Pfizer Inc v. Apotex Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Pfizer Inc., Warner-Lambert Company LLC, PF Prism CV., Pfizer Manufacturing Holdings LLC, and Pfizer PFE Ireland Pharmaceuticals Holding 1 B.V. (collectively "Pfizer") (Delaware & Netherlands)
  • Defendant: Apotex Inc. and Apotex Corp. (collectively "Apotex") (Canada & Delaware)
  • Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Williams & Connolly LLP
• Case Identification: 1:19-cv-00747, D. Del., 04/25/2019
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Apotex Corp. is a Delaware corporation, and Defendant Apotex Inc., a Canadian corporation, is subject to personal jurisdiction in the district through its business activities and control of its Delaware-based subsidiary.
• Core Dispute: Plaintiff alleges that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA for generic versions of the breast cancer drug IBRANCE® (Palbociclib) constitutes an act of infringement of three patents covering the compound, pharmaceutical compositions, and methods of use.
• Technical Context: The technology relates to small-molecule chemical compounds that function as selective inhibitors of cyclin-dependent kinases (Cdks), a class of enzymes critical for regulating cell division, for the treatment of cell proliferative disorders such as cancer.
• Key Procedural History: This patent infringement action was filed under the Hatch-Waxman Act, triggered by a notice letter dated March 14, 2019, in which Apotex informed Pfizer of its ANDA submission seeking to market generic Palbociclib. The complaint alleges that the notice letter did not contest infringement of the asserted patents, but instead asserted that the patents are invalid or unenforceable. The patents-in-suit are listed in the FDA's Orange Book in connection with IBRANCE®.

Case Timeline

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 6,936,612 - "2-(PYRIDIN-2-YLAMINO)-PYRIDO[2,3-D] PYRIMIDIN-7-ONES"

• Patent Identification: U.S. Patent No. 6,936,612, issued August 30, 2005.

The Invention Explained

• Problem Addressed: The patent's background describes that abnormally high activity of cellular enzymes known as cyclin-dependent kinases (Cdks) is associated with the development of human tumors (Compl. Ex. A, ’612 Patent, col. 1:45-56). It notes the technical challenge of identifying small-molecule compounds that can selectively inhibit specific Cdk proteins without inhibiting other enzymes, which is critical for developing effective cancer therapies with manageable side effects (’612 Patent, col. 2:20-29).
• The Patented Solution: The invention provides novel substituted 2-aminopyridine compounds that are potent and selective inhibitors of Cdk4 (’612 Patent, Abstract). The patent discloses a class of compounds based on a 2-(pyridin-2-ylamino)-pyrido[2,3-d]pyrimidin-7-one chemical scaffold, which are described as useful for treating cell proliferative diseases like cancer and inflammation (’612 Patent, col. 1:9-14).
• Technical Importance: The invention provided a specific chemical compound with the potential to treat cancer by targeting a key mechanism of uncontrolled cell growth, offering a therapeutic approach with improved selectivity over other kinase inhibitors.

Key Claims at a Glance

• The complaint asserts independent claim 1 and dependent claim 2 (Compl. ¶¶ 32, 36).
• Independent Claim 1:
  • A compound which is 6-Acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one.
• Dependent Claim 2:
  • A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 1.
  • A pharmaceutical carrier therefor.

U.S. Patent No. 7,208,489 - "2-(pyridin-2-ylamino)-pyrido [2,3-d]pyrimidin-7-ones"

• Patent Identification: U.S. Patent No. 7,208,489, issued April 24, 2007.

The Invention Explained

• Problem Addressed: Similar to the ’612 Patent, this patent addresses the need for compounds that can selectively inhibit Cdk enzymes to treat cell proliferative disorders like cancer and inflammation (’489 Patent, col. 1:10-14, 21-46).
• The Patented Solution: This patent, a continuation of the application leading to the ’612 Patent, claims a broader chemical genus of 2-aminopyridine compounds defined by a Markush formula (’489 Patent, col. 2:48-65). The specific compound identified in the ’612 patent (Palbociclib) is a species that falls within the scope of this broader genus.
• Technical Importance: The invention defines a larger class of potentially therapeutic Cdk inhibitors, thereby expanding the patented chemical space for developing treatments for Cdk-mediated diseases.

Key Claims at a Glance

• The complaint asserts claims 1-7 and 9 (Compl. ¶ 71). Claim 7 is an independent species claim, and claim 9 depends from it.
• Independent Claim 7:
  • A compound according to claim 1 which is 6-acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one.
• Dependent Claim 9:
  • A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 7 and a pharmaceutical carrier.

U.S. Patent No. 7,456,168 - "2-(pyridin-2-ylamino)-pyrido [2,3-d]pyrimidin-7-ones"

• Patent Identification: U.S. Patent No. 7,456,168, issued November 25, 2008.

Technology Synopsis

Continuing from the same patent family, the ’168 patent addresses the specific problem of treating breast cancer in a mammal (’168 Patent, col. 21:28-34). The patented solution is a method of treatment comprising the administration of a compound of a specified formula, which includes Palbociclib (’168 Patent, claim 1).

Asserted Claims

Claims 1-4 are asserted (Compl. ¶ 110). Claim 1 is the independent method claim.

Accused Features

The accused feature is the future use of Apotex's ANDA Product, which, as directed by its proposed labeling, would be for the treatment of breast cancer, thereby infringing the patented method (Compl. ¶¶ 110, 115).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Apotex's ANDA No. 213066 product ("Apotex's ANDA Product"), which consists of generic Palbociclib capsules in 75 mg, 100 mg, and 125 mg dosages (Compl. ¶ 2).

Functionality and Market Context

The Apotex ANDA Product is a generic pharmaceutical composition containing Palbociclib as its active pharmaceutical ingredient (Compl. ¶ 1). Palbociclib is the specific chemical compound claimed in the ’612 Patent and the ’489 Patent. The product is intended to be a generic equivalent of Pfizer’s branded breast cancer drug, IBRANCE® (Compl. ¶ 1). The act of infringement alleged in the complaint is Apotex's submission of its ANDA to the FDA seeking approval to market this generic product prior to the expiration of the patents-in-suit, which is a technical act of infringement under 35 U.S.C. § 271(e)(2)(A) (Compl. ¶ 34). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 6,936,612 Infringement Allegations

U.S. Patent No. 7,208,489 Infringement Allegations

Identified Points of Contention

• Scope Questions: The complaint asserts that Apotex's notice letter did not contest that its product infringes the asserted claims, but instead challenged the patents' validity (Compl. ¶¶ 33, 72, 111). This suggests that the scope of infringement is not the primary point of contention. The central issue for the court may be whether the patents-in-suit are valid and enforceable.
• Technical Questions: In this Hatch-Waxman context involving a generic version of a small molecule drug, the technical question is one of bioequivalence. The complaint's allegations are premised on the fact that Apotex's ANDA Product contains the identical active pharmaceutical ingredient as Pfizer's IBRANCE®, which is the patented compound. The complaint does not present facts suggesting a technical dispute over the chemical structure of the accused product.

V. Key Claim Terms for Construction

The complaint does not present allegations that suggest a dispute over the construction of specific claim terms. The asserted composition of matter claims (’612 Patent, claim 1; ’489 Patent, claim 7) recite a specific chemical compound by its IUPAC name. Such terms have well-understood meanings in the relevant art and are not typically subject to significant construction disputes. The method of treatment claims (’168 Patent, claim 1) likewise use standard terms (e.g., "treating breast cancer," "administering") whose construction is not identified as a point of contention in the complaint.

VI. Other Allegations

• Indirect Infringement: The complaint alleges active inducement on the basis that Apotex knows of the patents and intends for its generic product to be used in an infringing manner upon approval, as directed by its proposed product labeling (Compl. ¶¶ 38, 77, 116). Contributory infringement is alleged on the grounds that the ANDA Product is especially made for infringing uses and is not a staple article of commerce suitable for substantial non-infringing use (Compl. ¶¶ 39, 78, 117).
• Willful Infringement: Willfulness is alleged based on Apotex's pre-suit knowledge of the patents, as evidenced by its ANDA submission and notice letter, and its alleged lack of a reasonable basis to believe it would not be liable for infringement (Compl. ¶¶ 42, 81, 120). Pfizer also seeks a declaration that the case is "exceptional" to support an award of attorneys' fees (Compl. p. 25(e)).

VII. Analyst’s Conclusion: Key Questions for the Case

• A central issue will be one of patent validity: The complaint alleges that Apotex's defense is based on the invalidity and/or unenforceability of the patents-in-suit, not on non-infringement. The case will therefore likely focus on Apotex's challenges to the novelty, non-obviousness, or other legal requirements for patentability of the claimed compound and methods.
• A key question for potential damages will be one of objective reasonableness: Given Apotex’s pre-suit knowledge of the patents inherent in the ANDA process, the analysis of willfulness will likely turn on whether Apotex’s asserted belief in the patents' invalidity was objectively reasonable at the time it challenged the patents.