Sandoz’s request for inter partes review (“IPR”) of U.S. Patent Numbers 9,512,216 (“the ’216 patent”) and 8,802,100 (“the ’100 patent”) was denied by the Patent Trial and Appeal Board (“the Board”) on the grounds that Sandoz did not show that the patents were likely unpatentable.  The decisions not to institute an IPR of either patent were entered on February 9, 2018.

The Board’s decision denying the request for review of the ’216 patent indicates that a threshold issue was whether there was an adequate showing that the Humira® package insert is prior art.  In an IPR, the patent claims may only be challenged based on prior art consisting of patents and printed publications.

Sandoz asserted that all of the claims in the ’216 patent were obvious over the combination of the Humira® package insert; psoriasis press release; Aulton ed., 2d ed.2002, Pharmaceutics: The Science of Dosage Form Design; Weinstein & Gottlieb eds, 2d ed. 2003, Therapy of Moderate-to-Severe Psoriasis; and in view of Ortega et al., Infliximab is Effective in the Treatment of Resistant Psoriatic Arthritis & Skin Psoriasis: A Clinical & MRI Study, Rheumatology 2002.  The key issue was whether the package insert was sufficiently accessible to the public before the effective filing date of the ’216 patent. MPEP §2128 states that a reference is considered to be a printed publication if “upon a satisfactory showing that such document has been disseminated or otherwise made available to the extent that persons interested and ordinarily skilled in the subject matter or art, exercising reasonable diligence, can locate it.” In re Wyer, 655 F.2d 221, 210 USPQ 790 (CCPA 1981) (quoting I.C.E. Corp. v. Armco Steel Corp., 250 F. Supp. 738, 743, 148 USPQ 537, 540 (SDNY 1966)).  Sandoz argued that Humira® was approved in December 2002, and that the package insert included the language “Issued: December 2002” and contained the date “December 20, 2002” in the header.    In addition, Sandoz pointed out a December 31, 2002 letter from the FDA approving the biologics license application.  However, Sandoz did not point out any source identifying information from the FDA, a publication date, or any other evidence indicating when the package insert or the information in the package insert became publicly available.

AbbVie responded that Sandoz did not sufficiently establish that the insert was publicly accessible in December 2002. The December 31, 2002 FDA letter stated that Humira® “will be marketed in 40 gm/0.8 mL single use” vials and syringes.  The Board interpreted the language “will be marketed” as an indication that the Humira® drug product was not yet marketed or available to the public.  The Board concluded that there was not sufficient evidence that the Humira® package insert was disseminated or publicly accessible before the April 9, 2004 priority date of the ’216 patent, and thus Sandoz failed to demonstrate a reasonable likelihood that the package insert was a printed publication for purposes of 35 USC §§102(b) and 311(b).  Since the insert was the only cited reference which disclosed subcutaneously administering 40 mg of adalimumab every other week, the Board was not persuaded that the record established a reasonable likelihood that Sandoz would prevail at trial as to the challenged claims.

Sandoz also requested review of all of the claims in the ’100 patent.  Sandoz asserted that all of the claims in the patent were obvious over the combination of Salfeld (U.S. Patent No. 6,090,382); van de Putte et al., Efficacy of the Fully Human Antibody D2E7 in Rheumatoid Arthritis, 42 Arthritis & Rheumatism S400 (1999); Barrera et al, Effects of Treatment with a Fully Human Anti-Tumor Necrosis Factor a Monoclonal Antibody on the Local & Systemic Homeostasis of Interleukin 1 and TNFa in Patients with Rheumatoid Arthritis, 60 ANN. RHEUM. DIS. 660-69 (2001); Remington: THE SCIENCE & PRACTICE OF PHARMACY (Alfonso R. Gennaro et al. eds, 20^th ed. 2000); and Lam (U.S. Patent No. 6,171,586).  Sandoz argued that Salfeld disclosed “stable, buffered, subcutaneously-injectable aqueous D2E7 formulations containing a polyol, and a surfactant,” thereby providing a roadmap to the challenged claims.  Salfeld did not disclose the antibody concentration or the surfactant type and concentration.  Van de Putte was cited as disclosing the antibody concentration, Remington was cited as disclosing the surfactant, and Lam was cited as disclosing the concentration of the surfactant.  The Board was not persuaded by Sandoz’s arguments, finding that the evidence “indicates that the art of antibody formulation was unpredictable in August 2002,” and that no evidence had been provided showing that one skilled in the art would have a reason to combine the cited prior art with a reasonable expectation of success in preparing a stable, liquid formulation with the concentration of antibody and surfactant recited in the claims.  The Board pointed out that it is not clear that the reference relied on as disclosing the antibody concentration (van de Putte), discloses a stable liquid formulation or a lyophilized formulation.

AbbVie pointed out that all commercially available high-concentration antibody formulations available in August 2002 were lyophilized, while the available liquid formulations contained low antibody concentrations.  AbbVie also pointed out evidence that one skilled in the art would not have used teachings regarding lyophilized formulations to prepare stable, liquid formulations, as lyophilized formulations do not have the same stability issues as high concentration liquid antibody formulations. In addition, AbbVie argued that references which disclose formulations containing antibodies other than D2E7 do not provide a reasonable expectation of success for preparing a D2E7 formulation. Abbvie further argued there is a high degree of unpredictability in the antibody formulation art and thus a formulation for a specific, stable, high concentration, liquid antibody formulation cannot be applied to a different antibody with a reasonable expectation of success.  In addition, Abbvie asserted structural differences between different proteins do not allow stabilization strategies to be universally applied.  The Board concluded that Sandoz did not establish a reasonable likelihood of prevailing in its assertion that the claims in the ’100 patent would have been obvious, and therefore did not institute review.

Humira is the best-selling biologic in the world and AbbVie’s more than 100 patents covering Humira-related technology will likely face more challenges from generic competitors.  However, for now, AbbVie’s strategy of obtaining numerous patents covering every aspect of the Humira technology is successfully keeping competitors out of their $16 billion a year market.