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.

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: 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: 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.

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.

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.

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.

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.

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.

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.

Abstract: The present invention provides a compound of Formula (I): an enantiomer, diastereoisomer, atropisomer thereof, a mixture thereof, or a pharmaceutically acceptable salt thereof, that inhibits voltage-gated sodium channels, in particular NaV1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders, cough, and itch. Also provided are pharmaceutical compositions containing the compounds of the present invention. Also further provided is an atropi-selective preparation of said compounds of Formula (I), and intermediate thereof.

Abstract: Compounds of Formula I and Formula II, pharmaceutically acceptable salts 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: Figure I and Figure II where the definitions of the variables are provided herein.

Abstract: A drug delivery device includes a casing and a storage container with a dose delivery member, at least a portion of which extends through an opening in the casing. A guard is movable relative to the casing between extended and retracted positions. The guard surrounds the extended portion of the dose delivery member in the extended position, and exposes the extended portion in the retracted position. An interference arrangement is included for providing selected threshold of resistance to movement of the guard from the extended position to the retracted position during insertion of the dose delivery member into body tissue. The arrangement has first and second members engaging one another to retain the guard in the extended position. The first or second member can move if the selected threshold of resistance is exceeded to allow the members to slide and allow the guard to move into the retracted position.

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.

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.

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.

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 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.