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 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 an innate immunity cell such as a gamma delta T (gdT) cell, Natural Killer (NK) cell, or macrophage having 2-[3-(1,3-dicarboxypropyl)ureido] pentanedioic acid (DUPA) chemically conjugated to the cell surface. The DUPA-conjugated cells provided herein demonstrate increased cytotoxicity toward cancer cells expressing PSMA. DUPA-conjugated cells can be primary cells or cells of a cell line. Also provided are methods of conjugating DUPA to the surface of NK cells, gamma delta T (gdT) cells, or macrophages and methods of treating cancer using DUPA-conjugated NK cells, gamma delta T (gdT) cells, or macrophages.

Abstract: Provided herein are, inter alia, nucleic acid-peptide conjugates including a non-cell penetrating protein (e.g., an Hdm2 targeting peptide) attached at its C-terminus to a phosphorothioate nucleic acid. Attachment of the phosphorothioate nucleic acid to the non-cell penetrating protein conveys stability to and allows for efficient intracellular delivery of the non-cell penetrating peptide. The nucleic acid-peptide conjugates provided herein including embodiments thereof are useful, inter alia, for the treatment of cancer.

Abstract: Provided are bispecific antibody compounds having the Formula I: wherein, FAB1, FAB2, and —X— are as defined herein. The provided bispecific antibody compounds can be used a modulators of target molecules, including CD3, PSMA, CD19, CXCR5, CD33, PDL1, VEGFR2, cMet, or Axl, and are useful in the treatment of one or more conditions.

Abstract: Provided are bispecific antibody compounds having the Formula I: wherein, FAB1, FAB2, and —X— are as defined herein. The provided bispecific antibody compounds can be used a modulators of target molecules, including CD3, PSMA, CD19, CXCR5, CD33, PDL1, VEGFR2, cMet, or Ax1, and are useful in the treatment of one or more conditions.

Abstract: Provided herein are, inter alia, nucleic acid-peptide conjugates including a non-cell penetrating protein (e.g., an Hdm2 targeting peptide) attached at its C-terminus to a phosphorothioate nucleic acid. Attachment of the phosphorothioate nucleic acid to the non-cell penetrating protein conveys stability to and allows for efficient intracellular delivery of the non-cell penetrating peptide. The nucleic acid-peptide conjugates provided herein including embodiments thereof are useful, inter alia, for the treatment of cancer.

Abstract: Provided herein are cell penetrating compounds having the Formula I: where, generally, each T is a thiol reactive group (e.g., a phosphorothioate), each L is a linker (e.g., a linear alkyl), and Y is a biologic (e.g., an antibody). Also provided are pharmaceutical compositions including the cell penetrating compounds, and methods of delivering the compound into a cell.

Abstract: Provided are bispecific conjugates having the general formula: pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and their use in the treatment of cancer.

Abstract: Provided herein are cell penetrating compounds having the Formula I: where, generally, each T is a thiol reactive group (e.g., a phosphorothioate), each L is a linker (e.g., a linear alkyl), and Y is a biologic (e.g., an antibody). Also provided are pharmaceutical compositions including the cell penetrating compounds, and methods of delivering the compound into a cell.

Abstract: Provided are bispecific conjugates having the general formula: pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and their use in the treatment of cancer.

Abstract: Provided are compounds having the Formula I or II: and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and their use in the treatment of cancers.

Abstract: Provided herein are cell penetrating compounds having the Formula I: where, generally, each T is a thiol reactive group (e.g., a phosphorothioate), each L is a linker (e.g., a linear alkyl), and Y is a biologic (e.g., an antibody). Also provided are pharmaceutical compositions including the cell penetrating compounds, and methods of delivering the compound into a cell.

Abstract: There is disclosed a process for forming chemically-locked bispecific or heterodimer antibodies, preferably in the IgG class, in high specificity and with high homogeneity. More specifically, there is disclosed a chemically-locked bispecific IgG class antibody having a linkage region joined together with bio-orthogonal click chemistry.

Abstract: Provided are bispecific antibody compounds having the Formula I: wherein, FAB1, FAB2, and —X— are as defined herein. The provided bispecific antibody compounds can be used a modulators of target molecules, including CD3, PSMA, CD19, CXCR5, CD33, PDL1, VEGFR2, cMet, or Ax1, and are useful in the treatment of one or more conditions.

Abstract: Provided are compounds having the Formula I: pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and their use in the intracellular delivery of antibodies.

Abstract: Provided are bispecific antibody compounds having the Formula I: wherein, FAB1, FAB2, and —X— are as defined herein. The provided bispecific antibody compounds can be used a modulators of target molecules, including CD3, PSMA, CD19, CXCR5, CD33, PDL1, VEGFR2, cMet, or Axl, and are useful in the treatment of one or more conditions.

Abstract: Provided are bispecific conjugates having the general formula: pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and their use in the treatment of cancer.

Abstract: There is disclosed an antibody drug conjugate (ADC) having an IgG antibody that binds to a c-Met target conjugated at both Cys sites in the hinge region of an IgG antibody. There is further disclosed a method for treating a breast cancer comprising providing an effective amount of a c-Met ADC.

Abstract: Provided are compounds having the Formula I or II: and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and their use in the treatment of cancers.