DCT
1:16-cv-00456
Shire Orphan Therapies LLC v. InnoPharma Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Shire Orphan Therapies LLC (Delaware) and Sanofi-Aventis Deutschland GMBH (Germany)
- Defendant: InnoPharma, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP
- Case Identification: 1:16-cv-00456, D. Del., 06/17/2016
- Venue Allegations: Venue is alleged to be proper as Defendant is a Delaware corporation and conducts systematic business in the district, including marketing and sales of pharmaceutical products.
- Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to the FDA to market a generic version of Plaintiffs' drug FIRAZYR® constitutes an act of patent infringement under the Hatch-Waxman Act.
- Technical Context: The technology concerns synthetic peptides that act as bradykinin antagonists, used for treating pathological conditions such as hereditary angioedema (HAE), a rare genetic disorder causing severe swelling.
- Key Procedural History: The patent-in-suit is listed in the FDA's "Orange Book" as covering the drug FIRAZYR® (icatibant). Defendant filed ANDA No. 208879 with a "Paragraph IV" certification, asserting that the patent is invalid or will not be infringed by its proposed generic product. Plaintiffs received a statutory notice letter from Defendant regarding the ANDA filing on May 10, 2016. The U.S. Patent and Trademark Office granted a five-year patent term extension for the patent-in-suit based on the FDA regulatory review period for FIRAZYR®.
Case Timeline
| Date | Event |
|---|---|
| 1988-11-24 | U.S. Patent No. 5,648,333 Priority Date |
| 1997-07-15 | U.S. Patent No. 5,648,333 Issue Date |
| 2011-08-25 | FDA approval of New Drug Application for FIRAZYR® |
| 2016-05-10 | Plaintiffs receive Defendant's Paragraph IV notice letter |
| 2016-06-17 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 5,648,333 - "Peptides Having Bradykinin Antagonist Action"
- Patent Identification: U.S. Patent No. 5,648,333, "Peptides Having Bradykinin Antagonist Action," issued July 15, 1997.
The Invention Explained
- Problem Addressed: The patent sought to create new and effective synthetic peptides that could counteract the biological effects of bradykinin, a natural peptide involved in inflammation, pain, and blood pressure regulation (’333 Patent, col. 1:54-55). Existing therapies for conditions mediated by bradykinin were insufficient, creating a need for novel antagonists.
- The Patented Solution: The invention is a family of specific peptide structures, defined by the general formula A-B-C-E-F-K-P-G-M-F'-I, where each letter represents a specific type of amino acid or chemical group (’333 Patent, col. 1:56-57). By arranging these building blocks in a precise sequence, including non-natural amino acids like D-Tic (1,2,3,4-Tetrahydroisoquinolin-3-ylcarbonyl), the resulting peptides are designed to block bradykinin receptors effectively (’333 Patent, col. 4:1-6, col. 18:59).
- Technical Importance: The development of potent and specific bradykinin antagonists provided a targeted mechanism for treating diseases where bradykinin is a key pathological mediator, such as the acute attacks of hereditary angioedema (HAE) (Compl. ¶12; ’333 Patent, col. 17:10-14).
Key Claims at a Glance
- The complaint alleges infringement of one or more claims and notes that Defendant's notice letter failed to address claims 1, 2, 4-6, 12-14, 25, and 27 (Compl. ¶18). The independent claims in this group are Claims 1 and 12.
- Independent Claim 1: This is a broad Markush claim to a peptide of the formula A-B-C-E-F-K-P-G-M-F'-I, followed by extensive definitions for each variable, covering a large chemical genus of potential bradykinin antagonists.
- Independent Claim 12: This is a much narrower claim that recites a specific list of preferred peptide compounds. One of the recited peptides is:
- H-D-Arg-Arg-Pro-Hyp-Gly-Thia-Ser-D-Tic-Oic-Arg-OH
III. The Accused Instrumentality
Product Identification
The accused instrumentality is "InnoPharma's ANDA Product," identified as "Icatibant Injection, 10 mg/mL, 3 mL single-use pre-filled syringes" (Compl. ¶9).
Functionality and Market Context
The product is a generic version of Plaintiffs' FIRAZYR® (Compl. ¶11, ¶14). Its active ingredient, icatibant, is a bradykinin B2 receptor antagonist. It is intended for subcutaneous administration to treat acute attacks of hereditary angioedema (HAE) in adults (Compl. ¶11-12). The filing of the ANDA seeks FDA approval to market this product as a therapeutically equivalent alternative to FIRAZYR® before the expiration of the ’333 Patent (Compl. ¶9).
IV. Analysis of Infringement Allegations
The complaint’s infringement theory centers on the chemical identity of Defendant's ANDA product. Icatibant, the active ingredient in both FIRAZYR® and the accused product, is the common name for the specific peptide molecule H-D-Arg-Arg-Pro-Hyp-Gly-Thia-Ser-D-Tic-Oic-Arg-OH, which is explicitly recited in claim 12 of the ’333 Patent.
'333 Patent Infringement Allegations
| Claim Element (from Independent Claim 12) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A peptide of the formula H-D-Arg-Arg-Pro-Hyp-Gly-Thia-Ser-D-Tic-Oic-Arg-OH | Defendant's ANDA Product is an "Icatibant Injection." Icatibant is the nonproprietary name for the specific peptide recited in the claim. The submission of an ANDA for a product containing this peptide is alleged to be an act of infringement. | ¶9, ¶21, ¶24 | col. 12:7-8; col. 44:30-31 |
- Identified Points of Contention:
- Technical Questions: A primary question for the court is one of chemical identity: does the active pharmaceutical ingredient in InnoPharma's ANDA No. 208879 product correspond precisely to the chemical structure "H-D-Arg-Arg-Pro-Hyp-Gly-Thia-Ser-D-Tic-Oic-Arg-OH" as recited in Claim 12? The complaint alleges this identity by referring to the product as "icatibant" (Compl. ¶9, ¶11). Under the ANDA regulatory framework, a generic drug must contain the same active ingredient as the reference listed drug, which strongly suggests chemical identity.
No probative visual evidence provided in complaint.
V. Key Claim Terms for Construction
In this ANDA case, where infringement may turn on the precise identity of a chemical compound, the definition of the non-standard amino acid moieties is critical.
- The Term: "D-Tic"
- Context and Importance: This term, appearing in the highly relevant Claim 12, represents a non-natural amino acid that is a key structural feature of the claimed peptide, icatibant. Infringement of this claim requires that the accused product contains this exact chemical structure. Practitioners may focus on this term to confirm that there is no structural ambiguity that could create a non-infringement argument.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The complaint does not provide sufficient detail for analysis of potential broader interpretations. The patent itself does not appear to provide language supporting a broader definition beyond the specific structure provided.
- Evidence for a Narrower Interpretation: The patent specification provides a single, unambiguous definition for the term. The "List of abbreviations" explicitly defines "Tic" as "1,2,3,4-Tetrahydroisoquinolin-3-ylcarbonyl" (’333 Patent, col. 18:59). Furthermore, the specification provides a chemical drawing of the Tic radical in Formula V, leaving little room for interpretation beyond this precise structure (’333 Patent, col. 4:1-6).
VI. Other Allegations
- Indirect Infringement: The complaint alleges inducement of infringement, stating that InnoPharma intends for third parties (e.g., physicians and patients) to use the ANDA product in an infringing manner. This intent is allegedly evidenced by the product's corresponding labeling, package insert, and medication guide, which will instruct users on the patented method of treatment (Compl. ¶27). Contributory infringement is also alleged on the basis that the ANDA product is a material part of the claimed methods of treatment and is not a staple article of commerce suitable for substantial non-infringing uses (Compl. ¶28).
- Willful Infringement: The complaint does not use the term "willful infringement" but does seek a declaration that the case is "exceptional" under 35 U.S.C. § 285, which allows for an award of attorneys' fees (Prayer for Relief ¶E). The basis for this allegation is that InnoPharma was aware of the ’333 patent, at least as of its May 10, 2016 notice letter, yet proceeded with seeking FDA approval "without a reasonable basis for believing that it would not infringe" (Compl. ¶30).
VII. Analyst’s Conclusion: Key Questions for the Case
- A central issue will be one of chemical identity: Does the defendant's proposed generic product, identified in its ANDA submission, contain the exact peptide molecule recited in Claim 12 of the ’333 patent? While the ANDA statutory scheme heavily implies such identity, this remains the threshold question for infringement.
- A second core question, arising from the defendant's statutorily-required Paragraph IV certification, is one of patent validity: Although not detailed in the complaint, the foundational dispute in this type of litigation is whether the defendant can prove, by clear and convincing evidence, that the asserted claims of the '333 patent are invalid on grounds such as obviousness or lack of adequate written description.
- Finally, a key question for remedies will be one of objective baselessness: Did the defendant, in filing its ANDA, lack a reasonable basis for its belief that the ’333 patent was invalid or not infringed? The answer will determine whether this case is "exceptional" and warrants an award of attorneys' fees to the plaintiffs.