IP Law Daily, TOP STORY—FedCir: Patent Claims for Eye Medication Were Invalid for Obviousness to the Extent Recited Dosages Were Disclosed in Prior Art, (Aug 9, 2012)

By Thomas Long, J.D.

The federal district court in Indianapolis erred in holding that six out of eight asserted claims in a patent for anti-allergy eye drops would not have been obvious over the prior art, the U.S. Court of Appeals has determined (Alcon Research, Ltd. v. Apotex Inc., August 8, 2012, Moore, K.). The appellate court affirmed the lower court’s determination that two of the claims were not invalid because prior art did not teach use of the drug in the dosages recited by those claims.

The patent at issue (U.S. Patent No. 5,641,805, “the '805 patent”) was owned by eye care products company Alcon. The '805 patent is directed to a method for treating allergic eye disease in humans. The method comprised stabilizing conjunctival mast cells by topically administering an olopatadine composition. The specification explains that the discovery that olopatadine can treat human eye allergies through this mechanism of action is the novel aspect of the '805 patent. Alcon’s Patanol® product, an anti-allergy eye drop with a 0.1% w/v concentration of olopatadine, is a commercial embodiment of the '805 patent.

Generic drug producer Apotex had submitted an Abbreviated New Drug Application (ANDA) to the Food and Drug Administration seeking approval to market a generic version of the anti-allergy eye drop Patanol®. Apotex’s ANA included a Paragraph IV certification that the '805 patent was invalid, unenforceable, and/or would not be infringed by Apotex’s generic product.

Alcon sued Apotex for patent infringement under 35 U.S.C. § 271(e)(2)(A). Alcon asserted claims 1-8 of the '805 patent, which is listed in the Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) entry for Patanol®. In a bench trial, the district court held that the '805 patent was enforceable and not invalid, and that Apotex’s generic product infringed the asserted claims. The district court held that Apotex failed to establish that the claims would have been obvious by clear and convincing evidence.

The '805 patent’s specification states that at the time of invention, it was already known in the art that olopatadine was an effective antihistamine and that some chemicals in olopatadine’s genus may have mast cell stabilizing activity. However, the district court found that at the time of invention a person skilled in the art “understood that there were significant barriers to adapting a known systemic antihistamine for topical use in the eye.” The district court also found that the prior art as a whole—and particularly one article (“Kamei”)—taught away from using olopatadine as a mast cell stabilizer. The district court rejected Apotex’s argument that the prior art need not teach mast cell stabilization because this mechanism of action was an inherent property of olopatadine.

Obviousness

Section 103(a) of the Patent Act provides that a patent is invalid for obviousness “if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains.”

Claims 1-3 and 5-7. The appellate court held that Apotex had established by clear and convincing evidence that claims 1-3 and 5-7 would have been obvious to one of ordinary skill in the art over the Kamei article, which disclosed every limitation of these claims except that the formulation can be used to treat eye allergies in humans. According to Apotex, Kamei disclosed eye drops with olopatadine concentrations that overlapped with the claimed concentration rates, rendering the claims invalid for obviousness. Even though Kamei tested olopatadine formulations only in guinea pig eyes, a person of ordinary skill in the art could use routine methods to adapt these formulations for human use with a reasonable expectation of success.

Kamei disclosed treating eye allergies in guinea pigs using eye drops with olopatadine concentrations ranging from 0.0001% w/v to 0.01% w/v. This range overlapped with the concentrations covered by claims 1-3 and 5-7, the court said.

The district court had found, as a factual matter, that animal tests, including guinea pig models, were predictive of a compound’s antihistaminic activity and its topical ocular availability in humans. Therefore, the appellate court said, the district court clearly erred when it concluded that a person of skill in the art would not have been motivated to use the olopatadine concentration disclosed in Kamei in human eyes. Given that the patent defined, and expressly claimed, olopatadine concentrations that were “therapeutically effective” to stabilize conjunctival mast cells, Kamei’s disclosure of overlapping concentrations—even if for a different purpose—met the limitations of claims 1-3 and 5-7.

Although Kamei did not expressly disclose that olopatadine would be safe for the human eye, neither did the '805 patent, the court noted. The patent was not based on testing in humans. Just as a skilled artisan would be able to practice the invention claimed in the '805 patent despite its lack of explicit instruction that olopatadine was safe for human ophthalmic use, the article would have a reasonable expectation of success for adapting Kamei’s formulation for the same use in a human eye, the court concluded.

Claims 4 and 8. Claims 4 and 8 were directed to a 0.1% olopatadine formulation only. Kamei did not disclose a concentration of olopatadine greater than 0.01%. Therefore, these claims were not obvious under Kamei, the court said. The court rejected Apotex’s argument that routine experimentation would have led a skilled artisan to try the formulation disclosed by claims 4 and 8. The district court correctly relied on expert testimony that a person of ordinary skill in the art would not have a reasonable expectation of success for increasing the highest dosage used in Kamei by an order of magnitude. The appellate court also agreed with the district court’s determination that a person of ordinary skill in the art would have been concerned that olopatadine might be biphasic at this concentration and thus would not have tried a formulation with ten times more olopatadine than the highest dosage used in Kamei.

The appellate court also stated that objective evidence further supported the district court’s holding that claims 4 and 8 would not have been obvious. The district court found that Patanol®—which used the concentration of olopatadine recited in claims 4 and 8—was “an outstanding commercial success.” The objective evidence demonstrated that the drug’s commercial success was caused by the merits of the invention as distinct from the prior art, the court held.

The case is No. 2011-1455.

Bruce R. Genderson (Williams & Connolly, LLP) for Alcon Research, Ltd. Robert B. Breisblatt (Katten Muchin Rosenman, LLP) for Apotex Inc.

MainStory: TopStory Patent FedCir