Hepatitis C virus (HCV) infection is a leading cause for liver cirrhosis and hepatocellular carcinoma worldwide.sup.2. Current therapeutic regimens are usually poorly tolerated and only effective in a proportion of infected individuals. We discovered a peptide with sequence of DEAQETAVSSHEQD (SEQ ID NO: 1), a fragment of rabbit α1-antiproteinase F, and its derivatives DEAQETAVSSHEQ (SEQ ID NO: 2) and QETAVSSHEQD (SEQ ID NO: 3), significantly inhibit serum-borne HCV replication in hADSC and human hepatocytes.

The present disclosure provides compositions and methods for treating an infection by EV-D68. In particular, the present disclosure provides methods that entail administering agents having an anchoring domain that anchors the compound to the surface of a target cell, and a sialidase domain that can act extracellularly to inhibit infection of a target cell by EV-D68.

The present invention relates to antibody-polypeptide-cytotoxin conjugates and methods of making, packaging, and using the conjugates. The polypeptide can be a Kunitz-type protease inhibitor or a derivative thereof that facilitates transport of the conjugate across the blood-brain barrier and/or into cancer cells outside the CNS, and the antibody moiety selectively binds a target within the CNS or in peripheral tumors to direct the cytotoxic agent to that target (e.g., a tumor or cancer cell). The conjugates can be further defined by the inclusion of a linker between the antibody moiety and the polypeptide; by the number of polypeptides and cytotoxic agents conjugated thereto; by the positions at which the entities within the conjugates are bound to one another; and by the larger configuration of the conjugate. Modified polypeptides (e.g., polypeptides conjugated to cytotoxic agents but not to an antibody moiety), pharmaceutical compositions, kits (e.g., including a modified polypeptide and an as-yet unconjugated antibody), and methods of making and using the conjugates are also features of the invention.

Camelid blood products their peptide isolates and synthetic sequences for wound fluid elevated protease enzyme inhibition. The present invention provides evidence that Metalloprotease and other Protease enzyme (e.g. elastase) peptide inhibitors are present in camelid serum/plasma can be used alone or combined with other agents to enhance healing in the treatment of chronic wounds and burns by inhibiting elevated wound fluid protease activity. These protease enzymes inhibitors present in camelid serum/plasma can be demonstrated to inhibit chronic non-healing wound fluid proteolytic enzymes by the use of wound fluid assay kits specifically designed to measure wound fluid protease activity. The serum/plasma and isolated or synthesised peptides of this patent have use in the treatment of a range of cosmetic skin indications and diseases such as disorders of the gastrointestinal tract, cardiovascular conditions and specifically in the treatment of wound healing and burns and in scar tissue healing.

Camelid blood products their peptide isolates and synthetic sequences for wound fluid elevated protease enzyme inhibition. The present invention provides evidence that Metalloprotease and other Protease enzyme (e.g. elastase) peptide inhibitors are present in camelid serum/plasma can be used alone or combined with other agents to enhance healing in the treatment of chronic wounds and burns by inhibiting elevated wound fluid protease activity. These protease enzymes inhibitors present in camelid serum/plasma can be demonstrated to inhibit chronic non-healing wound fluid proteolytic enzymes by the use of wound fluid assay kits specifically designed to measure wound fluid protease activity. The serum/plasma and isolated or synthesised peptides of this patent have use in the treatment of a range of cosmetic skin indications and diseases such as disorders of the gastrointestinal tract, cardiovascular conditions and specifically in the treatment of wound healing and burns and in scar tissue healing.

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.

The invention is directed to a composition comprising an (one or more) isolated peptide comprising a BF01 peptide, variants of a BF01 peptide and/or mutants of a BF01 peptide. In particular aspects, the composition is a pharmaceutical composition. The composition(s) can be used to inhibit thrombogenesis, selectively inhibit the intrinsic pathway of blood coagulation and selectively inhibit FX1 in an individual in need thereof comprising administering an effective amount of all or a biologically active portion of a BF01 peptide, one or more variants thereof and/or one or more mutants thereof.

The present invention relates a method for the diagnosis, prediction or risk stratification for mortality and/or disease outcome of a subject that has or is suspected to have sepsis, comprising determining the presence and/or level of antitrypsin (ATT) or fragments thereof in a sample taken from said subject and/or determining the presence and/or level of transthyretin (TTR) or fragments thereof, wherein the presence and/or level of ATT and/or TTR or fragments thereof is correlated with an increased risk of mortality and, wherein said increased risk of mortality and/or poor disease outcome is given if the level of ATT is below a certain cut-off value and/or the level of fragments thereof is above a certain cut-off value and/or said increased risk of mortality and/or poor disease outcome is given if the level of TTR is below a certain cut-off value and/or the level of fragments thereof is below a certain cut-off value. The invention relates in general to the use of ATT and/or TTR or its fragments for the diagnosis of sepsis, and to nucleotides of SEQ ID NO. 2 to 14.

The present invention provides purified protease inhibitors derived from microorganisms alone or in combination with bacteriocins and/or antibodies. The protease inhibitors may also be expressed by microbiome or probiotic microorganisms alone or in combination with bacteriocins and/or antibodies. The invention also provides methods and compositions for improving the expression of endogenous or heterologous protease inhibitors alone or in combination with bacteriocins and/or antibodies. The invention is useful for treating a variety of inflammatory disorders including acne, psoriasis, eczema, atopic dermatitis and inflammatory bowel disease.

The present invention provides purified protease inhibitors derived from microorganisms alone or in combination with bacteriocins and/or antibodies. The protease inhibitors may also be expressed by microbiome or probiotic microorganisms alone or in combination with bacteriocins and/or antibodies. The invention also provides methods and compositions for improving the expression of endogenous or heterologous protease inhibitors alone or in combination with bacteriocins and/or antibodies. The invention is useful for treating a variety of inflammatory disorders including acne, psoriasis, eczema, atopic dermatitis and inflammatory bowel disease.