The technology provided herein relates to novel isolated polypeptides and peptides having a growth inhibitory effect on human cancer cells. Nucleic acid molecules encoding said polypeptides/peptides, vectors, host cells containing the nucleic acids and methods for preparation and producing said polypeptides/peptides. Compositions and methods for using such polypeptides/peptides for the prevention and treatment of cancer are also encompassed by the present disclosure.

The invention features methods for treating or preventing pulmonary diseases, including acute respiratory distress syndrome (ARDS) and pneumonia, in a subject in need thereof that involve administering to the subject inter-alpha inhibitor proteins (IαIps), including, e.g., inter-alpha inhibitor (IαI) and/or pre-alpha inhibitor (PαI).

A2M polypeptide compositions containing a non-natural bait region are disclosed. Methods of producing wild-type and variant A2M polypeptides and polynucleotides containing a non-natural bait region are also disclosed. The bait regions of the variant A2M polypeptides demonstrate enhanced protease inhibitory characteristics compared to wild-type A2M. Variant A2M polypeptides that demonstrate longer half-lives upon administration to an organism compared to wild-type A2M are disclosed. The A2M compositions are useful in treating a number of diseases and conditions including inflammation, chronic wounds, and diseases with a pathology associated with proteases.

Disclosed are compositions and method related to variants of SPINK2 that bind to targets other than an endogenous target of SPINK2. In one embodiment, a peptide is provided that comprises the amino acid sequence SEQ ID NO: 1. In further embodiments, an amino acid sequences encoded by nucleotide positions 4 to 42 and/or nucleotide positions 94 to 189 in the nucleotide sequence of SEQ ID NO: 14 flank the amino terminus and the carboxyl terminus, respectively, of the amino acid sequence. In another embodiment, a peptide is provided that comprises an amino acid sequence derived from the amino acid sequence of SEQ ID NO: 1 in which a conservative substitution, deletion, addition and/or insertion of 1 to 5 (inclusive) amino acids has occurred at amino acids other than the 1st Xaa to the 12th Xaa counting from the amino terminus.

Disclosed herein are immunoglobulin fusion proteins comprising a first antibody region, a first therapeutic agent, and a first connecting peptide; wherein the first therapeutic agent is attached to the first antibody region by the connecting peptide; and wherein the connecting peptide does not comprise a region having beta strand secondary structure. The connecting peptide may comprise an extender peptide. The extender peptide may have an alpha helical secondary structure. The connecting peptide may comprise a linker peptide. The linker peptide may not comprise any secondary structure. Also disclosed herein are compositions comprising the immunoglobulin fusion proteins and methods for using the immunoglobulin fusion proteins for the treatment or prevention of a disease or condition in a subject.

Provided are non-naturally occurring cystine knot peptides (CKPs) that bind to VEGF-A. Additionally, provided are methods of using non-naturally occurring CKPs that bind to VEGF-A, including diagnostic and therapeutic compositions and methods. Non-naturally CKPs that bind low density lipoprotein receptor-related protein 6 (LRP6) are also provided.

In one aspect, the invention provides a method of making a bioactive peptide-bearing antibody, or fragment thereof, comprising (a) engrafting the amino acid sequence of at least one bioactive peptide of interest into (i) at least one of CDR-H1, CDR-H2 or CDR-H3 of a heavy chain variable region comprising one or more chicken framework regions and/or (ii) at least one of CDR-L1, CDR-L2 or CDR-L3 of the light chain variable region comprising one or more chicken framework regions, and (b) determining whether the antibody has substantially the same biological activity as the bioactive peptide.

SPINK2 mutant peptide conjugates are provided that inhibit KLK5. The KLK5 inhibitory peptide conjugates are Fc fusion peptides in which, in certain embodiments, the Fc region of the fusion peptides are the Fc region of human IgG1 or a fragment thereof. The KLK5 inhibitory peptide conjugates include an amino acid sequence of one of SEQ ID NOs: 34, 36, 38, 40, 42, 44, 46, 48, 96, 50, 52, 54, 56, 58, or 60. Pharmaceutical compositions that include the KLK5 inhibitory peptide conjugates useful for treating KLK5-related diseases are also provided.

The present invention relates to a cyclic inhibitor of a kallikrein protease comprising or consisting of (I) the peptide (X.sup.1 (X.sup.2)(X.sup.3)R(X.sup.4)(X.sup.5)(X.sup.6)(X.sup.7)(X.sup.8)(X.sup.9)(X.sup.10)(X.sup.11) (Formula (X)), wherein (X.sup.1) is present or absent and, is preferably present, and if present, is an amino acid, and is most preferably D-alanine or G; (X.sup.2) is an amino acid with a side chain; (X.sup.3) is an amino acid with a polar uncharged side chain, is preferably with a polar uncharged side chain comprising a hydroxyl group, is more preferably T or S and is most preferably T; (X.sup.4) is an amino acid, preferably citrulline, Q or E; (X.sup.5) is an amino acid, preferably an amino acid with a hydrophobic side chain; (X.sup.6) is present or absent, is preferably absent, and, if present, is an amino acid with a negatively charged side chain, preferably D; (X.sup.7) is present or absent, is preferably present, and, if present, is an amino acid, more preferably an amino acid with a side chain comprising a pyrrole of indole, even more preferably P, hydroxyl-proline, (R)-3-piperidine carboxylic acid or W, and most preferably P; (X.sup.8) is present or absent and, if present, is an amino acid, and is preferably absent; (X.sup.9) is present or absent and, if present, is an amino acid, and is preferably absent; (X.sup.10) is an amino acid with a side chain; and (X.sup.11) is present or absent and, if present, is an amino acid, and is preferably absent; wherein the side chains of (X.sup.2) and (X.sup.10) are connected via a connecting molecule, said connecting molecule having at least two functional groups, each functional group forming a covalent bond with one of the side chains of (X.sup.2) and (X.sup.10); and wherein the kallikrein protease is Kallikrein-related peptidase (KLK5); or (II) the peptide (Y.sup.1)(Y.sup.2)(Y.sup.3) (Y.sup.4)(Y.sup.5)(Y.sup.6)(Y.sup.7)(Y.sup.8)(Y.sup.9) (Formula (Y)), wherein (Y.sup.1) is present or absent, is preferably present, and, if present, is an amino acid, preferably P, L-beta-hydroxyl-proline, D-proline, (R)-3-piperidine carboxylic acid, Q or R, and is most preferably P; (Y.sup.2) is an amino acid with a side chain; (Y.sup.3) is I, L or L-Neopentylglycine, and is preferably L; (Y.sup.4) is Y or F, and is preferably Y; (Y.sup.5) is an amino acid, preferably an amino acid with a hydrophobic side chain, or Q or R, is more preferably L, norleucine, Q, I, R or M, and is most preferably norleucine or L; (Y.sup.6) is an amino acid, preferably an amino acid with a hydrophobic side chain and is most preferably A; (Y.sup.7) is absent or present, preferably present and, if present, is an amino acid prefer

A method for preventing and/or ameliorating skin aging in a subject includes administering to the subject in need of such treatments a synthetic peptide, which has an amino acid sequence that has 20-39 amino acid residues. The synthetic peptide has at least 20 consecutive residues that has at least 90% amino acid sequence identity to residues 11-30 of SEQ ID NO: 1.