DCT
1:13-cv-10020
Massachusetts Institute Of Technology v. Shire Pharma Inc
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Massachusetts Institute of Technology (MA) and Children's Medical Center Corporation (MA)
- Defendant: Shire PLC (Jersey), Shire Pharmaceuticals, Inc. (DE), and Shire Regenerative Medicine, Inc. (DE)
- Plaintiff’s Counsel: Goodwin Procter LLP
- Case Identification: 1:13-cv-10020, D. Mass., 01/04/2013
- Venue Allegations: Plaintiffs allege venue is proper in the District of Massachusetts because a substantial part of the events giving rise to the claims occurred in the district and because the defendants are subject to personal jurisdiction there, based on their marketing and sales of products to Massachusetts residents.
- Core Dispute: Plaintiffs allege that Defendants’ Dermagraft product, a bioengineered skin substitute, infringes three patents related to three-dimensional, biodegradable scaffolds used for in-vitro cell growth to create implantable, vascularized tissue.
- Technical Context: The technology at issue is in the field of tissue engineering, which aims to create functional biological tissues for therapeutic purposes, such as treating chronic wounds or organ failure.
- Key Procedural History: The complaint alleges that Plaintiffs sent multiple letters to Defendants notifying them of the patents-in-suit, beginning in June 2011. This alleged pre-suit knowledge forms the basis for the willfulness allegations.
Case Timeline
| Date | Event |
|---|---|
| 1986-11-20 | Earliest Priority Date for '830, '193, '417 Patents |
| 1998-06-02 | U.S. Patent No. 5,759,830 Issues |
| 1998-06-23 | U.S. Patent No. 5,770,193 Issues |
| 1998-06-23 | U.S. Patent No. 5,770,417 Issues |
| 2001 | FDA Approval for Dermagraft |
| 2007 | SRM Begins U.S. Sale of Dermagraft |
| 2011-06-22 | First Pre-Suit Notice Letter Sent to Defendants |
| 2011-07-27 | Second Pre-Suit Notice Letter Sent to Defendants |
| 2012-11-07 | Third Pre-Suit Notice Letter Sent to Defendants |
| 2013-01-04 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 5,759,830 - "Three-dimensional fibrous scaffold containing attached cells for producing vascularized tissue in vivo"
- Patent Identification: U.S. Patent No. 5,759,830, "Three-dimensional fibrous scaffold containing attached cells for producing vascularized tissue in vivo," issued June 2, 1998.
The Invention Explained
- Problem Addressed: The patent describes a central challenge in creating larger, three-dimensional engineered tissues: cells in the core of an implant often die from lack of nutrients and oxygen before the host's blood vessels can grow into the structure to supply them (’830 Patent, col. 4:56-col. 5:9).
- The Patented Solution: The invention is a cell-scaffold composition made from a biocompatible and biodegradable polymer formed into a three-dimensional fibrous structure. The key innovation is the specific architectural design where the fibers are spaced apart to ensure that the maximum distance for nutrient diffusion to any cell is between 100 and 300 microns (’830 Patent, Abstract). This configuration is designed to maintain cell viability throughout the entire scaffold in vitro and immediately after implantation, before neovascularization occurs (’830 Patent, col. 10:15-24). The overall process is depicted in Figure 1 of the patent.
- Technical Importance: This approach provided a potential solution to the critical diffusion-limitation problem, a significant bottleneck that had previously restricted the size and complexity of engineered tissues (’830 Patent, col.5:10-22).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" (Compl. ¶25). Independent claim 1 is representative and defines a composition comprising:
- a fibrous three-dimensional scaffold composed of fibers of a biocompatible, biodegradable, synthetic polymer;
- cells derived from a vascularized tissue attached in vitro to the surface of the fibers of the scaffold uniformly throughout the scaffold;
- wherein the fibers of the scaffold provide sufficient surface area to permit attachment in vitro of an amount of the cells effective to produce the functional vascularized organ tissue in vivo;
- wherein the fibers of the scaffold are spaced apart such that the maximum distance over which diffusion of nutrients and gases must occur through a mass of cells attached to the fibers is between 100 and 300 microns; and
- wherein the diffusion provides free exchange of nutrients, gases and waste to and from the cells uniformly attached to the fibers of the scaffold and proliferating throughout the scaffold in an amount effective to maintain cell viability throughout the scaffold in the absence of vascularization.
U.S. Patent No. 5,770,193 - "Preparation of three-dimensional fibrous scaffold for attaching cells to produce vascularized tissue in vivo"
- Patent Identification: U.S. Patent No. 5,770,193, "Preparation of three-dimensional fibrous scaffold for attaching cells to produce vascularized tissue in vivo," issued June 23, 1998.
The Invention Explained
- Problem Addressed: The patent addresses the same fundamental problem as its counterpart: prior art methods for creating artificial organs were limited because cells deep within a three-dimensional matrix could not survive due to insufficient nutrient diffusion before the implant was vascularized (’193 Patent, col. 2:54-col. 3:9).
- The Patented Solution: This patent claims a method for preparing the tissue scaffold. The method involves providing biocompatible, biodegradable polymer fibers and forming them into a three-dimensional scaffold where the fibers are spaced apart such that the maximum diffusion distance is between 200 and 300 microns (’193 Patent, Abstract). This specific construction method is intended to create a scaffold that supports cell life throughout its volume, which is then seeded with cells and grown in vitro before implantation (’193 Patent, col. 10:1-5).
- Technical Importance: The patent provides a methodology for constructing scaffolds with the specific micro-architecture required to overcome the diffusion barrier, a key manufacturing step for making larger-scale tissue engineering a viable therapeutic strategy (’193 Patent, col. 6:15-24).
Key Claims at a Glance
- The complaint asserts infringement of "one or more claims" (Compl. ¶30). Independent claim 1 is representative and recites a method with the following key steps:
- providing fibers made of a biocompatible, biodegradable, synthetic polymer;
- forming the fibers into a fibrous three-dimensional scaffold composed of the fibers;
- wherein the fibers of the scaffold are spaced apart such that the maximum distance over which diffusion of nutrients and gases must occur through a mass of cells attached to the fibers is between 200 and 300 microns;
- wherein the diffusion provides free exchange of nutrients, gases and waste to and from the cells uniformly attached to the fibers of the scaffold...in the absence of vascularization.
U.S. Patent No. 5,770,417 - "Three-dimensional fibrous scaffold containing attached cells for producing vascularized tissue in vivo"
- Patent Identification: U.S. Patent No. 5,770,417, "Three-dimensional fibrous scaffold containing attached cells for producing vascularized tissue in vivo," issued June 23, 1998.
Technology Synopsis
This patent discloses a cell-scaffold composition for producing functional organ tissue, sharing a common specification with the '830 and '193 patents. The technology centers on a three-dimensional scaffold composed of synthetic polymer fibers (including non-biodegradable options) that is specifically configured with controlled fiber spacing to maintain cell viability via nutrient diffusion prior to implantation and subsequent vascularization (’417 Patent, Abstract).
Asserted Claims
The complaint alleges infringement of "one or more claims" of the patent (Compl. ¶39). Independent claim 1 is representative.
Accused Features
The complaint accuses the manufacture, use, and sale of Dermagraft, which is described as a three-dimensional dermal substitute created by seeding living cells onto a polymer scaffold (Compl. ¶18, ¶39).
III. The Accused Instrumentality
Product Identification
- Dermagraft.
Functionality and Market Context
- The complaint describes Dermagraft as a "human fibroblast-derived dermal substitute" intended for the treatment of "full-thickness diabetic foot ulcers" (Compl. ¶18).
- Its manufacture is alleged to involve seeding human fibroblast cells, derived from newborn foreskin tissue, onto a "bioabsorbable polyglactin three-dimensional mesh scaffold" (Compl. ¶18). According to the complaint, these cells then proliferate and secrete collagen, matrix proteins, and growth factors to create a "three-dimensional human dermal substitute containing metabolically active, living cells" (Compl. ¶18).
- The product received FDA approval in 2001, and Defendant SRM is alleged to have begun manufacturing and selling it in the United States in 2007 (Compl. ¶19-20).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
'830 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A cell-scaffold composition prepared in vitro...comprising: a fibrous three-dimensional scaffold composed of fibers of a biocompatible, biodegradable, synthetic polymer; | Dermagraft is described as a "three-dimensional human dermal substitute" comprising a "bioabsorbable polyglactin three-dimensional mesh scaffold," which is prepared in vitro before use. | ¶18 | col. 10:40-44 |
| and cells derived from a vascularized tissue attached in vitro to the surface of the fibers of the scaffold uniformly throughout the scaffold; | Dermagraft is manufactured from "human fibroblast cells derived from newborn foreskin tissue" which are "seeded onto" the scaffold. | ¶18 | col. 24:28-34 |
| wherein the fibers of the scaffold are spaced apart such that the maximum distance over which diffusion of nutrients and gases must occur through a mass of cells...is between 100 and 300 microns; | The complaint alleges that Dermagraft infringes, implying its structure meets this limitation, but provides no specific factual allegations regarding the micron-level spacing of the scaffold. | ¶25 | col. 24:39-42 |
| wherein the diffusion provides free exchange of nutrients, gases and waste...in an amount effective to maintain cell viability throughout the scaffold in the absence of vascularization. | The complaint alleges Dermagraft is a "three-dimensional human dermal substitute containing metabolically active, living cells," implying viability is maintained throughout the structure. | ¶18 | col. 24:42-48 |
'193 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method for preparing a scaffold...comprising: providing fibers made of a biocompatible, biodegradable, synthetic polymer, | The manufacture of Dermagraft allegedly involves providing a "bioabsorbable polyglactin" scaffold. | ¶18, ¶30 | col. 10:1-3 |
| and forming the fibers into a fibrous three-dimensional scaffold composed of the fibers, | Dermagraft's scaffold is described as a "three-dimensional mesh scaffold." | ¶18 | col. 10:3-5 |
| wherein the fibers of the scaffold are spaced apart such that the maximum distance over which diffusion of nutrients and gases...is between 200 and 300 microns; | The complaint alleges the method of making Dermagraft infringes, which implies this structural limitation is met, but provides no specific facts regarding the scaffold's internal spacing. | ¶30 | col. 9:46-50 |
Identified Points of Contention
- Technical Question: The complaint offers a general description of Dermagraft but provides no specific evidence that its "mesh scaffold" meets the crucial quantitative limitation of a 100-300 micron maximum diffusion distance recited in the patent claims. A central evidentiary dispute will likely be whether the physical structure of the accused product, upon expert examination, actually falls within this claimed range.
- Scope Questions: The case may raise the question of whether the term "fibrous...scaffold," as used in the patents, is broad enough to read on the accused "mesh scaffold." Defendants might argue that the patent's emphasis on "branching" or "tree-like" structures (’830 Patent, col. 11:13-14) requires a more organized configuration than their product possesses.
V. Key Claim Terms for Construction
The Term: "a fibrous three-dimensional scaffold"
- Context and Importance: This term defines the fundamental structure of the invention. Its construction will be critical, as the infringement analysis depends on whether Dermagraft's "mesh" structure is properly characterized as a "fibrous...scaffold" within the meaning of the claims. Practitioners may focus on this term because it delineates the boundary between the patented invention and other porous materials.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification suggests flexibility in fiber configuration, stating the fibers may be "round, scalloped, flattened, star shaped, solitary or entwined with other fibers," which may support a construction that is not limited to a single geometry (’830 Patent, col. 11:18-20).
- Evidence for a Narrower Interpretation: The patent repeatedly highlights a "branching fiber network" and a "fibrillar structure" as the preferred embodiment (’830 Patent, col. 11:13-14). Figures such as Figure 1 depict a tree-like, branching structure, which could be used to argue for a narrower definition that excludes more randomly organized structures like a simple mesh.
The Term: "spaced apart such that the maximum distance over which diffusion...is between 100 and 300 microns"
- Context and Importance: This quantitative limitation represents the core technical solution to the problem of cell death from nutrient starvation. Proving that the accused product meets this precise numerical range is essential for the Plaintiffs' infringement case.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Plaintiffs may argue this is a functional limitation, defined by the outcome of enabling cell viability through diffusion, as supported by language describing it as the distance over which "adequate diffusion...can occur" (’830 Patent, col. 10:17-19).
- Evidence for a Narrower Interpretation: Defendants may argue that this limitation requires a specific, engineered, and regular spacing, rather than an average or incidental property of a random mesh. They could point to the patent’s discussion of theoretical calculations and experimental validation as evidence that a precise and controlled architecture is required (’830 Patent, col. 23:10-col. 24:14).
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for the '193 method patent. Inducement is based on allegations that Defendant SRM sells Dermagraft with a "package insert that includes instructions" for its use, which allegedly cause physicians to directly infringe the method claims (Compl. ¶33). Contributory infringement is alleged on the basis that Dermagraft is a "material component" of the invention that is "not a staple article of commerce capable of substantial noninfringing use" (Compl. ¶34). For all patents, inducement is also alleged against the parent Shire entities for their role in SRM's infringing activities (Compl. ¶26, ¶35, ¶40).
- Willful Infringement: The complaint alleges willful infringement for all three patents. The basis for this allegation is Defendants' alleged knowledge of the patents, supported by factual allegations that Plaintiffs sent multiple notice letters to Defendants starting in June 2011, approximately 18 months prior to filing the lawsuit (Compl. ¶22-23, ¶27, ¶36, ¶41).
VII. Analyst’s Conclusion: Key Questions for the Case
- A key evidentiary question will be one of structural identity: what evidence will Plaintiffs adduce to prove that the accused Dermagraft "mesh scaffold" possesses the specific, quantitative micro-architecture required by the claims, namely that its fibers are spaced to create a maximum nutrient diffusion distance within the 100-to-300-micron range?
- A central legal issue will be one of definitional scope: can the term "fibrous...scaffold," which the patent specification often describes with reference to "branching" or "tree-like" structures, be construed broadly enough to encompass the "mesh" configuration of the accused Dermagraft product, or is there a fundamental mismatch between the claimed invention and the accused device?
- A third question will relate to infringement of the method claims: can Plaintiffs demonstrate that Defendants' manufacturing process for Dermagraft performs the step of "forming the fibers into a...scaffold" with the specific diffusion properties required by the '193 patent, or will Defendants be able to distinguish their process from the claimed method?