DCT

1:20-cv-00859

Genentech Inc v. Samsung Bioepis Co Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-00859, D. Del., 06/28/2020
  • Venue Allegations: Venue is asserted under 28 U.S.C. § 1391(c)(3), which subjects foreign corporations to suit in any U.S. judicial district.
  • Core Dispute: Plaintiff alleges that Defendant's submission of an Abbreviated Biologics License Application (aBLA) for its proposed bevacizumab biosimilar product, SB8, constitutes an act of infringement of fourteen U.S. patents covering methods of manufacturing and using bevacizumab.
  • Technical Context: The technology relates to the manufacture and use of bevacizumab (Avastin®), a genetically engineered monoclonal antibody that inhibits angiogenesis (the formation of new blood vessels) and is a widely used therapy for various cancers.
  • Key Procedural History: This action arises under the Biologics Price Competition and Innovation Act (BPCIA). The complaint details the pre-suit information exchange, or "patent dance," alleging that Defendant failed to provide required information describing its manufacturing processes for SB8 and later provided only conclusory assertions of invalidity for a small subset of the identified patents. This procedural history may be central to the parties' litigation strategies and discovery disputes.

Case Timeline

Date Event
1997-03-24 Earliest Priority Date ('206 Patent)
2002-03-05 Earliest Priority Date ('660 Patent)
2003-07-01 U.S. Patent No. 6,586,206 Issues
2003-08-28 Earliest Priority Date ('704 Patent)
2008-06-24 U.S. Patent No. 7,390,660 Issues
2009-02-03 U.S. Patent No. 7,485,704 Issues
2009-03-12 Earliest Priority Date ('895, '983, '869, '293 Patents)
2011-09-21 Earliest Priority Date ('697 Patent)
2013-06-11 U.S. Patent No. 8,460,895 Issues
2013-08-20 U.S. Patent No. 8,512,983 Issues
2013-11-05 U.S. Patent No. 8,574,869 Issues
2014-07-14 Earliest Priority Date ('355 Patent)
2015-05-19 Earliest Priority Date ('809 Patent)
2015-08-28 Earliest Priority Date ('035 Patent)
2016-09-13 U.S. Patent No. 9,441,035 Issues
2016-11-08 U.S. Patent No. 9,487,809 Issues
2017-03-24 Earliest Priority Date ('672 Patent)
2017-07-25 U.S. Patent No. 9,714,293 Issues
2017-10-24 U.S. Patent No. 9,795,672 Issues
2018-03-15 Earliest Priority Date ('710 Patent)
2019-02-19 U.S. Patent No. 10,208,355 Issues
2019-11-18 FDA accepts for review Bioepis' aBLA for SB8
2019-12-24 U.S. Patent No. 10,513,697 Issues
2020-03-30 Bioepis provides notice of intent to begin commercial marketing
2020-05-26 U.S. Patent No. 10,662,237 Issues
2020-06-09 U.S. Patent No. 10,676,710 Issues
2020-06-28 Complaint Filed

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

U.S. Patent No. 6,586,206 - "Methods For Making Recombinant Proteins Using Apoptosis Inhibitors", issued July 1, 2003

The Invention Explained

  • Problem Addressed: The patent's background section describes that in cell cultures used for producing recombinant proteins, cells undergo programmed cell death, or apoptosis, which limits the overall yield of the desired protein product (’206 Patent, col. 1:20-44).
  • The Patented Solution: The invention claims to solve this problem by providing methods for making recombinant proteins that involve culturing host cells in the presence of one or more apoptosis inhibitors (’206 Patent, col. 2:5-13). This intervention is intended to reduce the rate of cell death, thereby prolonging the productive phase of the cell culture and increasing the total protein yield.
  • Technical Importance: Maximizing the yield of complex proteins from large-scale cell cultures is a critical factor in the economic viability of biopharmaceutical manufacturing.

Key Claims at a Glance

  • The complaint does not identify the specific claims asserted against Defendant. It refers generally to "claims of the '206 patent" (Compl. ¶37).
  • Consequently, a breakdown of asserted independent claim elements is not possible based on the complaint.

U.S. Patent No. 7,390,660 - "Methods for Growing Mammalian Cells In Vitro", issued June 24, 2008

The Invention Explained

  • Problem Addressed: The patent addresses the issue of lactate accumulation in mammalian cell cultures, a metabolic byproduct that adversely affects cell growth, culture longevity (CTI), and protein production (’660 Patent, col. 1:19-27).
  • The Patented Solution: The invention provides a method for reducing lactate formation and glucose consumption by adding a bi- or tricarbonic acid, such as citric acid or its salt citrate, to the culture medium (’660 Patent, Abstract; col. 2:1-15). This addition is purported to improve cell density, viability, and overall protein yield.
  • Technical Importance: Efficient management of metabolic waste products like lactate is a key challenge in achieving high-density, high-yield cell cultures for biomanufacturing.

Key Claims at a Glance

  • The complaint does not identify the specific claims asserted against Defendant. It refers generally to "claims of the '660 patent" (Compl. ¶49).
  • Consequently, a breakdown of asserted independent claim elements is not possible based on the complaint.

U.S. Patent No. 7,485,704 - "Reducing Protein A Leaching During Protein A Affinity Chromatography", issued February 3, 2009

  • Technology Synopsis: This patent addresses the problem of the protein A ligand leaching from the chromatography column during the antibody purification process. The solution involves reducing the temperature or pH of the composition, or adding protease inhibitors, to minimize this leaching and improve the purity of the final product.
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶61).
  • Accused Features: Defendant's methods for purifying its bevacizumab product are accused of infringement (Compl. ¶61-62).

U.S. Patent No. 8,460,895 - "Method For Producing Recombinant Proteins With A Constant Content Of PCO2 In The Medium", issued June 11, 2013

  • Technology Synopsis: This patent addresses problems in large-scale cell culture arising from fluctuations in dissolved carbon dioxide (pCO2). The invention describes a method for producing recombinant proteins by cultivating cells while maintaining the pCO2 content in the medium at a constant, optimized value, thereby increasing protein yield.
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶73).
  • Accused Features: Defendant's methods for manufacturing its bevacizumab product are accused of infringement (Compl. ¶73-74).

U.S. Patent No. 8,512,983 - "Production of Proteins in Glutamine-Free Cell Culture Media", issued August 20, 2013

  • Technology Synopsis: This patent addresses the adverse effects of glutamine in cell culture, a standard component that can lead to ammonia accumulation. The invention is a method of producing proteins in a glutamine-free culture medium supplemented with asparagine, which is claimed to increase cell viability, longevity, and protein titer.
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶85).
  • Accused Features: Defendant's methods for manufacturing its bevacizumab product are accused of infringement (Compl. ¶85-86).

U.S. Patent No. 8,574,869 - "Prevention of Disulfide Bond Reduction During Recombinant Production of Polypeptides", issued November 5, 2013

  • Technology Synopsis: This patent addresses the problem of disulfide bond reduction in antibodies during and after harvesting from cell culture, which compromises the protein's structure and function. The invention provides methods to prevent this reduction, such as by adding inhibitors of the thioredoxin system or by air sparging the harvested fluid.
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶97).
  • Accused Features: Defendant's methods for manufacturing and harvesting its bevacizumab product are accused of infringement (Compl. ¶97-98).

U.S. Patent No. 9,441,035 - "Cell Culture Media and Methods of Antibody Production", issued September 13, 2016

  • Technology Synopsis: This patent describes cell culture media compositions and methods that enhance the amount of antibody produced. The invention involves supplementing media with specific combinations of copper, insulin, and cystine to increase the final antibody titer.
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶109).
  • Accused Features: Defendant's cell culture media used for manufacturing its bevacizumab product are accused of infringement (Compl. ¶109-110).

U.S. Patent No. 9,487,809 - "Decreasing Lactate Level and Increasing Polypeptide Production By Downregulating the Expression of Lactate Dehydrogenase and Pyruvate Dehydrogenase Kinase", issued November 8, 2016

  • Technology Synopsis: This patent addresses the problem of lactate accumulation in cell cultures. The invention provides methods and compositions for reducing lactate by genetically engineering host cells to downregulate the expression of both lactate dehydrogenase (LDH) and pyruvate dehydrogenase kinase (PDHK), which is claimed to increase polypeptide production.
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶121).
  • Accused Features: Defendant's host cell line and methods for manufacturing its bevacizumab product are accused of infringement (Compl. ¶121-122).

U.S. Patent No. 9,714,293 - "Production of Proteins in Glutamine-Free Cell Culture Media", issued July 25, 2017

  • Technology Synopsis: This patent, related to the '983 patent, also describes methods of producing proteins in glutamine-free media supplemented with asparagine. It further specifies the addition of aspartic acid to enhance protein titer and culture longevity.
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶133).
  • Accused Features: Defendant's cell culture media used for manufacturing its bevacizumab product are accused of infringement (Compl. ¶133-134).

U.S. Patent No. 9,795,672 - "Treatment With Anti-VEGF Antibodies", issued October 24, 2017

  • Technology Synopsis: This is a method-of-treatment patent. It claims methods of treating various cancers by administering an anti-VEGF antibody (like bevacizumab) in combination with specific chemotherapeutic agents, such as irinotecan or oxaliplatin.
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶145).
  • Accused Features: Defendant is accused of inducing infringement by seeking approval for a product label that instructs physicians to use SB8 in a manner that would infringe the patented treatment methods (Compl. ¶152-153).

U.S. Patent No. 10,208,355 - "Method of Treatment for Glioblastoma by Administering a VEGF Antagonist", issued February 19, 2019

  • Technology Synopsis: This is a method-of-treatment patent. It describes methods for identifying and treating glioblastoma patients who are likely to respond to VEGF antagonist therapy by detecting the expression of one or more specified biomarkers.
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶159).
  • Accused Features: Defendant is accused of inducing infringement by seeking approval for a product label that instructs physicians to use SB8 to treat glioblastoma, which would allegedly infringe the claimed methods (Compl. ¶159-160, 166-167).

U.S. Patent No. 10,513,697 - "CO₂ Profile Cultivation", issued December 24, 2019

  • Technology Synopsis: This patent addresses the challenge of managing dissolved CO₂ levels in cell culture. The invention describes a method of cultivating cells using a specific CO₂ profile—starting with a first constant pCO₂ level and then increasing it to a second, higher level—to improve polypeptide production.
  • Asserted Claims: The complaint does not specify which claims are asserted (Compl. ¶173).
  • Accused Features: Defendant's methods for manufacturing its bevacizumab product are accused of infringement (Compl. ¶173-174).

U.S. Patent No. 10,662,237 - "Method to Improve Virus Filtration Capacity", issued May 26, 2020

  • Technology Synopsis: This patent addresses the problem of virus filters fouling during protein purification. The invention is a method for improving virus filtration capacity by using a prefiltration step that includes both endotoxin removal media and cation-exchange media.
  • Asserted Claims: The complaint alleges infringement of one or more claims, including claim 1 (Compl. ¶186).
  • Accused Features: Defendant's methods for purifying its bevacizumab product are accused of infringement (Compl. ¶185-186).

U.S. Patent No. 10,676,710 - "Cell Culture Compositions With Antioxidants and Methods for Polypeptide Production", issued June 9, 2020

  • Technology Synopsis: This patent addresses the problem of color intensity (yellowness) in final protein formulations. The invention provides cell culture media containing specific antioxidants, such as hypotaurine, to reduce the color intensity of the produced polypeptide.
  • Asserted Claims: The complaint alleges infringement of one or more claims, including claim 1 (Compl. ¶198).
  • Accused Features: Defendant's cell culture media and methods for manufacturing its bevacizumab product are accused of infringement (Compl. ¶197-198).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Samsung Bioepis's proposed bevacizumab biosimilar product, designated "SB8" (Compl. ¶5). The act of infringement alleged under 35 U.S.C. § 271(e)(2) is the submission of Abbreviated Biologics License Application (aBLA) No. 761159 to the U.S. Food and Drug Administration (FDA) (Compl. ¶5, ¶7).
  • Functionality and Market Context: SB8 is a biosimilar version of Genentech's Avastin® product, which contains the genetically engineered antibody bevacizumab (Compl. ¶5, ¶15). Bevacizumab functions by inhibiting the proliferation of blood vessels necessary for cancerous tumor growth (Compl. ¶15). The complaint alleges that Avastin® is one of the top-selling medicines in the United States, positioning SB8 to enter a significant market upon regulatory approval (Compl. ¶15). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint does not provide a claim chart or specific factual allegations mapping elements of the asserted claims to the accused product's manufacturing process or intended use. Instead, it incorporates by reference Genentech's "(l)(3)(C) Contentions," a document not attached to the complaint (Compl. ¶38, ¶50). Therefore, a detailed claim chart summary and identification of specific points of contention cannot be constructed from the provided documents. The complaint's infringement theory is based on the premise that the commercial manufacture, use, or sale of SB8, as described in the confidential information provided by Defendant, will practice the methods claimed in the patents-in-suit (Compl. ¶7, ¶38, ¶50).

V. Key Claim Terms for Construction

The complaint does not provide sufficient detail to identify specific claim terms that will be in dispute. However, based on the subject matter of the lead patents, practitioners may focus on the following terms:

  • For the ’206 Patent:

    • The Term: "apoptosis inhibitor"
    • Context and Importance: The scope of this term is central to infringement, as it defines the class of agents whose use in a cell culture process is claimed. The dispute may turn on whether a substance used in Defendant's process that has a general cell-preserving effect, but is not primarily classified as an apoptosis inhibitor, falls within the claim's scope.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification may contain general language defining the term functionally, such as any agent that "reduces, inhibits or prevents apoptosis" (’206 Patent, col. 6:5-13), potentially supporting a broad reading.
      • Evidence for a Narrower Interpretation: The patent lists specific examples of apoptosis inhibitors, such as caspase inhibitors and baculovirus p35 protein (’206 Patent, col. 4:3-5, col. 5:29-33). This may support a narrower construction limited to the disclosed classes of agents.

  • For the ’660 Patent:

    • The Term: "cultivating ... in the presence of citric acid or citrate"
    • Context and Importance: This term is critical because infringement depends on whether Defendant's manufacturing process involves "cultivating" cells with the requisite substance. A dispute could arise over whether the incidental presence of citrate as a metabolic intermediate, rather than its addition as a specific supplement to the culture medium, satisfies this limitation.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The plain language "in the presence of" could be argued to cover any situation where citrate is present in the culture medium, regardless of its source or purpose.
      • Evidence for a Narrower Interpretation: The patent describes the invention as involving the "addition" of the bi- or tricarbonic acid to inhibit lactate formation (’660 Patent, col. 2:1-5). This may support an interpretation requiring the active introduction of citrate for the claimed purpose.

VI. Other Allegations

  • Indirect Infringement: For the method-of-treatment patents (e.g., the ’672 and ’355 Patents), the complaint alleges that Defendant will induce infringement under 35 U.S.C. § 271(b). The basis for this allegation is that Defendant has sought FDA approval for a product label that specifies treatment methods which, if followed by doctors and patients, would directly infringe the claims of these patents (Compl. ¶152-153, ¶166-167). The complaint also asserts claims for declaratory judgment of infringement under 35 U.S.C. § 271(g) for each of the process patents, which covers the importation or sale of a product made abroad by a process patented in the U.S. (e.g., Compl. ¶¶42-47).
  • Willful Infringement: For each asserted patent, the complaint alleges that Defendant "has known of the [patent] since Bioepis was founded or has been willfully blind to its existence and contents since then," and that despite this knowledge, it proceeded to file its aBLA (Compl. ¶39, ¶51, ¶63, et al.). This forms the basis for a claim of willful infringement, seeking enhanced damages.

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

  • A central issue will be one of procedural compliance and its consequences: the complaint dedicates significant attention to Defendant's alleged failure to fully participate in the BPCIA's "patent dance." A key question for the court will be to determine if Defendant failed to provide required manufacturing information and, if so, what impact that has on the subsequent litigation, including potential limits on Defendant's non-infringement or invalidity defenses.
  • A primary technical question will be one of process overlap: given the large and diverse portfolio of fourteen asserted patents covering distinct aspects of biomanufacturing—from cell culture media and conditions to purification and final formulation—the case will require a detailed, fact-intensive comparison of Defendant's proprietary process for SB8 against the specific steps claimed in each patent.
  • For the method-of-use patents, a key legal question will be induced infringement: does the product label for which Defendant seeks FDA approval contain instructions that will necessarily lead physicians to practice the patented methods of administering bevacizumab for specific cancer indications, thereby satisfying the legal requirements for inducement?