Branched linker for protein drug conjugates

Patent metadata

Field	Value
Publication number	US-10214560-B2
Application number	US-201815933800-A
Country	US
Kind code	B2
Filing date	Mar 23, 2018
Priority date	Feb 25, 2011
Publication date	Feb 26, 2019
Grant date	Feb 26, 2019

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

The invention claimed is:

1. A compound of formula (VI):

wherein
AA 1 represents one alpha amino acid residue in which a carboxyl terminal thereof forms the shown amide bond to NH;

the alpha amino acid residue, AA 1 , having an alpha amino group denoted by structure (3);
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 a residue of an amino aid 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, ornithine with side chain amino group protected with acetyl or formyl groups, and citrulline.

2. A compound selected from the group consisting of the following compounds:

wherein R1 and R2 are identical or different and independently from each other selected from the group consisting of hydrogen and PGN; and
PGN is a protecting group selected from the group consisting of Boc, Fmoc and benzyloxycarbonyl.

3. A compound according to claim 2 , wherein the compound 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

• C07K5/06043 Primary

  Leu-amino acid · CPC title

• A61K47/65

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

• A61K47/6809

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

• A61K47/6845

  the antibody targeting a cytokine, e.g. growth factors, VEGF, TNF, a lymphokine or an interferon · CPC title