Abstract: An implantable delivery device and method for utilizing the device to delivery a bioactive agent to a subject in need thereof is described. The device includes a pattern of structures fabricated on a surface of the device to form a nanotopography. A random or non-random pattern of structures may be fabricated such as a complex pattern including structures of differing sizes and/or shapes. The device may be located adjacent tissue such as an endovascular implant or a perivascular implant, and may deliver the bioactive agent without triggering an immune or foreign body response to the bioactive agent.

Abstract: An application device for a fluid delivery includes a housing having a bore extending from a bottom of the housing. The bore is sized and shaped for receiving at least a portion of the fluid delivery apparatus. The application device also includes an impact component for impacting the fluid delivery apparatus and moving at least a portion of the fluid delivery apparatus towards a user's skin. The application device includes a safety arm that is positionable relative to the impact component between a locked configuration in which the impact component is secured in a safety position, and a released configuration in which the impact component is free to move within the housing for impacting the fluid delivery apparatus.

Abstract: A transdermal drug delivery device is disclosed that may comprise a housing including an upper housing portion and a lower housing portion. The lower housing portion may define a bottom surface including skin attachment means for releasably attaching the lower housing portion to skin of a user. The upper housing portion may at least partially surround a central region of the device. The device may also include a microneedle assembly and a reservoir disposed within the central region. The reservoir may be in fluid communication with the microneedle assembly. Additionally, the device may include a pushing element disposed above the microneedle assembly within the central region. The pushing element may be configured to provide a continuous bilateral force having a downward component transmitted through the microneedle assembly and an upward component transmitted through the skin attachment means.

Abstract: There is disclosed compositions and methods relating to or derived from anti-PD-L1 antibodies. More specifically, there is disclosed fully human antibodies that bind PD-L1, PD-L1-binding fragments and derivatives of such antibodies, and PD-L1-binding polypeptides comprising such fragments. Further still, there is disclosed 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 PD-L1 related disorders or conditions, including various inflammatory disorders and various cancers.

Abstract: The present disclosure provides, inter alia, a lateral flow device, and methods of use of the device, for accurately and rapidly detecting the presence of a coronavirus or a coronavirus infection in a subject, such as a SARS-CoV-2 virus or virus infection. The lateral flow device detects in a sample from the subject the presence or absence of a coronavirus protein (e.g., a SARS-CoV-2 protein), such as an S protein, an Si protein, or nucleocapsid protein. The lateral flow device comprises, for example, Pt or Au/Pt nanoparticle-antibody conjugates for detection of coronavirus protein or coronavirus infection, such as a SARS-CoV-2 protein or a SARS-CoV-2 infection.

Abstract: The present disclosure provides fully human antibodies that specifically bind the spike (S) protein of the SARS-CoV-2 coronavirus with high affinity, or antigen-binding proteins derived from such antibodies, and uses thereof. Included are anti-spike protein antibodies, antibody fragments, and single-chain antibodies, that are coronavirus neutralizing antibodies, as well as pharmaceutical compositions that include such antibodies and antibody fragments. Methods for using the anti-spike protein antibodies include methods of treating or preventing infection with a coronavirus, such as the SARS-CoV-2 coronavirus, by administering an antibody or antibody fragment as disclosed herein, including by intranasal delivery. Methods and compositions for treating or preventing coronavirus infection by administering a composition that includes a nucleic acid construct that encodes a neutralizing antibody are also provided.

Abstract: The present disclosure provides antigen-binding proteins, such as fully human antibodies, that specifically bind the spike (S) protein of the SARS-CoV-2 coronavirus and uses thereof. In various embodiments, the anti-spike protein antibodies are neutralizing antibodies that prevent binding of the SARS-CoV-2 coronavirus to a target cell expressing the ACE2 protein. Included are anti-spike protein antibodies, antibody fragments, and single-chain antibodies, as well as pharmaceutical compositions that include such antibodies and antibody fragments. Also provided herein are nucleic acids and recombinant expression vectors that encode the anti-spike protein antibodies and antibody fragments disclosed herein and transgenic cells transected with such nucleic acids and expression vectors. Further provided are methods for preparing and using such anti-spike protein antibodies.

Abstract: The present disclosure provides variant anti-OX40 antibodies that mimic the activity of OX40L by behaving as an agonist against receptor OX40 to enhance T cell clonal expansion and differentiation. The variant anti-OX40 antibodies exhibit improved binding affinity for OX40 and improved agnostic activity, compared to a wild type anti-OX40 antibody (wild type 2B4 clone) from which the variant clones are derived. The variant anti-OX40 antibodies specifically bind OX40 receptors on activated T lymphocytes, stimulate proliferation of effector T cells, stimulate proliferation of effector T cells in the presence of regulatory T cells, and stimulate production of at least one cytokine from effector T cells.

Abstract: There is disclosed a method for treating pulmonary inflammatory disease by neural ablation methods.

Abstract: There is disclosed compositions and methods relating to or derived from anti-CD38 antibodies. More specifically, there is disclosed fully human antibodies that bind CD38, CD38-antibody binding fragments and derivatives of such antibodies, and CD38-binding polypeptides comprising such fragments. Further still, there is disclosed 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 a disease.

Abstract: There is disclosed compositions and methods relating to or derived from anti-CD123 antibodies. More specifically, there is disclosed fully human antibodies that bind CD123, CD123-antibody binding fragments and derivatives of such antibodies, and CD123-binding polypeptides comprising such fragments. Further still, there is disclosed 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 a disease.

Abstract: A microneedle array assembly includes a microneedle array that has a plurality of microneedles. A distribution manifold includes a fluid supply channel that is coupled in flow communication to a plurality of resistance channels. Each of the resistance channels are coupled in flow communication to a respective one of the microneedles of the microneedle array. The resistance channels have a resistance value to a fluid flow through each resistance channel that is in the range between about 5 times greater to about 100 times greater than a resistance to the fluid flow through the supply channel.

Abstract: Disclosed herein are methods of administering resiniferatoxin (RTX) intravesically for treatment of bladder pain, and compositions for use in such methods.

Abstract: The present disclosure provides PD-1 binding proteins, particularly anti-PD-1 antibodies, or antigen-binding portions thereof, that specifically bind PD-1 and uses thereof. In one embodiment, the anti-PD-1 antibody comprises an antigen binding portion that binds a human PD-1 epitope or a non-human PD-1 epitope. Various aspects of the anti-PD-1 antibodies relate to antibody fragments, single-chain antibodies, pharmaceutical compositions, nucleic acids, recombinant expression vectors, host cells, and methods for preparing and using such anti-PD-1 antibodies. Methods for using the anti-PD-1 antibodies include in vitro and in vivo methods for binding PD-1, blocking interaction between PD-1 and PD-L1, detecting PD-1, and treating diseases associated with PD-L1 over-expression or PD-L1 detrimental expression.

Abstract: The present disclosure provides activatable masked antigen binding proteins comprising an antigen binding protein attached to universal masking moieties by peptide linkers. The universal masking moieties dimerize with each other to form a dimerized masking complex that blocks binding between the antigen binding domain and its target antigen. The individual masking moieties and the dimerized masking complex do not bind specifically to the antigen binding domain. The masking moieties form stable dimers because their association with each other mimics homodimers or heterodimers found in naturally-occurring immunoglobulin or cell receptor molecules. The dimerization of the masking moieties does not involve covalent bonding and can be optimized by engineering interchain association through structure complementarity such as knob-in-hole.

Abstract: The present disclosure provides transgenic cells that express memory dimeric antigen receptors (mDARs), where the mDAR constructs comprise a JAK-STAT intracellular region having a cytokine receptor intracellular region which includes Box 1 and Box 2 motifs for binding a Janus kinase (JAK) which can play a role in JAK-STAT cellular signaling pathway to induce effector cell activation and proliferation. In one embodiment, the JAK-STAT intracellular region further comprises a CD3zeta intracellular signaling region having an intact ITAM region, or having ITAM 1 and 3, or having only ITAM 3 with a partial deletion. Transgenic cells expressing the mDAR constructs exhibit potent cytotoxicity, and release reduced levels of cytokines, compared to traditional DARs that lack a cytokine receptor intracellular region. The mDAR constructs have antibody-like properties as they bind specifically to a target antigen. Transgenic cells expressing the mDAR constructs can be used for directed cell therapy.

Abstract: The present disclosure provides a lateral flow device, and methods of use of the device, for accurately and rapidly detecting a COVID-19 infection in a subject. The lateral flow device described herein detects in a liquid sample from the subject the presence or absence of neutralizing and non-neutralizing anti-S1 spike antibodies as IgM and IgG types. The anti-S1 antibodies neutralizing antibodies (e.g., both IgM and IgG) can block binding between ACE2 antigen and S1 spike protein which is the basis for the design of the lateral flow device.

Abstract: The present disclosure provides methods for treating a subject having a coronavirus infection by administering a composition that includes a sACE2 polypeptide to the lungs of a subject infected with a coronavirus. The sACE2 polypeptide includes the extracellular portion of the human ACE2 polypeptide and acts as a decoy, binding the spike (S) protein of coronavirus and thereby preventing the interaction of the S protein with membrane-associated ACE2 expressed on pulmonary cells, thus disrupting the infection process. The sACE2 polypeptide is derived from human ACE2, preventing potential immune reactions of the subject to the therapeutic polypeptide. The sACE2 polypeptide is administered locally to the site of the pathology, avoiding potential adverse effects of systemic delivery.

Abstract: The present disclosure provides fully human anti-LAG3 IgG class antibodies engineered to have amino acid sequence in their heavy chain variable region and/or light chain variable region to improve antigen binding, cell binding, T cell activation and cytokine release capabilities.

Abstract: The present disclosure provides anti-OX40 antibodies, and antigen-binding portions thereof. In certain embodiments, the antibodies or fragments thereof, are used for the treatment of cancer.