Renovo Limited

Hugh Gerard Laverty

Sharon O'Kane

Nick Occleston

Mark William James Ferguson

Phillip Mellors

Emma Atkinson

Jane Kelly

Wayne Burrill

Simon Higginbottom

Mark Ferguson

The invention provides TGF-&#x3b2;3s, or fragments or derivatives thereof, wherein the alpha-helix-forming domain between amino acid residues (58) and (67) of full-length wild type TGF-&#x3b2;3 comprises at least one alpha-helix-stabilizing substitution. The invention also provides TGF-&#x3b2;3s, or fragments or derivatives thereof, wherein the Glycine residue at position (63) of full-length wild type TGF-&#x3b2;3 is replaced with Proline. Further still, the invention provides TGF-&#x3b2;3s, or fragments or derivatives thereof, comprising a substitution of the Glutamic acid residue at position (12) of full-length wild type TGF-&#x3b2;3 and/or the Arginine residue at position (52) of full-length wild type TGF-&#x3b2;3. The invention also provides medicaments and methods of treatment using such TGF-&#x3b2;3s.

TGF-&#x3b2;3 mutants

There is provided the use of monomeric TGF-&#x3b2;s, or there fragments or derivatives, as medicaments. These medicaments preferably comprise monomeric TGF-&#x3b2;3, or fragments or derivatives thereof. The medicaments provided may be used in the acceleration of wounding and/or the inhibition of scarring, in the promotion of epithelial regeneration, or in the prevention and/or treatment of fibrotic disorders.

Medicaments and proteins based on TGF-&#x3b2; monomers for the treatment of wounds

The present invention concerns a method for folding a Transforming Growth Factor Beta, or a functional analogue thereof, into a dimeric, biologically active form. The method involves adding solubilized, unfolded monomeric growth factor to a solution containing 2-(cyclohexylamino)-ethanesulfonic acid (CHES) or a functional analogue thereof and a low molecular weight sulfhydryl/disulfide redox system. The solution is then incubated under conditions suitable for generating dimeric biologically active Transforming Growth Factor Beta.

Protein folding

The invention provides pharmaceutical compositions comprising TGF-&#x3b2; superfamily members and sugars, the compositions allowing improved recovery and/or increased biological activity of the TGF-&#x3b2; superfamily member incorporated therein. The invention also relates to uses of sugars to improve the recovery or increase the biological activity of TGF-&#x3b2; superfamily members in a pharmaceutical composition. Uses of the pharmaceutical compositions are also described, particularly with reference to wound healing and fibrosis. Furthermore, the invention discloses medicaments for the prevention or reduction of injection pain.

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Manchester, United Kingdom

Hugh Gerard Laverty