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

Anti-mcam antibodies and associated methods of use

Inactive Publication Date: 2015-08-27
PROTHENA BIOSCI LTD
View PDF2 Cites 9 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0007]TH17 cells play a significant role in the pathogenesis of various autoimmune diseases, particularly those displaying neuroinflammatory conditions involving T cells' infiltration into CNS. It has been newly discovered that (1) MCAM is selectively enriched on TH17 cells; and (2) MCAM interacts with a laminin α4 chain, such as, for example, the α4 chain of laminin 411, present in the endothelial basement membrane. An MCAM antagonist, e.g., a monoclonal antibody, capable of inhibiting MCAM's binding to a molecule containing a laminin α4 chain, such as, for example, a laminin 411 molecule, may inhibit the migration of TH17 cells into CNS, and thus can be used as a therapeutic agent to prevent or treat diseases displaying TH17-mediated neuroinflammatory conditions. MCAM antagonists, such as an MCAM monoclonal antibody or an antigen-binding fragment thereof, may also be useful to prevent or treat and TH17-mediated disease, including for example, autoimmune disease, for example, multiple sclerosis, inflammatory bowel disease, psoriasis, and rheumatoid arthritis.

Problems solved by technology

However, the role of these TH17 cytokines themselves has been called into question, as a conditional knockout of IL-17 is insufficient to affect EAE progression.

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
  • Anti-mcam antibodies and associated methods of use
  • Anti-mcam antibodies and associated methods of use
  • Anti-mcam antibodies and associated methods of use

Examples

Experimental program
Comparison scheme
Effect test

example 1

MCAM is a Gene Up-Regulated in IL-17-Producing Human CD4+ T Cells

[0442]To identify novel targetable molecules associated with TH17 cell infiltration of the CNS, human CD4+ T cells from three healthy donors were enriched by magnetic negative selection as described in Materials and Methods above. After the enriched human CD4+ T cells were stained for surface expression of CD161 and CCR6, cells were FACS sorted into two populations: CCR6− / CD161− (representing circulating non-TH17 cells) and CCR6+ / CD161+(representing circulating TH17 cells) as described in Materials and Methods above. RNA was isolated immediately from half of the cells in each population as described in Materials and Methods above. The other half was put into culture with plate-bound anti-CD3 and soluble anti-CD28, without exogenous cytokines, for four days to obtain activated non-TH17 cells and activated TH17 cells, respectively. RNA was similarly isolated from these two types of activated cells. RNA was subject to mic...

example 2

MCAM Expressing T Cells are Effector Memory T Cells Having a Unique Integrin Expression Profile

[0446]The CD45RO+ memory population of human CD4 T cells can be segregated into (1) effector memory cells with tissue tropism, and (2) central memory cells with lymphoid tissue homing based upon expression of CCR7. See, e.g., Sallusto et al., Nature 401: 708-712 (1999).

[0447]To determine which subpopulation includes the MCAM expressing T cells, MCAM expression in T cells was further characterized by staining peripheral human T cells with various markers (CCR6, CCR7, integrin subunits alpha 4, beta 1, and beta 7) as described in Materials and Methods above. MCAM expressing CD4+ T cells were largely CCR7 negative, indicating that most are effector memory T cells, and would be more likely to home to tissues (FIG. 2A). The TH17 enrichment protocol suggested that MCAM expressing T cells obtained would be disproportionately CCR6+. As shown in FIG. 2A, about 64% of MCAM+ cells (2.8% / (2.8%+1.6%)) ...

example 3

MCAM Expressing T Cells are Expanded by IL1β and Produce the Majority of Both IL-17 and IL-22 Under TH17 Conditions

[0449]MCAM expressing CD4+ T cells, at only 3-5% of cells, is a small minority of the T cell population. It is of interest to determine the conditions under which this population expands and exerts TH17 effector function. For this, human CD4+ / CD45RO+ T cells were purified as described in Materials and Methods above and stimulated in vitro with anti-CD3 and anti-CD28 in the presence of a number of cytokine conditions (TGFβ, IL-12, IL-1β, IL-23, and various combinations), and the percentage of MCAM expressing cells, as well as IL-17 expressing cells, was determined by flow cytometry (FIG. 3A). MCAM expression expanded upon stimulation with IL-1β alone (16.4% in the absence of IL-1β vs. 38.1% in the presence of IL-1β, FIG. 3B). Furthermore, while TGFβ alone did not expand the MCAM positive population greatly, it functioned synergistically with IL-1β, as the combination of ...

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
timeaaaaaaaaaa
flow rateaaaaaaaaaa
pHaaaaaaaaaa
Login to View More

Abstract

Described herein are anti-MCAM antibodies and antigen binding fragments thereof that are capable of inhibiting the interaction between MCAM and its ligand, a protein comprising a laminin α-4 chain. These anti-MCAM antibodies and antigen binding fragments thereof may be useful for, for example, treating inflammatory conditions characterized by the infiltration of MCAM-expressing cells into a site of inflammation in the body.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application No. 61 / 698,916, filed Sep. 10, 2012, U.S. Provisional Application No. 61 / 797,179, filed Nov. 30, 2012, and U.S. Provisional Application No. 61 / 797,356, filed Dec. 15, 2012, each of the aforementioned applications is incorporated in its entirety herein for all purposes.FIELD OF THE INVENTION[0002]The present invention is directed to antibodies that bind to melanoma cell adhesion molecule (MCAM) which are capable of blocking the interaction between MCAM and its ligand, the laminin alpha-4 chain. The present invention is also directed to methods of use of the novel anti-MCAM antibodies described herein.REFERENCE TO A “SEQUENCE LISTING”, A TABLE, OR A COMPUTER PROGRAM LISTING[0003]The Sequence Listing written in file 436599SEQLIST.txt was created on Sep. 16, 2013 for “ANTI-MCAM ANTIBODIES AND ASSOCIATED METHODS OF USE” is 144,190 bytes. The information contained in this file is...

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(United States)
IPC IPC(8): C07K16/28C07K16/30
CPCC07K16/2896C07K16/30C07K2317/56A61K2039/505C07K2317/24C07K2317/567C07K2317/76C07K16/3092C07K2317/92C07K2317/30C07K2317/565A61P17/04A61P17/06A61P19/02A61P25/00A61P25/16A61P25/28A61P29/00A61P35/00A61P37/02A61P37/06A61P37/08
Inventor FLANAGAN, KENNETHBAKER, JEANNEYEDNOCK, THEODORE A.
Owner PROTHENA BIOSCI LTD
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