Provided herein are compounds, compositions, and methods for the treatment of diseases and disorders associated with cancer, including tubulysins and protein (e.g., antibody) drug conjugates thereof.

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.

It is an object of the present invention to provide an antibody that binds to a human PGE.sub.2 receptor subtype EP4 and inhibits the function of EP4, or a functional fragment thereof. It is another object of the present invention to provide a medicament comprising the aforementioned antibody or a functional fragment thereof. Mice were immunized with the human PGE.sub.2 receptor subtype EP4, and a monoclonal antibody that suppresses the intracellular cAMP level increase induced by EP4 was screened. In addition, the CDR sequences of the obtained monoclonal antibody were determined.

The present disclosure relates to compositions and methods for enhancing cell response and/or expanding chimeric antigen receptor (CAR) cells and/or maintenance in vivo and/or in vitro. In embodiments, the method comprises obtaining CAR T cells comprising a CAR comprising a binding domain that binds a solid tumor antigen, a transmembrane domain, and an intracellular domain; and contacting the CART cells with white blood cells and a bispecific antibody, such as a Bispecific T cell engager (BiTE®), thereby activating the CAR T cells, wherein the level of activation of the CAR T cells is higher than the level of activation of CAR T ells that are contacted with B cells without the bispecific antibody. The bispecific antibody comprises a first binding domain binding CD3 and a second binding domain binding CD19, CD20, CD22, or BCMA.

The present invention provides antibodies that bind to the human glucagon receptor, designated GCGR and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human GCGR. The antibodies of the invention are useful for lowering blood glucose levels and blood ketone levels and are also useful for the treatment of diseases and disorders associated with one or more GCGR biological activities, including the treatment of diabetes, diabetic ketoacidosis and long-term complications associated with diabetes, or other metabolic disorders characterized in part by elevated blood glucose levels.

Provided herein are methods and compositions relating to glucagon-like peptide-1 receptor (GLP1R) libraries having nucleic acids encoding for a scaffold comprising a GLP1R binding domain. Libraries described herein include variegated libraries comprising nucleic acids each encoding for a predetermined variant of at least one predetermined reference nucleic acid sequence. Further described herein are protein libraries generated when the nucleic acid libraries are translated. Further described herein are cell libraries expressing variegated nucleic acid libraries described herein.

The present disclosure relates to chimeric small molecules, which find utility as modifiers of target substrates according to the formula A-L.sub.1-E-B or A-L.sub.1-E-L.sub.2-B, wherein A is a kinase binding moiety; B is a target binding moiety; L.sub.1 and L.sub.2 are each a linker; and E is an electrophilic reactive group. Molecules according to the present invention find use making substrate modifications such as post-translational modifications to targets that are not the natural substrate of the kinase; accordingly, diseases or disorders may be treated or prevented with molecules of the present disclosure.

Combination therapies are disclosed. The combination therapies can be used to treat or prevent cancerous conditions and/or disorders.

Compounds and methods for treating diseases or conditions affected by the activity or expression of genes/proteins related to human GH, GHR, STAT5, SOCS, IGF-1, insulin are provided. Monoclonal antibodies for treating diseases or conditions related to growth hormone and growth hormone receptor activity are also provided.

The present disclosure provides recombinantly manufactured ultra-long acting insulin-Fc fusion proteins for use in treating canine and feline diabetes. The insulin-Fc fusion proteins comprise an insulin polypeptide linked via a peptide linker to an Fc-fragment of canine or feline origin. Based on the results obtained, creating a treatment that is amenable to low cost manufacturing, exhibits sufficient in vivo bioactivity, displays extended duration of bioactivity, does not induce anti-drug antibodies, and substantially retains is potency over multiple administrations, requires a non-obvious combination of insulin polypeptide, peptide linkers, and species-specific Fc fragment, in addition to selective mutations on one or more of these components. Exemplary ultra-long acting insulin-Fc fusion proteins, polynucleotides encoding these insulin-Fc fusion proteins, and pharmaceutical formulations of exemplary insulin-Fc fusion proteins are provided, in addition to methods of use and preparation.