Adoptive cellular therapy using an agonist of retinoic acid receptor-related orphan receptor gamma & related therapeutic methods

A gamma agonist, cell technology, applied in animal cells, vertebrate cells, genetically modified cells, etc.

Inactive Publication Date: 2016-11-16
LICELLA PTY LTD
View PDF20 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In addition to the unmet need in cancer therapy, multiple bacterial infections have become a more significant health problem due to their increased resistance to current antibiotic treatments

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
  • Adoptive cellular therapy using an agonist of retinoic acid receptor-related orphan receptor gamma & related therapeutic methods
  • Adoptive cellular therapy using an agonist of retinoic acid receptor-related orphan receptor gamma & related therapeutic methods
  • Adoptive cellular therapy using an agonist of retinoic acid receptor-related orphan receptor gamma & related therapeutic methods

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0562] Example 1 --(S)-6-((2-Chloro-6-fluorophenoxy)methyl)-2-methyl-4-((3-(trifluoromethyl)phenyl)sulfonyl)-3 , Synthesis of 4-dihydro-2H-benzo[b][1,4]]oxazine

[0563]

[0564] Part I--Synthesis of methyl (S)-4-((1-methoxy-1-oxopropan-2-yl)oxy)-3-nitrobenzoate

[0565]

[0566] Methyl-4-hydroxy-3-nitrobenzoate (3g, 13.76mmol), methyl-(R)-lactate (1.433g, 13.8mmol) and triphenylphosphine (4.33g, 16.5 mmol) was suspended in dichloromethane (36 mL), and diisopropyl azodicarboxylate (3.25 mL, 16.51 mmol) was added dropwise. The reaction mixture was stirred for 1 h at room temperature, then the crude material was washed with water and dried (Na 2 SO 4 ) and concentrated to give a residue. The residue was purified via MPLC elution with a gradient of ethyl acetate in hexanes, followed by a second MPLC purification elution with dichloromethane to afford (S)-4-((1 -Methoxy-1-oxopropan-2-yl)oxy)-3-nitrobenzoate (2.56 g, 66%). 1 H-NMR (400MHz, DMSO-d 6 )8.37(s,1H),8.12(d...

Embodiment 2

[0579] Example 2 (S,E)-3-(6-(2-(2-chloro-6-fluorophenyl)prop-1-en-1-yl)-4-((3-(trifluoromethyl)phenyl Synthesis of )sulfonyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)propionic acid

[0580]

[0581] Part I--Synthesis of (R)-2-hydroxyglutaric acid dimethyl ester

[0582]

[0583] To a mixture of (2R)-5-oxotetrahydro-2-furoic acid (25 g, 192 mmol) in methanol (300 mL) was added concentrated hydrogen chloride (0.5 mL), and the mixture was refluxed overnight. The reaction mixture was then cooled to ambient temperature, solid sodium bicarbonate was added, and the resulting mixture was slurried for 20 minutes. Then, the mixture was filtered and concentrated to give (R)-dimethyl 2-hydroxyglutarate (34.7 g, 100%).

[0584] Part II--Synthesis of dimethyl (S)-2-(4-bromo-2-nitrophenoxy)glutarate

[0585]

[0586] (R)-Dimethyl 2-hydroxyglutarate (33.8g, 192mmol), 4-bromo-2-nitrophenol (50.2g, 230mmol) and triphenylphosphine with activated molecular sieves were added at 0°C ...

Embodiment 3

[0610] Example 3 --(S,E)-3-(6-(2-Chloro-6-(trifluoromethyl)styryl)-4-((3-(trifluoromethyl)phenyl)sulfonyl)- Synthesis of 3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)propionic acid

[0611]

[0612] Part I--Synthesis of 1-chloro-2-ethynyl-3-(trifluoromethyl)benzene

[0613]

[0614] To a solution of 2-chloro-6-(trifluoromethyl)benzaldehyde (10.0 g, 47.9 mmol) in methanol (100 mL) was added dimethyl(diazomethyl)phosphonate (11.05 g ,57.5mmol). The reaction mixture was cooled to 0 °C and potassium carbonate (16.6 g, 119 mmol) was added. The reaction mixture was stirred overnight at room temperature. Then, the resulting crude mixture was diluted with ether, washed with water, washed with brine, dried (MgSO 4 ) and concentrated to give 1-chloro-2-ethynyl-3-(trifluoromethyl)benzene (9.17 g, 93%).

[0615] Part II--(E)-2-(2-Chloro-6-(trifluoromethyl)styryl)-4,4,5,5-tetramethyl-1,3,2-dioxane Synthesis of pentaborane

[0616]

[0617] [2,3-bis(1-adamantyl)imidazolin-2-yl-...

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

No PUM Login to view more

Abstract

The invention relates to medical therapy using an agonist of the retinoic acid receptor-related orphan receptor gamma (ROR gamma) and provides adoptive cellular therapies using an agonist of ROR gamma, populations of lymphocyte cells that have been exposed to an agonist of ROR gamma, populations of dendritic cells that have been exposed to an agonist of ROR gamma, pharmaceutical compositions, and methods for enhancing therapeutic effects of lymphocyte cells and/or dendritic cells in a patient by administering an agonist of ROR gamma to a patient.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit and priority of US Provisional Patent Application Serial No. 61 / 945,431, filed February 27, 2014, the contents of which are incorporated herein by reference. field of invention [0003] The present invention relates to medical therapy using agonists of retinoic acid receptor-related orphan receptor gamma (RORγ) and providing adoptive cell therapy using agonists of RORγ, lymphocyte populations that have been exposed to RORγ agonists , Dendritic cell populations that have been exposed to RORγ agonists, compositions, and methods of enhancing the therapeutic effect of lymphocytes and / or dendritic cells in a patient by administering a RORγ agonist to the patient. Background technique [0004] Despite numerous research efforts and scientific advances reported in the literature, cancer, bacterial infections, fungal infections and immune diseases remain a significant health problem. Some of...

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): A61K35/17A61K35/15A61P35/00
CPCA61K35/15A61K35/17C12N5/0636C12N2501/385C12N2501/999A61P31/04A61P31/10A61P35/00A61P35/02A61P37/02A61P43/00A61K39/0011A61K31/4353A61K31/437A61K31/4375A61K31/47A61K31/4709A61K31/538A61K39/0002A61K39/02A61K2039/5158A61K2039/54C12N5/0646C12N2501/20C12N2510/00
Inventor G·D·格里克P·L·图谷德X·胡T·D·埃彻尔L·L·赛勒斯特X·刘C·B·泰勒C·A·万辉斯
Owner LICELLA PTY 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