Opinion ID: 2792379
Heading Depth: 4
Heading Rank: 2

Heading: The Merits of the Obviousness Determination

Text: Sandoz claims that the ’411 patent is an obvious modification of Ilotycin®—a topical formulation of erythromycin (an active ingredient similar to azithromycin)—and Zithromax®, an oral azithromycin formulation used to treat conjunctivitis. Sandoz argues that in light of the teachings of the prior art, it would have been obvious to try azithromycin as a topical treatment of bacterial conjunctivitis, with a reasonable expectation of success. It relies on the testimony of Dr. Reed that azithromycin was the “newer iteration” of erythromycin, with remarkably effective properties and contends that it would have been common sense to substitute a new and improved antibiotic for the antibiotic present in Ilotycin®. Id. at  (quoting the trial testimony of Dr. Reed). Sandoz also contends that persons of ordinary skill in the art would have been motivated to use azithromycin in a topical treatment given that it was well known, accordINSITE VISION INCORPORATED v. SANDOZ, INC. 11 ing to Sandoz’s expert, Dr. Goren, that topical treatments are generally more effective than oral treatments. It also asserts that while oral use of azithromycin worked through a unique process called phagocytosis, that process was not the only process at work in delivering the drug to infected tissue and persons of ordinary skill in the art would not have been deterred from investigating the topical administration of azithromycin. Finally, Sandoz relies on proposals for the topical use of azithromycin in the treatment of trachoma allegedly made at a 1997 World Health Organization meeting that occurred in Geneva (the “Geneva meeting”) and contends that the district court was wrong to disregard and discount this evidence. Plaintiffs counter by arguing that the district court’s factual findings were well-supported and not clearly erroneous. They argue that the district court considered all of the potential drug options and correctly concluded that those options would have directed persons of ordinary skill in the art away from the topical administration of azithromycin. They also assert that there is no correlation between oral and topical ophthalmic drug penetration. Finally, they point to Sandoz’s expert’s contemporaneous failure to use azithromycin topically prior to the ’411 invention as evidence of non-obviousness. The district court concluded that it would not have been obvious to a person of ordinary skill in the art to formulate a topical azithromycin formulation for ophthalmic treatment of any infection as recited in the asserted claims of the ’411 patent. The district court thoroughly and properly considered all of the evidence presented and the various arguments raised by the parties in ruling the asserted claims to be not invalid. We agree. First, the district court did not clearly err in finding that there were “innumerable” options for ophthalmic 12 INSITE VISION INCORPORATED v. SANDOZ, INC. treatments, including fluoroquinolones. Id. at . Fluoroquinolones “were known to be a better option than azithromycin,” because they “were bactericidal[,] could act on a broad range of bacteria [and] were known to penetrate ocular tissue.” Id. at , . Furthermore, the district court did not clearly err in determining that those of skill in the art would have been concerned that azithromycin might not penetrate ocular tissue based on its high molecular weight, charge and insolubility in water. Id. at . Even Sandoz’s expert, Dr. Reed, admitted that compounds with high molecular weights and charged compounds might not penetrate ocular tissue. See id. at . The district court also did not clearly err in crediting Dr. Asbell’s testimony that a person of ordinary skill in the art “would not assume that delivering high concentrations of a drug to the eye topically would ensure that the drug would penetrate the ocular tissue simply because the drug was successful when administered systemically.” Id. at . Dr. Asbell’s testimony is supported by the fact that oral azithromycin was delivered to the eye at least in part through phagocytosis—a bloodstream dependent process—which would not occur when azithromycin was administered topically. See id. at , . The district court did not clearly err in discounting the relevance of Ilotycin®, given that there was conflicting expert testimony on whether it had fallen out of favor by 1996. See id. at –10. The district court also did not clearly err in discounting Dr. Reed’s testimony that erythromycin formulations would make azithromycin formulations obvious, given that Dr. Reed’s own 1994 patent for topical ophthalmic treatments listed 24 potential antibiotics, including erythromycin, but did not list azithromycin. See id. at . For all of the above reasons, this court concludes that Sandoz has not met its clear and convincing burden and INSITE VISION INCORPORATED v. SANDOZ, INC. 13 therefore affirms the district court’s determination that the asserted claims of the ’411 patent are not invalid.