In vitro method and kit for prognosis or prediction of response by patients with rheumatoid arthritis to treatment with TNF-αfactor blocking agents
| Title: | In vitro method and kit for prognosis or prediction of response by patients with rheumatoid arthritis to treatment with TNF-αfactor blocking agents |
|---|---|
| Patent Number: | 9,441,274 |
| Publication Date: | September 13, 2016 |
| Appl. No: | 13/120445 |
| Application Filed: | September 18, 2009 |
| Abstract: | In vitro method and kit for prognosis or prediction of the response of rheumatoid patients to treatment with TNF-α factor blocking agents, which comprises determining, in a blood sample from said patients, the expression level of at least one of the eight genes selected from the group: HLA-DRB3, EAT2, GNLY, CAMP, SLC2A3, IL2RB, MXD4 and TLR5 or combinations thereof and comparing said expression level to the expression values obtained from responsive and non-responsive patients who showed responsiveness to the treatment and those who showed non-responsiveness thereto. |
| Inventors: | Marsal Barril, Sara (Barcelona, ES); Julia Cano, Antonio (Barcelona, ES) |
| Assignees: | FUNDACIO INSTITUT DE RECERCA DE L'HOSPITAL UNIVERSITARI VALL D'HEBRON (Barcelona, ES) |
| Claim: | 1. A method for treating rheumatoid arthritis in a patient, said method comprising: detecting in a sample from the patient the expression level of at least one of the eight genes selected from the group consisting of: HLA-DRB3, EAT2, GNLY, CAMP, SLC2A3, IL2RB, MXD4, and TLR5; and administering a TNF-α factor blocking agent to the patients which show over-expression of at least one of the genes selected from the group consisting of TLR5, CAMP and SLC2A3; and not administering the TNF-α factor blocking agent to patients which over-express at least one of the genes selected from the group consisting of MXD4, HLA-DRB3, IL2RB, EAT2, and GNLY, wherein the over-expression is based on the comparison of the expression level of the at least one of the eight genes and the expression values obtained from TNF-α factor blocking agent responsive and TNF-α factor blocking agent non-responsive patients. |
| Claim: | 2. The method, according to claim 1 , which comprises the detection of the overall expression level of the group of eight genes consisting of: HLA-DRB3, EAT2, GNLY, CAMP, SLC2A3, IL2RB, MXD4 and TLR5. |
| Claim: | 3. The method, according to claim 1 , which comprises the detection of the expression level of any combination of two or more genes of the group of eight genes selected from the group consisting of: HLA-DRB3, EAT2, GNLY, CAMP, SLC2A3, IL2RB, MXD4, and TLR5. |
| Claim: | 4. The method, according to claim 1 , which comprises the detection of the expression level of at least one of the six genes selected from the group consisting of: HLA-DRB3, EAT2, GNLY, CAMP, IL2RB, and TLR5. |
| Claim: | 5. The method, according to claim 4 , which further comprises the detection of the expression level of at least one of the genes: SLC2A3, MXD4, or both SLC2A3 and MXD4. |
| Claim: | 6. The method, according to claim 1 , which comprises the detection of the overall expression level of the group of six genes consisting of: HLA-DRB3, EAT2, GNLY, CAMP, IL2RB and TLR5. |
| Claim: | 7. The method, according to claim 6 , which further comprises the detection of the expression level of at least one of the genes: SLC2A3, MXD4, or both SLC2A3 and MXD4. |
| Claim: | 8. The method according to claim 1 , wherein the rheumatoid arthritis patients (a) fulfill the 1987 ACR (American College of Rheumatology) criteria for rheumatoid arthritis diagnosis and have a DAS28 index >3.2, (b) said patients are tolerant to ≦20 mg/week methotrexate, (c) said patients are able to receive ≦10 mg/day prednisolane and treatment with NSAID, wherein the doses of methotrexate, glucocorticoids and NSAID remaining stable during the four weeks prior to treatment with infliximab or adalimumab and said patients have not received any other DMARD during the four weeks prior to the aforesaid treatment with infliximab or adalimumab. |
| Claim: | 9. The method according to claim 1 , wherein the TNF-α factor blocking agent is selected from infliximab or adalimumab. |
| Claim: | 10. The method according to claim 1 , wherein the expression level is carried out by quantifying mRNA level in a blood sample from the patient. |
| Patent References Cited: | 2007/0275406 November 2007 Hakonarson et al. 2008150491 December 2008 |
| Other References: | Nelson et al.; HLA antigens in Tlingit Indians with rheumatoid arthritis; Tissue Antigens; vol. 40; No. 2; pp. 57-63; Aug. 1992; full text. cited by examiner Lequerré et al.; Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis; Arthritis Research & Therapy; vol. 8; No. 4; R105; published Jul. 3, 2006. cited by examiner Sugihara et al.; Effects of Infliximab Therapy on Gene Expression Levels of Tumor Necrosis Factor alpha, Tristetraprolin, T Cell Intracellular Antigen 1, and Hu Antigen R in Patients With Rheumatoid Arthritis; Arthritis & Rheumatism; vol. 56, No. 7, pp. 2160-2169; published online Jun. 28, 2007. cited by examiner Lindberg et al.; Effect of infliximab on mRNA expression profiles in synovial tissue of rheumatoid arthritis patients; Arthritis Research & Therapy; vol. 8; No. 6; R179; published Nov. 29, 2006. cited by examiner GPL6884; Illumina HumanWG-6 v3.0 expression beadchip; http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL6884; submitted May 21, 2008; pp. 1-3 and 2813. cited by examiner Williams R. C. et al. “Meta-analysis reveals association between most common class II haplotype in full-heritage Native Americans and rheumatoid arthritis” Human immunology, vol. 42, pp. 90-94, Jan. 1995. cited by applicant Nelson J. L. et al. “HLA antigens in Tlingit Indians with rheumatoid arthritis,” Tissue Antigens, vol. 40, pp. 57-63, Aug. 1992—Abstract. cited by applicant |
| Primary Examiner: | Gonzalez, Antonio Galisteo |
| Attorney, Agent or Firm: | Fuierer, Tristan A. Moore & Van Allen, PLLC |
| Accession Number: | edspgr.09441274 |
| Database: | USPTO Patent Grants |
| Language: | English |
|---|