US20160090629A1 - Variants of tnfsf15 and dcr3 associated with crohn's disease - Google Patents

Variants of tnfsf15 and dcr3 associated with crohn's disease Download PDF

Info

Publication number
US20160090629A1
US20160090629A1 US14/890,712 US201414890712A US2016090629A1 US 20160090629 A1 US20160090629 A1 US 20160090629A1 US 201414890712 A US201414890712 A US 201414890712A US 2016090629 A1 US2016090629 A1 US 2016090629A1
Authority
US
United States
Prior art keywords
seq
tnfsf15
variants
subject
dcr3
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US14/890,712
Other languages
English (en)
Inventor
Dermot P. McGovern
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cedars Sinai Medical Center
Original Assignee
Cedars Sinai Medical Center
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cedars Sinai Medical Center filed Critical Cedars Sinai Medical Center
Priority to US14/890,712 priority Critical patent/US20160090629A1/en
Assigned to CEDARS-SINAI MEDICAL CENTER reassignment CEDARS-SINAI MEDICAL CENTER ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MCGOVERN, DERMOT P.
Publication of US20160090629A1 publication Critical patent/US20160090629A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2875—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/112—Disease subtyping, staging or classification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/118—Prognosis of disease development
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/172—Haplotypes

Definitions

  • the claimed invention relates to prognosis, diagnosis and treatment of inflammatory bowel disease and related conditions, including methods and compositions for medical therapies.
  • IBD Inflammatory bowel disease
  • CD Crohn's disease
  • TL1A may drive intestinal inflammation through enhancing Th1, Th2 and Th17 effector function
  • TL1A appears to also drive fibrogenesis through increased number of fibroblasts and activated fibroblasts and constitutive TL1A expression in mice has been found to confer worsened murine ileo-cecal inflammation, and intestinal fibrostenosis.
  • TNFSF15 TNF superfamily member
  • DcR3 a known IBD susceptibility gene
  • FIG. 1 depicts, in accordance with embodiments herein, principal component analysis (PC1/PC2).
  • FIG. 2 depicts, in accordance with embodiments herein, pACTs of TNFSF15 region in NJ (Non-Jewish) and AJ (Ashkenazi Jewish) CD.
  • FIG. 3 depicts, in accordance with embodiments herein, pACTs of DcR3 (TNFRSF6B) region in NJ and AJ CD.
  • FIG. 4 depicts, in accordance with embodiments herein, linkage disequilibrium maps (r 2 ) of the associated TNFSF15 SNPs in NJ and SK.
  • Described herein is an assay for quantifying risk in a subject to Crohn's disease and/or fibrosist, including obtaining a sample from a subject, subjecting the sample to a genotyping assay adapted to determine the presence or absence of one or more variants at the TNFSF15 and/or DcR3 genetic loci, and quantifying risk in a subject to Crohn's disease and/or fibrosis based on the presence of one or more variants at the TNFSF15 and/or DcR3genetic loci.
  • the variants include one or more variants selected from the group including: SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO.
  • the variants are SEQ ID NO. 3 and/or SEQ ID NO.13. In other embodiments, the variant is SEQ ID NO. 22.
  • the subject is non-Jewish Caucasian, Ashkenazi, South Korean and/or Puerto Rican.
  • the subject is South Korean and the variant are SEQ ID NO. 3, SEQ ID NO.13 and/or SEQ ID NO. 22.
  • the variant is a risk variant.
  • the variant is a protective variant.
  • the protective variant quantifies a reduced risk in the subject for structuring, CD, small bowel involvement and/or need for surgical intervention.
  • variants consist of one or more variants selected from the group including: SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO.
  • variants are SEQ ID NO. 3 and/or SEQ ID NO.13.
  • variant is SEQ ID NO. 22.
  • subject is non-Jewish Caucasian, Ashkenazi, South Korean and/or Puerto Rican.
  • subject is South Korean and the variant are SEQ ID NO. 3, SEQ ID NO.13 and/or SEQ ID NO. 22.
  • the variants consist of one or more variants selected from the group including: SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 10, SEQ ID NO. 11, SEQ ID NO. 12, SEQ ID NO.
  • SEQ ID NO. 14 SEQ ID NO. 15, SEQ ID NO. 16, SEQ ID NO. 17, SEQ ID NO. 18, SEQ ID NO. 19, SEQ ID NO. 20, SEQ ID NO. 21, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 25, and SEQ ID NO. 26.
  • TL1A is the product of the TNFSF15 gene that is expressed by both lymphoid and myeloid derived cells. Variants in the TNFSF15 gene have been found to be associated with IBD.
  • TNFSF15 The protein product of TNFSF15, TL1A, is elevated in the intestinal mucosa of IBD patients.
  • Certain TNFSF15 haplotypes are associated with susceptibility in non-Jewish Caucasian CD and UC.
  • TNFSF15 haplotype B is not only associated with risk, but also with severity in Jewish CD patients.
  • monocytes from Jewish patients carrying the risk haplotype B express higher levels of TL1A in response to FcyR stimulation.
  • TL1A signals via death domain receptor 3 (DR3) and several studies implicate the TL1A/DR3 signaling pathway in mucosal inflammation.
  • DR3 death domain receptor 3
  • TL1A/DR3 signaling pathway in mucosal inflammation.
  • Neutralizing TL1A-antibody ameliorates inflammation in DSS and G ⁇ i2-/- T cell transfer chronic colitis models.
  • Constitutive TL1A expression in mice leads to mild spontaneous ileitis and increased collagen deposition.
  • TL1A modulates the adaptive immune response in the T-helper (Th)-1 effector arm, as shown by TL1A enhanced interferon (IFN)- ⁇ production from peripheral and mucosal T-cells.
  • TL1A is a TNF superfamily member.
  • TNFSF15 haplotype B has increased TL1A expression with a higher risk of small bowel surgery, and constitutive T11a expression in mice confers worsened murine ileo-cecal inflammation and intestinal fibrostenosis. While it is known TL1A can enhance Th1, Th2, and Th17 effector cell function, it is poorly understood which TL1A activated T-helper effector pathway induces intestinal inflammation and fibrosis. Thus, a critical scientific question is understanding the effect of T-helper pathway on TL1A induced colitis and effect of T-helper pathway on TL1A induced gut fibrosis.
  • the inventors performed trans-ethnic fine mapping across TNFSF15 and DcR3 in Caucasian, Puerto Rican, and Korean CD.
  • the inventors identified associations with Non Jewish Caucasian (NJ) Crohn's disease (CD) and rare TNFSF15 variants. This association is independent of previously reported common variants. Also, these variants are much more common in the South Korean (SK) population, and also associated with SK CD.
  • DcR3 is significantly associated with NJ CD, a finding replicated in SK and variation at this locus modifies stricturing phenotype.
  • Described herein is an assay for quantifying risk in a subject to Crohn's disease and/or fibrosist, including obtaining a sample from a subject, subjecting the sample to a genotyping assay adapted to determine the presence or absence of one or more variants at the TNFSF15 and/or DcR3 genetic loci, and quantifying risk in a subject to Crohn's disease and/or fibrosis based on the presence of one or more variants at the TNFSF15 and/or DcR3genetic loci.
  • the variants include one or more variants selected from the group including: SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO.
  • the variants are SEQ ID NO. 3 and/or SEQ ID NO.13. In other embodiments, the variant is SEQ ID NO. 22.
  • the subject is non-Jewish Caucasian, Ashkenazi, South Korean and/or Puerto Rican.
  • the subject is South Korean and the variant are SEQ ID NO. 3, SEQ ID NO.13 and/or SEQ ID NO. 22.
  • the variant is a risk variant.
  • the variant is a protective variant.
  • the protective variant quantifies a reduced risk in the subject for structuring, CD, small bowel involvement and/or need for surgical intervention.
  • variants consist of one or more variants selected from the group including: SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO.
  • variants are SEQ ID NO. 3 and/or SEQ ID NO.13.
  • variant is SEQ ID NO. 22.
  • subject is non-Jewish Caucasian, Ashkenazi, South Korean and/or Puerto Rican.
  • subject is South Korean and the variant are SEQ ID NO. 3, SEQ ID NO.13 and/or SEQ ID NO. 22.
  • the variants consist of one or more variants selected from the group including: SEQ ID NO. 1, SEQ ID NO. 2, SEQ ID NO. 3, SEQ ID NO. 4, SEQ ID NO. 5, SEQ ID NO. 6, SEQ ID NO. 7, SEQ ID NO. 8, SEQ ID NO. 9, SEQ ID NO. 10, SEQ ID NO. 11, SEQ ID NO. 12, SEQ ID NO.
  • SEQ ID NO. 14 SEQ ID NO. 15, SEQ ID NO. 16, SEQ ID NO. 17, SEQ ID NO. 18, SEQ ID NO. 19, SEQ ID NO. 20, SEQ ID NO. 21, SEQ ID NO. 22, SEQ ID NO. 23, SEQ ID NO. 24, SEQ ID NO. 25, and SEQ ID NO. 26.
  • the present invention provides a method of diagnosing susceptibility to Crohn's disease in a subject by obtaining a sample from the subject, assaying the sample to determine the presence or absence of one or more risk variants in the subject, and diagnosing susceptibility to Crohn's disease based on the presence of one or more risk variants.
  • the one or more risk variants are at the TNFSF15 and/or DcR3 genetic loci.
  • the one or more risk variants are described in Tables 2 and 3 herein.
  • the subject is Caucasian, Puerto Spainn, or South Korean.
  • the subject is Non-Caucasian.
  • the present invention provides a method of diagnosing a Crohn's disease subtype in a subject by obtaining a sample from the subject, assaying the sample to determine the presence or absence of one or more risk variants in the subject, and diagnosing the Crohn's disease subtype based on the presence of one or more risk variants.
  • the one or more risk variants are at the TNFSF15 and/or DcR3 genetic loci.
  • the one or more risk variants are described in Tables 2 and 3 herein.
  • the subject is Caucasian, Puerto Spainn, or South Korean.
  • the subject is Non-Caucasian.
  • the present invention provides a method of treating Crohn's disease in a subject by determining the presence of one or more one or more risk variants in the subject, and treating the subject.
  • the one or more risk variants are at the TNFSF15 and/or DcR3 genetic loci.
  • the one or more risk variants are described in Tables 2 and 3 herein.
  • the subject is Caucasian, Puerto Spainn, or South Korean.
  • the subject is Non-Caucasian.
  • the present invention provides a method of diagnosing susceptibility to fibrosis in a subject by obtaining a sample from the subject, assaying the sample to determine the presence or absence of one or more risk variants in the subject, and diagnosing susceptibility to fibrosis based on the presence of one or more risk variants.
  • the one or more risk variants are at the TNFSF15 and/or DcR3 genetic loci.
  • the one or more risk variants are described in Tables 2 and 3 herein.
  • the subject is Caucasian, Puerto Spainn, or South Korean.
  • the subject is Non-Caucasian.
  • the present invention provides a method of diagnosing a fibrosis subtype in a subject by obtaining a sample from the subject, assaying the sample to determine the presence or absence of one or more risk variants in the subject, and diagnosing the fibrosis subtype based on the presence of one or more risk variants.
  • the one or more risk variants are at the TNFSF15 and/or DcR3 genetic loci.
  • the one or more risk variants are described in Tables 2 and 3 herein.
  • the subject is Caucasian, Puerto Spainn, or South Korean.
  • the subject is Non-Caucasian.
  • the present invention provides a method of treating fibrosis in a subject by determining the presence of one or more one or more risk variants in the subject, and treating the subject.
  • the one or more risk variants are at the TNFSF15 and/or DcR3 genetic loci.
  • the one or more risk variants are described in Tables 2 and 3 herein.
  • the subject is Caucasian, Puerto Spainn, or South Korean.
  • the subject is Non-Caucasian.
  • the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.
  • the inventors performed trans-ethnic fine mapping across TNFSF15 and DcR3 in Caucasian, Puerto Rican (PR) and South Korean (SK) CD. Immunochip genotyping as performed on the following populations presented in Table 1.
  • TNFSF15-130 4.89E ⁇ 05 8.70E ⁇ 01 1.54E ⁇ 01 6.92E ⁇ 17 6.62 1.05 1.31 2.10 TNFSF15-150 4.12E ⁇ 05 7.23E ⁇ 01 3.10E ⁇ 02 5.28E ⁇ 17 8.95 1.13 1.75 2.12 TNFSF15-160 3.02E ⁇ 06 5.81E ⁇ 01 3.19E ⁇ 02 8.66E ⁇ 17 6.97 0.84 1.67 2.10 TNFSF15-271 4.48E ⁇ 05 7.99E ⁇ 01 1.25E ⁇ 02 3.15E ⁇ 10 6.70 1.09 2.02 1.76 Common Variants of TNFSF15 TNFSF15-90 5.31E ⁇ 05 2.92E ⁇ 01 3.70E ⁇ 01 5.70E ⁇ 16 1.30 0.88 1.15 2.26 TNFSF15-106 7.98E ⁇ 05 1.34E
  • TNFSF15-DcR3 SNPs SNP Gene NJ CD SK CD TNFSF15-160 TNFSF15 1.4% 41.4% TNFSF15-164 TNFSF15 17.0% 70.8% DcR3-9 DcR3 20.5% 9.0% TNFSF15-DCR3 3 SNPs — 32.3% 76.4%
  • the ‘rare’ and ‘common’ variants can each be tagged by a single SNP (SNP160 & SNP164 respectively) in both NJ and SK.
  • SNP160 & SNP164 SNP160 & SNP164 respectively
  • the ‘rare’ variants were associated with CD in PR (at higher allele frequency). No association was seen in PR with the common variants. (Table 4). No significant SNP associations were observed in AJ CD. ( FIG. 2 , Table 4). After correcting for multiple comparisons there were no significant associations with rare or common CD-associated SNPs with clinical subphenotypes in NJ CD.
  • the inventors identified associations with NJ CD and rare TNFSF15 variants. This association is independent of previously reported common variants. These variants are much more common in the SK population, and also associated with SK CD. DcR3 is significantly associated with NJ CD, a finding replicated in SK and variation at this locus modifies stricturing phenotype.
  • the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about.” Accordingly, in some embodiments, the numerical parameters set forth in the written description and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable. The numerical values presented in some embodiments of the invention may contain certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Analytical Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Transplantation (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
US14/890,712 2013-05-17 2014-05-16 Variants of tnfsf15 and dcr3 associated with crohn's disease Abandoned US20160090629A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US14/890,712 US20160090629A1 (en) 2013-05-17 2014-05-16 Variants of tnfsf15 and dcr3 associated with crohn's disease

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361824932P 2013-05-17 2013-05-17
US14/890,712 US20160090629A1 (en) 2013-05-17 2014-05-16 Variants of tnfsf15 and dcr3 associated with crohn's disease
PCT/US2014/038468 WO2014186750A2 (en) 2013-05-17 2014-05-16 Variants of tnfsf15 and dcr3 associated with crohn's disease

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2014/038468 A-371-Of-International WO2014186750A2 (en) 2013-05-17 2014-05-16 Variants of tnfsf15 and dcr3 associated with crohn's disease

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US15/946,632 Continuation US20180230543A1 (en) 2013-05-17 2018-04-05 Variants of tnfsf15 and dcr3 associated with crohn's disease

Publications (1)

Publication Number Publication Date
US20160090629A1 true US20160090629A1 (en) 2016-03-31

Family

ID=51899024

Family Applications (4)

Application Number Title Priority Date Filing Date
US14/890,712 Abandoned US20160090629A1 (en) 2013-05-17 2014-05-16 Variants of tnfsf15 and dcr3 associated with crohn's disease
US15/946,632 Abandoned US20180230543A1 (en) 2013-05-17 2018-04-05 Variants of tnfsf15 and dcr3 associated with crohn's disease
US17/392,098 Active 2036-05-12 US12281359B2 (en) 2013-05-17 2021-08-02 Variants of TNFSF15 and DCR3 associated with Crohn's disease
US19/084,586 Pending US20250243548A1 (en) 2013-05-17 2025-03-19 Variants of tnfsf15 and dcr3 associated with crohn's disease

Family Applications After (3)

Application Number Title Priority Date Filing Date
US15/946,632 Abandoned US20180230543A1 (en) 2013-05-17 2018-04-05 Variants of tnfsf15 and dcr3 associated with crohn's disease
US17/392,098 Active 2036-05-12 US12281359B2 (en) 2013-05-17 2021-08-02 Variants of TNFSF15 and DCR3 associated with Crohn's disease
US19/084,586 Pending US20250243548A1 (en) 2013-05-17 2025-03-19 Variants of tnfsf15 and dcr3 associated with crohn's disease

Country Status (7)

Country Link
US (4) US20160090629A1 (enExample)
EP (3) EP3498867B1 (enExample)
JP (5) JP6482533B2 (enExample)
KR (4) KR102295125B1 (enExample)
CN (1) CN105358713B (enExample)
ES (1) ES2894963T3 (enExample)
WO (1) WO2014186750A2 (enExample)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10316083B2 (en) 2013-07-19 2019-06-11 Cedars-Sinai Medical Center Signature of TL1A (TNFSF15) signaling pathway
US10633449B2 (en) 2013-03-27 2020-04-28 Cedars-Sinai Medical Center Treatment and reversal of fibrosis and inflammation by inhibition of the TL1A-DR3 signaling pathway
US11186872B2 (en) 2016-03-17 2021-11-30 Cedars-Sinai Medical Center Methods of diagnosing inflammatory bowel disease through RNASET2
US11236393B2 (en) 2008-11-26 2022-02-01 Cedars-Sinai Medical Center Methods of determining responsiveness to anti-TNFα therapy in inflammatory bowel disease
US12215147B2 (en) 2019-05-14 2025-02-04 Prometheus Biosciences, Inc. Methods of selecting, based on polymorphisms, an inflammatory bowel disease subject for treatment with an anti-TL1A antibody
US12281359B2 (en) 2013-05-17 2025-04-22 Cedars-Sinai Medical Center Variants of TNFSF15 and DCR3 associated with Crohn's disease

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BR112014007426B1 (pt) 2011-09-30 2023-01-03 Teva Pharmaceuticals Australia Pty Ltd Anticorpos contra tl1a e seus usos
EP3337509A4 (en) 2015-08-21 2019-01-02 The Children's Hospital of Philadelphia Methods of treating autoimmune conditions in patients with genetic variations in dcr3 or in a dcr3 network gene
TWI703158B (zh) 2015-09-18 2020-09-01 美商希佛隆公司 特異性結合tl1a之抗體
KR102481305B1 (ko) * 2016-05-20 2022-12-26 세다르스-신나이 메디칼 센터 유전자에 기반한 염증성 장 질환의 진단
CA3111819A1 (en) * 2018-09-07 2020-03-12 The Children's Hospital Of Philadelphia Compositions and methods for the diagnosis and treatment of lymphatic system disorders
AU2020346580A1 (en) * 2019-09-13 2022-03-31 Kyowa Kirin Co., Ltd. DcR3 variant
WO2022103961A1 (en) * 2020-11-13 2022-05-19 Prometheus Biosciences, Inc. Methods, systems, and kits for treatment of inflammatory diseases targeting tl1a
WO2025038473A1 (en) 2023-08-11 2025-02-20 Paragon Therapeutics, Inc. Tl1a binding antibodies and methods of use

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US20090186034A1 (en) * 2006-12-19 2009-07-23 Genetech, Inc. Gene expression markers for inflammatory bowel disease
WO2008106451A2 (en) * 2007-02-26 2008-09-04 Cedars-Sinai Medical Center Methods of using single nucleotide polymorphisms in the tl1a gene to predict or diagnose inflammatory bowel disease
WO2009052512A2 (en) 2007-10-19 2009-04-23 Cedars-Sinai Medical Center Methods of using genetic variants to diagnose and predict inflammatory bowel disease
AU2009215441B2 (en) * 2008-02-19 2015-07-02 The Children's Hospital Of Philadelphia Identification of pediatric onset inflammatory bowel disease loci and methods of use thereof for the diagnosis and treatment of the same
WO2010118210A1 (en) * 2009-04-08 2010-10-14 Cedars-Sinai Medical Center Methods of predicting complication and surgery in crohn's disease
CA2758531C (en) * 2009-04-14 2018-11-13 Derren Barken Inflammatory bowel disease prognostics
AU2011317149B2 (en) 2010-10-18 2015-05-07 Société des Produits Nestlé S.A. Methods for determining anti-drug antibody isotypes
ES2530175T3 (es) 2011-02-17 2015-02-26 Nestec S.A. Ensayos para la detección de autoanticuerpos contra fármacos anti-TNF
WO2012161856A1 (en) 2011-05-20 2012-11-29 Government Of The United States, As Represented By The Secretary, Department Of Health And Human Services Blockade of tl1a-dr3 interactions to ameliorate t cell mediated disease pathology and antibodies thereof
US20140170157A1 (en) 2011-06-15 2014-06-19 Glaxosmithkline Intellectual Property (No.2) Limited Method of selecting therapeutic indications
EP2565277A1 (en) 2011-09-05 2013-03-06 Progenika Biopharma, S.A. Method for predicting radiographic severity in ankylosing spondylitis
SG11201401536QA (en) 2011-10-21 2014-05-29 Nestec Sa Methods for improving inflammatory bowel disease diagnosis
KR102295125B1 (ko) 2013-05-17 2021-08-31 세다르스-신나이 메디칼 센터 크론병과 연관된 tnfsf15와 dcr3의 변이체
CR20180365A (es) 2015-12-16 2018-09-28 Amgen Inc PROTEÍNAS DE UNIÓN AL ANTÍGENO BISPECÍFICO DE ANTI-TL1A/ANTI-TNF-a Y SUS USOS
JP7082945B2 (ja) 2016-03-17 2022-06-09 シーダーズ―シナイ メディカル センター Ｒｎａｓｅｔ２により炎症性腸疾患を診断する方法

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11236393B2 (en) 2008-11-26 2022-02-01 Cedars-Sinai Medical Center Methods of determining responsiveness to anti-TNFα therapy in inflammatory bowel disease
US12084722B2 (en) 2008-11-26 2024-09-10 Cedars-Sinai Medical Center Methods of determining responsiveness to anti-TNFα therapy in inflammatory bowel disease
US10633449B2 (en) 2013-03-27 2020-04-28 Cedars-Sinai Medical Center Treatment and reversal of fibrosis and inflammation by inhibition of the TL1A-DR3 signaling pathway
US12281359B2 (en) 2013-05-17 2025-04-22 Cedars-Sinai Medical Center Variants of TNFSF15 and DCR3 associated with Crohn's disease
US10316083B2 (en) 2013-07-19 2019-06-11 Cedars-Sinai Medical Center Signature of TL1A (TNFSF15) signaling pathway
US11312768B2 (en) 2013-07-19 2022-04-26 Cedars-Sinai Medical Center Signature of TL1A (TNFSF15) signaling pathway
US12269873B2 (en) 2013-07-19 2025-04-08 Cedars-Sinai Medical Center Signature of TL1A (TNFSF15) signaling pathway
US11186872B2 (en) 2016-03-17 2021-11-30 Cedars-Sinai Medical Center Methods of diagnosing inflammatory bowel disease through RNASET2
US12215147B2 (en) 2019-05-14 2025-02-04 Prometheus Biosciences, Inc. Methods of selecting, based on polymorphisms, an inflammatory bowel disease subject for treatment with an anti-TL1A antibody
US12391752B2 (en) 2019-05-14 2025-08-19 Prometheus Biosciences, Inc. Methods of enriching or amplifying nucleic acids in a sample from a patient with inflammatory bowel disease

Also Published As

Publication number Publication date
US20180230543A1 (en) 2018-08-16
EP2997165A4 (en) 2017-03-08
KR20210107176A (ko) 2021-08-31
EP3988673A3 (en) 2022-08-03
CN105358713B (zh) 2020-02-28
KR102295125B1 (ko) 2021-08-31
US20210371931A1 (en) 2021-12-02
EP3498867A1 (en) 2019-06-19
JP2020127437A (ja) 2020-08-27
US20250243548A1 (en) 2025-07-31
EP2997165A2 (en) 2016-03-23
JP2016526875A (ja) 2016-09-08
JP6482533B2 (ja) 2019-03-13
ES2894963T8 (es) 2022-02-24
EP3498867B1 (en) 2021-09-29
JP2022111329A (ja) 2022-07-29
JP2018148931A (ja) 2018-09-27
JP2025023316A (ja) 2025-02-14
WO2014186750A2 (en) 2014-11-20
EP3988673A2 (en) 2022-04-27
WO2014186750A3 (en) 2015-01-08
US12281359B2 (en) 2025-04-22
KR20250130857A (ko) 2025-09-02
CN105358713A (zh) 2016-02-24
KR20160009582A (ko) 2016-01-26
KR20230093538A (ko) 2023-06-27
ES2894963T3 (es) 2022-02-16

Similar Documents

Publication Publication Date Title
US20250243548A1 (en) Variants of tnfsf15 and dcr3 associated with crohn's disease
KR101582321B1 (ko) 심장성 부정맥의 위험 관리를 위한 유전적 마커
US20110212855A1 (en) Genetic Variants Predictive of Cancer Risk
US10301679B2 (en) Genetic polymorphisms, associated with rheumatoid arthritis, methods of detection and uses thereof
US20160096885A1 (en) Distinct effects of ifn-gamma and il-17 on tl1a modulated inflammation and fibrosis
Diegelmann et al. Intestinal DMBT1 expression is modulated by Crohn’s disease-associated IL23R variants and by a DMBT1 variant which influences binding of the transcription factors CREB1 and ATF-2
Tängdén et al. A genome-wide association study in a large community-based cohort identifies multiple loci associated with susceptibility to bacterial and viral infections
CN108330179A (zh) 一种TNF-α拮抗剂应答疗效SNP位点检测试剂盒
HK40072596A (en) Variants of tnfsf15 and dcr3 associated with crohn's disease
CN113512589B (zh) Prune1基因检测在多发性骨髓瘤患者预后中的应用
Seo et al. Mutation spectrum of RB1 gene in Korean bilateral retinoblastoma patients using direct sequencing and gene dosage analysis.
CN105765077B (zh) 测定抗甲状腺药物诱导的粒细胞缺乏症风险的检测方法以及测定用试剂盒
CN107574240A (zh) 一个NF‑κB1基因插入/缺失多态性位点在制备检测丙型肝炎易感性产品中的应用
Khalaf et al. Association between non-coding transcript variant polymorphisms (rs3135499, rs3135500) of the NOD2 gene and the propensity to rheumatoid arthritis in the Iraqi population
JP2007503806A (ja) ヒト肥満感受性遺伝子およびその使用

Legal Events

Date Code Title Description
AS Assignment

Owner name: CEDARS-SINAI MEDICAL CENTER, CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:MCGOVERN, DERMOT P.;REEL/FRAME:037034/0176

Effective date: 20150126

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION