DCT

2:11-cv-03781

Shire LLC v. Amneal Pharma LLC

Key Events

Complaint

I. Executive Summary and Procedural Information

Parties & Counsel:
- Plaintiff: Shire LLC (Kentucky) and Shire Development Inc. (Delaware)
- Defendant: Amneal Pharmaceuticals, LLC (Delaware)
- Plaintiff’s Counsel: Gibbons P.C.
Case Identification: 2:11-cv-03781, D.N.J., 06/30/2011
Venue Allegations: Venue is alleged to be proper in the District of New Jersey because Defendant Amneal resides and conducts business in the district.
Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiff's ADHD drug Vyvanse® constitutes an act of infringement of fifteen patents listed in the FDA's Orange Book.
Technical Context: The technology relates to abuse-resistant amphetamine prodrugs, specifically lisdexamfetamine, designed to provide therapeutic effects for ADHD while reducing the potential for abuse via injection or insufflation.
Key Procedural History: This action was triggered by Defendant Amneal's filing of ANDA No. 202830 with the FDA and its subsequent issuance of a Paragraph IV certification notice to Shire, asserting that the patents covering Vyvanse® are invalid, unenforceable, or will not be infringed by Amneal's proposed generic product. Such a filing is a statutory act of infringement under the Hatch-Waxman Act.

Case Timeline

Date	Event
2002-02-22	Earliest Priority Date for ’486, ’630, ’253, ’787, ’030, ’031, ’774, ’770, ’771, ’466, ’467, ’561, ’619, ’305 Patents
2003-05-29	Earliest Priority Date for ’735 Patent
2006-09-12	U.S. Patent No. 7,105,486 Issued
2007-05-29	U.S. Patent No. 7,223,735 Issued
2010-02-02	U.S. Patent No. 7,655,630 Issued
2010-02-09	U.S. Patent No. 7,659,253 Issued
2010-02-16	U.S. Patent No. 7,662,787 Issued
2010-03-02	U.S. Patent No. 7,671,030 Issued
2010-03-02	U.S. Patent No. 7,671,031 Issued
2010-03-09	U.S. Patent No. 7,674,774 Issued
2010-03-16	U.S. Patent No. 7,678,770 Issued
2010-03-16	U.S. Patent No. 7,678,771 Issued
2010-03-30	U.S. Patent No. 7,687,466 Issued
2010-03-30	U.S. Patent No. 7,687,467 Issued
2010-04-20	U.S. Patent No. 7,700,561 Issued
2010-05-18	U.S. Patent No. 7,718,619 Issued
2010-05-25	U.S. Patent No. 7,723,305 Issued
2011-06-30	Complaint Filed

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

U.S. Patent No. 7,105,486 - "Abuse-Resistant Amphetamine Compounds"

The Invention Explained

Problem Addressed: The patent addresses the significant potential for abuse of amphetamine-based drugs, which are classified as Schedule II controlled substances. Specifically, it notes that abusers often crush tablets to snort or inject the drug, achieving a rapid onset and "high" that is not present with standard oral administration (Compl. ¶ 8; ’486 Patent, col. 1:13-21, col. 2:4-11).
The Patented Solution: The invention is a prodrug approach where amphetamine is covalently bonded to a chemical moiety, such as an amino acid or peptide. This renders the amphetamine pharmacologically inactive until the bond is cleaved by metabolic processes after oral ingestion. This design is intended to prevent the rapid release of the active drug if the formulation is crushed for snorting or injection, thereby reducing its abuse liability while maintaining therapeutic effect when taken as directed (Compl. ¶ 11; ’486 Patent, Abstract, col. 3:57-4:4).
Technical Importance: This chemical modification provides a mechanism for abuse deterrence that is inherent to the molecule itself, rather than relying solely on physical formulation techniques that can be defeated.

Key Claims at a Glance

The complaint alleges infringement of "one or more claims" but does not identify specific claims (Compl. ¶ 39). Independent claim 1 is representative of the patent’s broadest scope.
Claim 1 (paraphrased elements):
- A composition comprising a compound of Formula I: A-Xn-Zm
- Wherein A is amphetamine
- Wherein X is a chemical moiety
- Wherein n is an integer from 1 to 50
- Wherein m is 0

U.S. Patent No. 7,223,735 - "Abuse Resistant Lysine Amphetamine Compounds"

The Invention Explained

Problem Addressed: Similar to the ’486 patent, this patent addresses the high potential for abuse associated with amphetamine-based therapies for conditions like ADHD (’735 Patent, col. 1:13-21).
The Patented Solution: The patent claims a specific embodiment of the abuse-resistant prodrug concept: a composition comprising L-lysine covalently attached to d-amphetamine (lisdexamfetamine). This specific conjugate, which became the active ingredient in Vyvanse®, is designed to be orally bioavailable but exhibit reduced activity when administered through parenteral routes favored by abusers (Compl. ¶ 12; ’735 Patent, Abstract, col. 3:57-4:4).
Technical Importance: This patent claims the specific chemical entity that was successfully commercialized as an abuse-deterrent stimulant, demonstrating the viability of the broader prodrug concept.

Key Claims at a Glance

The complaint alleges infringement of "one or more claims" but does not identify specific claims (Compl. ¶ 48). Independent claim 1 is representative of the patent's scope.
Claim 1 (paraphrased elements):
- A composition comprising L-lysine-d-amphetamine
- or a salt thereof.

U.S. Patent No. 7,655,630 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to the compound L-lysine-d-amphetamine dimesylate, a specific salt form of the lisdexamfetamine prodrug (Compl. ¶ 13). This specifies the particular chemical form used in the commercial Vyvanse® product.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 57).
Accused Features: The accused feature is Amneal's proposed generic product, which the complaint alleges is a generic version of lisdexamfetamine dimesylate (Compl. ¶ 26).

U.S. Patent No. 7,659,253 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to crystalline lisdexamfetamine dimesylate (Compl. ¶ 14). This claim scope suggests a focus on the solid-state chemical properties of the drug substance, which can be critical for formulation, stability, and manufacturing.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 66).
Accused Features: The accused feature is Amneal's proposed generic product, which the complaint alleges is a generic version of lisdexamfetamine dimesylate (Compl. ¶ 26).

U.S. Patent No. 7,662,787 - "Abuse Resistant Lysine Amphetamine Compounds"

Technology Synopsis: This patent is directed to compositions comprising L-lysine-d-amphetamine compounds (Compl. ¶ 15). This patent appears to claim compositions containing the active ingredient.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 75).
Accused Features: The accused feature is Amneal's proposed generic product, which is alleged to be capsules containing lisdexamfetamine dimesylate for oral administration (Compl. ¶ 26).

U.S. Patent No. 7,671,030 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to compositions comprising L-lysine-d-amphetamine (Compl. ¶ 16). It appears to be another patent in the family covering formulations of the active ingredient.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 84).
Accused Features: The accused feature is Amneal's proposed generic product, which is alleged to be capsules containing lisdexamfetamine dimesylate (Compl. ¶ 26).

U.S. Patent No. 7,671,031 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to methods of delivering amphetamines via the administration of L-lysine-d-amphetamine (Compl. ¶ 17). This shifts the focus from the composition itself to the method of its use.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 93).
Accused Features: The accused feature is Amneal's proposed generic product, whose label will presumably instruct for the oral administration of lisdexamfetamine dimesylate to treat ADHD, thereby inducing infringement of the method claims (Compl. ¶ 26).

U.S. Patent No. 7,674,774 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to compositions comprising L-lysine-d-amphetamine (Compl. ¶ 18). It is another patent covering formulations of the active ingredient.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 102).
Accused Features: The accused feature is Amneal's proposed generic product, which is alleged to be capsules containing lisdexamfetamine dimesylate (Compl. ¶ 26).

U.S. Patent No. 7,678,770 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to methods of treatment comprising L-lysine-d-amphetamine (Compl. ¶ 19). It is another patent focused on the method of using the compound.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 111).
Accused Features: The accused feature is Amneal's proposed generic product, whose label will presumably instruct for the oral administration of lisdexamfetamine dimesylate to treat ADHD (Compl. ¶ 26).

U.S. Patent No. 7,678,771 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to compositions comprising L-lysine-d-amphetamine (Compl. ¶ 20). It is another patent covering formulations of the active ingredient.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 120).
Accused Features: The accused feature is Amneal's proposed generic product, which is alleged to be capsules containing lisdexamfetamine dimesylate (Compl. ¶ 26).

U.S. Patent No. 7,687,466 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to compositions comprising L-lysine-d-amphetamine (Compl. ¶ 21). It is another patent covering formulations of the active ingredient.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 129).
Accused Features: The accused feature is Amneal's proposed generic product, which is alleged to be capsules containing lisdexamfetamine dimesylate (Compl. ¶ 26).

U.S. Patent No. 7,687,467 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to compositions comprising L-lysine-d-amphetamine (Compl. ¶ 22). It is another patent covering formulations of the active ingredient.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 138).
Accused Features: The accused feature is Amneal's proposed generic product, which is alleged to be capsules containing lisdexamfetamine dimesylate (Compl. ¶ 26).

U.S. Patent No. 7,700,561 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to compositions comprising L-lysine-d-amphetamine (Compl. ¶ 23). It is another patent covering formulations of the active ingredient.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 147).
Accused Features: The accused feature is Amneal's proposed generic product, which is alleged to be capsules containing lisdexamfetamine dimesylate (Compl. ¶ 26).

U.S. Patent No. 7,718,619 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to compositions comprising L-lysine-d-amphetamine (Compl. ¶ 24). It is another patent covering formulations of the active ingredient.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 156).
Accused Features: The accused feature is Amneal's proposed generic product, which is alleged to be capsules containing lisdexamfetamine dimesylate (Compl. ¶ 26).

U.S. Patent No. 7,723,305 - "Abuse-Resistant Amphetamine Prodrugs"

Technology Synopsis: This patent is directed to compositions comprising L-lysine-d-amphetamine (Compl. ¶ 25). It is another patent covering formulations of the active ingredient.
Asserted Claims: The complaint does not specify which claims are asserted but alleges infringement of one or more claims (Compl. ¶ 165).
Accused Features: The accused feature is Amneal's proposed generic product, which is alleged to be capsules containing lisdexamfetamine dimesylate (Compl. ¶ 26).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is Defendant Amneal's proposed generic drug product, identified as "generic lisdexamfetamine dimesylate capsules, 20 mg, 30 mg, 40 mg, 50 mg, 60 mg, and 70 mg, for oral administration" (Compl. ¶ 26). The action is based on Amneal's filing of ANDA No. 202830 seeking FDA approval to market this product (Compl. ¶ 26).

Functionality and Market Context

The complaint alleges that the Amneal Proposed Product is a generic version of Shire's Vyvanse® product, which is approved for the treatment of Attention Deficit Hyperactivity Disorder ("ADHD") (Compl. ¶¶ 8, 26). As a generic drug submitted under an ANDA, the product is intended to be a bioequivalent substitute for the branded drug, thereby competing directly with Vyvanse® upon market entry (Compl. ¶ 26).
No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not contain a detailed claim chart. The infringement allegations are based on the statutory act of infringement under 35 U.S.C. § 271(e)(2)(A), which provides that submitting an ANDA for a generic version of a patented drug is an act of infringement (e.g., Compl. ¶ 38). The theory is that Amneal's proposed product, if approved, will be a bioequivalent version of Vyvanse® and will therefore necessarily practice the claims of the patents covering Vyvanse®.

7,105,486 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A composition comprising a compound of Formula I: A-Xn-Zm wherein: A is amphetamine	The Amneal Proposed Product is lisdexamfetamine dimesylate, which contains and releases d-amphetamine upon oral administration.	¶¶ 8, 26	col. 9:15-20
X is a chemical moiety	The Amneal Proposed Product contains L-lysine, an amino acid, which serves as the chemical moiety.	¶¶ 8, 12, 26	col. 9:46-51
covalently attached to [amphetamine]	In the Amneal Proposed Product, the L-lysine moiety is covalently bonded to d-amphetamine to form the prodrug lisdexamfetamine.	¶¶ 8, 12, 26	col. 3:57-65

7,223,735 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A composition comprising L-lysine-d-amphetamine	The Amneal Proposed Product is identified as lisdexamfetamine dimesylate, which is a salt form of L-lysine-d-amphetamine.	¶¶ 12, 26	col. 3:57-4:4
or a salt thereof	The Amneal Proposed Product is specifically the dimesylate salt of lisdexamfetamine.	¶ 26	col. 3:57-4:4

Identified Points of Contention

Scope Questions: Given the direct allegation that Amneal's product is "lisdexamfetamine dimesylate," infringement of a claim to "L-lysine-d-amphetamine or a salt thereof" (as in the '735 patent) may be straightforward if the patent is valid. For the broader '486 patent, a question may arise as to whether the term "chemical moiety" is definite and properly covers L-lysine.
Technical Questions: In Hatch-Waxman litigation, infringement is often a secondary issue to patent validity. The primary technical questions will likely be raised by Amneal in its invalidity defenses, such as whether it was obvious to attach L-lysine to d-amphetamine to achieve an abuse-deterrent effect. The complaint, being the initial pleading, does not provide sufficient detail to analyze specific technical disputes beyond the core allegation of bioequivalence.

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail to identify specific claim construction disputes. However, based on the asserted claims and the context of the case, the following terms may be central.

The Term: "a chemical moiety" ('486 Patent, Claim 1)
Context and Importance: This term's breadth is critical to the scope of the '486 patent. A broad construction would cover a wide range of amphetamine prodrugs, whereas a narrow construction could limit the claim to the specific embodiments disclosed. Practitioners may focus on this term to determine if the claim is supported by the specification or is overly broad.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification states the chemical moiety "may be for instance, amino acids, peptides, glycopeptides, carbohydrates, nucleosides, or vitamins" (’486 Patent, col. 4:61-65).
- Evidence for a Narrower Interpretation: A defendant may argue that the term should be limited by the examples provided in the patent, which focus primarily on single amino acids and short peptides, to avoid invalidity for lack of enablement or written description (’486 Patent, Examples 1-5).
The Term: "composition" ('735 Patent, Claim 1)
Context and Importance: While seemingly simple, this term could become a point of contention if Amneal's formulation includes excipients or has an impurity profile that, it might argue, fundamentally alters the "composition" from what is claimed. This is a common strategy in ANDA litigation.
Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent does not define "composition" in a restrictive way, suggesting its plain and ordinary meaning, which would include the active ingredient plus any conventional pharmaceutical carriers or excipients (’735 Patent, col. 13:4-14:52).
- Evidence for a Narrower Interpretation: A defendant might argue that the term should be interpreted in light of the specific formulations described in the specification, potentially excluding compositions with different excipients or properties (’735 Patent, Examples 31-32).

VI. Other Allegations

Indirect Infringement: The complaint alleges that Amneal's submission of its ANDA constitutes inducement and contributory infringement because it is a request for approval to market and sell a product with a label that will instruct physicians and patients to use the generic drug in an infringing manner (e.g., Compl. ¶ 38).
Willful Infringement: The complaint alleges that Amneal was aware of the patents-in-suit, as they are listed in the FDA Orange Book, and acted without a reasonable basis for believing it would not be liable, thereby rendering the infringement willful and the case "exceptional" under 35 U.S.C. § 285 (e.g., Compl. ¶ 40). This allegation is based on Amneal’s pre-suit knowledge.

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

A central issue will be one of patent validity: Can Amneal prove by clear and convincing evidence that the asserted claims, particularly those covering the specific L-lysine-d-amphetamine compound, are invalid as obvious in light of prior art on prodrugs and amphetamine analogs?
A key strategic question will be one of portfolio litigation: How will the parties manage a case involving fifteen patents? The dispute may ultimately narrow to a few key claims from the most relevant patents (e.g., those covering the specific compound, its commercial salt form, and its approved method of use), with the broader "patent thicket" serving as a strategic backdrop.
A secondary issue may be one of claim scope and infringement: For the patents claiming crystalline forms or specific compositions, a technical question may arise as to whether Amneal's proposed generic product—in its precise chemical structure, formulation, and manufacturing process—falls within the scope of those claims, or if it has been designed to avoid them.