Abstract: The present disclosure provides compositions and methods relating to antigen binding proteins, in particular, antibodies and bispecific antibodies which specifically bind to mesothelin. The disclosure provides nucleic acids encoding such antigen binding proteins and antibodies and methods of making and using such antibodies, including methods of treating and preventing cancer or other hypoproliferative disorders and related disorders by administering such antigen binding proteins and antibodies to a subject in need of such treatment.
Type:
Grant
Filed:
September 6, 2018
Date of Patent:
February 16, 2021
Assignee:
AMGEN INC.
Inventors:
William Christian Fanslow, III, Carl Kozlosky, Jean Marie Gudas
Abstract: Provided herein are compounds that are useful intermediates that may used to synthesize myeloid cell leukemia 1 protein (Mcl-1) inhibitors. Also provided are Mcl-1 inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.
Abstract: The present invention provides antibodies and immunologically functional fragments thereof that specifically bind DKK1 polypeptides. Methods for preparing such antibodies or fragments thereof as well as physiologically acceptable compositions containing the antibodies or fragments are also provided. Use of the antibodies and fragments to treat various diseases are also disclosed.
Type:
Application
Filed:
September 9, 2020
Publication date:
February 11, 2021
Applicant:
AMGEN INC.
Inventors:
William Gleason RICHARDS, Hsieng Sen LU, Hua Zhu KE, Chaoyang LI, Frederick W. JACOBSEN
Abstract: The disclosed methods are directed to preparing and detecting polypeptides using neutrophil elastase, such as human neutrophil elastase. The polypeptides are optionally denatured, reduced, and/or alkylated before being subjected to a first digestion. A second digestion comprises the use of neutrophil elastase, such as human neutrophil elastase. The prepared fragments are then analyzed chromatographically, electrophoretically, or spectrometrically, or a combination of these methods. The methods are especially useful for the preparation of therapeutic polypeptides for analysis, especially those that are not easily cleaved, such as some bi-specific T-cell engager (BiTEĀ®) molecules.
Type:
Application
Filed:
March 12, 2019
Publication date:
February 11, 2021
Applicant:
Amgen Inc.
Inventors:
Sabrina Amelle BENCHAAR, Andrew DYKSTRA
Abstract: The invention generally relates to methods for determining whether a peptide includes aspartate or isoaspartate. In certain aspects, methods of the invention involve binding an aspartate/isoaspartate residue in a peptide with a label to produce a labeled peptide. The labeled peptide is then ionized. The ionizing process causes the label to undergo rearrangement in a gas phase at a higher rate if the label is bound to the aspartate residue as compared to if the label is bound to the isoaspartate residue. The methods of the invention then involve performing a mass spectrometry analysis to detect the rearrangement of the label, thereby determining whether the peptide includes aspartate or isoaspartate.
Type:
Grant
Filed:
June 7, 2018
Date of Patent:
February 2, 2021
Assignees:
Purdue Research Foundation, AMGEN INC.
Inventors:
Stephen T. Ayrton, Robert Graham Cooks, Tawnya Flick, Da Ren
Abstract: Methods of treating metabolic diseases and disorders using a composition comprising an antigen binding protein specific for the GIPR polypeptide conjugated to a GLP-1 receptor agonist are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the composition comprises an antibody or functional fragment thereof comprising a cysteine at one or more conjugation site(s) wherein the GLP-1 receptor agonist is conjugated to the antibody or functional fragment thereof through the side-chain of the cysteine residue.
Type:
Grant
Filed:
January 16, 2018
Date of Patent:
February 2, 2021
Assignee:
Amgen Inc.
Inventors:
Yuan Cheng, Chawita Netirojjanakul, Jerry Ryan Holder, Bin Wu, James R. Falsey, Bradley J. Herberich, Kelvin Sham, Leslie P. Miranda, Shu-Chen Lu, Murielle M. Veniant-Ellison, Shanaka Stanislaus, Junming Yie, Jing Xu
Abstract: Methods of modulating the properties of a cell culture expressing a protein of interest are provided. In various embodiments the methods relate to the overexpression of proteins involved in the N-glycosylation pathway.
Abstract: Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: (I), (II) where the definitions of the variables are provided herein.
Type:
Grant
Filed:
November 3, 2017
Date of Patent:
February 2, 2021
Assignee:
AMGEN INC.
Inventors:
Ning Chen, Yinhong Chen, Mikkel V. Debenedetto, Paul John Dransfield, James S. Harvey, Julie Anne Heath, Jonathan Houze, Aarif Yusuf Khakoo, Su-Jen Lai, Zhihua Ma, Nobuko Nishimura, Vatee Pattaropong, Gayathri Swaminath, Wen-Chen Yeh, Charles Kreiman
Abstract: The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of the invention, a method for manufacturing compounds of the invention and therapeutic uses thereof.
Type:
Grant
Filed:
March 27, 2020
Date of Patent:
January 26, 2021
Assignees:
AMGEN INC., CYTOKINETICS, INC.
Inventors:
Luke Ashcraft, Alessandro Boezio, John Butler, Aroop Chandra, Chihyuan Chuang, Scott E. Collibee, Mikkel V. Debenedetto, Vincent DiMassa, Russell Graceffa, Justin Malinowski, David Moebius, Bradley Paul Morgan, Joshua Payette, Antonio Romero, David St. Jean, Jr., Richard Vargas, John Yeoman, Hanmo Zhang, Alan Cheng, Felix Gonzalez Lopez De Turiso, Michael Garrett Johnson
Abstract: The present invention concerns methods comprising co-administration of pegfilgrastim and romiplostim for treatment of diseases and conditions characterized by low neutrophil levels (neutropenia) and/or low platelet levels (thrombocytopenia). The present invention concerns an enhanced effect on neutrophil levels and on platelet levels resulting from co-administration of pegfilgrastim and romiplostim. The present invention further concerns a method of treating a patient who has been exposed to radiation, which comprises administering romiplostim at a dose of about 1 to about 10 ?g/kg. The invention further concerns such methods wherein a single dose of romiplostim is administered to the patient and wherein romiplostim is administered about 24 hours or less after the radiation exposure. The invention further concerns treatment with romiplostim and pegfilgrastim for radiation exposure.
Type:
Application
Filed:
March 11, 2019
Publication date:
January 21, 2021
Applicant:
Amgen Inc.
Inventors:
Ganesh BALASUBRAMANIAN, Deborah I. BUNIN, Polly Y. CHANG, Simon AUTHIER, Sameer V. DOSHI, James BAKKE, Janet GAHAGEN, Karen WONG, Mark FIELDEN
Abstract: The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.
Type:
Application
Filed:
July 1, 2020
Publication date:
January 21, 2021
Applicant:
AMGEN INC.
Inventors:
Neeraj Jagdish AGRAWAL, Irwin CHEN, Su CHONG, Bryna FUCHSLOCHER, Kevin GRAHAM, Agnes Eva HAMBURGER, Mark Leo MICHAELS, Christopher MOHR, Derek E. PIPER, Kenneth William WALKER, Zhulun WANG, Cen XU
Abstract: The present invention relates to methods of upregulating the high mannose glycoform content of a recombinant protein during a mammalian cell culture by manipulating the mannose to total hexose ratio in the cell culture media formulation.
Abstract: Constructs comprising GDF15, and mutants thereof are provided. In various embodiments the constructs comprising GDF15, and mutants thereof, can be of use in the treatment or ameliorating a metabolic disorder. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy.
Type:
Grant
Filed:
November 29, 2017
Date of Patent:
January 19, 2021
Assignee:
AMGEN INC.
Inventors:
Yumei Xiong, Yi Zhang, Jackie Z. Sheng, Agnes Eva Hamburger, Murielle M. Veniant-Ellison, Grant Shimamoto, Xiaoshan Min, Zhulun Wang, Jie Tang, Gunasekaran Kannan, Marissa Mock, Kenneth William Walker
Abstract: The present disclosure provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A, R1, R2, R2?, R3, R4, and R5 of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A? plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.
Type:
Grant
Filed:
December 13, 2017
Date of Patent:
January 12, 2021
Assignee:
Amgen Inc.
Inventors:
Jennifer R. Allen, Albert Amegadzie, Matthew P. Bourbeau, Jian J. Chen, Michael J. Frohn, Paul E. Harrington, Jonathan D. Low, Vu V. Ma, Thomas T. Nguyen, Alexander Pickrell, Corey Reeves
Abstract: The present disclosure provides a class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables R1, R1?, R2, R2?, R3, R4, R5, R6, R7, and b of Formula I are defined herein. This disclosure also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A? plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, and other central nervous system conditions.
Type:
Grant
Filed:
December 13, 2017
Date of Patent:
January 12, 2021
Assignee:
Amgen Inc.
Inventors:
Matthew P. Bourbeau, Paul E. Harrington, Qingyian Liu
Abstract: The present invention provides combination therapy that includes an MDM2 inhibitor and one or more additional pharmaceutically active agents, particularly for the treatment of cancers. The invention also relates to pharmaceutical compositions that contain an MDM2 inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers.
Type:
Grant
Filed:
December 21, 2018
Date of Patent:
January 5, 2021
Assignee:
AMGEN INC.
Inventors:
Sean Caenepeel, Jude Canon, Paul Hughes, Jonathan D. Oliner, Richard J. Rickles, Anne Y. Saiki
Abstract: The invention provides a method for culturing mammalian cells. The method provides greater control over cell growth to achieve high product titer cell cultures.
Type:
Application
Filed:
September 11, 2020
Publication date:
December 31, 2020
Applicant:
Amgen Inc.
Inventors:
Brian D. FOLLSTAD, Rebecca E. McCOY, Arvia E. MORRIS
Abstract: The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.
Type:
Grant
Filed:
August 25, 2017
Date of Patent:
December 22, 2020
Assignee:
AMGEN INC.
Inventors:
Michael Ollmann, Yang Li, Jun Zhang, Oliver Homann, Leslie P. Miranda, Justin K. Murray, Bin Wu, Oh Kyu Yoon, John Gordon Allen, Chawita Netirojjanakul