Abstract: An insertion mechanism for a drug delivery device. The insertion mechanism includes a proximal end, a distal end, a first opening disposed near the proximal end, and a second opening disposed in the distal end. A needle or cannula assembly is disposed within a housing and has a base with a proximal surface and a distal surface and a needle or cannula coupled to the distal surface. A retraction member is disposed within the housing to maintain the needle or cannula assembly in a retracted position before movement to an extended position, the retraction member in contact with the base. Upon supplying pressure through the first opening until an amount of pressure P1 applies an application force to the proximal surface of the base that surpasses a resistive force of the retraction member, the needle or cannula assembly is moved from the retracted position to the extended position.

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.

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: VEGFR-Fc fusion protein formulations and methods of making using such formulations are provided herein. In one embodiment, the formulation is an ophthalmic formulation, such as for intravitreal administration. In some embodiments, the VEGFR-Fc fusion protein is aflibercept.

Abstract: Described herein are immunosuppressive molecules including immunosuppressive variants of IL-2, and use of such molecules to treat inflammatory and autoimmune disorders.

Abstract: Methods of purifying proteins expressed in non-mammalian expression systems in a non-native soluble form directly from cell lysate are disclosed. Methods of purifying proteins expressed in non-mammalian expression systems in a non-native limited solubility form directly from a refold solution are also disclosed. Resin regeneration methods are also provided.

Abstract: The present invention relates to methods of migraine prophylaxis using anti-CGRP receptor antibodies or binding fragments. In particular, methods for preventing or reducing the occurrence of migraine headache in a patient in need thereof comprising administering to the patient an anti-CGRP receptor or binding fragment according to specific dosage regimens are disclosed. Pharmaceutical compositions and administration devices comprising anti-CGRP receptor antibodies or binding fragments for use in the methods are also described.

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): (Formula (I)) wherein variables X, Y, R2, R3, R4, R5, R6, and n 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.

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.

Abstract: Impact testing apparatuses are disclosed which simulate and measure various impact-related events associated with the operation of a drug delivery device. The impact testing apparatus may include an impactor configured to simulate a plunger rod of the drug delivery device, and a guide sleeve configured to receive a syringe corresponding to the drug delivery device. The syringe may have a proximal end, a distal end defining an outlet, and an interior chamber extending between the proximal and distal ends and carrying a plunger. Additionally, the impact testing apparatus may include an energy source configured to reduce a distance between the impactor and the plunger so that the impactor strikes the plunger. Various sensors may be included to measure characteristics of one or more impacts caused by the impactor. Methods of impact testing a syringe filled with a fluid and carrying a plunger are also disclosed.

Abstract: A drug delivery device includes a housing, a reservoir, a cannula, one or more light sources, a label, and a controller. The reservoir is disposed within the housing. The cannula is connected to the reservoir for delivering a drug from the reservoir to the patient. The light sources are disposed adjacent the exterior surface of the housing, and each serves to indicate one of one or more operational conditions of the device. The label is fixed to the housing adjacent the light sources, and includes one or more informational messages. Each informational message is aligned with one of the light sources for conveniently conveying to a user an operational condition of the device as indicated by the corresponding light source. Finally, the controller is operably connected to the reservoir and the light sources. The controller is configured to actuate the reservoir to deliver the drug, and to selectively illuminate the one or more light sources based on the operational condition of the drug delivery device.

Abstract: The disclosure provides compositions and methods relating to or derived from anti-activin A binding proteins, including antibodies. In particular embodiments, the disclosure provides fully human, humanized, and chimeric anti-activin A antibodies that bind human activin A, activin A-binding fragments and derivatives of such antibodies, and activin A-binding polypeptides comprising such fragments. Other embodiments provide nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having activin A-related disorders or conditions including cachexia related to gonadal cancer, other cancers, rheumatoid arthritis, and other diseases.

Abstract: A drug delivery device includes a container for storing a drug having a longitudinal axis. A plunger rod aligned with the longitudinal axis of the container has a first end and a second end, where the second end is disposed within the container. A stopper is disposed in and movable relative to the container for expelling the drug, and a drive mechanism is operatively coupled to the first end of the plunger rod. The drive mechanism is configured to deliver a drive force to move the plunger rod along the longitudinal axis and through the container. A chamber disposed between a plunger rod and the stopper is adapted to oppose the drive force of the drive mechanism.

Abstract: The invention provides a method for the treatment of EGFRvIII-positive cancer or glioblastoma, comprising administering to a subject in need thereof an initial dose of between about 15 ?g/day to about 6000 ?g/day of an anti-EGFRvIII agent. Diagnostic methods for assessing EGFRvIII expression are also provided.

Abstract: This invention provides improved methods for generation of hematopoietic precursor cells from a pluripotent stem cell and hematopoietic precursor cells generated thereof. The hematopoietic precursor cells express CXCR4 or runx1c and are capable of homing and/or engraftment in bone marrow.

Abstract: Systems and methods for drug delivery with pressure sensitive control are disclosed. A drug delivery system may include a reservoir filled or fillable with a drug, a drug delivery device coupled to the reservoir to deliver the drug from the reservoir to a patient, a pressure sensor, an output device, and a controller. The controller may be configured to determine if the drug delivery device has completed delivering a dose of the drug to the patient, and if delivery of the dose of the drug is complete, to measure tissue back pressure using the pressure sensor. Subsequently, the controller may be configured to determine if the tissue back pressure is below a first predetermined value, and if so, control the output device at least once and/or control a mechanism to retract an administration member from the patient.

Abstract: The disclosed methods are directed to detecting polypeptide fragments (“clips”) of parental polypeptides. Parental polypeptides and clips are optionally denatured and then fractionated using a matrix. After a first elution (high molecular weight fraction), an additional elution step retrieves a low molecular weight fraction containing clips. If the clips are an appropriate size for the targeted detection method, such as mass spectrometry, then analysis of this fraction proceeds separately from the high molecular weight fraction, or the clips fraction is mixed with the proteolyzed high molecular weight fraction before analysis. However, if the clips are too large for the intended analytical method(s), then the clips are also proteolyzed. The digested high molecular weight and low molecular weight fractions can be analyzed separately or combined. Analysis of combined samples favors clip quantitation because the clips are analyzed together with the remaining counterpart of the parental polypeptide.

Abstract: The disclosure provides novel antigen-binding proteins that bind STEAP1 and methods of use.