Patent Watch: Alcon Research, Ltd. v. Apotex Inc.

Alerts / August 10, 2012

[For purposes of an obviousness analysis,] the motivation to modify a prior art reference to arrive at the claimed invention need not be the same motivation that the patentee had.

On August 8, 2012, in Alcon Research, Ltd. v. Apotex Inc., the U.S. Court of Appeals for the Federal Circuit (Prost, Moore,* O'Malley) reversed-in-part and affirmed-in-part the district court's judgment that U.S. Patent No. 5,641,805, which related to the treatment of human allergic eye disease by stabilizing conjunctival mast cells using a topically administered olopatadine composition such as Alcon's product Patanol®, was not invalid for obviousness. The Federal Circuit stated:

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." "Obviousness is a question of law, which we review de novo, with underlying factual questions, which we review for clear error following a bench trial." These underlying factual inquires are: (1) the scope and content of the prior art; (2) the differences between the prior art and the claims at issue; (3) the level of ordinary skill in the field of the invention; and (4) objective considerations such as commercial success, long felt need, and the failure of others.

Despite the clear language of the '805 patent claims, Alcon argues that some olopatadine concentrations covered by claims 1-3 and 5-7 do not stabilize human conjunctival mast cells to a clinically relevant extent and should therefore be excluded from the claims' scope. The district court found that "[n]ot every concentration of olopatadine applied to the human eye will stabilize the mast cells in the human eye." . . . Alcon's counsel argued that, "to the extent that the dependent claims cover a broader range than the range that would be operative to stabilize mast cells," the inoperative portion of the range "wouldn't be covered by the claim by virtue of the limitation in claim 1" that mast cell stabilization must occur to a clinically relevant extent. Alcon's counsel thus contended that the claims "would be operative, just at a narrower concentration" than the claimed range. This is not how patent law works. When you claim a concentration range of 0.0001-5% w/v (as claim 2), you can't simply disavow the invalid portion and keep the valid portion of the claim. If everything up to 0.001% w/v is admittedly not enabled, then the entire claim is invalid. Similarly, if prior art discloses a portion of the claimed range, the entire claim is invalid. Courts do not rewrite the claims to narrow them for the patentee to cover only the valid portion. Alcon cannot have it both ways. Because claim 2 sets forth a concentration range, that range at a minimum must be included in claim 1, whatever its limitations. When analyzing the validity of claim 1 or claim 2, by the express claim language, the clinically relevant therapeutic amount must include 0.0001-5% w/v olopatadine. That is the claimed concentration range which should be compared to the disclosure of the prior art.

The Kamei reference discloses 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 overlaps with the concentrations covered by claims 1-3 and 5-7. Claims 4 and 8 are directed only to a 0.1% olopatadine formulation, and Kamei does not disclose a concentration of olopatadine greater than 0.01%. Kamei expressly discloses eye drops with olopatadine concentrations covered by claims 1-3 and 5-7 and thus overlaps with the ranges disclosed in the '805 patent. The only remaining dispute is whether there was a motivation to adapt the formulation disclosed in Kamei, which was tested in guinea pigs, for use in treating allergic eye disease in humans. The district court found, as a factual matter, that animal tests, including guinea pig models, are predictive of a compound's antihistaminic activity and its topical ocular availability in humans. Given this fact finding, 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. The district court's error stemmed from its refusal to look at any motivation beyond that articulated by the patent. [T]he motivation to modify a prior art reference to arrive at the claimed invention need not be the same motivation that the patentee had. Here, the motivation to adapt Kamei's formulation for human use is that it is an effective antihistamine in guinea pigs and that animals models are (as the district court expressly found) predictive of antihistaminic efficacy in humans.

The district court's fact finding that the prior art did not teach that olopatadine would stabilize human conjunctival mast cells, and indeed taught away from using olopatadine for this purpose, is not clearly erroneous. It is, however, not the only motivation to arrive at the claimed invention. A person of ordinary skill in the art at the time of invention would have been motivated to use olopatadine to treat human eye allergies as claimed for its established antihistaminic efficacy. . . . We conclude that, 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 is safe for human ophthalmic use, the artisan would have a reasonable expectation of success for adapting Kamei's formulation for the same use in a human eye. [T]he district court correctly held that claims 4 and 8 of the '805 patent would not have been obvious. These claims are limited to using formulations with an olopatadine concentration of about 0.1% w/v. Kamei, however, only tested formulations with olopatadine concentrations up to 0.01% w/v and thus does not disclose this limitation. We cannot say the district court clearly erred by finding that Kamei does not teach or suggest using olopatadine at a concentration of 0.1% w/v. As the court noted, the concentrations tested in Kamei were substantially lower than 0.1%. The court 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. We also agree with the court that a person of ordinary skill in the art would have been concerned that olopatadine might be biphasic at this increased concentration, and thus would not have tried a formulation with ten times more olopatadine than the highest dosage used in Kamei.

Objective evidence further supports the district court's holding that claims 4 and 8 would not have been obvious. The district court's fact findings regarding the objective considerations are not clearly erroneous. The court found that Patanol® was "an outstanding commercial success," achieving nearly 70% market share within two years of its launch, accounting for nearly $2 billion in sales within ten years, and garnering widespread praise within the industry. The 0.1% w/v olopatadine concentration recited in claims 4 and 8 is the same as is used in Patanol®. As a result, with respect to claims 4 and 8, Alcon's objective evidence demonstrates that "the commercial success was caused by the merits of the invention as distinct from the prior art." Because Alcon failed to prove by clear and convincing evidence that a 0.1% w/v olopatadine formulation would have been obvious over the prior art, we conclude the district court correctly held that claims 4 and 8 would not have been obvious.

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