Assessment, determination and treatment of pkal-mediated disorders

A mediation, disease technology, applied in the field of assessment, measurement and treatment of PKAL-mediated diseases, can solve problems such as bradykinin overproduction

Active Publication Date: 2019-08-02
TAKEDA PHARMA CO LTD
View PDF29 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Hereditary angioedema types I and II are caused by a genetic defect in C1-INH, which leads to overproduction of bradykinin

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Assessment, determination and treatment of pkal-mediated disorders
  • Assessment, determination and treatment of pkal-mediated disorders
  • Assessment, determination and treatment of pkal-mediated disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0286] Example 1. Composite ELISA for Quantification of Functional Cl-INH in Plasma Using Activated Factor XII and / or Plasma Kallikrein

[0287] Dysfunction of the C1 inhibitor, C1-INH, has been demonstrated in hereditary angioedema type II (HAE), which renders the inhibitor ineffective. Type I HAE has low total C1-INH protein levels. Type III HAE is associated with normal C1-INH levels. (“Enzymatic pathways in the pathogenesis of hereditary angioedema: Therole of C1 inhibitor therapy.” Kaplan, A., The Journal of Allergy and Clinical Immunology 126(5):918-252010). C1-INH inhibits Factor XIIa, Fragment of Factor XII (XIIf), kallikrein and plasmin. In the absence of C1-INH function, marked activation of the bradykinin formation cascade leads to severe angioedema. Type I HAE is usually characterized by decreased total C1-INH levels. Type II HAE is usually characterized by normal to increased C1-INH levels, however the function of C1-INH is abnormal. The mechanisms leading to...

Embodiment 2

[0293] Example 2. Diagnostic Assay for Hereditary Angioedema Based on Inhibition of Activated Factor XII and / or Plasma Kallikrein

[0294] method

[0295] Patient and Sample Collection: Diagnosis of HAE is made by clinical presentation, low C1-INH protein and / or functional levels (using commercial assays). Citrated plasma from 42 patients with HAE and 23 healthy controls was separated by centrifugation of freshly collected blood at 2000 rpm for 10 minutes at 4°C. All samples were immediately aliquoted and stored at -80°C. Samples were handled similarly at all participating sites (Odense, Denmark; Budapest, Hungary) and shipped overnight on dry ice. The protocol was approved by the Ethics Committee (Ethics Committee) and the Data Protection Agency (Data Protection Agency) of the two participating sites.

[0296] Purified human Factor XIIa and kallikrein were obtained from Enzyme Research Laboratories (South Bend, IN), biotinylation reagents were obtained from Thermo Scientif...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

PropertyMeasurementUnit
affinityaaaaaaaaaa
Login to view more

Abstract

The present invention provides assays for the detection of plasma protease C1 inhibitors (C1-INH) that bind plasma kallikrein, factor XII, or both, and their use to identify enzymes that are pKal-mediated or bradykinin-mediated. Risk of a disorder or use in a subject with a pKal-mediated or bradykinin-mediated disorder. The provided methods allow analysis of patients with plasma kallikrein-mediated angioedema (KMA) or other diseases mediated by pKal that can be used for evaluation and treatment.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of the filing date of US Provisional Application No. 61 / 754,600, filed January 20, 2013. The entire content of this referenced application is incorporated herein by reference. Background technique [0003] Plasma kallikrein (pKal) is the major circulating enzyme that produces bradykinin. Activation of pKal occurs systemically via exposure, which has been linked to disease pathology associated with hereditary angioedema (HAE). Bradykinin is a key mediator of pain, inflammation, edema and angiogenesis. [0004] Plasma protease C1 inhibitors (also known as C1-inhibitors or C1-INH) are protease inhibitors that belong to the serpin superfamily. Its main function is to inhibit the complement system to prevent spontaneous activation. Hereditary angioedema types I and II are caused by a genetic defect in C1-INH, which leads to overproduction of bradykinin. Contents of the invention [0...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Patents(China)
IPC IPC(8): C12Q1/56
CPCG01N33/6893G01N2333/4706G01N2800/32C12Q1/37C07K16/38G01N33/573A61P1/02A61P1/04A61P1/14A61P11/00A61P13/12A61P17/02A61P19/02A61P19/06A61P25/00A61P25/28A61P27/00A61P29/00A61P35/00A61P37/02A61P7/00A61P7/02A61P7/04A61P7/10A61P9/00A61P9/10A61P9/14A61K38/00C07K14/435C07K16/40C07K2317/21C07K2317/76G01N2333/8121G01N2333/96455G01N2333/96458G01N2800/52G01N2800/70
Inventor K·约瑟夫A·P·卡普兰
Owner TAKEDA PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap