Abstract: Provided herein are methods of processing a polypeptide or protein for analysis, e.g., peptide mapping analysis by mass spectrometry. In exemplary embodiments, the method comprises incubating a digested sample at a mildly acidic pH and/or in the presence of a chaotrope, wherein the digested sample is produced by digesting a polypeptide with a protease to produce a digested sample comprising at least two peptides. In exemplary embodiments, the method comprises digesting the polypeptide with a protease which cleaves C-terminal to tryptophan to produce a digested sample comprising at least two peptides. In exemplary embodiments, the method comprises digesting the polypeptide with trypsin at an enzyme:substrate (E:S) weight ratio of about 1:1 to about 1:15 to produce a digested sample comprising at least two peptides. In exemplary aspects, the digested sample comprises at least one or two peptides each comprising a tyrosine at the C-terminus.
Type:
Application
Filed:
September 17, 2021
Publication date:
November 2, 2023
Applicant:
AMGEN INC.
Inventors:
Gang XIAO, Pavel BONDARENKO, Liuqing SHI, Thomas M. DILLON, Da REN, Margaret Speed RICCI, Weidong CUI, John Joseph HARRAHY, Jake PAWLOWSKI, Andrew DYKSTRA, Dylan RIGGS
Abstract: An apparatus for nondestructive detection of transparent or reflective objects in a vessel includes an imager configured to acquire data that represent light reflected from spatial locations in the vessel as a function of time, a memory operably coupled to the imager and configured to store the data, and a processor operably coupled to the memory and configured to detect the objects based on the data by (i) identifying a respective maximum amount of reflected light, over time, for each location in the spatial locations based on the data representing light reflected from the spatial locations as a function of time, and (ii) determining a presence or absence of the objects in the vessel based on the number of spatial locations whose respective maximum amount of reflected light, over time, exceeds a predetermined value.
Type:
Grant
Filed:
October 12, 2022
Date of Patent:
October 31, 2023
Assignee:
AMGEN INC.
Inventors:
Graham F. Milne, Erwin Freund, Ryan L. Smith
Abstract: Systems and methods used to control tangential flow filtration are provided, including control systems and methods for use with connected systems with upstream processing units, such as chromatography processing units, in fluid communication with a tangential flow filtration processing unit. Also included are control systems and methods for performing continuous concentration using single-pass tangential flow filtration with permeate flow control.
Type:
Grant
Filed:
June 29, 2021
Date of Patent:
October 17, 2023
Assignee:
AMGEN INC.
Inventors:
Eva Gefroh, Randolph W. Schweickart, Krista Petty, Gregory Frank, Christine Salstrom Terpsma, Arthur C. Hewig, III, Joseph Edward Shultz
Abstract: The present invention relates to severe acute respiratory syndrome coronavirus 2 (“SARS-CoV2”) immunogens useful for the generation of therapeutic antibodies and vaccine development. Such therapeutic antibodies include human antibodies and antigen-binding portions thereof that specifically bind to human SARS-CoV2 S protein, and that function to neutralize SARS-CoV2. The present invention also relates to methods of generating antibodies and antigen-binding portions thereof that specifically bind to human SARS-CoV2 S protein.
Type:
Application
Filed:
July 22, 2021
Publication date:
October 12, 2023
Applicant:
AMGEN INC.
Inventors:
Fernando GARCES, Zhulun WANG, Timothy RILEY
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 antibodies, the driving of the HC/LC pairing in the Fab region represents one of the most difficult challenges yet in the field of multispecific engineering. Described here is the discovery of a new placement for a non-canonical disulfide bond and as such the generation of an asymmetric cysteine interface between two Fabs present in the same molecule which will further enable the production of multispecifics.
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:
February 15, 2022
Date of Patent:
October 10, 2023
Assignees:
AMGEN INC., CYTOKINETICS, INC.
Inventors:
Luke Ashcraft, Alessandro Boezio, John Butler, Aroop Chandra, Chihyuan Chuang, Scott E. Collibee, Mikkel Debenedetto, Vincent Dimassa, Russell Graceffa, Justin Malinowski, David Moebius, Bradley P. 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 relates to monoclonal antibodies that specifically bind to chemically-modified nucleic acid molecules, including pan-specific antibodies that bind to chemically-modified nucleic acid molecules independent of nucleotide sequence. The invention also relates to methods of generating monoclonal antibodies to chemically-modified nucleic acid molecules as well as methods of using such antibodies to detect nucleic acid molecules in biological samples. Various immunoassays incorporating the monoclonal antibodies of the invention are also disclosed.
Type:
Application
Filed:
March 22, 2021
Publication date:
October 5, 2023
Applicant:
AMGEN INC.
Inventors:
Brian CHAN, Weihsu Claire CHEN, Sara HUMPHREYS, Agnieszka KIELCZEWSKA, Mai THAYER
Abstract: A syringe de-capper including a base having a lower surface and an upper surface opposite the lower surface. The syringe de-capper also includes a de-capping member extending from the upper surface of the base, the de-capping feature including a proximal end adjacent to the base, a distal end spaced away from the base. The de-capping feature includes opposing first and second lateral surfaces defining a proximal thickness at the proximal end and a distal thickness at the distal end, the distal thickness is smaller than the proximal thickness. Also, the syringe de-capper includes a slot disposed in the de-capping member, the slot extending from the distal end of the de-capping member toward the proximal end of the de-capping member and configured to slidably receive a distal end of a syringe for removing a cap therefrom.
Abstract: The present invention provides processes for making 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid as well as intermediates and processes for making the intermediates. Also provided are crystalline forms of the compound and the intermediates.
Type:
Application
Filed:
May 8, 2023
Publication date:
September 28, 2023
Applicant:
AMGEN INC.
Inventors:
Matthew BIO, Sebastien CAILLE, Brian COCHRAN, Yuanqing FANG, Brian M. FOX, Brian S. LUCAS, Lawrence R. MCGEE, Filisaty VOUNATSOS, Sean H. WIEDEMANN, Sarah WORTMAN
Abstract: A robotic inspection platform comprises a robotic arm, an imager, and a controller. The controller causes the robotic arm to retrieve, using its end effector, a container, and to manipulate the container such that the container is sequentially placed in a plurality of orientations while in view of the imager. The controller also causes the imager to capture images, with each of the images being captured while the container is in a respective one of the orientations. The controller also determines one or more attributes of the container, and/or a sample within the container, by analyzing the images using a pattern recognition model and, based on the attribute(s), determines whether the container and/or sample satisfies one or more criteria. If the container and/or sample fails to satisfy the criteria, the controller causes the robotic arm to place the container in an area (e.g., bin) reserved for rejected containers and/or samples.
Type:
Grant
Filed:
June 12, 2019
Date of Patent:
September 26, 2023
Assignee:
AMGEN INC.
Inventors:
Dmitry Fradkin, Thomas C. Pearson, Neelima Chavali, Erwin Freund
Abstract: A flexible plunger rod, drug delivery mechanism, drug delivery device, and methods are described that utilize the flexible plunger rod perform drug delivery operations. In embodiments, the flexible plunger rod can be stored in a curved configuration to thereby reduce a footprint of the drug delivery mechanism and device.
Type:
Grant
Filed:
January 17, 2019
Date of Patent:
September 26, 2023
Assignee:
AMGEN INC.
Inventors:
Sudeshna Dutta Ray, Scott R. Gibson, Daniel Eduardo Groszmann, Mehran Mojarrad, Robert Allen Dees, Jonathan Dean Johnson, Antonio S. Murcia
Abstract: Provided herein are KRAS G12C inhibitors, composition of the same, and methods of using the same. These inhibitors are useful for treating a number of disorders, including pancreatic, colorectal, and lung cancers.
Type:
Grant
Filed:
June 30, 2021
Date of Patent:
September 26, 2023
Assignee:
Amgen Inc.
Inventors:
John Gordon Allen, Jennifer Rebecca Allen, Ana Elena Minatti, Qiufen Xue, Ryan Paul Wurz, Christopher M. Tegley, Alexander J. Pickrell, Thomas T. Nguyen, Vu Van Ma, Patricia Lopez, Longbin Liu, David John Kopecky, Michael J. Frohn, Ning Chen, Jian Jeffrey Chen, Aaron C. Siegmund, Albert Amegadzie, Nuria A. Tamayo, Shon Booker, Clifford Goodman, Mary Walton, Nobuko Nishimura, Youngsook Shin, Jonathan D. Low, Victor J. Cee, Anthony B. Reed, Hui-Ling Wang, Brian Alan Lanman
Abstract: The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.
Type:
Application
Filed:
June 7, 2023
Publication date:
September 21, 2023
Applicant:
AMGEN INC.
Inventors:
Jeonghoon SUN, Lei-Ting Tony TAM, Mark Leo MICHAELS, Thomas Charles BOONE, Rohini R. DESHPANDE, Yue-Sheng LI, Huiquan HAN
Abstract: An injector may include a container having a wall with an interior surface defining a closed sterile reservoir filled with a drug product. The injector may also include a fluid delivery system comprising a sterile container needle that is in fluid communication with the container in a delivery state, but may or may not be in fluid communication with the container in a storage state. Further, the injector may include an actuator that is adapted to move the container needle from the storage state to the delivery state.
Abstract: A drug delivery device includes a housing defining a shell, a container, a drive mechanism, a needle assembly having first and second ends, a fluid flow connection, and a flow adapter, each of which is at least partially disposed within the housing. The container has first and second ends and an inner volume to contain a medicament to be administered to a user. The drive mechanism is adapted to exert a force to urge the medicament out the second end of the container. The fluid flow connection is coupled to the second end of the container and the first end of the needle assembly and is adapted to allow the medicament to flow from the container to the needle assembly. The flow adapter includes at least one protrusion for generating a minor head loss to the medicament flowing within the fluid flow connection and helps to reduce variations of injection rates due to variations in drug product viscosities.
Type:
Grant
Filed:
September 26, 2018
Date of Patent:
September 19, 2023
Assignee:
AMGEN INC.
Inventors:
Carl Conrath, Ali Nekouzadeh, Basel Hasan Taha
Abstract: The present invention provides commercial processes for preparing 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid as well as intermediates thereof.
Type:
Grant
Filed:
August 30, 2019
Date of Patent:
September 12, 2023
Assignee:
Amgen, Inc.
Inventors:
Sebastien Caille, Michael Corbett, Austin Smith
Abstract: Provided herein is a synthesis for omecamtiv mecarbil dihydrochloride hydrate and various intermediates.
Type:
Grant
Filed:
May 19, 2021
Date of Patent:
September 12, 2023
Assignee:
AMGEN INC.
Inventors:
Sebastien Caille, Kyle Quasdorf, Philipp C. Roosen, Xianqing Shi, Andrew Cosbie, Fang Wang, Zufan Wu, Archana Neergunda, Bin Peter Quan, Lianxiu Guan
Abstract: Provided herein are oral dosage forms comprising a) a core tablet comprising (i) a drug layer comprising apremilast and hypromellose acetate succinate (HPMCAS) in an amorphous solid dispersion; and (ii) a swellable layer comprising one or more swellable polymers; and b) a coating layer disposed on the core tablet, wherein the oral dosage form surface comprises at least one drug release orifice. The disclosed oral dosage forms provide once-a-day dosing of apremilast and are suitable for treating diseases or disorders ameliorated by inhibiting phosphodiesterase subtype IV (PDE4).
Type:
Grant
Filed:
August 31, 2022
Date of Patent:
September 12, 2023
Assignee:
AMGEN INC.
Inventors:
Nathan Bennette, William Brett Caldwell, Christi Hostetler, Kazden Ingram, Dory King, Kyle Kyburz, Alison Viles