Salix Pharm., Ltd. et al. v. Norwich Pharm. Inc.

Docket No. 2022-2153, -1952 (https://cafc.uscourts.gov/opinions-orders/22-2153.OPINION.4-11-2024_2300049.pdf)

LOURIE, CHEN, CUNNINGHAM

April 11, 2024

Brief Summary:  DC obviousness of method of treatment and polymorph patents and ANDA-related (FDA cannot approve current ANDA, correctly denied ANDA amendment) decisions affirmed. 

NOTE: Salix argued it “actually succeed[ed]” and did not expect to succeed because the beta form “remained undisclosed”, which the FC panel summarized as incorrectly suggesting “that no unknown entity could ever be obvious, as one cannot reasonably expect what was hitherto unknown”.

Summary:  Salix appealed DC judgment holding claim 2 of US 8,309,569, claim 3 of US 10,765,667, claim 4 of US 7,612,199, and claim 36 of US 7,902,206 relating to rifaximin (the active ingredient of Xifaxan®).  The FC panel opinion explains that rifaximin was first approved as an antibiotic in Italy in 1985 and by the FDA in 2004 and 2010 (200 mg tablets for travelers’ diarrhea and 550 mg tablers for hepatic encephalopathy (HE) and irritable bowel syndrome with diarrhea (IBS-D)).  Norwich filed an ANDA in 2019 with a para. IV certification of invalidity.  The patents are grouped into the HE patents (‘573, ‘195, and ‘397), the IBS-D patents (‘569 and ‘667), and the polymorph patents (‘199 and ‘206).  Salix appealed the DC holding that the IBS-D and polymorph patents were infringed but invalid for obviousness. 

The IBD-S patents claim a method “comprising…administering 1650 mg/day” and “500 mg three times per day”.  The DC found a published clinical trial “Protocol” and the Pimentel journal article “disclose each and every limitation of the challenged IBS-D claims, and further found that a skilled artisan would have been motivated to combine those two references to arrive at what is claimed with a reasonable expectation of success.”  Salix argued the DC erred because the prior art does not provide a reasonable expectation of success for a dose above 1200 mg/day, but the FC panel disagreed because while Protocol and Pimentel used a 1200 mg/day dose, Pimentel “further teaches that ‘[r]ecent data suggest that the optimal dosage of rifaximin may, in fact, be higher than that used in our study’” (e.g., the FC panel writing that “the next higher dosage unit from the Protocol was 550 mg” and citing Almirall (FC 2022) and Acorda (FC 2018) (neither “absolute predictability of success” nor “clinical efficacy” required); also OSI Pharms., FC 2019 (““efficacy data [are] always required”); background knowledge consistent with reasonable expectation of success (In re Applied Materials, FC 2012 (where “general conditions” disclosed, it is not “not inventive to discover the optimum or workable ranges by routine experimentation”)).  The DC decision that the IBD-S patents are invalid for obviousness was affirmed.

The polymorph patents claim polymorphic form beta with a particular x-ray powder diffraction pattern and water content.  The DC concluded expert testimony supported its decision that the Cannata patent “discloses that rifaximin exists in crystalline form with ‘outstanding antibacterial properties’” and “several preparation protocols…that include solvents used for crystallization.”  Salix argued Grunenthal (FC 2019 (not obvious with no disclosure of particular conditions to produce Form B)) and Pharmacyclics (FC 2022) “compel the opposite result” as the DC “applied the wrong test”, but the FC panel disagreed (within DC’s discretion not to apply Pharmacylics) (“Here, the prior art included a process… the dispute centered around characterizing the crystalline form resulting from that process”; citing Graham, US 1966; Salix did not dispute motivation to explore potential polymorphs).  Salix argued it “actually succeed[ed]” and did not expect to succeed because the beta form “remained undisclosed”, which the FC panel summarized as incorrectly suggesting “that no unknown entity could ever be obvious, as one cannot reasonably expect what was hitherto unknown”.  The FC panel found the DC correctly found Cannata showed “potential polymorphism using routine, conventional methods and skill” (citing KSR, US 2007 and Pfizer, FC 2007).  It therefore affirmed the DC’s decision that the polymorph patents were shown to be obvious.

Norwich cross-appealed two ANDA-related issues:  1) the DC’s interpretation of “35 U.S.C. § 271(e)(4)(A)” under which it ordered the FDA not approve its ANDA, including a new noninfringing ANDA (delays ANDA for ““the drug . . . involved in the infringement”); and, 2) DC’s denial of Norwich’s request “to amend its ANDA to carve out the infringing HE use after final judgment”.  The FC panel agreed with the DC on the first point (e.g., restricts approval of “this infringing ANDA” but “said nothing that would prevent approval of a new non-infringing ANDA”).  The FC panel also found the DC “reasonably held that “consideration of the amended ANDA would be inequitable and inappropriate” (Rule 60(b)).

Patrick Halloran

Pat has a Ph.D. in Microbiology and Immunology from The University of Health Sciences / The Chicago Medical School (now the Rosalind Franklin Institute (North Chicago, IL) (1994)). He also completed post-doctoral studies at The National Cancer Institute (1994-1996) where he developed novel…

Pat has a Ph.D. in Microbiology and Immunology from The University of Health Sciences / The Chicago Medical School (now the Rosalind Franklin Institute (North Chicago, IL) (1994)). He also completed post-doctoral studies at The National Cancer Institute (1994-1996) where he developed novel approaches for gene therapy of melanoma. Pat has been an attorney (IL) since 1999 after graduating from Chicago-Kent College of Law, which was recently ranked as one of the top five law schools for Intellectual Property in the U.S. (U.S. News and World Report link). Pat also has a B.A. in Biology from Augustana College (Rock Island, IL; 1989) where he was on two NCAA Division III National Championship football teams (1985, 1986). He currently resides in Center Valley, PA.