Abstract: An antibody-drug conjugate (ADC) has a structure represented by Formula (I): a pharmaceutically acceptable salt thereof wherein Ab is an antibody without glycans (i.e., the protein portion an antibody); G1 and G2 are glycan moieties, which may be the same or different; Cn1 and Cn2 are conjugation moieties, which may be the same or different; L1 and L2 are linker moieties, which may be the same or different; D1 and D2; are drug units which may be the same or different; and x and y are independently an integer from 0 to 8, provided that x+y?0.
Abstract: The present invention provides transglutaminase-mediated antibody-drug conjugates with high anti-body-drug ratio (DAR) comprising 1) glutamine-containing tags, endogenous glutamines, and/or endogenous glutamines made reactive by antibody engineering or an engineered transglutaminase (e.g., with altered substrate specifity); and 2) amine donor agents comprising amine donor units, linkers, and agent moieties, wherein the DAR is at least about 5. The invention also provides methods of making and methods of using such higher drug loaded antibody-drug conjugates.
Type:
Grant
Filed:
April 21, 2015
Date of Patent:
March 14, 2023
Assignees:
RINAT NEUROSCIENCE CORP., PFIZER INC.
Inventors:
Pavel Strop, Katherine Anne Delaria, Magdalena Dorywalska, Davide Luciano Foletti, Russell George Dushin, David Louis Shelton, Arvind Rajpal
Abstract: The present disclosure relates to combination therapies for the treatment of pathological conditions, such as cancer. In particular, the present disclosure relates to combination therapies comprising treatment with an Antibody Drug Conjugate (ADC) and a secondary agent.
Type:
Grant
Filed:
April 20, 2018
Date of Patent:
March 7, 2023
Assignees:
ADC THERAPEUTICS SA, MEDIMMUNE LIMITED
Inventors:
Patricius Hendrikus Cornelis Van Berkel, Lisa Skelton, Francesca Zammarchi, Jay Marshall Feingold, Jens Wuerthner, John Hartley
Abstract: This disclosure provides reagents and methods of predicting the responsiveness of a patient to NaPi2b-targeted antibody-drug conjugates (e.g., NaPi2b-targeted antibody-polymer-drug conjugates).
Type:
Grant
Filed:
September 20, 2018
Date of Patent:
March 7, 2023
Assignee:
Mersana Therapeutics, Inc.
Inventors:
Rebecca Mosher, Laura L. Poling, Donald A. Bergstrom
Abstract: Provided is an antibody-drug conjugate (ADC) using one or more cysteine or derivatives thereof as linkers to couple one or more drugs at the limited binding sites of an antibody, making it possible to produce an ADC product with high drug payload, or to choose a drug with less toxicity, thereby obtaining an ADC product with wide therapeutic window. In addition, since a plurality of drugs may be coupled to one binding site, the ADC products obtained by the method of the present disclosure have better uniformity in the case of same DAR value. Moreover, the amount of antibody required for production may be greatly reduced, thereby lowering the cost. Compared with the antibody-drug conjugates coupled only one drug, the antibody-drug conjugates produced by the method of the present disclosure have the same inhibition or killing effect on tumor cells while using fewer drugs for coupling to the same site.
Type:
Grant
Filed:
October 23, 2019
Date of Patent:
March 7, 2023
Assignee:
MABPLEX INTERNATIONAL CO., LTD
Inventors:
Lele Li, Changjiang Huang, Youxiang Sun, Lina Liu
Abstract: The present invention concerns novel and improved antibody-conjugates for targeting CD30. The inventors found that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index.
Type:
Grant
Filed:
February 8, 2017
Date of Patent:
February 28, 2023
Assignee:
SYNAFFIX B.V.
Inventors:
Sander Sebastiaan Van Berkel, Jorge Merijn Mathieu Verkade, Maria Antonia Wijdeven, Ryan Heesbeen, Petrus Josephus Jacobus Maria Van De Sande, Remon Gvan Eel, Brian Maria Gerardus Janssen, Inge Catharina Josephina Hurkmans, Floris Louis Van Delft
Abstract: This invention provides novel 3-amino propanamide selective androgen receptor degrader (SARD) compounds, pharmaceutical compositions and uses thereof in treating prostate cancer, advanced prostate cancer, castration resistant prostate cancer, androgenic alopecia or other 5 hyperandrogenic dermal diseases, Kennedy's disease, amyotrophic lateral sclerosis (ALS), and uterine fibroids, and to methods for reducing the levels of androgen receptor-full length (AR-FL) including pathogenic or resistance mutations, AR-splice variants (AR-SV), and pathogenic polyglutamine (polyQ) polymorphisms of AR in a subject.
Type:
Grant
Filed:
January 29, 2020
Date of Patent:
February 28, 2023
Assignee:
University of Tennessee Research Foundation
Inventors:
Ramesh Narayanan, Duane D. Miller, Thamarai Ponnusamy, Dong-Jin Hwang, Charles B. Duke, Christopher C. Coss, Amanda Jones, James T. Dalton
Abstract: The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6?-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a target-binding moiety; and (c) optionally a linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate.
Type:
Grant
Filed:
March 2, 2017
Date of Patent:
February 28, 2023
Assignee:
Heidelberg Pharma Research GmbH
Inventors:
Christian Lutz, Jan Anderl, Christoph Müller, Werner Simon, Susanne Werner-Simon, Torsten Hechler, Michael Kulke
Abstract: The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell.
Type:
Grant
Filed:
December 17, 2020
Date of Patent:
February 28, 2023
Assignee:
MacroGenics, Inc.
Inventors:
Deryk T. Loo, Ling Huang, Leslie S. Johnson, Thomas Son, Juniper A. Scribner, Ezio Bonvini
Abstract: The present invention relates to antibodies against the human 5T4 oncofoetal antigen and corresponding antibody-drug conjugates that are suitable for testing in clinical trials. The antibodies are cross-reactive for humans and cynomolgus monkeys and exhibit an affinity for human 5T4 antigen which is in the same order of magnitude as their affinity for cynomolgus monkey 5T4 antigen. The invention further relates to the use of the antibodies and corresponding ADCs in the treatment of solid tumours and haematological malignancies.
Type:
Grant
Filed:
April 13, 2021
Date of Patent:
February 21, 2023
Assignee:
Byondis B.V.
Inventors:
Miranda Maria Cornelia Van Der Lee, Gerardus Joseph Andreas Ariaans, Jan Schouten, Marion Blomenrohr, Patrick Gerhard Groothuis, Rudy Gerardus Elisabeth Coumans
Abstract: The invention relates generally to pyrrolobenzodiazepine monomer and dimer prodrugs having a glutathione-activated disulfide prodrug moiety, a DT-diaphorase-activated quinone prodrug moiety or a reactive oxygen species-activated aryl boronic acid or aryl boronic ester prodrug moiety. The invention further relates to pyrrolobenzodiazepine prodrug dimer-antibody conjugates.
Type:
Grant
Filed:
November 20, 2019
Date of Patent:
February 14, 2023
Assignee:
Genentech, Inc.
Inventors:
Peter Dragovich, Zhonghua Pei, Thomas Pillow, Jack Sadowsky, Vishal Verma, Donglu Zhang
Abstract: The present disclosure relates to benzoselenophene-based compounds, method of preparing the benzoselenophene-based compounds, pharmaceutical compositions and antibody-drug conjugates including the benzoselenophene-based compounds.
Type:
Grant
Filed:
January 29, 2021
Date of Patent:
February 14, 2023
Assignee:
AIMED BIO INC.
Inventors:
Dongyeol Lim, Min Cheol Kim, Amol Mhetre, Do-Hyun Nam
Abstract: The present invention provides means and methods for functionalizing a polypeptide of interest at its C-terminus with an amino acid derivative.
Type:
Grant
Filed:
April 27, 2017
Date of Patent:
February 7, 2023
Assignees:
Forschungsverbund Berlin e.V., Ludwig-Mavimilians-Universität München
Inventors:
Christian Hackenberger, Dominik Schumacher, Jonas Helma-Smets, Heinrich Leonhardt
Abstract: The invention provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD117+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure.
Type:
Grant
Filed:
November 17, 2020
Date of Patent:
February 7, 2023
Assignee:
Magenta Therapeutics, Inc.
Inventors:
Bradley R. Pearse, Anthony Boitano, Rahul Palchaudhuri, Sean McDonough, Rajiv Panwar, Jonathan Philip Belk, Matthew Duncan Smith
Abstract: Sulfonamide-containing linkage systems for release of payload compounds from an attached targeting moiety in drug conjugates. The conjugates have the formula of [(P)-(L)]m-(T), wherein (P) is a payload compound, (L) is a linker, (T) is a targeting moiety and m is an integer from 1- to 10. Also provided are pharmaceutical compositions comprising such conjugates and there use in treating cancer.
Type:
Grant
Filed:
December 29, 2014
Date of Patent:
January 24, 2023
Inventors:
Geoffrey C. Winters, Alexander L. Mandel, Elyse Marie Josée Bourque, James R. Rich, Tom Han Hsiao Hsieh
Abstract: The subject matter described herein is directed to methods of preparing certain antibody-drug conjugates (ADCs) wherein the antibody is linked to the drug through a linker, wherein the drug contains a heteroaryl group having a secondary nitrogen, and the linker is attached to the drug via the secondary nitrogen. The resulting conjugates are useful in treating various diseases and conditions.
Abstract: The invention relates to compounds of general structure (1): Q-(L1)n-(L2)o-(L3)p-(L4)q-D (1), wherein Q is a click probe; D is a cytotoxin containing an enediyne moiety; L1, L2, L3 and L4 are each individually linkers that together link Q to D; n, o, p and q are each individually 0 or 1, provided that n+o+p+q=1, 2, 3 or 4, wherein D comprises a functional moiety (21): wherein R12?C1-3-alkyl, the wavy line indicates the connection to the remainder of the cytotoxin, and wherein D is conjugated to (L4)q by replacing the amine H atom, and to conjugates obtainable by reacting the compound according to the invention with a protein comprising a click probe F capable of reacting with click probe Q in a click reaction. The invention further relates to a bioconjugate according to general structure (2): Pr-[(L6)-Z-(L1)n-(L2)o-(L3)p-(L4)q-D]xx (2), wherein Z is a connecting group that is formed in a click reaction, L6 is a linker that links Z to Pr and Pr is a (glyco)protein.
Type:
Grant
Filed:
June 5, 2020
Date of Patent:
January 10, 2023
Assignee:
SYNAHIX B.V.
Inventors:
Jorge Merijn Mathieu Verkade, Jorin Hoogenboom, Maria Antonia Van Berkel, Floris Louis Van Delft
Abstract: Provided herein are poly-1-hydroxymethylethylene hydroxymethyl formal (PHF)-based drug delivery systems. Also disclosed are methods of making antibody-drug conjugates and methods of treatment using these conjugates.
Abstract: The addition of a selective, fast-acting, short half-life CDK 4/6 inhibitor in a very specific dosage regimen to the combination of chemotherapy with a checkpoint inhibitor provides superior results in the treatment of a tumor or cancer. The unexpected discovery is that the short pulsatile specifically-timed administration of a selective, fast-acting, short half-life CDK 4/6 inhibitor during administration of the chemotherapy portion of the triple combination therapy has a profound effect on the immune cells in the cancer microenvironment.
Type:
Grant
Filed:
June 5, 2019
Date of Patent:
December 20, 2022
Assignee:
G1 Therapeutics, Inc.
Inventors:
Jessica A. Sorrentino, Anne Y. Lai, Jay C. Strum, Patrick Joseph Roberts