The invention relates to a compilation of detection reagents, wherein the compilation comprises a first and a second detection reagent, wherein the first detection reagent binds non-mutated leptin with a first binding value, but does not bind mutated leptin or binds it with a maximum of 50% of the binding value of non-mutated leptin, and wherein the second detection reagent binds both mutated and non-mutated leptin with a second binding value. The invention furthermore relates to an in-vitro method for detecting mutated leptin and the use of a detection reagent.

Methods and compositions are provided for extending the half-life of a therapeutic agent. A modified therapeutic agent (mTA) comprises a therapeutic agent, a staple, and a half-life extending molecule. The mTAs disclosed herein may be used to treat a disease or a condition in a subject in need thereof.

The disclosure relates to engineered strains of yeast that express a therapeutic polypeptide(s) and/or comprise a nucleic acid encoding a therapeutic polypeptide(s), as well as methods and uses for the same.

A peptide includes SEQ ID NO: 1 (Xaa1-Tyr-Phe-Ala-Tyr-His-Pro-Asn-Ile-Pro-Gly-Leu-Xaa2-Tyr-Phe), wherein Xaa1 is any one selected from the group consisting of tyrosine, tryptophan, phenylalanine and non-natural amino acids having characteristics identical to tyrosine, tryptophan or phenylalanine; and Xaa2 is any one selected from the group consisting of tyrosine, tryptophan, phenylalanine, and non-natural amino acids having the characteristics identical to tyrosine, tryptophan or phenylalanine.

Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including once weekly administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

Modified canine leptin polypeptides and formulations and uses thereof, are provided including polyethylene glycol (PEG) modified canine leptin polypeptides, wherein the PEG moiety is covalently attached to a para-acetyl-phenylalanine (pAF) residue of the polypeptide, and related compositions and methods useful in treating companion animal obesity and other leptin-related disorders.

The present invention provides methods for generating functional derivatives of effector polypeptides (e.g., hormones and receptor ligands) embedded in a different protein scaffold (e.g., antibody scaffolds). The methods involve modifying the effector polypeptide with a combinatorial library of terminal linker sequences, inserting the modified sequences into the host scaffold, and then selecting functional derivatives from the library of modified polypeptide sequences embedded in the host scaffold. As exemplifications, the invention also provides specific functional derivatives of leptin, scFSH and scRelaxin embedded in an antibody scaffold, as well as therapeutic applications of such functional fusion molecules.

The disclosure provides chimeric polypeptides and nucleic acid molecules encoding chimeric polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including lipodystrophy, dyslipidemia, hyperlipidemia, overweight, obesity, hypothalamic amenorrhea, Alzheimer's disease, leptin deficiency, fatty liver disease or diabetes (including type I and type II). Additional diseases and disorders which can be treated by the compounds and methods described herein include nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), metabolic syndrome X and Huntington's Disease.

The present invention relates to agents capable of inhibiting the binding between Leptin and Neuropilin-1 (NRP1) and uses thereof in the therapeutic field.

Disclosed is an oral delivery system that overcomes major barriers encountered in the gastrointestinal tract, particularly rapid proteolytic degradation and low intestinal permeability. Provided is a method for oral delivery of an engineered microorganism to a mammal where the microorganism produces a macromolecule having a desired bioavailability outcome.