties and the ion of an alpha-emitting thorium radionuclide, where at least one of the four HOPO moieties is substituted at the N-position with a hydroxyalkyl solubilising group and wherein the tissue targeting moiety has binding affinity for the CD33 receptor.
The complex as claimed in any preceding claim wherein the N-substituents on each of the four HOPO groups are each independently chosen from HO—, HOCH2—, HOCH2CH2—, HO—CH2CH2CH2—, HO—CH(CH3)CH2—, HO—CH2CH2CH2CH2—, HO—CH(CH3)CH2CH2—, HO—CH(CH2CH3)CH2—, HO—C(CH3)2CH2—, HO—CH(CH3)CH(CH3)— and HOCH2CH(CH2CH3)—.
A complex as claimed in any preceding claim wherein the tissue targeting moiety is a monoclonal or polyclonal antibody, an antibody fragment (such as Fab, F(ab′)2, Fab′ or scFv), or a construct of such antibodies and/or fragments.
A complex as claimed in any preceding claim wherein the tissue targeting moiety comprises at least one peptide chain having at least 90% sequence similarity with one or both of the following sequences:
- Fragment variable VH domain:
- QVQLVQSGAEVKKPGSSVKVSCKASGYTFTDYNMHWVRQAPGQGLEWIGY
- IYPYNGGTGYNQKFKSKATITADESTNTAYMELSSLRSEDTAVYYCARGR
- PAMDYWGQGTLVTVSS
- Fragment variable VL domain:
- DIQMTQSPSSLSASVGDRVTITCRASESVDNYGISFMNWFQQKPGKAPKL
- LIYAASNQGSGVPSRFSGSGSGTDFTLTISSLQPDDFATYYCQQSKEVPW
- TFGQGTKVEIK
Use of a tissue targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand comprising four HOPO moieties and the ion of an alpha-emitting thorium radionuclide, where at least one of the four HOPO moieties is substituted at the N-position with a hydroxyalkyl solubilising group and wherein the tissue targeting moiety has binding affinity for the CD33 receptor, in the manufacture of a medicament for the treatment of hyperplastic or neoplastic disease.
A method of treatment of a human or non-human animal (particularly one in need thereof) comprising administration of at least one tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand comprising four HOPO moieties and the ion of an alpha-emitting thorium radionuclide, where at least one of the four HOPO moieties is substituted at the N-position with a hydroxyalkyl solubilising group wherein the tissue targeting moiety has binding affinity for the CD33 receptor.
A pharmaceutical composition comprising a tissue-targeting complex comprising a tissue targeting moiety, an octadentate hydroxypyridinone-containing ligand comprising four HOPO moieties and the ion of an alpha-emitting thorium radionuclide, where at least one of the four HOPO moieties is substituted at the N-position with a hydroxyalkyl solubilising group wherein the tissue targeting moiety has binding affinity for the CD33 receptor, together with at least one pharmaceutical carrier or excipient.
A method of formation of a tissue-targeting complex, said method comprising coupling a tissue targeting moiety to an octadentate hydroxypyridinone-containing ligand in aqueous solution, the complex comprising four HOPO moieties and the ion of an alpha-emitting thorium radionuclide, where at least one of the four HOPO moieties is substituted at the N-position with a hydroxyalkyl solubilising group and wherein the tissue targeting moiety has binding affinity for the CD33 receptor.
Dependencies are inferred from the claim text.