Opinion ID: 178456
Heading Depth: 2
Heading Rank: 2

Heading: AstraZeneca's Budesonide Drug and Patents

Text: In 2000, the FDA approved AstraZeneca's NDA for a budesonide inhalation suspension that AstraZeneca now markets under the name PULMICORT RESPULES®. Each respule is a plastic vial containing a single dose of budesonide, an anti-inflammatory corticosteroid, suspended in a sterile liquid. The drug is administered by squeezing the entire contents of a vial into a jet nebulizer and inhaling the resulting mist through a mask attached to the nebulizer. The Orange Book entry for AstraZeneca's budesonide product includes the '099 Patent and its parent, the '603 Patent. Both patents are owned by AstraZeneca and have specifications that are nearly identical in all relevant respects. The patents explain that [t]he invention provides a new method of treating respiratory diseases such as asthma that involves administering a budesonide composition with a nebulizer not more than once per day. '603 Patent col.1 ll.20-23; '099 Patent col.1 ll.26-29. The invention also features a kit for treating respiratory diseases, the kit including a budesonide composition in a sealed container . . . and a label indicating administration by nebulization in a continuing regimen at a frequency of not more than once per day. '603 Patent col.2 ll.1-6; '099 Patent col.2 ll.7-12. Both patents include method claims directed to administering a budesonide composition once daily and product claims directed to the described kit containing either a budesonide composition or suspension and a label indicating once-daily administration by nebulization. While AstraZeneca's patents are directed to once-daily treatment, the label that accompanies AstraZeneca's budesonide product indicates that the drug may be administered once or twice daily. The label states that the drug is available in three strengths0.25 mg, 0.5 mg, and 1.0 mg per 2 mL vialand provides a table of recommended starting doses based on a patient's history of therapy. The label repeatedly warns that patients should titrate down to the lowest effective dose of the medication to avoid any adverse effects from excessive use of the medication. For example, in its DOSAGE AND ADMINISTRATION section, the label states that [i]n all patients, it is desirable to downward-titrate to the lowest effective dose once asthma stability is achieved and [o]nce the desired clinical effect is achieved, consideration should be given to tapering to the lowest effective dose. The PRECAUTIONS section also warns that suppression of HPA function may be associated . . . when the dose is not titrated to the lowest effective dose and [t]o minimize the systemic effects of orally inhaled corticosteroids . . . each patient should be titrated to his/her lowest effective dose. It is undisputed that the FDA requires all manufacturers of inhaled corticosteroids such as budesonide to include this downward titration language in the labels of their inhaled corticosteroid products.