Serum-derived peptides

Abstract

The present invention provides a composition comprising one or more mammalian serum peptides separated via dialysis, preferably non-human origin, for use in aiding wound healing, as identified by the

Description

SERUM-DERIVED PEPTIDESField of the InventionThe present invention concerns the use of mammalian serum peptides of non-human origin in wound care.Background of the InventionWound healing can be divided into three or four sequential overlapping phases: (1) hemostasis, (2) inflammation, (3) proliferation and (4) remodeling. Upon injury to the skin, a set of complex biochemical events takes place in a closely orchestrated cascade to repair the damage. Within the first few minutes after the injury, platelets adhere to the site of injury, become activated, and aggregate (join together); followed by activation of the coagulation cascade which forms a clot of aggregated platelets in a mesh of cross-linked fibrin protein. This dot stops active bleeding (hemostasis).During the inflammation phase, bacteria and cell debris are phagocytosed and removed from the wound by white blood cells. Platelet-derived growth factors (stored in the alpha granules of the platelets) are released into the wound that cause the migration and division of cells during the proliferative phase.The proliferation phase is characterized by angiogenesis, collagen deposition, granulation tissue formation, epithelialization, and wound contraction. In angiogenesis, vascular endothelial cells form new blood vessels. In fibroplasia and granulation tissue formation, fibroblasts grow and form a new, provisional extracellular matrix (ECM) by excreting collagen and fibronectin. Concurrently, re- epithelialization of the epidermis occurs, in which epithelial cells proliferate and 'crawl' atop the wound bed, providing cover for the new tissue.During wound contraction, myofibroblasts decrease the size of the wound by gripping the wound edges and contracting using a mechanism that resembles that in smooth muscle cells. When the cells' roles are close to complete, unneeded cells undergo apoptosis.During maturation and remodeling, collagen is remodeled and realigned along tension lines, and cells that are no longer needed are removed by apoptosis.However, this process is not only complex but fragile, and is susceptible to interruption or failure leading to the formation of non-healing chronic wounds. Factors that contribute to non-healing chronic wounds are diabetes, venous or arterial disease, infection, and metabolic deficiencies of old age. There remains a need in the art for effective therapies which aid the healing of such wounds.Summary of the InventionThe present invention is based, at least in part, on the discovery that a specific molecular weight fraction of mammalian serum (as defined below) may be used to aid the healing of wounds (Example 1 ; Figure 2). Peptide analysis of said serum fraction by mass spectrometry (MALDI-ToF MS), performed by the present inventors, has identified a number of peptides and the proteins from which they are derived, of which one or more (of the peptides) can be utilised as the active agent(s) (Example 3; Figures 7-9). Without wishing to be bound by theory, it is thought by the present inventors that the active agent(s) act through the general mechanism of enhancing circulation as part of the proliferative phase of wound healing when administered systemically, and not topically.US 2005 / 0042635 (Thacker et al.) also relates to therapeutic agents derived from mammalian serum. It describes the use of a class of lipopeptides isolated from caprine serum, due to their alleged immunoregulatory properties, in the treatment of a number of disorders which may be ameliorated through stimulation of the innate immune system. Therein, the lipopeptides were isolated from mammalian serum by, initially, dialysis and centrifugation followed by reversed-phase high performance liquid chromatography, as can be seen in Figure 1. This active component is said to be present in the “major component” (see paragraph

[0056] ) of RP-HPLC-separated serum, which the inventors isolate, characterise and use in a number of disease models.The serum fraction with which the present invention is concerned is isolated by dialysis using a semi-permeable membrane with an appropriate molecular weight cut-off, specifically in acetate solution (in contrast to US2005 / 0042635, where only an aqueous solution is used - paragraph 0055). It may then be eluted by reversed-phase high performance liquid chromatography, when using a linear, binary gradient (Figure 3). Preferred means for isolating the serum fraction of interest (to the present invention) are defined below. As anexample, the present inventors have separated this fraction from sheep serum in Example 2 (Figure 3), however other mammalian sources may be used.As such, the use of active peptides identified in said fraction in, particularly, the therapy of wounds has not been described in the art. Moreover, a pharmaceutical preparation comprising the fraction (as obtained by the specific isolation method) has yet to be disclosed.According to a first aspect of the invention, there is provided a composition comprising one or more mammalian serum peptides for use in aiding wound healing; wherein said one or more peptides are selected from the group consisting of SEQ ID NO: 1-79, or homologues thereof having at least 80% sequence identity to any of SEQ ID NO: 1-79.According to a second aspect of the invention, there is provided a pharmaceutical composition comprising a mammalian serum fraction; said fraction comprising mammalian serum peptides each having a molecular weight of less than 10 kilodaltons; said fraction being obtainable by a method comprising:(a) dialysis of mammalian serum, performed such that peptides having a molecular weight of greater than 10 kilodaltons are removed; characterised in that said dialysis is performed using a solution comprising acetate; and thereafter(b) reversed-phase high-performance liquid chromatography, comprising the use of a linear gradient of increasing volume of a first eluent relative to the volume of a second eluent.According to a third aspect of the invention, there is provided a composition comprising one or more synthetic peptides of sequence selected from the group consisting of SEQ ID NO: 1-79, or homologues thereof having at least 80% sequence identity to any of SEQ ID NO: 1-79.Brief Description of the FiguresFigure 1A: Comparison - weight development for lean (blue) and obese (red), obese treated with low molecular weight goat serum (green) and obese treated with low molecular weight sheep serum (dark blue);Figure 1 B: Comparison - blood glucose development for lean (blue) and obese (red), obese treated with tow molecular weight goat serum (green) and obese treated with low molecular weight sheep serum (dark blue);Figure 2A: Comparison - wound size development (in mm) for lean (blue) and obese (red), obese treated with low molecular weight goat serum (green), obese treated with low molecular weight sheep serum (dark blue). All starts with an 8mm wound at study day 1 ;Figure 2B: Comparison - wound size closure (in %) for lean (blue) and obese (red), obese treated with low molecular weight goat serum (green), obese treated with low molecular weight sheep serum (dark blue). All start with an open wound at study day 1, at day 15 a difference can be seen, and at study day 29 all wounds are closed;Figure 3 shows separation of the serum fraction by reversed-phase high performance liquid chromatography. 20ul of the serum fraction containing the peptide(s) was applied to a C18 HPLC column (Ascentis Express peptide ES ) equilibrated with 20% acetonitrile in 0.1% aqueous TFA (buffer A / second eluent) at the flow rate of 1ml min-1. A linear, binary gradient was established over 9 min to a final eluent containing 100% acetonitrile, 0.1% TFA (buffer Bffirst eluent). The effluent was monitored at 220nm;Figure 4 shows the m / z range 1000-2000 for the samples; <8kD, <2kD and for heat treated <8kD;Figure 5 shows the m / z range 2000-2200 for the samples; <8kD, <2kD and for heat treated <8kD; andFigure 6 shows the m / z range 2200-4000 for the samples; <8kD, <2kD and for heat treated <8kD.In the figures, the following key is used:Vehicle- Lean is shown by reference numeral A Vehicle- Obese is shown by reference numeral B LMG is shown by reference numeral C LMS is shown by reference numeral DDetailed Description of the InventionAs used here, the term “serum” refers to the non-cellular liquid phase of blood, comprising all non-cellular components found therein, but substantially absent of clotting factors, “serum fraction” refers to a composition containing only a subset of the proteins / peptides present in native serum, as the result of purification by any means (although serum fractions resulting from the method of purification taught herein are especially envisaged).As used herein, the term “therapy” encompasses measures that cure, slow down, and / or halt progression of a disorder; or prevent and / or slow the development of a disorder.As used herein, “wound” has its conventional meaning as used in the art; that is, generally, a discontinuity in a tissue usually resulting from physical trauma. Both “open” wounds (discontinuities in the skin or mucosa) and "closed" wounds (for example contusions and haematomas) are within the scope of the invention, although open wounds are especially envisaged.As used herein, “wound healing" refers to the biological process by which a discontinuity in a tissue (especially envisaged, the skin or mucosa) is reformed such that the tissue becomes continuous. Wound healing generally, but not necessarily, comprises the stages haemostasis, inflammation, proliferation and remodelling. “Aiding" wound healing refers to the promotion of this process through intervention, such, that the speed and / or quality of healing is greater than in the absence of intervention.As used herein, "dialysis” refers to a means for the purification of proteins and / or peptides based on their separation due to differing rates of (or the occurrence or lack of occurrence of) diffusion through a semi-permeable membrane. Separation based on the molecular weight of the peptides / proteins, resulting from the structure of the semi-permeable membrane, is especially envisaged.As used herein, “eluent”, with reference to reversed-phase high performance liquid chromatography, refers to a solvent passed through the chromatography column, as part of the mobile phase.As used herein, the “origin” of a peptide refers to said peptide being natively present in (the serum of) animals belonging to a given taxonomic class (forexample “mammals”, or animals of a given species); though not necessarily exclusively. A peptide being described as “of [a given species]” refers to its origin.As used herein, the term “synthetic”, with respect to a peptide, has its standard meaning as used in the art; that is, that the peptide is of non-natural origin, especially synthesised in vitro. Thus, peptides natively present in, or isolated from, mammalian serum are not within the scope of the term “synthetic peptide”.All other terms used herein have their standard meanings as used in the art, and as understood by the skilled person.According to a first aspect of the invention, there is provided a composition comprising one or more mammalian serum peptides, for use in aiding wound healing; wherein said one or more peptides are selected from the groups consisting of SEQ ID NO: 1-79, or homologues thereof having at least 80% sequence identity to any of SEQ ID NO: 1-79.According to a second aspect of the invention, there is provided a pharmaceutical composition comprising a mammalian serum fraction; said fraction comprising mammalian serum peptides each having a molecular weight of less than 10 kilodaltons; said fraction being obtainable by a method comprising:(a) dialysis of mammalian serum, performed such that peptides having a molecular weight of greater than 10 kilodaltons are removed; wherein said dialysis is performed using a solution comprising acetate and thereafter(b) reversed-phase high-performance liquid chromatography, comprising the use of a linear gradient of increasing volume of a first eluent relative to the volume of a second eluent.According to a third aspect of the invention, there is provided a composition comprising one or more synthetic peptide of sequence selectyed from the group consisting of SEQ ID NO: 1-79, or homologues thereof having at least 80% sequence identity to any of SEQ ID NO: 1-79.In one embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 1 , or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 1, for use in aiding wound healing. In one embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 1 , or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 1.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 2, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 2, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 2, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 2.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 3, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 3, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 3, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 3.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 4, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 4, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 4, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 4.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 5, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 5, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 5, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 5.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 6, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 6, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 6, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 6.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 7, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 7, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having thesequence of SEQ ID NO: 7, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 7.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 8, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 8, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 8, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 8.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 9, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 9, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 9, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 9.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 10, or a homologue thereof having at least 80% sequence identity to SEQ ID NO:10, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 10, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 10.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 11 , or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 11, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 11, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 11.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 12 or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 12, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 12, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 12.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 13, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 13, for use in aiding wound healing. In another embodimentof said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 13, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 13.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 14, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 14, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 14, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 14.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 15, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 15, for use in aiding wound healing. . In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 15, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 15.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 16, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 16, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 16, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 16.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 17, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 17, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 17, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 17.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 18, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 18, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 18, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 18.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 19, or a homologue thereof having at least 80% sequenceidentity to SEQ ID NO: 19, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 19, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 19.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 20, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 20, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 20, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 20.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 21 , or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 21 , for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 21, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 21.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 22, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 22, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 22, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 22.In another embodiment of said first aspect, the composition comprises the peptide of SE Z. Q NO: 23, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 23, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 23, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 23.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 24, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 24, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 24, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 24.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 25, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 25, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 25, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 25.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 26, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 26, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 26, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 26.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 27, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 27, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 27, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 27.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 28, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 28, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 28, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 28.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 29, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 29, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 29, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 29.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 30, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 30, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having thesequence of SEQ ID NO: 30, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 30.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 31 , or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 31 , for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 31 , or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 31.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 32, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 32, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 32, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 32.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 33, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 33, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 33, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 33.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 34, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 34, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 34, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 34.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 35, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 35, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 35, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 35.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 36, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 36, for use in aiding wound healing. In another embodimentof said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 36, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 36.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 37, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 37, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 37, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 37.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 38, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 38, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 38, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 38.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 39, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 39, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 39, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 39.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 40, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 40, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 40, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 40.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 41 , or a homologue thereof having at least 80% sequence identity to SEQ ID No. 41 , for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 41 , or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 41.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 42, or a homologue thereof having at least 80% sequenceidentity to SEQ ID No. 42, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 42, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 42.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 43, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 43, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 43, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 43.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 44, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 44, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 44, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 44.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 45, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 45, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 45, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 45.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 46, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 46, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 46, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 46.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 47, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 47, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 47, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 47.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 48, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 48, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 48, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 48.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 49, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 49, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 49, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 49.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 50, or a homologue thereof having at least 80% sequence identity to SEQ ID NO: 50, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 50, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 50.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 51 , or a homologue thereof having at least 80% sequence identity to SEQ ID No. 51 , for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 35, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 35.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 52, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 52, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 52, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 52.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 53, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 53, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having thesequence of SEQ ID NO: 53, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 53.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 54, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 54, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 54, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 54.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 55, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 55, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 55, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 55.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 56, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 56, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 56, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 56.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 57, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 57, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 57, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 57.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 58, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 58, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 58, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 58.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 59, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 59, for use in aiding wound healing. In another embodimentof said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 59, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 59.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 60, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 60, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 60, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 60.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 61 , or a homologue thereof having at least 80% sequence identity to SEQ ID No. 61 , for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 61, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 61.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 62, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 62, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 62, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 62.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 63, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 63, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 63, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 63.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 64, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 64, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 64, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 64.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 65, or a homologue thereof having at least 80% sequenceidentity to SEQ ID No. 65, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 65, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 65.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 66, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 66, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 66, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 66.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 67, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 67, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 67, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 67.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 68, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 68, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 68, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 68.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 69, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 69, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 69, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 69.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 70, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 70, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 70, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 70.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 71 , or a homologue thereof having at least 80% sequence identity to SEQ ID No. 71 , for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 71 , or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 71.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 72, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 72, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 72, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 72.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 73, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 73, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 73, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 73.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 74, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 74, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 74, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 74.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 75, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 75, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 75, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 75.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 76, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 76, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having thesequence of SEQ ID NO: 76, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 76.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 77, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 77, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 77, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 77.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 78, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 78, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 78, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 78.In another embodiment of said first aspect, the composition comprises the peptide of SEQ ID NO: 79, or a homologue thereof having at least 80% sequence identity to SEQ ID No. 79, for use in aiding wound healing. In another embodiment of said third aspect, the composition comprises a synthetic peptide having the sequence of SEQ ID NO: 79, or a homologous sequence having at least 80% sequence identity to SEQ ID NO: 79.With respect to all aspects, the terms “homologue” and “homologous” refer to a peptide having 80% or greater, preferably 85% or greater, more preferably 90% or greater sequence identity with respect to a given peptide selected from SEQ ID NO: 1-79; as determined by standard methods known in the art (particularly Protein BLAST (NCBI), available atttp: / / blast.ncbi.nlm.nih.gov / Blast.cgi?PROGRAM=blastp&PAGE_TYPE=BlastS earch&BLAST_SPEC=blast2seq&LINK_LOC=blasttab, as accessed in October 2014), including visual comparison of the sequences. The term “homologue”, as defined above, encompasses fragments of a given peptide selected from SEQ ID NO: 1-79 having the requisite sequence identity; for example those having 80% or more of the residues present in a given peptide selected from SEQ ID NO: 1- 79, said residues being in the same positions with respect to one another as in the peptide in question.In another embodiment of said first, second and third aspects, the (pharmaceutical) composition comprises 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14,15, 16, 17, 18, 19, 20, 21 ,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38. 39, 40, 41 , 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71 , 72, 73, 74, 75, 76, 77, 78 or 79 of any peptides of SEQ ID NO: 1-79, (or synthetic peptides having the sequence of any of SEQ ID NO: 1-79, according to said third aspect), or homologous sequences thereof having at least 80% sequence identity thereto, preferably at least 85%, more preferably at least 90% sequence identity to any of SEQ ID NO: 1-79.Further according to said first, second and third aspects, the one or more (synthetic) peptides selected from the group consisting of SEQ ID NO: 1-79 preferably each have a molecular weight of less than 10 kilodaltons (kD), more preferably less than 8 kD, more preferably less than 5kD, even more preferably less than 4kD; as determined by standard methods known in the art.Further according to said first and second aspects, the one or more peptides may be (according to said first aspect), or are, (according to said second aspect), present in a serum fraction which is obtainable by, preferably which has been obtained by, a method comprising dialysis of mammalian serum (characterised in that a solution comprising acetate is used), and thereafter, reversed-phase high performance liquid chromatography. Mammalian blood may be obtained from an animal and treated so as to yield serum using any suitable method known in the art. However, those excluding treatment of the blood and serum, once obtained, with a temperature greater than 50°C (preferably 35°C, more preferably 30°C), an acid and / or a detergent are especially preferred; one such especially preferred method comprises leaving blood to clot (once clotting is initiated) at a temperature of from 5 to 25°C, preferably 8 to 22°C, for a period of, for example, 24 hours, so as to yield serum. Preferably, blood from multiple animals (preferably at least 10) is pooled prior to dialysis. It is especially preferred that, prior to said pooling, a solution comprising acetate is added to the serum. This can be derived from any acetate salt, preferably ammonium acetate. It is thought by the present inventors that adding acetate at this stage prevents aggregation of the peptides; this will improve the stability of the final product. By way of example and not limitation, this may be performed using Example Method A (see Examples). Serum may be preserved thereafter by lyophilisation.Further according to said first and second aspects, concerning the dialysis of mammalian serum, this is performed after collection (and possibly reconstitutionfollowing lyophilisation; wherein, by way of example, 3ml serum may be reconstituted in a further 0.5ml of solvent prior to dialysis) such that peptides having a molecular weight greater than 10 kD, preferably greater than 8kD are removed. Specifically, this is performed using a solution comprising acetate as the dialysis buffer. The skilled person will be able to select an appropriate level of acetate, for example 0.01 -20%, preferably 0.1 -10%, more preferably 0.2-5%, even more preferably 0.5-3% by volume, or, for example 1 .5% by volume. This can be derived from any acetate salt, for example ammonium acetate. Preferably, the remaining volume of the solution is substantially composed of water, for example at least 95% by volume (of said remaing volume) water. Preferably, the solution has a pH of 4.5-S.5, preferably 5.5-7.5, for example pH 6. The present inventors have noted that the use of an acetate buffer during dialysis results in a more reproducible reconstituted product following lyophilisation, than saline. Any appropriate method for effecting this separation that is available in the art may be used, the method preferably comprising the use of one or more dialysis membranes having a molecular weight cut-off that is appropriate for the desired separation. Preferably, the dialysis is performed using passive semi-permeable dialysis tubing; by way of example and not limitation, this may be performed using Example Method B. Peptide quantification following dialysis may be performed, by way of example and not limitation, using Example Method C.Further according to said first and second aspects, following dialysis, the serum fraction will then be separated using reversed-phase high performance liquid chromatography, so as to substantially separate peptides having differing interactions with a non-polar adsorbent material (the stationery phase). Any such suitable method, available in the art, may be used. Over time, the mobile phase of the chromatography column will comprise an increasing volume of a first eluent (relative to the volume of a second eluent), said volume of first eluent increasing in a linear fashion with time (a linear, binary gradient). Said first eluent will have a lesser polarity than said second eluent, preferably as a result of being composed of a greater volume of an organic solvent. In one embodiment, preferably the first eluent is more than 80%, preferably more than 90%, more preferably more than 95% organic solvent by volume, and the second eluent is less than 30%, preferably less than 20%, more preferably less than 10% organic solvent by volume. Preferably, the organic solvent in said first and second eluents is acetonitrile. More preferably, the first and second eluents further comprisetrifluoroacetic acid (TFA). This may be present in trace amounts (for example, between 0.05 and 0.2%, for example 0.1%). The remaining volume of both said eluents is preferably water (more preferably HPLC grade water). In a further embodiment, the run time of the reverse-phase high performance liquid chromatography gradient is for no less than 9, 10, 12 or 15 minutes, preferably no less than 9 minutes. Wherein the run time of the gradient is no less than 9 minutes, the fractions of interest will have eluted before 8 minutes of said gradient has passed (see Figure 3). By way of example and not limitation, the reversed phase liquid chromatography may be performed using the following method: 20ul of the serum fraction containing the peptide(s) may be applied to a C18 HPLC column (Ascentis Express peptide ES ) equilibrated with 20% acetinitril in 0.1% aqueous TFA (buffer A / second eluent) at the flow rate of 1ml min-1. A linear, binary gradient may be established over 9 min to a final eluent containing 100% acetonitrile, 0.1 % TFA (buffer B / first eluent). The effluent is monitored at 220nm.Further according to said first and second aspects, preferably the peptides are of non-human origin, more preferably they are of a sheep, goat, horse, bovine or llama.Further according to said third aspect, preferably the one or more synthetic peptides have been obtained via in vitro synthesis. This includes any suitable in vitro method of of peptide synthesis known in the art, for example solid or liquid phase synthesis. Having knowledge of their amino acid sequence, the skilled person will be able to synthesise said peptides, using such methods.Further according to said first second and third aspects, preferably, before the dialysis described above, pre-treatment of the serum with a temperature greater than 50°C (preferably 35°C, more preferably 30°C), an acid and / or a detergent is not performed, more preferably none of the above pre-treatments are performed. Without wishing to be bound by theory, it is thought by the present inventors that such pre-treatment (which is often performed for the purpose of killing pathogens), may deactivate the bioactivity of the serum fraction of interestFurther according to said second aspect, the pharmaceutical composition may further comprise a pharmaceutically-acceptable excipient, preferably selected from any such suitable excipient available in the art. More preferably, the excipient may be selected from the group consisting of lipids, liposomes, polymers, polysaccharides, organic solvents, organic acids, mineral acids, surfactants, stabilizers, preservatives, emulsifiers, anti-oxidants, and solubilizers.Further according to said second and third aspects, the (pharmaceutical) composition is for use in therapy. Preferably, the therapy is treatment of a subject in need of such treatment. More preferably, the treatment is the aiding of wound healing.Further according to said first, second and third aspects, preferably the composition of the invention is administered to a subject via the parenteral route; more preferably wherein the administration via the parenteral route is selected from subcutaneous, intradermal, subdermal, intraperitoneal, intravenous, or intravesicular injection and / or infusion; even more preferably wherein the administration via the parenteral route is subcutaneous injection and / or infusion only.Further according to said first, second and third aspects, preferably the composition of the invention is administered to the subject at a concentration between 0.05 and 3000 mg / ml, preferably between 0.1 and 300 mg / ml. The skilled person will be able to select an appropriate (or optimal) dose from within the ranges above.Compositions according to the first, second and third aspects of the invention may be stored in any container suitable for the storage of medicinal compositions. Alternatively, prior to administration they may be present in a means or device suitable for the particular mode of administration, for example a syringe for intravenous injection.According to a further aspect of the invention, there is provided a method of treating a wound (i.e. aiding the healing thereof) in a subject in need of such treatment; said method comprising administering a therapeutically effective amount of the composition for use or pharmaceutical composition according to the invention; said method having the same optional and preferred features as are applicable to the first, second and / or third aspects of the invention.The invention is now illustrated with reference to the following non-limiting Examples.ExamplesExamge Method AAnimal SelectionAnimal selection is based on age, health and general robustness of the animal. For a sheep the following criteria include:Age: Old enough to have a fully functioning immune system, but not so old the system could be waining. (Age 6 months through 4 years would be ideal.Sex: Male, female, or castrated male are acceptable. Avoid pregnant females as the pregnancy can suppress the immune system.Thrifty & robust animals: Animals with a history or respiratory diseases or parasites should be avoided as it suggests a less than optimal immune system.Whole Serum CollectionSerum is obtained by collecting whole blood and allowing it to clot. Plasmaphoresis and defibrinating to obtain serum is not the desired method as the time and chemicals used in the defibrination process are not conducive to the preservation of the low molecular weight peptides.On large animals, whole blood is usually obtained via a jugular stick. Whole blood is collected in a blood bag or other closed system to eliminate environmental contamination. Blood volume is monitored to assure the long term health of the animal. Typically no more than 1% by weight of blood is removed every two weeks. (1 litre whole blood per 100kg animal).Once collected the blood is allowed to stand between for at least 6 hours to initiate clotting at room temperature, and up to 24 hours to complete the process. The temperature for the remaining clotting process can range between 22°C and 8°C. The blood bag with the clotted blood and serum is centrifuged at ~3500 RCF for 30 minutes with a temperature between 5 and 20°C with 10°C being preferred. This step is to only increase the yield of serum from the clot. After centrifugation, the resulting serum is transferred from the blood bag to a sterile 500 ml conical tube under a biologies hood. This step is to remove any residual red or white blood cells. Once spun, the serum is ready for processing or storage at -20°C or colder. From the whole blood, one would expect to obtain 60 to 70%of the starting volume as serum using this process (1 litre whole blood would yield between 600 and 750 ml of serum.It is important to note that the serum is being processed at 22°C or colder, and no additives are addedPooling of serumTo assure batch to batch consistency, pooling serum from acceptable animals is the preferred method. For research use, different donor animals should be sufficient to provide a reasonable batch to batch consistency. For a commercial product, serum from at least 10 and possibly 30 animals should make up the pool.Example Method BThe standard method for producing research level material by passive dialysis tubing is using a 8 to 10 KD MWCO regenerated cellulose dialysis membrane with a diameter of 30 to 35mm. The large diameter gives a significant serum volume to membrane surface area to reduce any significant peptide stickiness to the membrane. The standard method involves, for example, an equal volume of serum on the retentate side of the membrane to the volume of buffer on the filtrate side of the membrane. The dialysis takes between 21 and 24 hours on an orbital tray at 4°C. If more than 24 hours is elapsed, one will notice a higher yield of peptide on the filtrate side of the membrane.The protocol may be as follows:All Activities take place under a biologies hood.1) About 30 cm of 8KD Spectrium regenerated cellulose dialysis tubing (32mm wide) is rinsed in distilled water 3x to remove any azide. This is allowed to soak in the distilled water until use.2) 50 ml of pooled normal sheep serum is sterile filtered using a 0.2um acrodisc syringe filter. The filtered serum is placed into a sterile conical tube, then transferred to a 60 ml syringe.3) The dialysis bag is clipped on the bottom with a tubing clamp.Example 1 - Effects of Low Molecular Weight Sheep Peptide in a MurineExcisional Wound ModelThe objective of this study is to evaluate the wound healing effect of the test article in an excisional wound model of diabetes in the db / db mouse. Primary end points include body weights, whole blood glucose levels, clinical observations as well as digital photographs, and wound area in response to treatment of the wound biopsy.Table 1 - Study Design*ln this case, there were two products being studied, Low Molecular Sheep (IMS) and Low Molecular Goat (IMG), thus four bars are shown in Figures 2A and 2BTest MaterialsTest Article 1Identification: LMS (Low Molecular Sheep)Lot No.: The lot number will be recorded and included in the study file.Storage: Nominally -70°C (protected from light)Vehicle and Diluent for T est ArticlesIdentification: 0.9% sterile salineLot No.: The lot number will be recorded and included in the study file.Storage: 22°C ± 5°CT est Article CharacterizationThe Sponsor will hold information on the composition and method of synthesis of the bulk test article. The test article will be assumed to be 100% pure / active unless otherwise stated.Dose PreparationThe Test Article (TA) is provided in a bulk sterile botle by the Sponsor in ready to use form. Daily aliquots of test material dosing solutions will be performed in a Class II safety cabinet using clean technique. Test material aliquots will be stored at nominally -70°C (protected from light). Material should be removed from the freezer on day of dosing, thawed at room temperature and stored on wet ice no longer than 1 hour prior to dose administration. The test material contains no stabilizers or preservatives and should not be exposed to excessive temperatures for long periods of time.Test SystemSpecies: Mus musculusStrain: db / db mice (JAX stock # 000642)Number of Females (Non-diabetic): 12 + 3 alternates (BKS.Cg-Dock7<m> + / + Lepr<db> / J,Genotype: M02 Heterozygous for Lepr<db>, Heterozygous for Dock7<m>) Number of Females (Diabetic): 36 + 3 alternates (BKS.Cg-Dock7<m> + / + Lepr<db> / J,Genotype: HOM1 Homozygous for Lepr<db>)Age at arrival: ~10 weeks of ageAge at dose initiation: ~14 weeks of ageSource: Jackson LaboratoriesLocation: Bar Harbor, MEUpon arrival animals will be aged from 10 - 14 weeks of age. Each animal will be identified by a unique number, which will be indicated by ear notch and posted on the animal's enclosure.The peptide fraction under study is associated with large molecules with immunomodulatory properties. The db / db mouse was chosen for this studybecause it is immunomodulatorily compromised, thus would have the greater chance of having a clinical response to the peptide fraction. The hypothesis is that the test materials will improve the immunomodulation of db / db mice which in turn would stimulate wound healing.The total number of animals to be used in this study is the minimum required to properly characterize the acute clinical response effects of the test article when administered by subcutaneous injection to db / db mouse model.Housing and HusbandryUpon arrival animals are group housed in a procedure room, in conventional housing seting. Post-surgery animals are individually housed in clear polycarbonate cages with contact bedding with wire mesh inserts and resting platforms meeting the requirements of the Guide for the Care and Use of Laboratory Animals. Rodent Diet 5008 - Irradiated is provided to the animals ad libitum. Before whole blood glucose collections, animals are fasted for a minimum of 4 hours (not to exceed 6 hours). Food, including any dietary supplements, are withheld, and bedding is changed to clean alpha-dry bedding material. Animals are transferred to a fresh cage. Filtered tap water acidified with 1 N HCI to a targeted pH of 2.5 -3.0 is provided to the animals ad libitum, including during times of fasting.Procedure room environmental controls are set to maintain temperatures of 22°C to 26°C (72°F to 79°F) with a relative humidity of 30% to 70%. A 12-hour light / 12-hour dark cycle is maintained, except when interrupted to accommodate study procedures. Ten or greater air changes per hour with 30% fresh air (no air recirculation) and 70% recirculated air will be maintained in the animal rooms. Upon receipt at the Test Facility, the animals undergo a period of environmental acclimation for at least 3 days. Manual restraint is used as necessary to facilitate animal handling and performance of the technical procedures. Light anesthesia (ketamine HCI [50-100 mg / kg]: xylazine HCI [5-13 mg / kg], intraperitoneally [IP] or light anesthesia (isoflurane (3-5%), inhaled via facemask or chamber, to effect) is used, as necessary, to facilitate wound excision technical procedures. All restraint is performed according to the appropriate Test Facility standard operating procedures. All animals (including spares) are tested for diabetes between Day - 3 to Day 1 (diabetes will be defined as a fasted whole blood glucose level > 250mg / dL) using a handheld glucometer. Non-diabetic animals are assigned to Group1. Diabetic animals are assigned to Groups 2-3 by blood glucose distribution.Justification of Route and Dosage LevelsThe route of administration is selected to provide systemic exposure to the test material and is the intended route of administration in humans.The IMS dosage scheme is selected based on a murine melanoma study performed at Mississippi State University, 2006 using a related product. In this case a single dose of 25 mg of desiccated product was administered to mice. No adverse events were observed. It is postulated that significant activity was lost when the product was desiccated. The product being presented has not been concentrated or desiccated, thus it is anticipated it will be in its most active form. LMS was also dosed in db / db mice at a volume of 0.5mL Fat a concentration of 0.14mg / mL for 28 days at BRM, Study ARP11-01 with no obvious adverse events (no behavior, no acute toxicity) observed. At 14 injections of -0.07 to 0.08 mg / animal, the individual mouse received -1.4 to 1.6 mg of test material during the study. This study is used to confirm ARP11-01 results and to find optimum study parameters.Administration of Test MaterialsDoses of test material are administered daily (QD) over a 24-day period by subcutaneous injection (SC) beginning after time of wound creation on anesthetized animals (see Section 13.6). Doses are administered at a dose volume of 0.5 mL / animal. Doses are rounded to the nearest 0.01 mL.Location of the SC administration is dorsally, but away from the wound site. Administration is not “in” the wound as a systemic reaction is anticipated.Surgical ProcedurePrior to surgery and while under anesthesia (isoflurane) all animals have their dorsum shaved and biopsy punch location marked with a permanent marker. There will be sufficient distance between each punch to be easily collected at time of necropsy. The animal is warmed with either a heating pad or with a hot air blower.On anesthetized animals, using strict aseptic procedures, an 8-mm skin biopsy punch is used to create two full thickness excisional skin wounds permouse on Day 1. Two wounds will be created dorsally on each side of the back of the animal. The animal will remain on either a heating pad and / or warmed with a hot air blower and allowed to recover from anesthesia. Once the animal has regained consciousness and is ambulatory, the animal is returned to its home cage. The wound will remain undressed.Animals are given buprenorphine (0.1 mg / kg, subcutaneously [SC]) beginning on Day 1 before the procedure and continuing every 8-12 hours, as needed. Additional analgesics are administered in animals demonstrating signs of pain on palpation or locomotion or distress (such as, but not limited to, hunched posture, vocalization, lethargy, and / or decreased food consumption) if deemed appropriate by the Test Facility veterinarian in consultation with the Study Director and Sponsor. The drug, dose, route, and site of administration will be documented in the study file.Wound sites are observed and assessed at least once daily for any apparent problems (e.g. infection), and genera! integrity. If the wound has healed, the observations are recorded as such and no further daily wound observations are documented. The Study Director and / or Test Facility veterinarian is notified of any abnormalities. Appropriate supportive therapy will be initiated as necessary and documented in the study file.In-Life observations and MeasurementsAnimal health checks are performed at least once daily in which all animals are checked for general health, mortality, and moribundity.Clinical observations are performed at least once prior to and 1 - 4 hours after creating excisional skin wounds. Clinical observations are performed at least once daily, beginning before the initial dose and continuing until the completion of the study. Animals are also monitored for appetite, stool production, urination, locomotive capacity, and any abnormalities are documented (Table 4).Body weights are recorded twice / week beginning before the initial excisional skin wound on Day 1. Weights are rounded to the nearest 0.1 g and reported in the data submission. Additional body weights may be taken as needed per Study Director recommendation.Baseline whole blood samples are collected between Day -3 and Day1 and on day of scheduled euthanasia (Days 3, 15 and 29 for n= 6 / group). Whole bloodglucose levels are determined using a handheld glucometer. Results are recorded in the data submission.Terminal Procedures If an animal appears in poor condition or in extremis, and unlikely to survive until the next scheduled observation, it is euthanized per protocol with Study Director approval. Body weights are recorded, and wound tissue collected for Sponsor.If an animal dies on study, a necropsy is conducted as soon as possible, or the animal is refrigerated to minimize autolysis, and a necropsy conducted as soon as practical. In either case, specified tissues will be saved.Euthanasia (carbon dioxide asphyxiation, to effect, in conjunction with exsanguination [terminal blood collection], followed by thoracotomy) is performed in accordance with accepted American Veterinary Medical Association (AVMA) guidelines.Blood is collected from a terminal maximum obtainable blood collection by cardiac puncture. Blood volumes represent whole blood and are approximate amounts. After collection, samples are processed as described below (Table 2), Table 2 - Sample Collection ScheduleMOV = maximum obtainable volume.aBlood samples will be collected into serum separator tubes. The whole blood samples are collected into serum separator tubes, centrifuged, and the serum will be extracted by the Test Facility. The serum is stored at nominally -70°C until shipped on dry ice by an overnight courier service to the Sponsor at the completion of the study for possible analysis of cytokines.Photographs are taken with a digital camera of the wound sites after euthanasia. A scale reference and caliper measurement of the wound is conducted at time of collection. Wound closure is expressed as the proportion ofthe initial wound areas. This is determined and reported as the percentage closed and calculated as:% Closed = [(Area on Day 1 - Open Area on Final Day) / Area on Day 1] X 100Day 1 area is assumed to be 8mm based on skin biopsy punch.A limited necropsy is conducted and consist of examination of the thoracic cavity and gross lesions or masses (if applicable) for animals that are found dead or euthanized in moribund condition. Observations noted at necropsy are recorded.Table 3 - Pathology ProceduresL = LimitedThe wound site and surrounding areas is collected from animals that are euthanized in moribund condition and scheduled necropsy on Days 3, 15 and 29. Wounds are examined in situ and dissected free. The area of the wound is determined using digital photographs.Wound sites are fixed in 10% neutral buffered formalin and stored ambient, until shipped to the Sponsor by overnight service for possible histomorphometric analyses.Histology And HistopathologyHistology and histopathology is performed only per amendment at the request of the Sponsor.Rt = right; Lt = left; THN = thin; DHY = dehydrated; HP = hunched posture; RHC = rough hair coatRt = right; Lt = left; THN = thin; DHY = dehydrated; HP = hunched posture; RHC = rough hair coatExample 2 - HPLC Characterisation of Low Molecular Weight MaterialFigure 3 shows separation of the serum fraction by reversed-phase high performance liquid chromatography. 20ul of the serum fraction containing the peptide(s) was applied to a C18 HPLC column (Ascentis Express peptide ES ) equilibrated with 20% acetonitrile in 0.1% aqueous TFA (buffer A / second eluent) at the flow rate of 1ml min-1. A linear, binary gradient was established over 9 min to a final eluent containing 100% acetonitrile, 0.1% TFA (buffer B / first eluent). The effluent was monitoring at 220nm.ExamBle_3_zdPeBtide_Characte^^(8KD) of Caprine Origin by Matrix-Assisted Laser Desorption / lonisation (MALDI) - ToF Mass SpectrometryThree goat serum samples which had undergone different preparations were compared. Specifically:1) Bag A: Goat 2210 6 April 2011 Purification.... 0.11 mg / ml..... Dialysis with <8KD MWCO in 0.9% Saline. Heat treated (100°C) for 3 hours2) Bag A: Goat 2210 6 April 2011 Purification.... 0.11 mg / ml.....Dialysis with <8KD MWCO in 0.9% Saline. Not Heat Treated3)Bag J: Goat 2210 6 April 2011 Purification.... 0.11 mg / ml..... Dialysis with <2KD MWCO in 0.9% Saline. Not Heat T restedSamples were desalted prior to MALDI ToF analysis using C18 Zip Tips. Specifically, a 500ul aliquot of each sample was acidified with 0.1% Tri-Fluoro Acetic acid (TFA). The Zip Tip was washed with 100% acetonitrile (ACN) and equilibrated with 0.1% TFA. Peptides were bound with 10 cycles of aspirating and disparaging 10ul volumes of the sample over the resin. Bound peptides were washed with 0.1% TFA and peptides were eluted in 5ul of 50% ACN / 0.1% TFA. Each sample was zip-tipped in duplicate.The peptide eluant (1 ul was pre-mixed with with 1 ul of a cyano-4-hydroxy cinnamic acid (20mg / ml in 30%ACN / 0.1% TFA), 0.5 ul was then spotted onto a MALDI target plate and allowed to air dry. Each sample was spotted / analysed in duplicate.The MALDI MS (Bruker Ultraflex) was calibrated with standard peptides over the mass range 900-3200. Two hundred laser shots were taken per spectra and a total of five spectra were collected and average per sample spotted. The resultant averaged spectra are displayed in Figures 4 to 6.Peptide profiles for each sample are displayed in Figures 4 to 6. Four spectral profiles were acquired per serum sample i.e. two desalting preparations for each sample with each analysed in duplicate. The spectra displayed for each serum is a representative spectra chosen from the four spectra acquired. The m / z range was divided in three sections for display purposes 1000-2000 (Figure 4), 2000-2200 (Figure 5) and 2200-4000 (Figure 6).Comparison of the three samples showed that essentially the same ions were detected in all three samples with very close replication of the ions detected across all samples. Only a couple of very minor ions (m / z 1363, 2153, 2168; highlighted in Figures), which were found in the <8kDa heat treated reference sample were not observed in the other two reference samples. On inspection of the other spectra acquired in each group ion at m / z 2153 was actually detected in other replicas of the <8kDa and <2kDa serum samples and ions at m / z 1263 and 2168 were detected in other replicas of the <8kDa serum sample but not the <2kDa serum sample. As these ions are at low signal intensity it is difficult to say that these ions are depleted in the <2kDa sample rather than just not detected in the replicas analysed.Peptides identified by the scan, and the known proteins of which they are fragments, are summarised in Table 5.Sequence IDsSEQ ID NO: 1LDYDEVDDNRASEQ ID NO: 2GYLDYDEVDDNRASEQ ID NO: 3DYDEVDDNRAKLPSEQ ID NO: 4DEVDDNRAKLPLDASEQ ID NO: 5LDYDEVDDNRAKLPSEQ ID NO: 6YLDYDEVDDNRAKLSEQ ID NO: 7YDEVDDNRAKLPLDASEQ ID NO: 8DYDEVDDNRAKLPLDSEQ ID NO: 9YLDYDEVDDNRAKLPSEQ ID NO: 10DYDEVDDNRAKLPLDASEQ ID NO: 11GYLDYDEVDDNRAKLPSEQ ID NO: 12YLDYDEVDDNRAKLPLSEQ ID NO: 13LDYDEVDDNRAKLPLDASEQ ID NO: 14YLDYDEVDDNRAKLPLDASEQ ID NO: 15GYLDYDEVDDNRAKLPLDASEQ ID NO: 16GGEFLAEGGGVSEQ ID NO: 17VGGEFLAEGGGVSEQ ID NO: 18ADDSDPVGGEFSEQ ID NO: 19PVGGEFLAEGGGVSEQ ID NO: 20DSDPVGGEFLAEGGGVSEQ ID NO: 21DDSDPVGGEFLAEGGGVSEQ ID NO: 22ADDSDPVGGEFLAEGGGVSEQ ID NO: 23RILWESASLLSEQ ID NO: 24HRILWESASLLSEQ ID NO: 25EETKENERFTVSEQ ID NO: 26SEETKENERFTVSEQ ID NO: 27SLVKHRILWESASLSEQ ID NO: 28GLKSHVLQLTNHQSEQ ID NO: 29DDPEAHSRPVTPLQSEQ ID NO: 30SGLKSHVLQLTNHQSEQ ID NO: 31GLKSHVLQLTNHQVHSEQ ID NO: 32RQLFHPEQLITGKEDAANNSEQ ID NO: 33KDYEEVGIDSYEDEDEGEESEQ ID NO: 34PTKETIEQEKQASEQ ID NO: 35TLPTKETIEQEKQSEQ ID NO: 36TLPTKETIEQEKQASEQ ID NO: 37SLTLTDVENLHLPLPLSEQ ID NO: 38TESQSLTLTDVENLHLPLPLSEQ ID NO: 39PPTVELQGLVPRSEQ ID NO: 40EPMIGVNQELAYFYPELFRSEQ ID NO: 41YLDYDEVDDNRSEQ ID NO: 42DEVDDNRAKLPLDSEQ ID NO: 43GYLDYDEVDDNRASEQ ID NO: 44DEVDDNRAKLPLDASEQ ID NO: 45LDYDEVDDNRAKLPSEQ ID NO: 46YDEVDDNRAKLPLDASEQ ID NO: 47YLDYDEVDDNRAKLPSEQ ID NO: 48DYDEVDDNRAKLPLDASEQ ID NO: 49YLDYDEVDDNRAKLPLSEQ ID NO: 50YLDYDEVDDNRAKLPLDSEQ ID NO: 51YLDYDEVDDNRAKLPLDASEQ ID NO: 52GYLDYDEVDDNRAKLPLDASEQ ID NO: 53GGEFLAEGGGVSEQ ID NO: 54VGGEFLAEGGGVSEQ ID NO: 55ADDSDPVGGEFSEQ ID NO: 56DDSDPVGGEFLSEQ ID NO: 57PVGGEFLAEGGGVSEQ ID NO: 58DSDPVGGEFLAEGGGVSEQ ID NO: 59DDSDPVGGEFLAEGGGVSEQ ID NO: 60ADDSDPVGGEFLAEGGGVSEQ ID NO: 61RILWESASLLSEQ ID NO: 62HRILWESASLLSEQ ID NO: 63SEETKENERFTVSEQ ID NO: 64NSLVKHRILWESASEQ ID NO: 65NSLVKHRILWESASLLRSEQ ID NO: 66YLGYLEQLLRSEQ ID NO: 67FFVAPFPEVFGKSEQ ID NO: 68EPMIGVNQELAYFYPELFRSEQ ID NO: 69AEKAYHEQLSVAEITNSEQ ID NO: 70TYAPVISAEKAYHEQLSEQ ID NO: 71RQLFHPEQLITGKEDAANNSEQ ID NO: 72RQLFHPEQLITGKEDAANNYSEQ ID NO: 73YRQLFHPEQLITGKEDAANNYSEQ ID NO: 74PTKETIEQEKQASEQ ID NO: 75TLPTKETIEQEKQASEQ ID NO: 76TKPAASDLPVPAEGVRNISEQ ID NO: 77SRAGGRVSEAKEAEGTSQVEAGKRLESEQ ID NO: 78TESQSLTLTDVENLHLPLPLSEQ ID NO: 79 GLKSHVLQLTNHQ

Claims

Claims1. A composition comprising one or more mammalian serum peptides, for use in aiding wound healing; wherein said one or more peptides are selected from the group consisting of SEQ ID NO: 1-79, or homologues thereof having at least 80% sequence identity to SEQ ID NO: 1-79.

2. A composition for use according to claim 1 , wherein said one or more peptides each have a molecular weight of less than 10 kilodaltons, preferably less than 8 kilodaltons.

3. A composition for use according to claim 1 or claim 2, wherein said one or more peptides are present in a serum fraction; said fraction being obtainable by a method comprising:(a) dialysis of mammalian serum, performed such that peptides having a molecular weight of greater than 10 kilodaltons, preferably greater than 8 kilodaltons, are removed; wherein said dialysis is performed using a solution comprising acetate, preferably having a pH of 4.5 to 8.5, more preferably 5.5 to 7.5; and thereafter(b) reversed-phase high-performance liquid chromatography, comprising the use of a linear gradient of increasing volume of a first eluent relative to the volume of a second eluent.

4. A composition for use according to claim 3, wherein the serum fraction has been obtained by said method.

5. A composition for use according to any preceding claim, wherein said one or more peptides are non-human.

6. A composition for use according to claim 5, wherein said one or more peptides are of a sheep, goat, horse, bovine or Hama.

7. A composition for use according to any of claims 4 to 6, wherein the method does not comprise, prior to step (a), treatment of the serum with a temperature greater than 50°C, an acid and / or a detergent.

8. A composition for use according to any of claims 3 to 7, wherein the reversed-phase high-performance liquid chromatography first eluent is less polar than the second eluent; preferably wherein the first eluent is more than 80%, preferably more than 90%, more preferably more than 95% by volume organic solvent, and wherein the second eluent is less than 30%, preferably less than 20%, more preferably less than 10% by volume organic solvent.

9. A composition for use according to any of claims 3 to 8, wherein the reversed-phase high-performance liquid chromatography linear gradient is for no less than 9 minutes, and wherein the serum fraction elutes after no longer than 8 minutes of said gradient.

10. A composition for use according to any preceding claim, wherein the composition is administered to a subject via the parenteral route.

11. A composition for use according to claim 10, wherein the administration via the parenteral route is selected from subcutaneous, intradermal, subdermal, intraperitoneal, intravenous, or intravesicular injection and / or infusion, preferably subcutaneous injection.

12. A composition for use according to claim 10 or claim 11, wherein the composition is administered at a peptide concentration of between 0.05 and 3000 mg / ml.

13. A pharmaceutical composition comprising a mammalian serum fraction; said fraction comprising mammalian serum peptides each having a molecular weight of less than 10 kilodaltons; said fraction being obtainable by a method comprising:(a) dialysis of mammalian serum, performed such that peptides having a molecular weight of greater than 10 kilodaltons are removed; wherein said dialysis is performed using a solution comprising acetate; and thereafter;(b) reversed-phase high-performance liquid chromatography, comprising the use of a linear gradient of increasing volume of a first eluent relative to the volume of a second eluent.

14. A pharmaceutical composition according to claim 13, wherein in (a), said solution has a pH of 4.5 to 8.5, preferably 5.5 to 7.5.

15. A pharmaceutical composition according to claim 13 or claim 14, wherein said peptides each have a molecular weight of less than 8 kilodaltons, wherein the dialysis is performed such that peptides having a molecular weight of greater than 8 kilodaltons are removed.

16. A pharmaceutical composition according to any of claims 13 to 15, wherein the mammalian serum fraction has been obtained by said method.

17. A pharmaceutical composition according to any of claims 13 to16, further comprising a pharmaceutically acceptable excipient, preferably selected from the group consisting of lipids, liposomes, polymers, polysaccharides, organic solvents, organic acids, mineral acids, surfactants, stabilizers, preservatives, emulsifiers, anti-oxidants, and solubilizers.

18. A pharmaceutical composition according to any of claims 13 to 17, wherein one or more of said peptides are selected from the group consisting of SEQ ID NO: 1-79.

19. A pharmaceutical composition according to any of claims 13 to 18, wherein said peptides are non-human.

20. A pharmaceutical composition according to claim 19, wherein said peptides are of a sheep, goat, horse, bovine or llama.

21. A pharmaceutical composition according to any of claims 13 to 20, wherein the method does not comprise, prior to step (a), treatment of the serum with a temperature greater than 50°C, an acid and / or a detergent.

22. A pharmaceutical composition according to any of claims 13 to 21 , wherein the reversed-phase high-performance liquid chromatography first eluent is less polar than the second eluent; preferably wherein the first eluent is more than 80%, preferably more than 90%, more preferably more than 95% by volume organic solvent, and wherein the second eluent is less than 30%, preferably less than 20%, more preferably less than 10% by volume organic solvent.

23. A pharmaceutical composition according to any of claims 13 to 22, wherein the reversed-phase high-performance liquid chromatography linear gradient is for no less than 9 minutes, and wherein the serum fraction elutes after no longer than 8 minutes of said gradient.

24. A pharmaceutical composition according to any of claims 13 to 23, for use in therapy, preferably in aiding wound healing.

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