Seattle Genetics, Inc.

Neorx Corporation

Seagen Inc.

Damon L Meyer

Shan Jiang

Hui Li

Mary Wallace

Peter Senter

Svetlana Doronina

Scott C Jeffrey

Toni Beth Kline

Sudhakar Kasina

Robert Lyon

John Fay Valliere-Douglass

Michael Sun

Robert W Mallett

Kevin Beam

Bradley Hayes

The present invention provides a method for making uncapped cysteine protein preparations, including uncapped engineered cysteine antibody preparations. The methods include, inter alia, contacting a reducing agent with engineered cysteine antibody molecules, each of the antibody molecules having at least one capped engineered cysteine residue and at least one interchain disulfide bond and reacting the reducing agent with the antibody molecules under conditions sufficient to uncap engineered cysteine residues and form cap byproducts. The method also includes removing the cap byproduct during the reduction reaction. Substantially all of the interchain disulfide bonds present in the antibody molecules prior to reduction are retained following reduction. Antibody conjugates and methods for preparing antibody conjugates using uncapped antibody preparations are also described.

Selective reduction of proteins

The invention is based in part on the observation that a CHO cell oxidizing enzyme, particularly QSOX1, can survive a seemingly rigorous antibody purification process to reduce subsequent conjugation efficiency of the antibody to a drug. Whether the oxidizing enzyme survives the purification procedure depends on which purification techniques are employed which can vary from one antibody to another. With knowledge that contamination with a CHO cell oxidizing enzyme is a potential problem for subsequent conjugation, a suitable purification scheme can be devised for any antibody that eliminates or at least reduces CHO oxidizing enzyme(s) to an acceptable level.

Preparing antibodies from CHO cell cultures for conjugation

Disclosed are formulations, including both liquid and lyophilized formulations, comprising a benzodiazepine antibody-drug conjugate (ADC) and a cyclodextrin. Also disclosed are methods of purifying mixtures comprising benzodiazepine antibody-drug conjugates and process drug-related impurities.

Cyclodextrin and antibody-drug conjugate formulations

Disclosed are formulations, including both liquid and lyophilized formulations, comprising a benzodiazepine anti-body-drug conjugate (ADC) and a cyclodextrin. Also disclosed are methods of purifying mixtures comprising benzodiazepine anti-body-drug conjugates and process drug-related impurities.

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

Disclosed are methods of purifying mixtures comprising benzoidiazepine antibody-drug conjugates.

Activated carbon filtration for purification of benzodiazepine ADCs

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.

Monomethylvaline compounds having phenylalanine carboxy modifications at the C-terminus

A compound comprising a ligand portion which has binding affinity for an opioid receptor, and a therapeutically or diagnostically effective group selected from radionuclide chelating agents, fluorochromes, toxins, drugs, polyboron moieties, proteins, biological response modifiers, chemical moieties capable of binding to other molecules of interest, and radioisotopes selected from therapeutically effective alpha and beta emitters, and diagnostically effective gamma emitters. The compound may be used in a method of treating cancer, and in a method of imaging opioid receptors either inside or outside of the central nervous system.

Opioid receptor targeting

Methods, compounds, compositions and kits that relate to pretargeted delivery of diagnostic and therapeutic agents are disclosed.

Growing community of inventors

Bellevue, WA, United States of America

Damon L Meyer