Bothell, WA, United States
Bothell, WA, United States

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


This disclosure provides optimized formulations for CD19 antibodies and antibody-drug conjugates (ADCs)


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.


This disclosure provides optimized formulations for CD19 antibodies and antibody-drug conjugates (ADCs)


Patent
Seattle Genetics | Date: 2017-01-20

This invention relates methods of using a non-fucosylated anti-CD40 antibody for treatment of cancer and chronic infectious diseases.


Patent
Seattle Genetics | Date: 2017-02-15

Methods of optimal dosing of CD19-antibody drug conjugates are disclosed.


Patent
Seattle Genetics | Date: 2016-12-28

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


Patent
Seattle Genetics and MEDIMMUNE Ltd | Date: 2017-02-01

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


Sievers E.L.,Seattle Genetics | Senter P.D.,Seattle Genetics
Annual Review of Medicine | Year: 2013

An antibody-drug conjugate (ADC) provides the possibility of selectively ablating cancer cells by combining the specificity of a monoclonal antibody (mAb) for a target antigen with the delivery of a highly potent cytotoxic agent. ADC target antigens are typically highly expressed on the surface of cancer cells compared to normal cells. The tumor target, the cytotoxic agent, and the manner in which the agent is attached to the antibody are key determinants of clinical activity and tolerability. Recently, several clinical trials have demonstrated that ADCs achieve higher clinical response rates than unconjugated mAbs targeting the same cell surface antigen. Brentuximab vedotin represents one such ADC that has recently been approved for the treatment of relapsed Hodgkin and systemic anaplastic large cell lymphomas-both characterized by high expression of the target antigen, CD30, on the surface of malignant cells. This review summarizes key characteristics of current, clinically active ADCs and highlights recent clinical data illustrating the benefit of antibody-targeted delivery of cytotoxic agents to cancer cells. Copyright © 2013 by Annual Reviews.


Outcomes in acute myeloid leukemia (AML) remain unsatisfactory, and novel treatments are urgently needed. One strategy explores antibodies and their drug conjugates, particularly those targeting CD33. Emerging data with gemtuzumab ozogamicin (GO) demonstrate target validity and activity in some patients with AML, but efficacy is limited by heterogeneous drug conjugation, linker instability, and a high incidence of multidrug resistance. We describe here the development of SGN-CD33A, a humanized anti-CD33 antibody with engineered cysteines conjugated to a highly potent, synthetic DNA cross-linking pyrrolobenzodiazepine dimer via a protease-cleavable linker. The use of engineered cysteine residues at the sites of drug linker attachment results in a drug loading of approximately 2 pyrrolobenzodiazepine dimers per antibody. In preclinical testing, SGN-CD33A is more potent than GO against a panel of AML cell lines and primary AML cells in vitro and in xenotransplantation studies in mice. Unlike GO, antileukemic activity is observed with SGN-CD33A in AML models with the multidrug-resistant phenotype. Mechanistic studies indicate that the cytotoxic effects of SGN-CD33A involve DNA damage with ensuing cell cycle arrest and apoptotic cell death. Together, these data suggest that SGN-CD33A has CD33-directed antitumor activity and support clinical testing of this novel therapeutic in patients with AML.

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