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Treatment of diseases and conditions mediated by eicosanoids

A technology of eicosanoids, diseases, applied in the field of compositions of diseases and disorders

Inactive Publication Date: 2011-05-18
NATURAL ENVIRONMENT RES COUNCIL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Montelukast has not been approved for cystic fibrosis, but there is some evidence of therapeutic efficacy (Stellmach et al., 2005)

Method used

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  • Treatment of diseases and conditions mediated by eicosanoids
  • Treatment of diseases and conditions mediated by eicosanoids
  • Treatment of diseases and conditions mediated by eicosanoids

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0118] Example 1: OmCI binding to 12(S)-HETE (12(S)-hydroxyeicosatetraenoic acid) in a competition ELISA

[0119] background:

[0120] OmCI binds to fatty acids ( figure 1 ). Mass spectrometry analysis showed that ricinoleic acid (C 18 h 34 o 3 ) and palmitoleic acid (C 16 h 30 o 2 ) are the major forms seen in OmCI expressed in P. methanolica and E. coli, respectively. However, the actual physiological ligands are more likely to be one or more of many eicosanoids derived from host cell membranes that mediate inflammation, oxidative stress, and cell signaling.

[0121] Eicosanoids can be quantified using a competitive enzyme immunoassay (EIA) from Assay Designs Inc. One such EIA kit uses a polyclonal antibody against 12(S)-HETE to compete with 12(S)-HETE labeled with alkaline phosphatase, and unlabeled in samples or standards of known concentration. 12(S)-HETE binding. After simultaneous incubation at room temperature and antibody capture on the plate, excess reagen...

Embodiment 2

[0129] Example 2: Parameters affecting the combination of 12(S)-HETE and OmCI

[0130] method:

[0131] A method similar to that described in Example 1 was used.

[0132] Results and discussion

[0133] A significant molar excess of bOmCI to 12(S)-HETE is required to provide results that clearly demonstrate 12(S)-HETE binding ( image 3 ). exist image 3 In the tests shown, bOmCI was in excess of approximately 634, 127 and 25.5 molar relative to 12(S)-HETE. The need for a significant molar excess of OmCI may reflect competition of bOmCI for binding to 12(S)-HETE with anti-12(S)-HETE antibodies, low binding affinity of bOmCI for 12(S)-HETE, and / or binding only to those not protected by palmitate. Oleic acid-occupied bOmCI binding.

[0134] Prolonged incubation (overnight at room temperature) did not increase the proportion of 12(S)-HETE bound to bOmCI ( Figure 4 )

[0135] At equivalent concentrations, yeast (y)OmCI bound less 12(S)-HETE ( Figure 5 ). At a 634 molar...

Embodiment 3

[0137] Example 3: OmCI binds LTB4 but not TXB2 or cysteinyl leukotrienes

[0138] method:

[0139] Buy for Leukotriene B 4 (LTB 4 ), thromboxane B 2 (TXB 2 ) and cysteinyl leukotriene (cys-LK) solution measured Assay Design Inc. EIA kit and used according to product instructions. Mix 100 μl of the standard solution with ≤9 μl of PBS or a diluted stock solution of OmCI or RaHBP2. The mixture was incubated at room temperature for 20 minutes before being used in the immunoassay according to the manufacturer's instructions. The absorbance readings of the treated samples are compared to a standard curve to estimate the concentration of eicosanoid in solution that can be bound by the anti-eicosanoid polyclonal antibody.

[0140] result:

[0141] bOmCI showed no association with the cyclic eicosanoid TXB2 ( Figure 6 ) or amino acid-coupled Cys-LK binding (data not shown). This is in line with our crystallographic data showing that the binding pocket of OmCI is not large eno...

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Abstract

The method of the invention relates to an OmCI polypeptide or a polynucleotide encoding an OmCI polypeptide for the treatment of a disease or condition mediated by a leukotriene or hydroxyeicosanoid.

Description

technical field [0001] The present invention relates to compositions for the treatment of diseases and conditions mediated by eicosanoids, in particular to tick-derived complement inhibition for the treatment of diseases and conditions mediated by leukotrienes and hydroxyeicosanoids agent. Background technique [0002] Eicosanoids are derived from the 20-carbon fatty acid arachidonic acid through 3 major enzymatic pathways: cyclooxygenase (COX), lipoxygenase (LO), and cytochrome P450 monooxygenase (CYP450). Acidic acid (AA) family of bioactive lipid mediators of oxidation. Eicosanoids include prostanoids from the COX pathway (including prostaglandins (ie, PG) and thromboxanes (ie, TXB)), leukotrienes from the LO pathway, and from the LO and P450 monooxygenase pathways Hydroxyeicosatetraenoic acid (HETE) and epoxyeicosatrienoic acid (EET) (Curtis-Prior, 2004; Peters-Golden & Henderson Jr., 2007). Eicosanoids mediate numerous effects on various cell types and organs. These...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/44C12N15/30A61K38/16A61K48/00A61P17/00A61P1/04A61P35/00A61P11/08A61P1/02A61P37/02A61P21/00A61P29/00A61P9/10A61P17/06A61P19/02A61P19/06A61P13/12
CPCA61K31/19A61K38/04A61P1/00A61P1/02A61P1/04A61P11/00A61P11/06A61P11/08A61P13/12A61P17/00A61P17/04A61P17/06A61P17/10A61P19/02A61P19/06A61P21/00A61P25/00A61P25/02A61P25/28A61P27/02A61P29/00A61P35/00A61P35/04A61P37/00A61P37/02A61P37/08A61P43/00A61P9/00A61P9/10
Inventor 苏珊·利迈尔斯·纳恩彼得罗·罗韦尔西
Owner NATURAL ENVIRONMENT RES COUNCIL
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