The present invention relates to methods of treating chemotherapy-induced peripheral neuropathy. In particular, the methods provide a new way of reducing neuropathic pain associated with chemotherapy-induced peripheral neuropathy by administering a nucleic acid construct encoding human HGF proteins. This application further provides nucleic acid constructs, pharmacological compositions, and methods of administration of the nucleic acid constructs that are effective in treating the neuropathic pain.

The NK1 fragment of hepatocyte growth factor (HGF) binds to and activates the Met receptor, a transmembrane receptor tyrosine kinase that plays a critical role in embryonic development and organ formation. The instant application discloses NK1 variant polypeptides which act as agonists or antagonists of HGF. Further disclosed are covalently linked NK1 variant polypeptides. Many of the disclosed variant polypeptides possess improved stability characteristics.

The present invention provides a method for producing active hepatocyte growth factor activator (HGFA) and active hepatocyte growth factor (HGF) without using animal serum. The present invention relates to a method for producing active HGFA without using animal serum. The method is characterized in that it comprises a step of obtaining a culture supernatant comprising pro-HGFA by culturing mammalian cells expressing inactive hepatocyte growth factor activator (pro-HGFA) in a medium without serum, and a step of adjusting the culture supernatant comprising pro-HGFA obtained in the above step to weakly acidic to convert pro-HGFA into active HGFA. The present invention also relates to a method for producing active HGF with HGFA produced by said method.

New designed ankyrin repeat proteins with binding specificity for HGF are described, as well as nucleic acids encoding such HGF binding proteins, pharmaceutical compositions comprising such proteins and the use of such proteins in the treatment of diseases.

The present invention provides a method of inhibiting progression of or preventing renal disorder, the method comprising applying a cell sheet composition for inhibiting progression of or preventing renal disorder to at least one part of the surface of a kidney, wherein the part of the surface is uncovered by a fibrous capsule of the kidney. The present invention also provides a cell sheet composition for inhibiting progression of or preventing renal disorder, the cell sheet composition comprising a cell that has a function of producing a hepatocyte growth factor (HGF). The present invention also provides a method of producing a cell sheet composition for inhibiting progression of or preventing renal disorder.

A recombinant protein expressing one or more human growth factors, tumor antigens, and/or receptors or epitopes thereof on or within an immunogenic expression creating a recombinant protein in which one or more epitopes are presented on the surface of the sequence in their natural configuration. The growth factor, tumor antigen, and/or receptor, sequence(s) may be expressed within the encoding sequence at appropriate internal positions or at the termini as single expressions or as two or more tandem repeats.

The present invention provides HGF polypeptide variants, including dimers, for use in treatment, in particular to treat ocular diseases and disorders.

A recombinant protein expressing one or more human growth factors, tumor antigens, and/or receptors or epitopes thereof on or within an immunogenic expression creating a recombinant protein in which one or more epitopes are presented on the surface of the sequence in their natural configuration. The growth factor, tumor antigen, and/or receptor, sequence(s) may be expressed within the encoding sequence at appropriate internal positions or at the termini as single expressions or as two or more tandem repeats.

A polyethylene glycol-modified form of a hepatocyte growth factor or an active fragment thereof achieves both an in vivo half-life extending effect of polyethylene glycol modification and the retainment of bioactivity. The polyethylene glycol-modified form of a hepatocyte growth factor or an active fragment thereof has one molecule of forked-type polyethylene glycol covalently bound to two molecules of the hepatocyte growth factor or the active fragment thereof at each of their respective carboxyl-terminal regions to form a homodimer.

This application discloses ophthalmic formulations and methods for treating and preventing corneal haze and scarring with an hepatocyte growth factor (HGF) agent.