Disclosed herein are materials and methods for the treatment of stress-related disorders and cancer. The disclosure provides an antibody, or antigen binding fragment thereof, that specifically binds to a region of corticotropin-releasing hormone (CRH). The disclosure also provides methods of treating a disorder associated with HPA axis activation, such as a stress-related disorder or cancer, comprising administering to a subject in need thereof an antibody or antigen binding fragment thereof described herein in an amount effective to treat the disorder.

Disclosed herein are materials and methods for the treatment of stress-related disorders and cancer. The disclosure provides an antibody, or antigen binding fragment thereof, that specifically binds to a region of corticotropin-releasing hormone (CRH). The disclosure also provides methods of treating a disorder associated with HPA axis activation, such as a stress-related disorder or cancer, comprising administering to a subject in need thereof an antibody or antigen binding fragment thereof described herein in an amount effective to treat the disorder.

The present disclosure is directed to methods (e.g., in vitro methods) for detecting the presence of neutralizing antibodies to PTH or PTHrP analog in a sample. The in vitro method comprises the steps of obtaining a sample from a subject; contacting the sample with a cell; measuring cyclic adenosine monophosphate (cAMP) levels; and detecting the presence of neutralizing antibodies when cAMP levels are reduced relative to a negative control sample without neutralizing antibodies. An in vitro method of detecting the presence of neutralizing antibodies in a sample from a subject treated with Abaloparatide, is also provided. Further provided herein is a kit for carrying out the methods described herein comprising components required to carry out the obtaining, contacting, measuring and detecting steps and instructions for use.

Disclosed is a method for improving affinity of an antibody for an antigen, the method comprising: in the antibody, changing at least 3 amino acid residues of framework region 3 (FR3) as defined by Kabat method to arginine residues or lysine residues, thereby improving affinity of an antibody for an antigen as compared with that of an antibody before said at least 3 amino acid residues are changed to arginine residues or lysine residues, wherein said at least 3 amino acid residues comprise at least 3 selected from the group consisting of amino acid residues at positions 68, 70, 72, 74, 75, 77, 79, 81, 82A, 82B, 83, 84, 85 and 87 of a heavy chain as defined by the Kabat method.

Disclosed is a method for improving affinity of an antibody for an antigen, the method comprising: in the antibody, changing at least 3 amino acid residues of framework region 3 (FR3) as defined by Kabat method to arginine residues or lysine residues, thereby improving affinity of an antibody for an antigen as compared with that of an antibody before said at least 3 amino acid residues are changed to arginine residues or lysine residues, wherein said at least 3 amino acid residues comprise at least 3 selected from the group consisting of amino acid residues at positions 68, 70, 72, 74, 75, 77, 79, 81, 82A, 82B, 83, 84, 85 and 87 of a heavy chain as defined by the Kabat method.

The present disclosure relates to an antibody that specifically binds a mutated NT-proBNP having i) a mutation substituting arginine at position 46 with histidine or ii) a mutation substituting glutamic acid at position 43 with aspartic acid. Moreover, the present disclosure relates to a mutated NT-proBNP or fragment thereof. Further, envisaged by the present disclosure are kits containing the antibody of the present disclosure, or the mutated NT-proBNP of the present disclosure. The present disclosure also concerns a method for diagnosing heart failure.

The present disclosure relates to an antibody that specifically binds a mutated NT-proBNP having i) a mutation substituting arginine at position 46 with histidine or ii) a mutation substituting glutamic acid at position 43 with aspartic acid. Moreover, the present disclosure relates to a mutated NT-proBNP or fragment thereof. Further, envisaged by the present disclosure are kits containing the antibody of the present disclosure, or the mutated NT-proBNP of the present disclosure. The present disclosure also concerns a method for diagnosing heart failure.

Disclosed herein is a bi-specific antibody that specifically directs a therapeutic agent to a cancer cell by targeting a tumor antigen of the cancer cell, and thereby suppressing the growth of the cancer or blocking the invasion or metastasis of the cancer. The bi-specific antibody of the present disclosure includes a first antigen binding site that binds to polyethylene glycol (PEG); and a second antigen binding site that binds to a target ligand, such as a tumor antigen.

Disclosed herein is a bi-specific antibody that specifically directs a therapeutic agent to a cancer cell by targeting a tumor antigen of the cancer cell, and thereby suppressing the growth of the cancer or blocking the invasion or metastasis of the cancer. The bi-specific antibody of the present disclosure includes a first antigen binding site that binds to polyethylene glycol (PEG); and a second antigen binding site that binds to a target ligand, such as a tumor antigen.

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.