Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Human amylin analog polypeptides and methods of use

An optional amino acid technology, applied in the field of amylin analog polypeptides, treating metabolic diseases or conditions such as type 1 and type 2 diabetes and providing weight loss, can solve the problem that pramlintide cannot be mixed with insulin

Pending Publication Date: 2021-07-30
INTARCIA THERAPEUTICS INC
View PDF67 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Pramlintide cannot be mixed with insulin; use a separate syringe

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
  • Human amylin analog polypeptides and methods of use
  • Human amylin analog polypeptides and methods of use
  • Human amylin analog polypeptides and methods of use

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1004] Example 1: Generation of Amylin Analog Polypeptides

[1005]Using the Fmoc strategy with N-[(dimethylamino)-1H-1,2,3-triazolo-[4 ,5-b]pyridin-1-ylmethylene]-N-methylmethylammonium hexafluorophosphate N-oxide (HATU) or 2-(6-chloro-1-H-benzotriazole-1 -base)-1,1,3,3-tetramethylammonium hexafluorophosphate (HCTU) activation (amino acid 5-fold molar excess), synthesized in N,N-dimethylformamide (DMF) as shown in Table 3 The amylin analog polypeptide of the present invention provided in , and N'N-diisopropylethylamine (DIEA) was used as the base. 20% piperidine / DMF solution was used for Fmoc deprotection. The resin used was Rink Amide MBHA LL (Novabiochem) with a loading of (0.30-0.40) mmol / g on a (20-400) μmol scale.

[1006] Final deprotection and cleavage of the peptide from the solid support was performed by treating the resin with (92.5% TFA, 2.5% phenol, 2.5% water and 2.5% triisopropylsilane) for 2-3 hours. The cleaved peptide was precipitated using cold diethyl e...

Embodiment 2

[1008] Example 2: Purification and Characterization of Amylin Analog Polypeptides, i.e. Linear Polypeptides Without Any Lipophilic Substituents and Optional Spacers

[1009] The purified product was lyophilized and analyzed by ESI-LC / MS and analytical HPLC and proved to be pure (>98%). The mass results were all in agreement with the calculated values.

[1010] Performed via C18 HPLC and LC / MS analysis (Acquity SQD Waters Corp, Milford, MA) with UV detection provided by dual absorbance signals at 215 nm and 280 nm using one of Method A, Method B, Method C or Method D Characterization of Peptide Analogs.

[1011] Method A, LC / MS conditions: using Phenomenex UPLC Aeris TM Peptide XB C18 35 column, 1.7pm, 2.1×100mm or ACQUiTY BEH300 or BEH130 CT8 column, 1.77pm, 2.1×100mm, using 5-65% acetonitrile / water with 0.05% TFA in 30 minutes, flow rate 0.5mL / min, λ-215nm, 280nm.

[1012] Method B, C18 HPLC conditions: On Acquity BEH130, C18 column, 1.7 μm, 100 × 2.10 mm column at 25 °C...

Embodiment 3

[1017] Embodiment 3: synthetic amylin analog polypeptide intermediate

[1018] Synthesis of polypeptides with modifications at e.g. D-Lys16 or L-Lys16 positions (compounds B2, A129, B4 and B8)

[1019] After completion of the synthesis of linear polypeptides as described in Example 1, the resin was washed with dichloromethane (DCM) and dried under vacuum for 30 minutes. For analogs containing allyloxycarbonyl protecting groups, via Pd(PPh 3 ) 3 Its removal is facilitated in a solution of (chloroform / acetic acid / n-methyl-morpholine, 37:2:1). The resulting deprotected resin was washed with 2% sodium diethyldithiodicarbamate trihydrate / DMF (6 x 30 sec), 2% DIEA / DMF (6 x 30 sec) and finally DMF (6 x 30 sec). The extension of the spacer subregions was performed with the manual addition of each building block under preactivation conditions in a stepwise fashion. To 1 ml of a 200 mmol solution of Fmoc-γGlu-(OH)-OtBu in DMF was added 0.5 ml DIEA (800 mmol), followed by 0.5 ml HCTU...

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
particle sizeaaaaaaaaaa
diameteraaaaaaaaaa
diameteraaaaaaaaaa
Login to View More

Abstract

This invention relates to isolated polypeptides that are analogs of human amylin. The disclosed amylin analog polypeptides have beneficial physicochemical properties relative to endogenous amylin, such as longer elimination half-lives (ti / 2) and improved solubility and thermal stability. This invention also relates to methods of using presently disclosed amylin analog polypeptides in a variety of therapeutic indications, as well as methods of producing the same. The disclosed amylin analog polypeptides are particularly useful in methods of treating metabolic diseases or disorders, such as types 1 and 2 diabetes, and providing weight loss.

Description

[0001] This application claims priority to and benefit of U.S. Provisional Application No. 62 / 744,236, filed October 11, 2018, which is hereby incorporated by reference in its entirety. [0002] sequence listing [0003] This application contains a Sequence Listing, which has been filed electronically in ASCII format and is hereby incorporated by reference in its entirety. The ASCII copy, created on October 11, 2019, is named 616782_102487-055PC_SL-10-10-2019.txt and is 123,647 bytes in size. technical field [0004] The present invention relates to isolated polypeptides that are analogs of human amylin. The disclosed amylin analogue polypeptides have favorable physicochemical properties relative to endogenous amylin, such as longer elimination half-life (t 1 / 2 ) and improved solubility and thermal stability. The invention also relates to methods of using the amylin analog polypeptides disclosed herein in various therapeutic indications, as well as methods of making them. ...

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 Applications(China)
IPC IPC(8): C07K14/575A61K38/22
CPCC07K14/575A61K38/28A61K2300/00A61K38/22A61P3/04A61P3/10A61K9/0004A61K9/0019A61K38/00
Inventor W·布莱克威尔V·P·斯里瓦斯塔瓦J·M·韦
Owner INTARCIA THERAPEUTICS INC
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com