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

Monoclonal antibody against muramyl peptides in prevention and treatment of immune-mediated diseases

A therapeutic and preventive technology, applied in the field of immunology and immune-mediated diseases, which can solve the problem of lack of response to therapeutic biologics

Active Publication Date: 2017-08-29
AGENCY FOR SCI TECH & RES
View PDF10 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, many patients with rheumatoid arthritis do not respond well to currently available therapeutic biologics

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
  • Monoclonal antibody against muramyl peptides in prevention and treatment of immune-mediated diseases
  • Monoclonal antibody against muramyl peptides in prevention and treatment of immune-mediated diseases
  • Monoclonal antibody against muramyl peptides in prevention and treatment of immune-mediated diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0106] Example 1 - Characterization of mAbs against MDP

[0107] mAb (2E7) was obtained by immunizing mice with N-acetylmuramoyl-L-alanyl-D-isoglutamine. Antibody isotyping test identifies 2E7 as IgG 1 , and the Kd of 2E7 for N-acetylmuramoyl-L-alanyl-D-isoglutamine was calculated to be 8.7pM ( figure 1 ). By competitive ELISA, it was found that the binding of 2E7 to N-acetylmuramoyl-L-alanyl-D-isoglutamine conjugated to OVA was inhibited in a concentration-dependent manner by muramyl-L-alanyl- Inhibition by D-isoglutamine, N-acetylmuramoyl-L-alanyl-D-glutamate, and muramyl-L-alanyl-D-glutamate was almost identical to that of N- Acetylmuramoyl-L-alanyl-D-isoglutamine was equally effective, suggesting that 2E7 recognizes a common epitope among the four MDPs. However, 2E7 exhibited no response to muramic acid, N-acetylmuramic acid, N-acetylglucosamine, alanine, D-isoglutamine, glutamic acid, glucose, or the 20 common amino acids in proteins Detectable affinity for any one o...

Embodiment 2-2E7

[0108] Determination of the Amino Acid Sequences of Embodiment 2-2E7 Heavy Chain and Light Chain Variable Region

[0109] Messenger RNA was prepared from a 2E7-producing hybridoma clone, which was then used as a template to generate complementary DNA. Variable sequences encoding heavy and light chains, respectively, were amplified by polymerase chain reaction (PCR) using oligonucleotide primer pairs (Table 1) that specifically targeted conserved sequence motifs flanking the coding regions of the variable regions. The DNA fragment of region (this method is described in Kettleborough et al., 1993, Optimization of primers for cloning libraries of mouseimmunoglobulin genes using the polymerase chain reaction. Eur J Immunol 23,206-211 and Pope et al., 1996, Construction of use of antibodies. generepertoire In Antibody Engineering-A Practical Approach. Edited by McCafferty J. Hoogenboom H, and Chiswell D., the contents of both are incorporated herein by reference). The PCR product ...

Embodiment 3

[0116] Example 3 - 2E7 detection of bacterial peptidoglycan in culture medium and on cell surface

[0117] To demonstrate the utility of 2E7, the antibody was first tested for its ability to detect MPs normally present in bacterial cultures. It has been established that β-lactam antibiotics inhibit peptidoglycan polymerization by causing cells to accumulate and secrete MP. The beta-lactam antibiotic amoxicillin (a drug often used in hospitals) was added to the culture and was expected to inhibit 2E7 binding to N-acetylmuramoyl-L-alanyl-D-isoglutamine material increased significantly. For this test, the Gram-positive bacteria Staphylococcus aureus (which has a thick peptidoglycan layer) and Gram-negative E. Grow without amoxicillin. Cultures grown to OD 600 = 1.5 density, then divided into two equal parts. For one aliquot, amoxicillin was added to a final concentration of 40 μg / ml, while for the other aliquot, no drug was added. Both cultures were allowed to continue grow...

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

Disclosed are methods of treating an autoimmune or inflammatory disease using a composition comprising an isolated antibody or an antigen-binding fragment or variant thereof that is capable of binding to muramyl peptide, derivative, analog or salt thereof, wherein said muramyl peptide comprises muramic acid and an amino acid selected from the group consisting of alanine, isoglutamine, glutamic acid and a salt thereof. In one preferred embodiment, the composition can comprise of the isolated antibody or an antigen-binding fragment and one or more therapeutic agents such as Tumor Necrosis Factor (TNF) inhibitor. The autoimmune or inflammatory disease is selected from a group consisting of sepsis, septic shock, Crohn's disease, rheumatoid arthritis, asthma, allergy, atopic disorders, multiple sclerosis, pertussis, gonorrhea, inflammatory bowel disease, and antibiotic associated disorder.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority from Singapore Patent Application No. 10201500223V filed on 12 January 2015, the contents of which are hereby incorporated by reference in their entirety for all purposes. technical field [0003] The present invention relates generally to the fields of immunology and immune-mediated diseases. In particular, the present invention relates to antibodies, compositions comprising the antibodies, and uses of the antibodies and compositions in preventing and treating diseases. Background of the invention [0004] All bacteria contain peptidoglycan as a major cell wall component. The peptidoglycan formed from subunits of muramyl peptides undergoes cycles of assembly and disassembly required for cell wall remodeling during cell growth and division. Muramyl peptides are produced during breakdown and are reused during cell growth and division to build new peptidoglycan. Thus, mu...

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): A61K39/02A61K39/085C07K16/12A61P37/08A61P31/00
CPCA61K39/40A61K2039/505A61K2039/54A61K2039/545C07K2317/33C07K2317/76C07K2317/92C07K16/12A61P1/04A61P11/06A61P11/14A61P15/00A61P17/00A61P19/02A61P25/00A61P29/00A61P31/00A61P31/04A61P37/02A61P37/08A61P43/00A61K2300/00A61K39/085
Inventor 王跃黄振兴
Owner AGENCY FOR SCI TECH & RES
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