Raymond Wai Yu

US Patent:

8404824, Mar 26, 2013

Filed:

Apr 3, 2012

Appl. No.:

13/438456

Inventors:

Gant Gallagher - Milltown NJ, US
Raymond Yu - East Brunswick NJ, US
Shih-hsin Kan - Ewing PA, US
Giacomo Mancini - Millstone NJ, US

Assignee:

Medical Diagnostic Laboratories, LLC - Hamilton NJ

International Classification:

C07H 21/02
C12P 19/34

US Classification:

536 231, 435 911

Abstract:

There is disclosed the cloning and identification of human IL-23R splice variants caused by alternative splicing of the IL-23R mRNA in human. Alternative mRNA forms occur through skipping one, multiple full exons or partial exons, within the IL-23R gene. A total of twenty-five (25) different IL-23R transcripts were identified. A novel exon deletion (exon 9) isoform in the interleukin 23 receptor is disclosed, denoted as Δ9. The present application also describes a quantitative assay to measure different IL-23R isoform. Detection of Δ9 isoform of IL-23R is predominantly present in colon and cervical tissues. A decrease in Δ9 is observed in inflamed colon tissues in Crohn's patients. There is disclosed a method of predicting Crohn's disease by measuring Δ9 isoform of IL-23R.

US Patent:

8618070, Dec 31, 2013

Filed:

May 2, 2011

Appl. No.:

13/068064

Inventors:

Grant Gallagher - Milltown NJ, US
Raymond Yu - East Brunswick NJ, US
Jonathan Brazaitis - Parlin NJ, US

Assignee:

Medical Diagnostic Laboratories, LLC - Hamilton NJ

International Classification:

C12N 15/11

US Classification:

514 44A

Abstract:

The present invention relates to anti-sense oligonucleotides (AONs) used to induce exon 9 skipping in IL-23Rα gene. Exon 9 skipping of the IL23Rα gene ultimately causes specific induction of a novel soluble truncated IL-23Rα (Δ9) protein, characterized by a lack in a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end as a result of frame-shift. The present invention provides a utility application of the use of AONs to induce production of a Δ9 protein which inhibits IL-23R-mediated cell signaling. More particularly, Δ9 protein blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of AONs in treating a mammal such as a human patient inflicted with Crohn's disease.

US Patent:

8206925, Jun 26, 2012

Filed:

Apr 14, 2009

Appl. No.:

12/386146

Inventors:

Grant Gallagher - Milltown NJ, US
Raymond Yu - East Brunswick NJ, US
Shih-hsin Kan - Riverside CA, US
Giacomo Mancini - Millstone NJ, US

Assignee:

Medical Diagnostic Laboratories, LLC - Hamilton NJ

International Classification:

C12Q 1/68
C12P 19/34
C07H 21/04

US Classification:

435 612, 435 911, 536 231, 536 243

Abstract:

There is disclosed the cloning and identification of human IL-23R splice variants caused by alternative splicing of the IL-23R mRNA in human. Alternative mRNA forms occur through skipping one, multiple full exons or partial exons, within the IL-23R gene. A total of twenty-five (25) different IL-23R transcripts were identified. A novel exon deletion (exon 9) isoform in the interleukin 23 receptor is disclosed, denoted as Δ9. The present application also describes a quantitative assay to measure different IL-23R isoform. Detection of Δ9 isoform of IL-23R is predominantly present in colon and cervical tissues. A decrease in Δ9 is observed in inflamed colon tissues in Crohn's patients. There is disclosed a method of predicting Crohn's disease by measuring Δ9 isoform of IL-23R.

US Patent:

20120071422, Mar 22, 2012

Filed:

Mar 31, 2011

Appl. No.:

13/065878

Inventors:

Grant Gallagher - Milltown NJ, US
Raymond Yu - East Brunswick NJ, US
Jonathan Brazaitis - Parlin NJ, US

Assignee:

Medical Diagnostic Laboratories LLC - Hamilton NJ

International Classification:

A61K 38/17
C12P 21/02
C12N 5/071
C07K 14/715

US Classification:

514 212, 530350, 435 691, 435375, 435366

Abstract:

The present invention relates to an isolated naturally-occurring soluble truncated IL-23Rα protein, which is a translated protein resulting from a mRNA splice variant of IL-23Rα. The soluble IL-23Rα proteins (e.g., Δ9 and Δ8,9) represents a novel soluble IL-23Rα protein, which is lacking a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end (due to frame-shift). ELISA reveals that Δ9 is present in blood and can serve as a diagnostic tool for auto-immune diseases including Crohn's disease. There is also provided a method of recombinant production for this soluble truncated form of IL-23Rα protein. More importantly, the present invention provides an utility application of the Δ9 and Δ8,9 protein in inhibit IL-23R-mediated cell signaling. More particularly, Δ9 and Δ8,9 blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of Δ9 and Δ8,9 in treating a human patient inflicted with Crohn's disease.

US Patent:

20120171704, Jul 5, 2012

Filed:

Mar 31, 2011

Appl. No.:

13/065867

Inventors:

Grant Gallagher - Milltown NJ, US
Raymond Yu - East Brunswick NJ, US
Joyce Eskdale - Milltown NJ, US
Jonathan Brazaitis - Parlin NJ, US

Assignee:

Medical Diagnostic Laboratories, LLC - Hamilton NJ

International Classification:

G01N 33/577
G01N 33/566

US Classification:

435 794, 435 792

Abstract:

A naturally-occurring soluble truncated IL-23Rα protein (i.e., Δ9 IL-23Rα) is shown to be present in a biological sample and can serve as a diagnostic tool for autoimmune diseases. There is provided an enzyme-linked immunosorbent assay (ELISA) and test kit for the serological detection of the soluble truncated form of IL-23Rα protein. More particularly, antibody-sandwich ELISA method and kits for Δ9 IL-23Rα as an antigen were developed to detect Δ9 IL-23Rα levels in biological samples from a mammal and a human patient and are used as a diagnostic index. The present disclosed ELISA has utility as a diagnostic tool to detect Crohn's disease in patients using EDTA-plasma.

US Patent:

20120244542, Sep 27, 2012

Filed:

Apr 3, 2012

Appl. No.:

13/438464

Inventors:

Grant Gallagher - Milltown NJ, US
Raymond Yu - East Brunswick NJ, US
Shih-hsin Kan - Ewing PA, US
Giacomo Mancini - Millstone NJ, US

Assignee:

MEDICAL DIAGNOSTIC LABORATORIES, L.L.C. - Hamilton NJ

International Classification:

C12Q 1/68

US Classification:

435 612

Abstract:

There is disclosed the cloning and identification of human IL-23R splice variants caused by alternative splicing of the IL-23R mRNA in human. Alternative mRNA forms occur through skipping one, multiple full exons or partial exons, within the IL-23R gene. A total of twenty-five (25) different IL-23R transcripts were identified. A novel exon deletion (exon 9) isoform in the interleukin 23 receptor is disclosed, denoted as Δ9. The present application also describes a quantitative assay to measure different IL-23R isoform. Detection of Δ9 isoform of IL-23R is predominantly present in colon and cervical tissues. A decrease in Δ9 is observed in inflamed colon tissues in Crohn's patients. There is disclosed a method of predicting Crohn's disease by measuring Δ9 isoform of IL-23R.

US Patent:

20130029907, Jan 31, 2013

Filed:

Jun 14, 2012

Appl. No.:

13/523286

Inventors:

Grant Gallagher - Milltown NJ, US
Raymond Yu - East Brunswick NJ, US
Jonathan Brazaitis - Parlin NJ, US

Assignee:

MEDICAL DIAGNOSTIC LABORATORIES, LLC - Hamilton NJ

International Classification:

A61K 38/10
C07K 7/06
C12N 5/07
A61P 1/00
A61P 17/06
C07K 7/64
C07K 7/08
A61K 38/08

US Classification:

514 76, 530326, 530327, 530328, 435375

Abstract:

The present invention relates to novel polypeptides that bind to IL-23 receptor and inhibit the binding of IL-23 to its corresponding receptor and cell signaling thereof. The novel polypeptides of the present invention has a core structure of WXXXW, where W is tryptophan, and X, Xand Xare amino acids, with the proviso that when one of X, Xor Xis W, the remaining two of X, Xor Xcannot be W. The present invention relates a composition containing the novel polypeptides, and use of same in treating IL-23 associated human diseases including, for example, inflammatory bowel diseases, psoriasis and Crohn's disease.

US Patent:

20130172272, Jul 4, 2013

Filed:

Feb 20, 2013

Appl. No.:

13/771305

Inventors:

Grant Gallagher - Milltown NJ, US
Raymond Yu - East Brunswick NJ, US
Jonathan Brazaitis - Parlin NJ, US

Assignee:

Medical Diagnostic Laboratories - Hamilton NJ

International Classification:

C07K 7/08

US Classification:

514 211, 530327, 514 215, 530300, 435375

Abstract:

The present invention relates to novel polypeptides that bind to IL-23 receptor and inhibit the binding of IL-23 to its corresponding receptor and cell signaling thereof. The novel polypeptides of the present invention has a core structure of WXXXW,where W is tryptophan, and X, Xand Xare amino acids, with the proviso that when one of X, Xor Xis W, the remaining two of X, Xor Xcannot be W. Preferred core structures include WVDYW or WQDYW. The present invention relates a composition containing the novel polypeptides, and use of same in treating IL-23 associated human diseases including, for example, inflammatory bowel diseases, psoriasis and Crohn's disease.