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method for disease treatment

An amino acid and sequence technology, applied in bone diseases, nervous system diseases, respiratory system diseases, etc., can solve problems such as reducing morbidity and mortality, and missing pathophysiological mechanisms.

Active Publication Date: 2021-09-17
SERPIN PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although these interventions each provide increased benefit and significantly reduce morbidity and mortality, the incidence of heart failure continues to increase after STEMI, suggesting that one or more key pathophysiological mechanisms are still missing from current treatment paradigms

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0338] Example 1 - Treatment of Acute Myocardial Infarction Using SP163M Peptide

[0339] The SP16 peptide is a short fragment derived from the circulating serum protein alpha-1-antitrypsin (AAT). The US FDA has approved the use of three α1-antitrypsin products derived from human plasma: Prolastin, Zemaira, and Aralast.

[0340] As described herein, the SP163M peptide contains the reported anti-inflammatory properties of the parent AAT. In pilot clinical studies conducted at Virginia Commonwealth University (VCU), AAT has been initially shown to safely and effectively block the inflammatory response that occurs after AMI. Furthermore, SP163M has shown equal or better anti-inflammatory activity in preclinical models of AMI. Working with researchers at VCU, we rapidly developed SP16 for the treatment of AMI, a major unmet medical need in the United States and worldwide.

[0341] Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality in the United...

Embodiment 2

[0387] Met was replaced by Nle to improve peptide stability, for example in SEQ ID NO: 57-Ac-Val-Lys-Phe-Asn-Lys-Pro-Phe-Val-Phe-Leu-Nle-Ile-Glu-Gln-Asn- In the peptide of Thr-Lys-NH2 (SEQ ID NO: 57). Oxidizable methionine.

Embodiment 3

[0388] Example 3 - LRP1 mediates SP16-induced cardioprotection

[0389] SP163M was demonstrated herein to bind LRP1 (low density lipoprotein receptor-related protein) and to be an agonist of LRP1 (as shown for parent AAT). It was also shown that blocking LRP1 abolishes the cardioprotective effects of SP163M and AAT.

[0390] introduce

[0391] LRP1 is the receptor responsible for the plasma clearance of SEC (serine protease inhibitory protease complex accumulated during inflammatory responses). Therefore, the role of LRP1 is to prevent and interrupt inflammation. LRP1 may act via direct regulation of key inflammatory pathways; such as NFkB, IRF-3 and AP-1 (eg ERK p42 / p44, p38 and JNK).

[0392] In murine peritoneal macrophages, LRP1 downregulates LPS-driven inflammatory responses through intracellular interaction with IRF-3. In addition, LRP1 regulates inflammatory cytokines, affects phagocytosis and cell migration, and Treg distribution. Serpins, including peptides such ...

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Abstract

Peptides and their use for the treatment of eg acute myocardial infarction and other conditions associated with cytokine storms are described.

Description

[0001] This application is a divisional application of the Chinese patent application with application number 201680063220.6. The filing date of the parent application is August 26, 2016, and the title of the invention is "Method for treating diseases". [0002] Cross References to Related Applications [0003] This application claims priority under 35 U.S.C. §119(e) to Provisional Patent Application Serial No. 62 / 211,296, filed August 28, 2015, the contents of which are incorporated herein by reference in their entirety. [0004] sequence listing [0005] This application contains a Sequence Listing, which has been submitted via EFS-Web in ASCII format, and is hereby incorporated by reference in its entirety. Said ASCII copy, created on December 31, 2012, is named 65292741.txt and is 18,884 bytes in size. [0006] field of invention [0007] The present disclosure provides novel methods of treating diseases including acute myocardial infarction (AMI); gout; ischemia; stroke;...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K14/81C07K19/00A61K38/55A61K47/60A61P9/10A61P25/00A61P19/06
CPCA61P9/10A61K38/55A61K47/60A61K9/0053A61P19/06A61P9/00A61P25/00A61P11/00A61P31/04A61P31/16A61P29/00A61P31/20A61P31/14
Inventor C·格伯
Owner SERPIN PHARMA
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