Methods of treating progressive forms of multiple sclerosis comprising subcutaneously administering daclizumab

#This application contains a Sequence Listing which has been submitted in ASCII format via EFS and is hereby incorporated by reference. The ASCII copy, created on Aug. 8, 2012, is named 240WO.TXT and is 34,203 bytes in size.

#The parties to the joint research agreement are Abbott Biotherapeutics Corp. and Biogen Idec MA Inc.

#Daclizumab (DAC) is a humanized IgG1 monoclonal antibody that binds to the alpha subunit (CD25 or Tac) of the human high-affinity interleukin-2 (IL-2) receptor, which is expressed on the surface of activated, but not resting, T- and B-lymphocytes. When bound to CD25 on the activated cells, DAC blocks the formation of the high affinity IL-2 receptor complex, thereby blocking IL-2-induced proliferation of the activated cells.

#FIG. 1 provides DAC-HYP light chain cDNA (SEQ ID NO:1) and translated amino acid (SEQ ID NO:2) sequences. The bold, underlined aspartate (D) residue is the first amino acid in the properly processed mature protein; the amino acid sequence upstream of this residue corresponds to the signal sequence.

#FIG. 2 provides DAC-HYP heavy chain cDNA (SEQ ID NO:3) and translated amino acid sequences (SEQ ID NO:4). The bold, underlined glutamaine (Q) residue is the first amino acid in the properly processed mature protein; the amino acid sequence upstream of this residue corresponds to the signal sequence.

#FIG. 3A-FIG. 3D together provide the full nucleotide sequence for vector pHAT.IgG1.rg.dE (SEQ ID NO:5).

#The present disclosure provides methods of treating patients suffering from progressive forms of multiple sclerosis as well as patients suffering from forms or stages of MS in which the patient has not experienced a relapse or exacerbation for a significant period of time, for example a period of at least 6 months. Multiple sclerosis (“MS”) is generally understood to be an autoimmune disease clinically described as a central nervous system white matter disorder disseminated in time and space. It can be diagnosed by brain and spinal chord magnetic resonance imaging (“MRI”), analysis of somatosensory evoked potentials, and analysis of cerebrospinal fluid to detect increased amounts of immunoglobulin or oligoclonal bands. MRI is a particularly sensitive tool. MRI abnormalities indicating the presence or progression of MS include hyperintense white matter signals on T2-weighted and fluid attenuated inversion recovery images, gadolinium enhancement of active lesions, hypointensive “black holes” (representing gliosis and axonal pathology) and brain atrophy on T1-weighted studies.

#MS presents in several forms, generally characterized by two main forms: relapsing forms and progressive forms. In relapsing forms, new symptoms tend to occur in discrete attacks. In progressive forms, new symptoms accumulate progressively over time (see, e.g., Lublin & Reingold, 1996 Neurology 46(4):907-911)). The four currently recognized forms of MS and their main characteristics are: Relapsing-remitting MS: characterized by unpredictable acute attacks, called “exacerbations,” with worsening of symptoms followed by full, partial, or no recovery of some function. These attacks appear to evolve over several days to weeks. Recovery from an attack takes weeks sometimes months. The disease does not worsen in the periods between the attacks. This pattern usually occurs early in the course of MS in most people. Primary-progressive MS: characterized by a gradual but steady progression of disability, without any obvious relapses and remissions. This form of disease occurs in just 15% of all people with MS, but it is the most common type of MS in people who develop the disease after the age of 40. Secondary-progressive MS: initially begins with a relapsing-remitting course, but later evolves into progressive disease. The progressive part of the disease may begin shortly after the onset of MS, or it may occur years or decades later. Progressive-relapsing MS: This is the least common form of the disease and is characterized by a steady progression in disability with acute attacks that may or may not be followed by some recovery. People with progressive relapsing MS initially appear to have primary progressive MS.

#The present disclosure concerns the treatment of progressive forms of MS, including both primary progressive and secondary progressive, as well as forms or stages of MS that are characterized by a lack of relapses or exacerbations. Diagnostic criteria for assessing whether an individual is suffering from primary progressive MS or secondary progressive MS are well-known. For example, for primary progressive MS (“PPMS”), three levels of diagnostic certainty have been defined—definite, probable and possible-based on clinical findings, abnormal cerebrospinal fluid, abnormalities on MRI of the brain and special cord and evoked potentials. According to one set of criteria, in definite PPMS, evidence of intrathecal synthesis of immunoglobulin G together with one of the following three MRI criteria is indicative of PPMS: (1) nine brain lesions, (2) two spinal cord lesions, (3) four to eight brain lesions and one spinal cord lesion (see, e.g., Thompson et al., 2000, Ann. Neurol. 47(6):831-835). These and other well-established diagnostic criteria can be used to diagnose an individual as having PPMS. Ultimate diagnosis will depend upon the judgment of the neurologist.