Abstract: The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.

Abstract: Described herein are compositions and methods related to antigen binding proteins that bind to human ST2, including antibodies. In particular embodiments, the disclosure provides fully human anti-ST2 antibodies and deriviatives and variants thereof. Further provided are nucleic acids encoding such antibodies and antibody fragments, variants, and derivatives. Also, provided are methods of making and using such antibodies including methods of treating and preventing autoimmune and inflammatory disorders.

Abstract: The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.

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 single chain Fab module that utilizes a novel linker between VL-CL and VH-CH1 domains which will further enable the production of multispecifics.

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: 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: 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.

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: GDF15 polypeptides, constructs comprising GDF15, and mutants thereof are provided. In various embodiments the GDF15 polypeptides, constructs comprising GDF15, and mutants thereof, can be of use in the treatment or ameliorating a metabolic disorder. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy.

Abstract: The present invention relates to novel multispecific antigen binding proteins that are capable of binding to multiple targets. Pharmaceutical compositions comprising the multispecific antigen binding proteins as well as methods for producing them are also disclosed.

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: The present invention relates to engineered neuregulin-1 variants that selectively activate ErbB4 receptors but do not activate ErbB3 receptors. The invention also provides methods for using such variants to treat heart failure.

Abstract: The present invention relates to heterodimers comprising antibody CH3 domains and mutations useful for the facilitation of the formation of heterodimers. Methods of optimizing purification of the heterodimers at certain pHs in also disclosed.

Abstract: Provided herein are PD-1 antigen-binding proteins and related nucleic acids, vectors, host cells, kits and pharmaceutical compositions. Methods of making PD-1 antigen-binding proteins and methods of treating a subject are further provided.

Abstract: The present invention relates to antagonist antibodies of the human calcitonin gene-related peptide (CGRP) receptor as well as bispecific antigen binding proteins derived from the anti-CGRP antibodies that bind to and inhibit both the human CGRP receptor and another target, such as the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) receptor. Pharmaceutical compositions comprising the anti-CGRP receptor antibodies and bispecific antigen binding proteins as well as methods for producing them are also disclosed. Methods of using the anti-CGRP receptor antibodies and bispecific antigen binding proteins to ameliorate, treat, or prevent conditions associated with the CGRP and PAC1 receptors, such as chronic pain, migraine, and cluster headache, are also described.

Abstract: Provided herein are IL-2 muteins and IL-2 mutein Fc fusion molecules that preferentially expand and activate cells and are amenable to large scale production. Also provided herein are methods of making and using the compositions of the present invention.

Abstract: The clinical potential of multispecific antibodies like bispecific and trispecific antibodies shows great promise for targeting complex diseases. However, the generation of those molecules presents great challenges as in many cases it is desired to specifically drive the specific pairing of multiple polypeptide chains that are present in solutions. In the case of the heavy chains, there are two main regions that form a dimer interface. One of them is the CH3 region, which has been widely exploited by inserting either charge-pair mutations (CPMs) to steer the dimer interface or inserting large bulky residues into cavities (Knob in Hole) to physically favor and disfavor the dimer formation. However, each of these strategies may not be applied to every molecule and therefore there is the need for more tools. Here, we describe the engineering of the Hinge region with a small number of mutations that are capable to alone successfully drive the heavy chain dimerization.

Abstract: The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.

Abstract: Described herein are compositions and methods related to antigen binding proteins that bind to human ST2, including antibodies. In particular embodiments, the disclosure provides fully human anti-ST2 antibodies and deriviatives and variants thereof. Further provided are nucleic acids encoding such antibodies and antibody fragments, variants, and derivatives. Also, provided are methods of making and using such antibodies including methods of treating and preventing autoimmune and inflammatory disorders.

Abstract: The present invention relates to neutralizing antibodies of the human pituitary adenylate cyclase activating polypeptide type I receptor (PAC1) and pharmaceutical compositions comprising such antibodies. Methods of treating or preventing headache conditions, such as migraine and cluster headache, using the neutralizing antibodies are also described.