Combigan is made up of the well-known α2-adrenergic receptor agonist Alphagan (0.2% brimonidine) and the well-known β-adrenergic receptor antagonist Timoptic (0.5% timolol). Both of these drugs are used to treat glaucoma. Several generics companies, including Sandoz, challenged the validity of the patents that protect Combigan on grounds of obviousness.
The US Court of Appeals for the Federal Circuit (CAFC) found that several items of prior art rendered the combination of brimonidine and timolol obvious. For example, an earlier patent described fixed-dose combinations of α2-adrenergic receptor agonists and β-adrenergic receptor antagonists (such as timolol) for the treatment of glaucoma. In addition, journal articles highlighted that combining timolol with other drugs could reduce the number of required doses. Moreover, it was known that the serial administration of brimonidine and timolol reduced intraocular pressure to a greater extent than either timolol or brimonidine alone, which provided motivation to formulate fixed combinations of these drugs to increase patient compliance.
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