Ariad patents molecule for treatment of Parkinson Disease

March 2014 Patent re use of ponatinib for PD


[0064] In pharmacokinetic experiments in rodents, We have
found that the potent multi-kinase inhibitor, ponatinib, can
actually accumulate in brain to levels betWeen tWo- and three
foldhigher than inblood. This Was an unexpectedly fortuitous
?nding. The very favorable accumulation of ponatinib in
brain combined With its signi?cant inhibitory potency against
kinases such as Abl, permits delivery of pharmacologically
relevant concentrations of drug to the brain, e.g., at levels
effective to inhibit the phosphorylation of parkin in brain
Which has been associated With the development of PD. This
noW makes compounds of Formula I such as ponatinib very 
attractive agents for treating PD.


[0065] As discussed herein, this disclosure provides a 
method for treating PD by administering to a patient in need 
thereof an effective amount of a compound of Formula I such 
as ponatinib or a pharmaceutically acceptable salt thereof. 

Therapy
[0068] Therapy according to the invention may be provided
at home, the doctor’s of?ce, a clinic, a hospital’s outpatient
department, or a hospital. Treatment generally begins at a
hospital so that the doctor can observe the therapy’s effects
closely and make any adjustments that are needed. The dura
tion of the therapy depends on the age and condition of the
patient, the stage of the patient’s Parkinson’s disease, and
hoW the patient responds to the treatment. Additionally, a
person having a greater risk of developing Parkinson’s dis
ease (e.g., a person Who is genetically predisposed) may 
receive ponatinib therapy to inhibit or delay symptoms of the 
disease.

etc., as illustrated beloW.
[0174] For example, White opaque capsules Were prepared 
containing nominally 2 mg of ponatinib free base, provided as
the hydrochloride salt, With no excipients. White opaque cap
sules Were also prepared containing 5 mg, 15 mg, or 20 mg of
ponatinib free base, provided as the hydrochloride salt, mixed
With conventional excipients.

Applicant’s oWn WO 2007/075869, Which is hereby
incorporated herein by reference for all purposes, discloses
certain compounds that inhibit inter alia Abl. One notable Abl
inhibitor is ponatinib, Which is currently the subject of a
clinical trial to determine the e?icacy of ponatinib in patients
With chronic myeloid leukemia (CML) in chronic phase (CP),


Korean Patent Info