Method of treatment
A reagent, proliferative technology, applied in pharmaceutical formulations, peptide/protein components, sensory diseases, etc., can solve the problems of not found effective, therapeutic molecules cannot achieve effective effects, etc.
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[0464] Preparation of reagents
[0465] Proteins and their functional equivalents can be produced in recombinant form by expression in host cells. Such expression methods are well known to those skilled in the art and described in detail by [54] and [55]. Recombinant forms of nomacopan proteins and functional equivalents thereof are preferably unglycosylated. Preferably, the host cell is Escherichia coli.
[0466] The nomacopan protein and functional equivalents thereof are preferably in isolated form, eg from at least one component of the host cell and / or the cell growth medium expressing it. In some embodiments, the nomacopan protein or functional equivalent thereof is purified to at least 90%, 95%, or 99% purity as determined, eg, by electrophoresis or chromatography. The proteins and fragments of the invention can also be prepared using conventional techniques of protein chemistry. For example, protein fragments can be prepared by chemical synthesis. Methods for produ...
Embodiment 1
[0538] Example 1 EAU treatment with topical application of nomacopan-type proteins
[0539] Such as image 3 As shown in , compared with only saline-treated mice, after topical administration of nomacopan (5mg / ml), PAS-nomacopan (20mg / ml), L-nomacopan (5mg / ml), in EAU mice Clinical scores were lower, where the results were statistically significant for L-nomacopan. A tendency was observed for nomacopan and PAS-nomacopan treated mice. The clinical scores of L-nomacopan-treated mice were consistent with those of dexamethasone-treated mice. Mean score ± SEM; 8.083 ± 0.848; n = 12) relative to saline control group (10.33 ± 0.666; n = 12; P = 0.048), in which there was no significant change in CD4+ T cell number or subtype in treated mice .
[0540] These results were unexpected because the test molecules were not previously known to cross the cornea. The reduced potency of PAS-nomacopan compared to the non-PASylated form may reflect the fact that the PASylated form is large...
Embodiment 2
[0541] Example 2 Co-expression of BLT1 and C5a receptors in mouse retinal cells
[0542] Confocal microscopy of mouse retinal sections in UAE mice using monoclonal antibodies recognizing BLT1 and C5a receptors counterstained with DAPI (blue indicates nuclei) shows both receptors expressed in inflamed cells. Some individual cells co-expressed both receptors, while many cells expressing a single receptor were also observed. It is believed that at least some of these cells are M2 macrophages, which are known to migrate to areas of retinal damage where they release VEGF in response to LTB4 stimulation (see Figure 4 , Fig. 7 and embodiment 4).
[0543] This is consistent with other results presented herein that nomacopan-type proteins may be useful agents in the treatment of such diseases (eg, diseases in which LTB4 is involved and / or the complement pathway is involved).
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