# US 10,119,976 B2 · Method of assessing risk of PML > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,119,976 B2 - Document ID: US10119976B2 - Status: Granted - Kind: B2 - Application number: 14/893,989 - Filed: 2014-05-27 - Published: 2016-04-28 - Granted: 2018-11-06 - Earliest claimed: 2013-05-28 - Assignees: Biogen MA Inc. - Applicants: Biogen MA Inc. - Inventors: Gary Lewis Bloomgren; Carmen Bozic; Sophia Lee; Amy Pace; Tatiana Plavina; Meena Subramanyam - Web page: https://patentgrep.com/patent/US10119976B2 ## CPC - G01N 33/6854: {Immunoglobulins} - C07K 16/2842: {against integrin beta1-subunit-containing molecules, e.g. CD29, CD49} - C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) - G01N 33/56983: {Viruses} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C12N 2710/22011: Polyomaviridae, e.g. polyoma, SV40, JC - C12Q 1/70: involving virus or bacteriophage {(immunoassay for viruses G01N33/56983)} - G01N 2333/025: Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus - G01N 2469/20: Detection of antibodies in sample from host which are directed against antigens from microorganisms - G01N 2800/24: Immunology or allergic disorders - G01N 2800/28: Neurological disorders - G01N 2800/50: Determining the risk of developing a disease - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES ## Abstract The invention relates to methods of assessing a patient's risk of developing Progressive multifocal leukoencephalopathy (PML). ## Claims ### Claim 1 A method of evaluating a patient's risk of developing Progressive Multifocal Leukoencephalopathy (PML), the method comprising: determining a JC virus (JCV) antibody titer in a biological sample from the patient, wherein the patient has a negative prior immunosuppressant exposure classification; wherein if the titer is determined to be above a pre-determined level, the patient is determined to be at a higher risk of developing PML, and wherein if the titer is determined to be at or below an index level of 0.9, the patient is determined to be at a lower risk of developing PML. ### Claim 2 (depends on 1) The method of claim 1, wherein the pre-determined level is 0.9. ### Claim 3 (depends on 1) The method of claim 1, wherein the pre-determined level is 1.2. ### Claim 4 (depends on 1) The method of claim 1, wherein the pre-determined level is 1.5. ### Claim 5 (depends on 1) The method of claim 1, wherein the negative prior immunosuppressant exposure classification comprises that the patient has been free of a non-anti-VLA-4 immunosuppressant therapy for a period within 1, 3, or 5 years. ### Claim 6 (depends on 1) The method of claim 1, wherein the negative prior immunosuppressant exposure classification comprises that the patient has been free of a non-anti-VLA-4 immunosuppressant therapy for the patient's lifetime. ### Claim 7 (depends on 1) The method of claim 1, wherein if the patient is determined to be at lower risk of developing PML, then the patient is classified as being suitable for treatment with an anti-VLA-4 therapy. ### Claim 8 (depends on 7) The method of claim 7, further comprising administering an anti-VLA-4 therapy to the patient. ### Claim 9 (depends on 7) The method of claim 7, wherein the anti-VLA-4 therapy is a natalizumab therapy. ### Claim 10 (depends on 1) The method of claim 1, wherein the patient has previously received an anti-VLA-4 therapy. ### Claim 11 (depends on 1) The method of claim 1, further comprising determining a second or further JCV antibody titer in a second or further biological sample from the patient, wherein the second or further biological sample is obtained from the patient at a period of time after the first biological sample, and wherein: if the titer is determined to be above zero, but at or below a pre-determined level in the two or more samples, the patient is determined to be at a lower risk of developing PML, and if the titer is determined to be above a pre-determined level in the two or more samples, the patient is determined to be at a higher risk of developing PML. ### Claim 12 (depends on 11) The method of claim 11, wherein the pre-determined level is an index level of 0.9. ### Claim 13 (depends on 11) The method of claim 11, wherein the pre-determined level is an index level of 1.2. ### Claim 14 (depends on 11) The method of claim 11, wherein the pre-determined level is an index level of 1.5. ### Claim 15 (depends on 11) The method of claim 11, wherein the period of time is 6 months. ### Claim 16 (depends on 11) The method of claim 11, wherein the period of time is 12 months. ### Claim 17 (depends on 11) The method of claim 11, wherein the period of time is 18 months. ### Claim 18 (depends on 11) The method of claim 11, wherein the two or more samples are consecutive samples. ### Claim 19 (depends on 11) The method of claim 11, wherein the titer in every sample obtained from the patient over a period of time is determined to be at or below a pre-determined level. ### Claim 20 (depends on 11) The method of claim 11, wherein the titer in every sample obtained from the patient over a period of time is determined to be above a pre-determined level. ### Claim 21 (depends on 11) The method of claim 11, wherein the patient as has received an anti-VLA-4 therapy during the period of time. ### Claim 22 A method of evaluating a patient's risk of developing Progressive Multifocal Leukoencephalopathy (PML), the method comprising: determining a JC virus (JCV) antibody titer in a biological sample from the patient, wherein the patient has a negative prior immunosuppressant exposure classification; wherein if the titer is determined to be at or below an index level of 0.9, the patient is determined to be at a lower risk of developing PML. ### Claim 23 (depends on 22) The method of claim 22, further comprising administering an anti-VLA4 antibody if the patient is determined to be a lower risk of developing PML. ### Claim 24 (depends on 23) The method of claim 23, wherein the anti-VLA4 antibody is natalizumab. ### Claim 25 A method of treating an MS patient, comprising: administering an anti-VLA4 antibody responsive to a determination of a JC virus (JCV) antibody titer at or below an index level of 0.9 in a patient having a negative prior immunosuppressant exposure classification, thereby treating the patient. ### Claim 26 (depends on 25) The method of claim 25, wherein the anti-VLA4 antibody is natalizumab.