Branched Linker for Protein Drug Conjugates

Patent metadata

Field	Value
Publication number	US-2018258136-A1
Application number	US-201815933800-A
Country	US
Kind code	A1
Filing date	Mar 23, 2018
Priority date	Feb 25, 2011
Publication date	Sep 13, 2018
Grant date	—

Abstract

The present invention relates to method for connecting a protein and a drug to a protein drug conjugate, wherein the drug is linked to the protein through a specific branched linker, said branched linker comprises a peptide chain and is derived from o-hydroxy p-amino benzylic alcohol, wherein the peptide chain is connected to the phenyl ring via the p-amino group, the drug is connected to the phenyl ring via the benzylic alcohol moiety, and the protein is connected to the phenyl ring via the o-hydroxy group; further to a process for the preparation of said protein-drug-conjugates via various intermediates, to the pharmaceutical use of such protein drug conjugates, such as methods of controlling the growth of undesirable cells, to pharmaceutical compositions comprising such protein drug conjugates, and to intermediates of the preparation of the protein drug conjugates.

First claim

1 - 17 . (canceled)

18 . A compound of formula (VI):

wherein
AA 1 represents one alpha amino acid structure in which carboxyl terminal is amide bonded to NH;
(3) denotes the alpha amino group of said alpha amino acid structure,
R1 and R2 are identical or different and independently from each other selected from the group consisting of hydrogen and PGN;
PGN is a protecting group selected from the group consisting of Boc, Fmoc and benzyloxycarbonyl; and
AA 1 is selected from the group consisting of alanine, valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, lysine, lysine with side chain amino group protected with acetyl or formyl groups, arginine, histidine, ornithine, omithine with side chain amino group protected with acetyl or formyl groups, and citrulline.

19 . A compound of formula (VI) according to claim 18 , wherein the compound of formula (VI) is selected from the group consisting of a compound of formula (6-3), a compound of formula (6-4), a compound of formula (6b-3), and a compound of formula (6b-4), as follows:

Assignees

• Lonza Ag
• Lonza Guangzhou Nansha Ltd

Inventors

• Ducry Laurent
• Stump Bernhard
• Wong Heilam
• She Jin
• Allway Gayle

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/64

  Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title

• A61K47/6809

  Antibiotics, e.g. antitumor antibiotics anthracyclins, adriamycin, doxorubicin or daunomycin · CPC title

• A61K47/65

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title

• A61K47/60 Primary

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title