Claims for Patent: 9,717,453

Summary for Patent: 9,717,453

Title:	Cognitive composite parameters and uses thereof for evaluating multiple sclerosis
Abstract:	Methods, systems and kits for the identification, assessment and/or treatment of a subject having multiple sclerosis are disclosed.
Inventor(s):	Cadavid; Diego (Concord, MA), Erlanger; David (New York, NY), DeLuca; John (Rockaway, NJ), Benedict; Ralph (Buffalo, NY), Foley; Frederick W. (River Edge, NJ), Wilken; Jeffrey A. (Fairfax, VA)
Assignee:	BIOGEN IDEC MA INC. (Cambridge, MA)
Application Number:	14/395,802
Patent Claims:	1. A method of treating or preventing multiple sclerosis (MS), in a subject having MS, or at risk of developing MS, comprising: acquiring a value of a composite parameter from the subject, said composite parameter comprising a first value for an attention and/or processing speed (PS) factor and a second value for a memory factor, wherein: (i) the first value is acquired by obtaining an average of scores from at least one assessment of one or both of complex scanning or visual tracking, and at least one or two assessment(s) of processing speed, flexibility or calculation ability, and (ii) the second value is acquired by obtaining an average of scores from at least one or two assessments indicative of verbal learning and delayed recall, combined with at least one or two assessments indicative of visual learning and delayed recall; and responsive to said value, administering to the subject an MS therapy in an amount sufficient to reduce one or more symptoms associated with MS, wherein, in response to an increased value of said composite parameter relative to a reference value, the MS therapy is initiated or continued; and wherein, in response to a decreased value of said composite parameter relative to a reference value, the MS therapy is modified or an alternative MS therapy is used. 2. The method of claim 1, wherein the first value is obtained by one or both of: (i) as a function of a score based on a Symbol Digit Modalities Test (SMDT)) and a score based on at least one or two Paced Auditory Serial Addition Test (PASAT); or (ii) calculating the first value using the following equation: {SMDT score+[PASAT 3 score+PASAT 2 score]/2)}/2. 3. The method of claim 2, wherein the value of the composite parameter comprises a score value chosen from one or more of: -0.6 to -1.6 for SDMT, -0.2 to -1.2 for PASAT 3, -0.12 to -1.12 for PASAT 2, -0.25 to -1.25 for SRT Total, -0.3 to -1.3 for SRT Delay, -0.8 to -1.8 for BVMT-R Total, or -1.2 to -2.2 for BVMTR Delay. 4. The method of claim 1, wherein the second value is obtained by one or both of: (i) averaging the scores at least one or two components of a Selective Reminding Test (SRT) and at least one or two components of a Brief Visuospatial memory Test (BVMT); or (ii) calculating the second value using the following equation: [SRT learning score+SRT delay score+BVMT learning score and BVMT delay score]/4. 5. The method of claim 1, wherein the first and the second values are weighed equally or differentially in generating the value of the composite parameter. 6. The method of claim 1, wherein the scores from the assessments used to obtain the second value are weighed equally or differentially. 7. The method of claim 1, wherein the scores from the assessments are weighed equally or differentially, wherein the assessments are selected from the group consisting of: (i) verbal and visual memory; (ii) learning and delayed recall components; and (iii) complex scanning and/or visual tracking, and the at least one or two assessment(s) of processing speed, flexibility and/or calculation ability. 8. The method of claim 1, wherein the reference value is acquired from: a healthy subject or an average of healthy subjects; the subject prior to, during, or after the MS therapy; the subject at two, three or more time intervals; or at least two or more MS patients having the same or different disease progressions. 9. The method of claim 1, wherein the subject is monitored in one or more of the following periods: prior to beginning of treatment; during the treatment; after the treatment has been administered; or at a first and second time point at least months apart. 10. The method of claim 1, wherein the value of the composite parameter has a reliability of at least 0.65 or higher. 11. The method of claim 10, wherein the value of the composite parameter has a reliability of at least 0.85 or higher. 12. The method of claim 1, wherein an increase in the value of the composite parameter, relative to the reference value, by at least 5% or 0.2 to 1.5 SD, or more is indicative of improved cognitive function in the subject or wherein a decrease in the value of the composite parameter, relative to the reference value, by at least 5%, or 0.2 to 1.5 SD, or more is indicative of decreased cognitive function in the subject. 13. The method of claim 12, wherein an increase in the value of the composite parameter, relative to the reference value, by at least 20%, or more is indicative of improved cognitive function in the subject; or wherein a decrease in the value of the composite parameter, relative to the reference value, by at least 20%, or more is indicative of decreased cognitive function in the subject. 14. The method of claim 1, wherein the value of the composite parameter is lower in a patient having secondary progressive multiple sclerosis (SPMS) compared to a patient with relapse remitting multiple sclerosis (RRMS). 15. The method of claim 1, wherein the subject is a patient having one of: benign MS, relapse/remitting MS (RRMS), primary progressive MS, secondary progressive MS (SPMS), clinically isolated syndrome (CIS), or clinically defined MS (CDMS). 16. The method of claim 1, further comprising one or more steps of: performing a neurological examination, evaluating the subject's status on the Expanded Disability Status Scale (EDSS), or detecting the subject's lesion status as assessed using an MRI. 17. The method of claim 1, wherein the MS therapy comprises one or more of an IFN-.beta.1 molecule; a polymer of glutamic acid, lysine, alanine and tyrosine; an antibody or fragment thereof against alpha-4 integrin; an anthracenedione molecule; a fingolimod; a dimethyl fumarate; an antibody to the alpha subunit of the IL-2 receptor of T cells; an antibody against CD52 or alemtuzumab; an inhibitor of a dihydroorotate dehydrogenase or teriflunomide; or an anti-LINGO-1 antibody. 18. The method of claim 17, wherein the IFN-.beta. 1 molecule comprises one or more of an IFN-.beta.1a or IFN-.beta. 1b polypeptide, a variant, a homologue, a fragment or a pegylated variant thereof. 19. The method of claim 1, wherein the MS therapy comprises an IFN-1b molecule; a polymer of glutamic acid, lysine, alanine and tyrosine; or the MS therapy comprises an alternative MS therapy chosen from an antibody or fragment thereof against alpha-4 integrin; a dimethyl fumarate; an anthracenedione molecule; a fingolimod; a dimethyl fumarate; an antibody to the alpha subunit of the IL-2 receptor of T cells; or an anti-LINGO-1 antibody. 20. A method of evaluating and/or quantifying cognitive function in a subject having multiple sclerosis (MS), or at risk of developing MS, comprising: acquiring a value of a composite parameter from the subject, said composite parameter comprising a first value for an attention and/or processing speed (PS) factor and a second value for a memory factor, wherein: (i) the first value is acquired by obtaining an average of scores from at least one assessment of complex scanning or visual tracking or both, and at least one or two assessment(s) of processing speed, flexibility or calculation ability, and (ii) the second value is acquired by obtaining an average of scores from at least one or two assessments indicative of verbal learning and delayed recall, combined with at least one or two assessments indicative of visual learning and delayed recall; and comparing the value of the composite parameter from the subject to a reference value, wherein an increase in the value of the composite parameter, relative to a reference value, is indicative of improved cognitive function in the subject, and wherein a decrease in the value of the composite parameter, relative to a reference value, is indicative of decreased cognitive function in the subject.

Details for Patent 9,717,453

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	05/07/2001		2032-04-20
Genzyme Corporation	LEMTRADA	alemtuzumab	Injection	103948	11/14/2014		2032-04-20
Genzyme Corporation	CAMPATH	alemtuzumab	Injection	103948	10/12/2004		2032-04-20