Novel biocompatible linker for bioorthogonal applications

A method of making an antibody drug conjugate compound comprising an antibody covalently attached by a heterofunctional biolinker to a drug moiety, the compound having the formula:

• Ab-(H-(D)x)y
• or a pharmaceutically acceptable salt or solvate thereof;
• wherein Ab is an antibody or an antigen binding fragment thereof;
• wherein D is the drug moiety, wherein x is an integer from 1 to 20, y is an integer from 1 to 10,000, and wherein H is a heterofunctional biolinker according to the structure:
• wherein R′ is —ONH2 or absent;
• wherein A is a spacer;
• wherein Y is absent or an additional spacer;
• wherein Z is a carboxylic acid activator that provides a reactive ester site;
• and wherein p is an integer from 1 to 10,000;
• wherein the method comprises:
• reacting Ab with the heterofunctional biolinker to form an antibody-biolinker intermediate and reacting the antibody-biolinker intermediate with the drug moiety D to form the antibody drug conjugate;
• or
• reacting the drug moiety D with the heterofunctional biolinker to form a drug-biolinker intermediate, and then reacting the drug-biolinker intermediate with the antibody to form the antibody drug conjugate.

A heterofunctional biolinker composition comprising:

• a heterofunctional biolinker according to the structure:
• wherein R′ is —ONH2 or absent;
• wherein A is a spacer;
• wherein Y is absent or an additional spacer;
• and wherein Z is a carboxylic acid activator that provides a reactive ester site.