Abstract: Provided herein are Camptothecin Conjugates, Camptothecin-Linker Compounds, Camptothecin Compounds, intermediates thereof, and method of preparing the same. Also provided herein are methods of treating cancer and autoimmune diseases with the Conjugates described herein.
Type:
Application
Filed:
April 5, 2019
Publication date:
November 14, 2019
Applicant:
SEATTLE GENETICS, INC.
Inventors:
Scott Jeffrey, Ryan Lyski, Maureen Ryan, Julia Cochran
Abstract: 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.
Abstract: 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.
Type:
Grant
Filed:
November 21, 2014
Date of Patent:
October 29, 2019
Assignee:
Seattle Genetics, Inc.
Inventors:
Kevin Beam, Damon Meyer, Bradley Hayes, Robert Lyon, John Valliere-Douglass
Abstract: Compounds and compositions are disclosed in which a NAMPT Drug Unit is linked to a targeting Ligand Unit through a Unit from which a NAMPT inhibitor compound or derivative thereof is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as cancer or an autoimmune disease, using the compounds and compositions of the invention are also disclosed.
Type:
Application
Filed:
October 18, 2017
Publication date:
October 17, 2019
Applicant:
SEATTLE GENETICS, INC.
Inventors:
Christopher Scott Neumann, Kathleen Olivas
Abstract: Disclosed are antibodies, including antibody drug conjugates, that specifically bind to NTB-A. Also disclosed are methods for using the anti-NTB-A antibodies to detect or modulate activity of (e.g., inhibit proliferation of) an NTB-A-expressing cell, as well as for diagnoses or treatment of diseases or disorders (e.g., cancer) associated with NTB-A-expressing cells. Further disclosed is a method of treating multiple myeloma using an anti-NTB-A antibody drug conjugate, which optionally includes an anti-NTB-A antibody as disclosed herein.
Abstract: The present invention provides a method for removing cysteine caps from antibodies and re-capping the antibodies with cysteine molecules. The methods include, inter alia, culturing a host cell comprising a protein molecule having at least one capped engineered cysteine residue, and contacting the cell culture with cystine. Dissolved oxygen levels can be manipulated in the cell culture to further enhance the removal and re-capping process.
Type:
Application
Filed:
November 6, 2017
Publication date:
September 26, 2019
Applicant:
SEATTLE GENETICS, INC.
Inventors:
Swapnil Bhargava, Cheng-Wei Aaron Chen, Matthew J. Leith
Abstract: 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.
Type:
Grant
Filed:
November 13, 2017
Date of Patent:
September 17, 2019
Assignee:
Seattle Genetics, Inc.
Inventors:
Svetlana O. Doronina, Peter D. Senter, Brian E. Toki, Toni Beth Kline
Abstract: The present invention provides variant target binding agents and methods relating to the use of such binding agents for the prophylaxis or treatment of cancers and immunological disorders. The variant target binding agent is conjugated to a therapeutic agent that exerts a cytotoxic, cytostatic, or immunomodulatory effect on target cells.
Abstract: This invention relates to treatment of cancer using a antibody drug conjugates that comprise PBD molecules in combination with FLT3 inhibitors.
Type:
Application
Filed:
June 8, 2017
Publication date:
August 29, 2019
Applicant:
SEATTLE GENETICS, INC.
Inventors:
William Arthur, Travis Biechele, Rory Rohm, Robert Thurman
Abstract: 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.
Type:
Grant
Filed:
April 30, 2018
Date of Patent:
August 27, 2019
Assignee:
Seattle Genetics, Inc.
Inventors:
Hui Li, Shan Jiang, Mary Wallace, Damon Meyer
Abstract: Methods for the treatment of CD30-expressing cancers are provided. The methods comprise administering to a subject in need thereof a weekly dose of from about 0.8 mg/kg to about 1.8 mg/kg of an antibody-drug conjugate compound having formula (I); or a pharmaceutically acceptable salt thereof; wherein: mAb is an anti-CD30 antibody unit, S is a sulfur atom of the antibody, A? is a Stretcher unit, and p is from about 3 to about 5.
Abstract: The application provides to methods for treating Hodgkin lymphoma or non Hodgkin lymphoma in a subject comprising—nivolumab, or pembrolizumab, two PD-1-blocking antibodies that inhibits tumor immune evasion in patients with relapsed or refractory Hodgkin's lymphoma in combination with—an anti CD30 antibody, such as brentuximab vedotin.
Type:
Application
Filed:
June 1, 2017
Publication date:
July 18, 2019
Applicants:
Bristol-Myers Squibb Company, Seattle Genetics, Inc.
Inventors:
Benedetto FARSACI, Neil JOSEPHSON, Anthony CAO, Ryan HEISER
Abstract: The invention provides methods and compositions for the inhibition of fucosylation of proteins, including antibodies, in vivo by administration of a fucose analog.
Type:
Grant
Filed:
October 21, 2016
Date of Patent:
July 9, 2019
Assignee:
Seattle Genetics, Inc.
Inventors:
Peter Senter, Stephen Alley, Dennis Benjamin
Abstract: The invention provides humanized antibodies that specifically bind to BCMA. The antibodies are useful for treatment and diagnoses of various cancers and immune disorders as well as detecting BCMA.
Type:
Application
Filed:
February 16, 2017
Publication date:
June 27, 2019
Applicant:
SEATTLE GENETICS, INC.
Inventors:
Django Sussman, Maureen Ryan, Lori Westendorf, Michael Feldhaus
Abstract: This invention relates to pyrrolobenzodiazepines (PBDs), in particular pyrrolobenzodiazepine dimers having a C2-C3 double bond and an aryl group at the C2 position in each monomer unit, and their inclusion in targeted conjugates. The differing substituent groups may offer advantages in the preparation and use of the compounds, particularly in their biological properties and the synthesis of conjugates, and the biological properties of these conjugates.
Abstract: A compound, or a pharmaceutically acceptable salt or solvate thereof, or conjugates thereof, selected from the group consisting of: wherein: (a) R10 is H, and R11 is OH, ORA, where RA is saturated C1-4 alkyl; (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R10 is H and R11 is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation, or both M together are a divalent pharmaceutically acceptable cation.
Abstract: Humanized antibodies, including masked antibodies that specifically bind to CD47 are provided. Methods for using anti-CD47 antibodies, including masked antibodies, to modulate activity of (e.g., inhibit proliferation of) a CD47-expressing cell, as well as for the treatment of one or more diseases or disorders (e.g., cancer) associated with CD47-expressing cells, are provided.
Type:
Application
Filed:
November 29, 2018
Publication date:
June 20, 2019
Applicant:
Seattle Genetics, Inc.
Inventors:
Shyra Gardai, Matthew Levengood, Vivian Trang, Lori Westendorf, Christopher Carosino, Che Leung-Law, Michael Feldhaus