DCT
1:18-cv-00914
Huvepharma EOOD v. Ei Du Pont De Nemours Co
Key Events
Complaint
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Huvepharma EOOD (Republic of Bulgaria) and Huvepharma, Inc. (United States)
- Defendant: E.I. Du Pont De Nemours and Company, DuPont Industrial Biosciences USA, LLC, Danisco USA Inc., and Danisco US Inc. (United States)
- Plaintiff’s Counsel: Bayard, P.A.
- Case Identification: 1:18-cv-00914, D. Del., 06/20/2018
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because the named defendants are Delaware corporations.
- Core Dispute: Plaintiff alleges that Defendant’s Phyzyme phytase product line, which is manufactured abroad and imported into the U.S., infringes patents related to methods of producing the phytase enzyme using genetically modified yeast systems.
- Technical Context: The technology concerns the recombinant production of phytase, an enzyme added to animal feed to help animals like swine and poultry digest phosphorus, which increases nutrient absorption and reduces environmental pollution from manure.
- Key Procedural History: The patents-in-suit, originally assigned to Cornell Research Foundation, Inc., are exclusively licensed to Plaintiff. Subsequent to the filing of this complaint, all three patents-in-suit were the subject of Inter Partes Review (IPR) proceedings before the U.S. Patent and Trademark Office. These IPRs resulted in the cancellation of all asserted claims of U.S. Patent Nos. 7,312,063 and 8,455,232, and the cancellation of the primary asserted claims of U.S. Patent No. 7,026,150.
Case Timeline
| Date | Event |
|---|---|
| 1998-06-25 | Earliest Priority Date for ’150, ’063, and ’232 Patents |
| 2003-01-01 | Accused Phyzyme XP phytase development begins (approx. date) |
| 2006-04-11 | ’150 Patent Issued |
| 2007-12-25 | ’063 Patent Issued |
| 2010-01-01 | Defendant begins manufacturing/importing accused products (approx. date) |
| 2013-06-04 | ’232 Patent Issued |
| 2018-06-20 | Complaint Filed |
| 2019-01-23 | IPR proceedings initiated for all three patents-in-suit |
| 2023-03-08 | IPR Certificate Issued for ’063 Patent, cancelling asserted claims |
| 2023-03-10 | IPR Certificate Issued for ’150 Patent, cancelling asserted claims |
| 2023-03-14 | IPR Certificate Issued for ’232 Patent, cancelling asserted claims |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 7,026,150 - "Overexpression of Phytase Genes in Yeast Systems"
- Issued: April 11, 2006
The Invention Explained
- Problem Addressed: The patent’s background section describes that prior microbial phytases used in animal feed, such as those derived from the fungus Aspergillus niger, were expensive to produce and lacked sufficient heat stability (thermotolerance) to survive the high temperatures of the feed pelleting manufacturing process (’150 Patent, col. 2:5-33). This instability limited their practical use in the animal feed industry, which sought to improve nutrient utilization in animals and reduce environmental phosphate pollution (Compl. ¶41-43; ’150 Patent, col. 1:12-35).
- The Patented Solution: The invention is a method for producing phytase by introducing a heterologous gene—one from a non-yeast organism like the fungus Aspergillus niger (PhyA gene) or the bacterium E. coli (AppA gene)—into a yeast host system (’150 Patent, Abstract). Expressing the gene in a yeast host, such as Pichia pastoris, allegedly enables high-yield, economical production of a phytase enzyme with increased thermostability compared to phytase produced in a non-yeast host cell (’150 Patent, col. 6:58-65, col. 44:12-25).
- Technical Importance: This method offered a pathway to mass-produce a more robust and commercially viable phytase enzyme for widespread use in animal feed, addressing both economic and environmental challenges in the industry (Compl. ¶44-45).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶94).
- Claim 1 of the ’150 Patent recites:
- A method of producing phytase in yeast comprising:
- providing a heterologous polynucleotide from a non-yeast organism which encodes a protein or polypeptide comprising either a PhyA phytase or an AppA phytase;
- expressing the protein or polypeptide in a yeast; and
- isolating the expressed protein or polypeptide, wherein said protein or polypeptide catalyzes the release of phosphate from phytate and has increased thermostability as compared to that of said protein or polypeptide expressed in a non-yeast host cell.
- The complaint also purports to assert dependent claims 2-4, 6-7, 16, 29, and 31-33 (Compl. ¶94).
U.S. Patent No. 7,312,063 - "Overexpression of Phytase Genes in Yeast Systems"
- Issued: December 25, 2007
The Invention Explained
- Problem Addressed: The ’063 Patent, a continuation of the application leading to the ’150 Patent, addresses the same technical problem: the need for an economical method to produce a phytase enzyme with sufficient thermal stability for use in animal feed manufacturing processes (’063 Patent, col. 2:9-37).
- The Patented Solution: The solution is substantively identical to that of the ’150 patent, disclosing a method of expressing a heterologous phytase gene in a yeast host system to achieve improved yields and thermostability (’063 Patent, Abstract). The claims of the ’063 patent are directed more specifically to producing a phytase from Escherichia coli.
- Technical Importance: The technical importance is the same as described for the ’150 Patent (Compl. ¶44-45).
Key Claims at a Glance
- The complaint asserts independent claims 1 and 5 (Compl. ¶102).
- Claim 1 of the ’063 Patent recites:
- A method of producing phytase in yeast comprising:
- providing a heterologous polynucleotide from a non-yeast organism which encodes a protein or polypeptide comprising a phytase from Escherichia coli;
- expressing the polynucleotide in a yeast; and
- isolating the expressed protein or polypeptide, wherein said protein or polypeptide catalyzes the release of phosphate from phytate and has increased thermostability as compared to that of said protein or polypeptide expressed in a non-yeast host cell.
- Claim 5 of the ’063 Patent recites:
- The method according to claim 1, wherein the protein or polypeptide has an optimal phytase activity at a pH of less than about 4.
- The complaint also purports to assert dependent claims 2 and 6-7 (Compl. ¶102).
U.S. Patent No. 8,455,232 - "Overexpression of Phytase Genes in Yeast Systems"
- Issued: June 4, 2013
- Technology Synopsis: This patent, from the same family as the ’150 and ’063 patents, addresses the need for an efficient method to produce thermostable phytase for animal feed. The claimed solution is a method of expressing a phytase from Escherichia coli in a yeast host and isolating the resulting enzyme.
- Asserted Claims: Independent claim 1 is asserted (Compl. ¶110).
- Accused Features: The accused feature is the manufacturing process for the Phyzyme product line, which allegedly involves expressing an E. coli-derived phytase gene in a yeast host and isolating the resulting enzyme, a process alleged to fall within the scope of the ’232 Patent’s claims (Compl. ¶57-61, 112).
III. The Accused Instrumentality
Product Identification
The accused instrumentalities are products made by an allegedly infringing process, identified as the "Phyzyme phytase product line." This line includes various formulations such as Phyzyme XP, Phyzyme XP TPT, Phyzyme XP G, and Phyzyme XP Liquid (Compl. ¶9, 48).
Functionality and Market Context
The Phyzyme products are alleged to be 6-phytase enzyme feed additives manufactured using a genetically modified heterologous yeast host, Schizosaccharomyces pombe ("S. pombe") (Compl. ¶57, 66). The complaint alleges that the process begins with a polynucleotide sourced from an E. coli species bacterium, which is then expressed in the yeast host through a process of fermentation, after which the resulting enzyme is recovered, purified, and formulated (Compl. ¶57, 61). The complaint describes the packaging label for a Phyzyme XP product, which indicates it was manufactured in Finland and sold by Genencor (Compl. ¶58). The resulting products are marketed as having "unrivalled heat stability" for use in animal feed to increase the bioavailability of phosphorus (Compl. ¶78, 86). The complaint alleges these products are manufactured outside the United States and then imported, offered for sale, and sold within the U.S. by Defendants (Compl. ¶9, 48, 52-54).
IV. Analysis of Infringement Allegations
’150 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| providing a heterologous polynucleotide from non-yeast organism which encodes a protein or polypeptide comprising either a PhyA phytase or an AppA phytase | The accused process allegedly uses a polynucleotide from the non-yeast bacterium E. coli that encodes an AppA 6-phytase. | ¶59, ¶61 | col. 6:1-8 |
| expressing the protein or polypeptide in a yeast | The AppA phytase gene is allegedly expressed in the heterologous yeast host Schizosaccharomyces pombe. | ¶57, ¶60 | col. 5:36-48 |
| isolating the expressed protein or polypeptide | The accused process allegedly isolates the phytase protein through multi-step recovery and purification processes, including cell separation and filtration, to produce a final cell-free product. | ¶71, ¶72 | col. 44:12-25 |
| wherein said protein or polypeptide catalyzes the release of phosphate from phytate | The accused Phyzyme products are sold as phytase enzymes specifically developed to hydrolyze phytate and increase the digestibility of phytin-bound phosphorus in animal diets. | ¶74, ¶77 | col. 1:12-16 |
| and has increased thermostability as compared to that of said protein or polypeptide expressed in a non-yeast host cell | The accused products are marketed as having "unrivalled heat stability" and being "more heat stable than other leading phytase products," which would include those expressed in non-yeast hosts. | ¶86, ¶87 | col. 35:25-29 |
’063 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| providing a heterologous polynucleotide from a non-yeast organism which encodes a protein or polypeptide comprising a phytase from Escherichia coli | The accused process allegedly uses a polynucleotide from the non-yeast bacterium E. coli that encodes an AppA 6-phytase. | ¶59, ¶61 | col. 6:1-8 |
| expressing the polynucleotide in a yeast | The AppA phytase gene is allegedly expressed in the heterologous yeast host Schizosaccharomyces pombe. | ¶57, ¶60 | col. 5:36-48 |
| isolating the expressed protein or polypeptide | The accused process allegedly isolates the phytase protein through multi-step recovery and purification processes to produce a final cell-free product. | ¶71, ¶72 | col. 45:12-25 |
| wherein said protein or polypeptide catalyzes the release of phosphate from phytate | The accused Phyzyme products are sold as phytase enzymes specifically developed to hydrolyze phytate and increase the bioavailability of phosphorus. | ¶74, ¶77 | col. 1:12-16 |
| and has increased thermostability as compared to that of said protein or polypeptide expressed in a non-yeast host cell | The accused products are marketed as having "unrivalled heat stability" and superior heat stability performance compared to other phytase products. | ¶86, ¶87 | col. 36:25-29 |
Identified Points of Contention
- Scope Questions: The claims in the ’150 and ’063 patents require "increased thermostability as compared to that of said protein or polypeptide expressed in a non-yeast host cell." An issue for the court may be to define the proper baseline for this comparison. This raises the question of whether the comparison should be to the phytase enzyme as produced in its native bacterial or fungal host, or as produced in a different recombinant non-yeast system.
- Technical Questions: The complaint alleges the use of Schizosaccharomyces pombe, a fission yeast, as the expression host (Compl. ¶57). The patents primarily provide examples using budding yeasts like Pichia pastoris and Saccharomyces cerevisiae (’150 Patent, col. 6:41-43). This may raise the factual question of whether the functional benefits described in the patent specification, particularly regarding protein processing and secretion, are achieved in the same manner in the accused fission yeast system.
V. Key Claim Terms for Construction
The Term: "yeast"
- Context and Importance: This term defines the host organism for the claimed method. The accused process allegedly uses Schizosaccharomyces pombe, which is a fission yeast (Compl. ¶57). The patent specifications provide more detailed examples using budding yeasts such as Saccharomyces and Pichia. The construction of "yeast" is critical to determining whether the claims encompass processes that use fission yeasts.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification explicitly lists Schizosaccharomyces as a type of yeast that can be used in the invention, alongside other genera (’150 Patent, col. 6:41-42). This language may support a construction that is not limited to the specific types of yeast used in the working examples.
- Evidence for a Narrower Interpretation: A party could argue that the patent's teachings on protein expression and secretion are tied to the biological mechanisms of the exemplified budding yeasts, suggesting the term’s scope should be understood in that context.
The Term: "increased thermostability as compared to that of said protein or polypeptide expressed in a non-yeast host cell"
- Context and Importance: This comparative limitation is a cornerstone of the asserted independent claims of the ’150 and ’063 patents. Infringement depends on proving that the phytase produced by the accused yeast-based process is more heat-stable than the same phytase produced by a "non-yeast host cell." The definition of this baseline comparator is central to the dispute.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent background criticizes the thermal instability of prior art phytases from their native fungal sources (’150 Patent, col. 2:5-12). This may support an interpretation where the baseline "non-yeast host cell" refers to the native organism from which the gene was sourced (e.g., E. coli or A. niger).
- Evidence for a Narrower Interpretation: The claim language refers to the protein "expressed in" a non-yeast host cell, which could be interpreted to require a comparison to a recombinant non-yeast expression system rather than the native organism. The patent abstract itself contrasts the invention with expression in a "non-yeast host cell," suggesting a direct comparison between host system types (’150 Patent, Abstract).
VI. Other Allegations
- Indirect Infringement: The complaint does not contain separate counts for induced or contributory infringement. The infringement allegations are primarily based on 35 U.S.C. § 271(g), which makes it an act of direct infringement to import, offer to sell, sell, or use within the United States a product which is made by a process patented in the United States (Compl. ¶94, 102, 110).
- Willful Infringement: The complaint’s prayer for relief requests a judgment that Defendants' acts were willful (Compl., p. 29). However, the complaint does not allege specific facts to support that Defendants had pre-suit knowledge of the patents-in-suit.
VII. Analyst’s Conclusion: Key Questions for the Case
- A threshold issue for the court will be one of viability and mootness: given the post-filing IPR proceedings that resulted in the cancellation of all asserted claims of the ’063 and ’232 patents and the primary asserted claims of the ’150 patent, a central question is whether any viable infringement claims remain. The case may turn on whether Plaintiff can proceed on any surviving, unasserted claims from the ’150 patent.
- Should the case proceed, a core issue will be one of definitional scope: how is the claim limitation "increased thermostability as compared to... a non-yeast host cell" to be measured? The case will likely involve significant disputes over defining the proper baseline for this comparison and presenting evidence to meet that standard.
- A key technical question will be one of functional scope: does the term "yeast," which is foundational to the claims, read on the accused process's use of the fission yeast Schizosaccharomyces pombe? The resolution will depend on whether the patent's teachings are viewed as broadly applicable to all yeasts or limited to the budding yeasts emphasized in the specification's examples.