Abstract: The invention relates to the treatment of bone disorders. In particular, the invention provides an approach involving administration of a high initial dose or doses of an sclerostin antibody to bring about a rapid increase in bone formation, followed by administration of lowers doses of the antibody to give a sustained lower rate of bone formation after the initial burst of bone formation. The invention also provides an approach involving decreasing dosing frequency with such an antibody to control bone formation. The approaches may be used in particular in those subjects who would benefit most from such an initial rapid burst of bone formation. Examples of such subjects include subjects who have been recently diagnosed or are experiencing severe symptoms of the disorder, as well as those subjects who have been administered a different treatment for the bone disorder which is proving ineffective. The approaches may be used in combination with each other.
Type:
Grant
Filed:
December 11, 2015
Date of Patent:
December 26, 2023
Assignees:
AMGEN INC., UCB PHARMA S.A.
Inventors:
Martyn Kim Robinson, Michael Stuart Ominsky, Xiaodong Li, Hua Zhu Ke
Abstract: The invention generally relates to electrophoretic mass spectrometry probes and systems and methods of uses thereof. In certain aspects, the invention provides a mass spectrometry probe having a hollow body with a distal tip, an electrically conductive hollow conduit, and an electrode. The electrically conductive hollow conduit may be operably coupled to a reservoir and a power source, and the electrically conductive hollow conduit may be configured to transport a liquid sample into the hollow body and polarize the liquid sample as it flows through the electrically conductive hollow conduit and into in the hollow body. The electrode and the electrically conductive hollow conduit are disposed within the hollow body (e.g., at different heights within the hollow body).
Abstract: The present invention relates to methods for treating or preventing atherosclerotic cardiovascular disease and other conditions associated with elevated levels of lipoprotein (a) (Lp(a)) using RNAi constructs targeting the LPA gene, which encodes apolipoprotein(a), a component of Lp(a) particles. In particular, the present invention relates to methods for reducing serum Lp(a) levels and reducing the risk of cardiovascular events in patients with elevated levels of Lp(a) comprising administering an LPA-targeted RNAi construct according to specific dosage regimens. Pharmaceutical compositions comprising the LPA-targeted RNAi constructs for use in the methods are also disclosed.
Abstract: Described herein are novel PRMT5 inhibitors of Formula I and pharmaceutically acceptable salts thereof, as well as the pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity and may have use in treating proliferative, metabolic and blood disorders.
Type:
Grant
Filed:
December 15, 2021
Date of Patent:
December 19, 2023
Assignee:
AMGEN INC.
Inventors:
Shon Booker, Matthew Paul Bourbeau, John R. Butler, Sanne Ormholt Schroder Glad, Brian Alan Lanman, Patricia Lopez, Francesco Manoni, Liping H. Pettus, Ian Sarvary, Nuria A. Tamayo, Mikkel Vestergaard, Nicholas Anthony Weires
Abstract: The present invention relates to methods for administering therapeutic doses of bispecific T-cell engaging molecules for the treatment of cancer in a patient. The administration methods reduce the incidence and/or severity of adverse events, such as cytokine release syndrome, and entail administering to a patient a priming dose of the bispecific T-cell engaging molecule by continuous intravenous infusion over a period of days followed by administration of a therapeutic dose of the bispecific T-cell engaging molecule by a bolus intravenous infusion at dosing intervals of at least a week.
Type:
Application
Filed:
September 15, 2021
Publication date:
December 14, 2023
Applicants:
AMGEN INC., AMGEN RESEARCH (MUNICH) GmbH
Inventors:
Adam B. MCCULLOUGH, Hosein KOUROS-MEHR, Peter KUFER, Mark SALVATI, Alexander C. MINELLA, Dirk NAGORSEN, Vijay UPRETI, Mukul MINOCHA, Brett HOUK
Abstract: The present invention is directed to methods of identifying and treating a human subject harboring a tumor or other disease comprising assessing HRG gene expression at an mRNA level in the human subject and administering a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at an mRNA level is assessed as high. The present invention is also directed to methods of identifying a human subject harboring a tumor or other disease comprising assessing HRG gene expression at an mRNA level in the human subject and withholding a treatment comprising an anti-HER3 antibody to the human subject whose HRG gene expression at an mRNA level is assessed as low.
Type:
Grant
Filed:
August 21, 2019
Date of Patent:
December 12, 2023
Assignees:
Daiichi Sankyo Co., Ltd., U3 Pharma GmbH, Amgen, Inc.
Inventors:
Matthias Schneider, Sabine Blum, Renee Jeanne Mendell-Harary, Daniel J. Freeman, Robert Allen Beckman, Xiaoping Jin
Abstract: Provided herein is a process comprising heating a composition comprising (P)-compound A or a salt thereof and a solvent to a temperature of 250° C. to 350° C. to form racemized compound A. Also provided is a process for isolating (P)-compound A from a composition comprising (P)-compound A and a tartrate, as described herein. Further provided herein, is a process for isolating a free acid of a tartrate or a hydrate thereof from a composition comprising a tartrate, (P)-compound A, and an organic solvent.
Type:
Application
Filed:
October 6, 2021
Publication date:
December 7, 2023
Applicant:
AMGEN INC.
Inventors:
Matthew G. BEAVER, Michael T. CORBETT, Yuanqing FANG, David D. FORD, Andrew T. PARSONS, Gabrielle ST-PIERRE, Reem TELMESANI
Abstract: Provided herein are IL-21 muteins and fusion proteins comprising the same for use in methods of treating a disease. Related conjugates, nucleic acids, vectors, host cells, pharmaceutical compositions and kits are also provided herein. Methods of making the IL-21 muteins and fusion proteins comprising the same, as well as methods of treating a subject in need thereof, are provided by the present disclosure. Further provided are PD-1 antigen-binding proteins.
Type:
Application
Filed:
December 1, 2022
Publication date:
November 30, 2023
Applicant:
AMGEN INC.
Inventors:
Khaled M.K.Z. ALI, Neeraj Jagdish AGRAWAL, Gunasekaran KANNAN, Ian FOLTZ, Zhulun WANG, Darren BATES, Marissa MOCK, Shunsuke TAKENAKA
Abstract: The present disclosure provides crystalline and amorphous forms of 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one, including several anhydrous, hydrate and solvate forms, and solid state forms thereof, pharmaceutical compositions, and methods of treating a disease mediated by KRAS G12C inhibition.
Type:
Grant
Filed:
December 16, 2021
Date of Patent:
November 28, 2023
Assignee:
Amgen Inc.
Inventors:
Mary Chaves, Patricia Lopez, Prashant Agarwal, Albert Amegadzie, Stephanie Azali, Roman Shimanovich, Ron C. Kelly, Darren Leonard Reid
Abstract: The invention provides a method for culturing mammalian cells. The method provides greater control over cell o growth to achieve high product titer cell cultures.
Type:
Grant
Filed:
March 8, 2023
Date of Patent:
November 28, 2023
Assignee:
AMGEN INC.
Inventors:
Brian D. Follstad, Rebecca E. McCoy, Arvia E. Morris
Abstract: A drug delivery sterilization system includes a housing defining at least one receptacle, a container assembly having first and second ends, an elongated portion extending therebetween, and an electron beam or x-ray generator disposed near the housing. The container assembly includes a container having a container contact region at the second end and an inner volume to contain a medicament, a seal member having a seal member contact region to form a sealing interface with the container contact region, and a coupling device adapted to sealingly couple the seal member to the container. The container assembly is at least partially disposed in the receptacle such that the second end of the container is exposed through the housing. The electron beam or x-ray generator generates a sterilizing beam that penetrates the seal member to sterilize the sealing interface.
Abstract: An on-body injector system includes a drug container assembly including a container, a seal member, and a sealing interface between the seal member and the container. The container includes an opening and the seal member at least partially covers the opening in the container. A fluid pathway assembly is coupled to the drug container assembly and includes a needle that is movable between a storage position, in which a point of the needle is spaced from the seal member, and a delivery position, in which the point of the needle is disposed at least partially through the seal member. A radiation generator is configured to emit rays of radiation to sterilize and/or disinfect the sealing interface. A barrier is disposed adjacent to the sealing interface and has an opening. At least a portion of the drug container assembly is positioned adjacent to the opening in the barrier.
Abstract: The ability to generate a single antibody-based construct that can recognize multiple targets simultaneously, is paramount to advance many therapeutics candidates to clinic. Often, this implies extensive protein design with vary degrees of success. In the case of multispecific antibody constructs, there are multiple modalities from which to choose and often multiple antigen binders as well. Described here is the discovery of new methods to optimally pair antigen binders with the proper format, including the selection of common light chains.
Type:
Application
Filed:
October 5, 2021
Publication date:
November 23, 2023
Applicant:
AMGEN INC.
Inventors:
Danyang GONG, Fernando GARCES, Zhulun WANG
Abstract: Techniques for computationally screening a set of single-chain variable fragments (scFvs). The techniques include determining, using a machine learning model, a thermostability indication for each scFv in a set of scFvs to obtain a plurality of thermostability indications, the set of scFvs comprising a first scFv having a first residue sequence, the determining comprising: obtaining, using information indicative of a 3D structure of the first scFv, interaction energy metrics for each of a plurality of pairs of residues in the first residue sequence; generating a first set of features using the interaction energy metrics; and providing the first set of features as input to the machine learning model to obtain a corresponding output indicative of a first thermostability for the first scFv; identifying a subset of the set of scFvs for subsequent production based on the plurality of thermostability indications; and producing at least one of the identified scFvs.
Abstract: Provided herein are processes for synthesizing Mcl-1 inhibitors and intermediates such as compound Y that can be used to prepare them where the variable R1 is as defined herein. In particular, provided herein are processes for synthesizing compound A1, and salts or solvates thereof, compound A2, and salts and solvates thereof, and compound A3 and salts and solvates thereof.
Type:
Application
Filed:
September 1, 2021
Publication date:
November 16, 2023
Applicant:
AMGEN INC.
Inventors:
MATTHEW G. BEAVER, JOSEPH MICHAEL DENNIS, PETER DORNAN, STEVEN MENNEN, JASON S. TEDROW, NEIL F. LANGILLE, CAROLYN MICHELLE COHEN, ANDREAS RENE ROTHELI
Abstract: A method for reducing the viscosity of a pharmaceutical formulation is provided that utilizes a viscosity-reducing concentration of an excipient selected from the group consisting of the n-acetyl arginine, n-acetyl lysine, n-acetyl proline and mixtures thereof in combination with a therapeutiv protein. A stable pharmaceutical formulation is also provided.
Type:
Grant
Filed:
October 22, 2015
Date of Patent:
November 14, 2023
Assignee:
AMGEN INC.
Inventors:
Christopher James Sloey, Sekhar Kanapuram
Abstract: Drug delivery devices and related methods of assembly are disclosed. The drug delivery device may include a housing, a container, a trigger member, and an interlock assembly. The trigger member may be selectively moveable relative to the housing to activate operation of at least one activatable element of the drug delivery device. The interlock assembly may include a lever mounted rotatably relative to the housing, a proximity sensor moveable between a first position extending beyond an exterior surface of the housing and a second position retracted toward the housing, and a rotational biasing member operably connected to the proximity sensor via the lever. When the proximity sensor is in the first position, the interlock assembly may limit movement of the trigger member relative to the housing. The rotational biasing member may be configured to exert a torque biasing the proximity sensor toward the first sensor position.
Type:
Grant
Filed:
October 1, 2018
Date of Patent:
November 14, 2023
Assignee:
AMGEN INC.
Inventors:
Ronald Forster, Gregory Gordon, Martin Hering, Matthew Wayne Janke, Andrew N. King, Wael Mismar
Abstract: Provided herein are processes for synthesizing mcl-1 inhibitors and intermediates such as compound Z that can be used to prepare them. In particular, provided herein are processes for synthesizing compound A1, and salts or solvates thereof and compound A2, and salts and solvates thereof.
Type:
Application
Filed:
April 28, 2021
Publication date:
November 9, 2023
Applicant:
AMGEN INC.
Inventors:
Neil Fred LANGILLE, Jason S. TEDROW, Jonathan Vinh-Phu TRUONG, Robert Ronald MILBURN, Alessandro ARENA
Abstract: The invention provides modified apelin polypeptides having increased stability, circulating half-life, and/or potency relative to the native apelin-13 polypeptide. Compositions comprising the modified apelin polypeptides and methods of using the polypeptides for treating cardiac disorders, such as heart failure, are also disclosed.
Type:
Grant
Filed:
January 28, 2021
Date of Patent:
November 7, 2023
Assignee:
AMGEN INC.
Inventors:
Jerry Ryan Holder, Gayathri Swaminath, Michael J. Frohn, Brian Alan Lanman, Anthony B. Reed, Leslie P. Miranda, John Gordon Allen, Alexander J. Pickrell, Aaron C. Siegmund, Lewis D. Pennington, Bryant Yang