Seattle Genetics, Inc.

University of Washington

Sutro Biopharma, Inc.

Novartis Vaccines & Diagnostics, Gmbh

Seagen Inc.

Toni Beth Kline

Svetlana Doronina

Peter Senter

Brian E Toki

Paul Polakis

Mark X Sliwkowski

Allen J Ebens

Keith Bruce Pfister

Allan S Wagman

Susan D Spencer

Simon C Ng

Niels H Andersen

Eric Harwood

Asha Yabannavar

Jason Bowman

Alice L Erwin

Khisimuzi E Mdluli

Ribhi Shawar

Svetlana O Doronina

Ryan Stafford

Gang Yin

Alice Yam

Xiaofan Li

Cristina Abrahams

Venita De Almeida

Scott C Jeffrey

Qun Yin

Damon L Meyer

Krishna Bajjuri

Nephi Stella

Samuel I Miller

Heather B Felise

Niels H Anderson

Peter D Senter

The present disclosure relates to antibody conjugates with binding specificity for folate receptor alpha (FOLR1) and its isoforms and homologs, and compositions comprising the antibody conjugates, including pharmaceutical compositions. Also provided are methods of producing the antibody conjugates and compositions as well as methods of using the antibody conjugates and compositions, such as in therapeutic and diagnostic methods.

Anti-folate receptor antibody conjugates, compositions comprising anti-folate receptor antibody conjugates, and methods of making and using anti-folate receptor antibody conjugates

The present disclosure relates to antibody conjugates with binding specificity for folate receptor alpha (FOLR1) and its isoforms and homologs, and compositions comprising the antibody conjugates, including pharmaceutical compositions. The variable light chains are those of trastuzumab. Also provided are methods of producing the antibody conjugates and compositions as well as methods of using the antibody conjugates and compositions, such as in therapeutic and diagnostic methods. The antibody conjugates comprise a non-natural amino acid at a site selected from the group consisting of HC-F404, HC-K121, HC-Y180, HC-F241, HC-221, LC-T22, LC-S7, LC-N152, LC-K42, LC-E161, LC-D170, HC-S136, HC-S25, HC-A40, HC-S119, HC-S190, HC-K222, HC-R19, HC-Y52, or HC-S70, according to the Kabat, Chothia, or EU numbering scheme.

Anti-folate receptor alpha antibody conjugated with hemiasterlins

Provided herein are hemiasterlin derivatives, conjugates thereof, compositions comprising the derivatives or conjugates thereof, methods of producing the derivatives and conjugates thereof, and methods of using the derivatives, conjugates, and compositions for the treatment of cell proliferation. The derivatives, conjugates, and compositions are useful in methods of treatment and prevention of cell proliferation and cancer, methods of detection of cell proliferation and cancer, and methods of diagnosis of cell proliferation and cancer. In an embodiment, the hemiasterlin derivatives are according to Formula 1000: or a pharmaceutically acceptable salt, solvate, or tautomer thereof, wherein Ar, L, W, W, W, SG, and R are as described herein.

Hemiasterlin derivatives for conjugation and therapy

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

Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) are provided having C-terminal phenylalanine residue side chain replacements or modifications which are provided alone or attached to ligands through various linkers. The related conjugates can target specific cell types to provide therapeutic benefit.

Monomethylvaline compounds having phenylalanine side-chain modification at the C-terminus

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

The disclosure provides methods of treating glioblastoma, methods of screening for compounds that treat glioblastoma, and pharmaceutical compositions useful the treatment of glioblastoma. 

Composition and methods for treating glioblastoma

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

Monomethylvaline compounds having phenylalanine side-chain replacements at the C-terminus

A method for inhibiting Gram-negative bacterial pathogenesis, a method of screening for compounds that inhibit type III secretion in Gram-negative bacteria, and compounds that inhibit type III secretion in Gram-negative bacteria.

5-substituted-2-imino-thiazolidinone compounds and their use as inhibitors of bacterial infection

Antibacterial compounds of formula I are provided:  As well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.

Antibacterial agents

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Seattle, WA, United States of America

Toni Beth Kline