Alvogen Pine Brook LLC v. Celgene Corporation

1. Case Identification

• Case #: UNASSIGNED
• Patent #: 7,968,569
• Filed: September 12, 2018
• Petitioner(s): Alvogen Pine Brook LLC
• Patent Owner(s): Celgene Corp.
• Challenged Claims: 1-15

2. Patent Overview

• Title: Methods for Treatment of Multiple Myeloma Using Lenalidomide and Dexamethasone
• Brief Description: The ’569 patent is directed to methods of treating multiple myeloma (MM). The methods involve cyclically administering the drug lenalidomide in combination with dexamethasone according to a specific dosing schedule, namely a 28-day cycle comprising 21 days of administration followed by a 7-day rest period.

3. Grounds for Unpatentability

Ground 1: Claims 1-15 are obvious over Palumbo, the May Press Release, and the August Press Release.

• Prior Art Relied Upon: Palumbo (a 2001 journal article in Hematologica), May Press Release (a May 2001 Celgene press release), and August Press Release (an August 2001 Celgene press release).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the claimed invention was an obvious combination of known elements. Palumbo taught a method for treating refractory or relapsed MM by administering thalidomide in combination with 40 mg/day of dexamethasone on a monthly cycle. The May and August Press Releases, issued by the Patent Owner, disclosed that lenalidomide (then called "Revimid") was a more potent and safer analog of thalidomide being tested in clinical trials for MM. The May Press Release specifically disclosed testing daily doses of 5 mg, 10 mg, 25 mg, and 50 mg, which encompasses the dosage range of independent claims 1 and 13. Petitioner asserted that a person of ordinary skill in the art (POSA) would have been motivated to substitute the superior lenalidomide for thalidomide in Palumbo’s established combination therapy with dexamethasone.
  • Motivation to Combine: A POSA would combine these teachings to improve upon Palumbo's therapy. The May Press Release explicitly stated lenalidomide was designed to be "more potent and potentially have a better safety profile" than thalidomide. It also noted lenalidomide was effective in thalidomide-resistant patients and lacked common thalidomide side effects like sedation and constipation. This provided a strong rationale to replace thalidomide with lenalidomide in the known thalidomide-dexamethasone regimen to achieve better efficacy and safety.
  • Expectation of Success: A POSA would have had a reasonable expectation of success. The press releases reported positive clinical trial results for lenalidomide in MM patients. The specific claimed dosing element—a 28-day cycle with 21 days of treatment and 7 days of rest—was argued to be a routine and predictable optimization. The May Press Release noted that lenalidomide caused reductions in granulocyte and white blood cell counts. Petitioner contended that incorporating a 7-day rest period was a well-known, standard practice in oncology to manage such hematopoietic toxicity and allow patient recovery, making its application to a lenalidomide regimen obvious.

Ground 2: Claims 1-15 are obvious over Palumbo, Hideshima, and the ’230 Patent.

• Prior Art Relied Upon: Palumbo (a 2001 journal article in Hematologica), Hideshima (a 2000 journal article in Blood), and Patent 6,281,230 (’230 patent).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground presented an alternative obviousness combination. As in Ground 1, Palumbo established a baseline therapy of thalidomide plus dexamethasone for MM. Hideshima provided extensive in vitro data demonstrating that lenalidomide and other thalidomide analogs (IMiDs) were significantly more potent than thalidomide at inhibiting MM cell growth. Crucially, Hideshima showed that dexamethasone enhanced the anti-proliferative effect of the IMiDs, suggesting the "potential utility of coupling these agents therapeutically." The ’230 patent, owned by Celgene, explicitly claimed methods of treating cancer by administering lenalidomide (from 1-100 mg) in combination with a steroid, specifically naming dexamethasone as a suitable option.
  • Motivation to Combine: The motivation to modify Palumbo's method was even more direct under this ground. Hideshima provided the scientific rationale, showing that lenalidomide was more potent and acted synergistically with dexamethasone against MM cells. The ’230 patent provided an express teaching to combine lenalidomide with a steroid like dexamethasone to treat cancer. A POSA, aware of Palumbo's thalidomide/dexamethasone regimen, would have been motivated by the superior in vitro results from Hideshima and the explicit teachings of the ’230 patent to substitute the more potent lenalidomide for thalidomide.
  • Expectation of Success: A POSA would have had a high expectation of success. Hideshima’s in vitro data directly correlated with clinical utility, and the ’230 patent already claimed the general combination for cancer. Hideshima taught that IMiDs like lenalidomide were 100 to 1000 times more potent than thalidomide, making it obvious to use a lower dose (such as the claimed 5-25 mg) as a matter of routine dose-finding optimization. The cyclical dosing regimen was, again, argued to be a standard and obvious modification to manage potential toxicity from a highly potent compound.

4. Key Technical Contentions (Beyond Claim Construction)

• Priority Date Challenge: A central contention of the petition was that the ’569 patent was not entitled to the May 17, 2002 filing date of its provisional application (’842 provisional). Petitioner argued the ’842 provisional failed to provide adequate written description under §112 for the claimed invention for two reasons. First, it did not disclose the claimed 28-day cycle with a 7-day rest period. Second, it disclosed combining a small molecule like lenalidomide with a large biological molecule (e.g., a protein or cytokine), and did not describe combining it with another small molecule like dexamethasone. Therefore, Petitioner argued the patent’s effective priority date could be no earlier than November 6, 2002, which rendered all the asserted prior art (published in 2000 and 2001) available under §102(b).

5. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1-15 of Patent 7,968,569 as unpatentable under 35 U.S.C. §103.