Checkpoint inhibitor-induced pneumonitis (CIP) is characterized clinically by dyspnea, cough and tachypnea. Hypoxia results from a lymphocyte-dominated alveolitis leading to ground glass opacities and consolidations observed by CT scan. Histological findings include lymphocytic infiltrates, granuloma formation and eosinophilic accumulation. In the management of CIP, systemic administration of steroids such as methylprednisolone is the standard therapy. Moreover, CIP in most cases leads to discontinuation of checkpoint inhibitory therapy and steroids limit the therapeutic effect of checkpoint inhibitors resulting in progression of the underlying malignant disease. Therefore, there is a need of other therapeutic options in CIP that ideally could abrogate the alveolar inflammation induced by checkpoint inhibitors without affecting the systemic effect on the immune system. The focus of the present invention is to deliver a solution to that problem by the topic application of VIP (vasoactive intestinal peptide, a peptide of 28 amino acids). A drug for inhalative VIP therapy is commercially available under the name Aviptadil.

The purpose of the present invention is to provide a composition for preventing or treating neurotrophic keratitis. It is found that PACAP peptide exerts an effect to prevent corneal damages in a neurotrophic keratitis model and can promote neurite extension in a cultured nerve cell model. Furthermore, stability can be significantly increased by substituting a carboxyl group in an aspartic acid residue located at position-3 and/or position-8 in the sequence for PACAP by tetrazole. Provided are: a composition for preventing or treating neurotrophic keratitis, which contains PACAP peptide or stabilized PACAP peptide, and a neurite extension promoting agent.

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.

Provided is an incretin, or analogue thereof, an incretin receptor agonist, an incretin enhancer, or any combination thereof, for use in a method of reducing elevated intracranial pressure (ICP) in a subject. Methods of reducing elevated ICP in a subject may comprise administering an incretin, or analogue thereof, an incretin receptor agonist, an incretin enhancer, or any combination thereof to the subject. The elevated ICP may be associated with idiopathic intracranial hypertension (IIH), secondary pseudotumour cerebri, hydrocephalus, normal pressure hydrocephalus, raised intracranial pressure secondary to a brain tumour, meningitis, brain trauma, brain injury, and venous sinus thrombosis.

This disclosure relates to a method of generating conditionally active biologic proteins from wild type proteins, in particular therapeutic proteins, which are reversibly or irreversibly inactivated at the wild type normal physiological conditions. For example, evolved proteins are virtually inactive at body temperature, but are active at lower temperatures.

The present application provides methods and compositions for AAV-mediated delivery of PYY and Glucagon-like Peptide 1 or an analog thereof (e.g., Exendin-4) to a subject (e.g., the saliva of a subject). In some embodiments, compositions and methods for topical delivery of Ex-4 and PYY peptides also are provided. Methods and compositions are useful to promote weight loss and/or altered lipid taste sensitivity, as well as for the treatment of diabetes.

In certain embodiments novel PAC1 receptor agonists are provided wherein the agonists comprise a targeting sequence that binds to the PAC1 receptor and said targeting sequence is attached to an amino acid sequence comprising a fragment of the maxadilan amino acid sequence, wherein the targeting sequence comprises a full-length 38 amino acid PACAP peptide or an N-terminus fragment thereof containing the amino acid sequence HSDGIF, wherein said targeting sequence optionally comprises an amino acid insertion between residues 11 and 12 of said PACAP peptide or fragment thereof; and the fragment of the maxadilan amino acid sequence comprises a fragment of the maxadilan sequence effective to activate PAC1 signaling.

The present invention relates to a long-acting exendin-4 in which an albumin binding domain (ABD) and an anti-FcRn affibody are fused to exendin-4, and a use thereof. A long-acting exendin-4 according to the present invention has an in vivo half-life that is significantly increased over that of exendin-4, which is conventionally used as an agent for treating diabetes, and resultantly acts as a diabetes therapeutic agent, which is a conventional use of exendin-4, and also exhibits both an effect of treating other metabolic diseases and diabetes complications, such as obesity and fatty liver, and an effect of alleviating cognitive impairment caused by metabolic diseases.

This disclosure relates to VIP antagonist for uses in managing the treatment or prevention of cancer and viral infections. In certain embodiments, this disclosure relates to chimeric variants of VIP antagonists, as peptides disclosed herein, and pharmaceutical composition comprising the same. In certain embodiments, this disclosure contemplates methods of stimulating immune cells to target cancer by mixing immune cells in vitro with peptides disclosed herein and further administering an effective amount of stimulated immune cells to a subject in need of cancer treatment.

A recombinant protein comprising multiple multi-peptide sets includes first through fifth sequencing primers and first through fourth multi-peptide regions. The first multi-peptide region is between the first and the second sequencing primers. The second multi-peptide region is between the second and the third sequencing primers. The third multi-peptide region is between the third and the fourth sequencing primers. The fourth multi-peptide region is between the fourth and the fifth sequencing primers. In each of the multi-peptide regions, multiple functional peptides can be inserted, and manufacturing thereof can be done through expression of the recombinant protein, thereby significantly enhancing the concentrations of the functional peptides. With the combination of peptide having different functions, the recombinant protein product can provide more complete and more comprehensive functionality. This application also discloses a pharmaceutical composition comprising the recombinant protein and a method for preparing the recombinant protein.