Seattle Genetics, Inc.

Seagen Inc.

Bristol-myers Company

Medimmune Limited

Bristol-myers Squibb Compnay

Agensys, Inc.

The Picower Institute for Medical Research

Oncogen

Spirogen Sarl

Oncogen, a Limited Partnership

Psma Development Company, LLC

Peter Senter

Svetlana Doronina

Brian E Toki

Toni Beth Kline

Scott C Jeffrey

Philip Wilson Howard

Patrick J Burke

Paul Polakis

Mark X Sliwkowski

Allen J Ebens

Dennis R Benjamin

Susan D Spencer

Svetlana O Doronina

John F Kadow

Mark George Saulnier

Stephen C Alley

Robert Lyon

Peter S Linsley

Hans Marquardt

Luke Masterson

Damon L Meyer

Arnaud Charles Tiberghien

Martha S Hayden

Vivian Trang

Timothy Bovee

Peter C Su

Aya Jakobovits

William C Olson

Karen Jane Meyrick Morrison

Robert Kendall Morrison

Takushi Kaneko

Richard J Bucala

Xiao-Chi Jia

Jean M Gudas

Paul J Maddon

Yousef Al-Abed

Dangshe Ma

Joseph P Brown

Zili An

Robert A Mitchell

Nathan O Siemers

Matthew R Levengood

Nicole Okeley

David E Kerr

Ruth Moser

Susan Yarnold

Vivekanada M Vrudhula

Noah Bindman

Divya Awasthi

Stephen Alley

Arnaud Tiberghien

Hydrophilic Linkers, Drug-Linker compounds, Drug-Ligand Conjugate compounds and Ligand-Linkers and methods of making and using the same are provided.

Hydrophilic antibody-drug conjugates

The invention relates to conjugates of biologically active compounds, wherein such a conjugate is comprised of a sequence of amino acids containing a tripeptide that confers selective cleavage by tumor tissue homogenate for release of free drug and/or improves biodistribution into the tumor tissue in comparison to normal tissue homogenate from the same species, wherein the normal tissue is the site of an adverse event associated with administration to a human subject in need thereof of a therapeutically effective amount of a comparator conjugate whose amino acid sequence is a dipeptide known to be selectively cleavable by Cathepsin B.

Selective drug release from internalized conjugates of biologically active compounds

The invention provides bivalent antibodies including two light and heavy chain pairs. The N-termini of one or both light and heavy chain pairs are linked via linkers comprising a protease cleavage site to coiled-coil forming peptides that associate to form a coiled coil reducing binding affinity of at least one light-heavy chain pair to a target.

Bivalent antibodies masked by coiled coils

The invention provides methods and compositions for the inhibition of fucosylation of proteins, including antibodies, in vivo by administration of a fucose analog.

Methods of inhibition of protein fucosylation in vivo using fucose analogs

Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.

Monomethylvaline compounds capable of conjugation to ligands

Provided are Conjugate comprising PBDs conjugated to a targeting agent and methods of using such PBDs.

Targeted pyrrolobenzodiazapine conjugates

Pyrrolobenzodiazepine dimers having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds.

Pyrrolobenzodiazepines used to treat proliferative diseases

Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) having a carboxylic acid equivalent at the C-terminal phenylalanine were prepared and attached to ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand-drug conjugates were active in vitro and in vivo in inhibiting cell proliferation and are represented by the general structure ofL-[(LU)-(D)]wherein L- is Ligand unit; LU is a Linker unit (LU); v is 1; p is an number ranging from about 1 to about 20; and D is a drug moiety having the formula: wherein the moiety &#x2014;N(R)Zis a phenylalanine bioisostere, wherein Zis &#x2014;CH(R)Zso that the phenylalanine bioisostere has the structure of Formula A: and wherein the substituents R-R, Xand Zare as defined.

Methods of using monomethylvaline compositions having phenylalanine carboxy modifications at the C-terminus

Drug Linker compounds and Drug Linker Ligand conjugates are provided that have auristatins linked via the C-terminus. The conjugates show efficacy without the need for a self-immolative group to release the drug.

Auristatin drug linker conjugates

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Seattle, WA, United States of America

Peter Senter