DCT

2:18-cv-02684

CSL Ltd v. Creative Biolabs Inc

Log In

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 2:18-cv-02684, E.D.N.Y., 05/07/2018
  • Venue Allegations: Plaintiffs allege venue is proper as Defendants are New York corporations that reside in the Eastern District of New York and have a regular and established place of business in the district.
  • Core Dispute: Plaintiff alleges that Defendant’s sale of various research-use antibodies constitutes infringement of five patents covering therapeutic monoclonal antibodies developed by Plaintiff.
  • Technical Context: The technology relates to monoclonal antibodies designed to bind to specific protein targets (such as G-CSFR, VEGF-B, IL-3Rα, and IL-11Rα) to treat diseases including inflammatory conditions and cancers.
  • Key Procedural History: The complaint does not mention any prior litigation, Inter Partes Review (IPR) proceedings, or licensing history related to the patents-in-suit.

Case Timeline

Date Event
2002-05-17 U.S. Patent Nos. 7,517,524 and 8,822,644 Priority Date
2009-04-14 U.S. Patent No. 7,517,524 Issued
2010-08-17 U.S. Patent No. 8,569,461 Priority Date
2013-10-29 U.S. Patent No. 8,569,461 Issued
2014-02-14 U.S. Patent No. 9,340,618 Priority Date
2014-09-02 U.S. Patent No. 8,822,644 Issued
2014-10-02 U.S. Patent No. 9,193,793 Priority Date (Filing Date)
2015-11-24 U.S. Patent No. 9,193,793 Issued
2016-05-17 U.S. Patent No. 9,340,618 Issued
2018-05-07 Complaint Filed

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

U.S. Patent No. 9,193,793 - "Antibodies Against G-CSFR and Uses Thereof"

  • Patent Identification: U.S. Patent No. 9,193,793, titled “Antibodies Against G-CSFR and Uses Thereof,” issued on November 24, 2015 (Compl. ¶19).

The Invention Explained

  • Problem Addressed: The patent addresses conditions mediated by granulocyte-colony stimulating factor (G-CSF), a key regulator of granulocyte production which is induced by inflammatory stimuli (’793 Patent, col. 1:16-24). Modulating the activity of G-CSF is a therapeutic goal for certain inflammatory conditions and cancers where this signaling pathway is active (’793 Patent, col. 1:62-67).
  • The Patented Solution: The invention provides proteins, particularly antibodies, that bind to the G-CSF receptor (G-CSFR) and neutralize the signaling that results from G-CSF binding (’793 Patent, Abstract). By blocking the receptor, these antibodies inhibit the biological activity of G-CSF, offering a way to treat G-CSF-mediated diseases (’793 Patent, Abstract).
  • Technical Importance: This approach provides a targeted biological therapy for modulating the immune response in specific diseases by interrupting the G-CSF signaling pathway at the receptor level.

Key Claims at a Glance

  • The complaint asserts independent claim 1, as well as dependent claims 20 and 21 (Compl. ¶113).
  • Essential elements of independent claim 1 include:
    • A protein comprising an antibody antigen binding site that binds to human G-CSFR and neutralizes G-CSF signaling.
    • The protein competitively inhibits the binding of a reference antibody (C1.2 or C1.2G) to specific mutant forms of G-CSFR.
    • The protein exhibits a lower level of binding to other specified mutant forms of G-CSFR compared to the non-mutated version.
    • The protein comprises a heavy chain variable region (VH) and a light chain variable region (VL) containing specific Complementarity Determining Region (CDR) amino acid sequences or defined variants thereof.

U.S. Patent No. 7,517,524 - "Immunoreactive Molecules"

  • Patent Identification: U.S. Patent No. 7,517,524, titled “Immunoreactive Molecules,” issued on April 14, 2009 (Compl. ¶20).

The Invention Explained

  • Problem Addressed: The patent’s background section identifies pathological angiogenesis (the abnormal growth of new blood vessels) as a key factor in the development of a wide range of diseases, including rheumatoid arthritis and malignant tumors (’524 Patent, col. 1:47-54). The growth factor Vascular Endothelial Growth Factor-B (VEGF-B) is implicated in this process.
  • The Patented Solution: The invention provides antibodies that bind to VEGF-B and inhibit its biological activity (’524 Patent, Abstract). As described in the specification, these antibodies are designed to block the binding of VEGF-B to its receptor, VEGF-R1, thereby inhibiting the signaling that promotes angiogenesis (’524 Patent, col. 2:50-53).
  • Technical Importance: The invention provides a targeted anti-angiogenic therapy, a significant approach for treating cancer and inflammatory diseases, by specifically neutralizing the VEGF-B signaling pathway.

Key Claims at a Glance

  • The complaint asserts independent claim 3 (Compl. ¶118).
  • Essential elements of independent claim 3 include:
    • An isolated chimeric antibody or an antigen-binding fragment thereof that binds to human VEGF-B.
    • The binding of the antibody antagonizes the interaction between human VEGF-B and its receptor, VEGF-R1.
    • The antibody comprises a variable region that is the same as the variable region of a specific deposited monoclonal antibody, 2H10 (ATCC Accession No. PTA-6889).
    • The variable region is fused to a constant region of a human antibody.

U.S. Patent No. 8,822,644 - "Method of Treating Cancer Comprising a VEGF-B Antagonist"

  • Patent Identification: U.S. Patent No. 8,822,644, titled “Method of Treating Cancer Comprising a VEGF-B Antagonist,” issued September 2, 2014 (Compl. ¶21).
  • Technology Synopsis: This patent, related to the ’524 Patent, claims methods for treating cancer by administering an antagonist of VEGF-B, such as a humanized antibody. The technical approach is to inhibit tumor growth by blocking VEGF-B-mediated angiogenesis (’644 Patent, Abstract).
  • Asserted Claims: Claim 1 (Compl. ¶123).
  • Accused Features: The accused products TAB-660CL and AFC-634CL, which Defendants allegedly identify as CSL’s anti-VEGF-B antibody CSL346 (Compl. ¶66, ¶71-72).

U.S. Patent No. 8,569,461 - "Humanized Anti-Interleukin 3 Receptor Alpha Chain Antibodies"

  • Patent Identification: U.S. Patent No. 8,569,461, titled “Humanized Anti-Interleukin 3 Receptor Alpha Chain Antibodies,” issued October 29, 2013 (Compl. ¶22).
  • Technology Synopsis: The patent discloses humanized antibodies that specifically bind to the interleukin-3 receptor alpha chain (IL-3Rα), also known as CD123. IL-3Rα is expressed on certain cancer cells, such as those in acute myeloid leukemia (AML), making it a target for antibody-based cancer therapies (’461 Patent, Abstract; Compl. ¶78).
  • Asserted Claims: Claim 1 (Compl. ¶128).
  • Accused Features: The accused products PABZ-159, PABL-617, and related antibody fragments, which Defendants allegedly identify as CSL’s anti-IL-3Rα antibody CSL362 (Compl. ¶88, ¶92-93).

U.S. Patent No. 9,340,618 - "IL-11R Binding Proteins"

  • Patent Identification: U.S. Patent No. 9,340,618, titled “IL-11R Binding Proteins,” issued May 17, 2016 (Compl. ¶23).
  • Technology Synopsis: The patent describes proteins, including antibodies, that bind to the human interleukin-11 receptor α (IL-11Rα). This technology is aimed at treating diseases such as gastric and colon cancers where IL-11 signaling is implicated (’618 Patent, Abstract; Compl. ¶100).
  • Asserted Claims: Claims 1 and 5 (Compl. ¶133).
  • Accused Features: The accused antibody TAB-062ZJ and its fragments, which Defendants allegedly identify as CSL's 8E2 product (Compl. ¶102, ¶108).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentalities are multiple antibodies and antibody fragments offered for sale by Defendants for research use on their website, www.creativebiolabs.net (Compl. ¶48, ¶66, ¶80, ¶102). These include products identified by catalog numbers such as TAB-190CL, TAB-191CL, TAB-660CL, PABZ-159, and TAB-062ZJ, among others (Compl. ¶48, ¶66, ¶88, ¶102).

Functionality and Market Context

  • The complaint alleges that Defendants manufacture and sell "blatant knock-offs" of CSL's patented therapeutic antibodies (Compl. ¶1). The infringement theory is based on allegations that Defendants use information from CSL's publicly available patents and scientific papers to create these products (Compl. ¶35, ¶49). Further, Defendants are alleged to promote these products using CSL’s internal development designations (e.g., “CSL324,” “CSL346”), thereby representing that the accused products have the same properties as CSL's patented antibodies (Compl. ¶55, ¶57, ¶72, ¶74). For one accused product (TAB-191CL), the complaint alleges that direct laboratory testing confirmed that its key amino acid sequences are identical to those of CSL's corresponding patented antibody (Compl. ¶61).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

U.S. Patent No. 9,193,793 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A protein comprising an antigen binding site of an antibody that (i) binds to human G-CSFR, [and] (ii) neutralizes G-CSF signaling… Defendants’ product information for TAB-190CL, TAB-191CL, and AFC-180CL allegedly describes them as fully human antibodies that bind to G-CSFR and neutralize the activity of G-CSF. ¶53 col. 1:16-24
...and wherein the protein comprises a VH ... and a VL... [reciting specific CDR sequences] For TAB-191CL, CSL alleges direct testing revealed key amino acid sequences identical to those of CSL's patented CSL324 antibody. For the other products, infringement is alleged based on Defendants' use of the "CSL324" identifier, which allegedly represents that they have the same binding site and properties. ¶57, ¶61, ¶62 col. 27:3-67

U.S. Patent No. 7,517,524 Infringement Allegations

Claim Element (from Independent Claim 3) Alleged Infringing Functionality Complaint Citation Patent Citation
An isolated chimeric antibody or an antigen-binding fragment thereof which binds to human VEGF-B, and the binding...antagonizes binding between human VEGF-B and VEGF-R1 Defendants allegedly identify the accused products (TAB-660CL and AFC-634CL) as humanized monoclonal antibodies that bind to and antagonize human VEGF-B. ¶71 col. 2:50-53
wherein said antibody comprises a variable region that is the same as the variable region of monoclonal antibody 2H10 produced by the hybridoma deposited at the American Type Culture Collection (ATCC) as PTA-6889... The complaint alleges that by expressly identifying the accused products as "CSL346," Defendants are representing they have the same properties as CSL's antibody, which is the humanized form of 2H10. ¶72, ¶74, ¶75 col. 12:45-48

Identified Points of Contention

  • Evidentiary Questions: For most of the accused products, the complaint's infringement theory relies on Defendants' own product descriptions and their use of CSL's internal product codes (e.g., "CSL324"). A primary point of contention may be whether this circumstantial evidence is sufficient to prove that the accused products meet the specific structural and functional limitations of the patent claims, or if direct physical evidence (e.g., amino acid sequencing) for each product will be required. The allegation of direct testing for one product (TAB-191CL) suggests a different evidentiary basis for that specific product (Compl. ¶61).
  • Scope Questions: The case raises the question of whether research-grade antibodies, as sold by Defendants, practice the claims of patents directed to therapeutic compositions and methods. The analysis will likely focus on whether the accused products perform the claimed functions (e.g., "neutralizes...signaling") in the manner required by the claims, irrespective of their intended market.

V. Key Claim Terms for Construction

  • The Term: "neutralizes...signaling" (’793 Patent, Claim 1)

  • Context and Importance: This functional limitation is central to the infringement allegation for the '793 patent. Practitioners may focus on this term because the degree of neutralization required is not quantified in the claim. The dispute may center on whether the accused research-grade antibodies perform this function to the extent required to infringe, and what the proper standard for measuring "neutralization" is.

    • Intrinsic Evidence for a Broader Interpretation: The patent abstract describes the invention as proteins that "neutralize G-CSF signaling," suggesting a general functional definition.
    • Intrinsic Evidence for a Narrower Interpretation: The specification provides detailed examples of assays used to measure the activity of its exemplary antibodies (’793 Patent, FIG. 1; col. 45:20-46:50). A party could argue that "neutralizes" should be construed in light of the specific levels of activity and methodologies disclosed in these embodiments.

  • The Term: "is the humanized form of antibody 2H10" (’524 Patent, Claim 3)

  • Context and Importance: This language appears to define the claimed antibody by reference to a specific biological material (the 2H10 antibody from a deposited hybridoma) and a process ("humanized form"). The construction of this term is critical because it defines the precise identity of the infringing article.

    • Intrinsic Evidence for a Broader Interpretation: A party might argue the term should be construed functionally to cover any humanized antibody that retains the key binding properties of the original 2H10 antibody, regardless of the specific humanization technique used.
    • Intrinsic Evidence for a Narrower Interpretation: The use of the definitive article "the" may support a narrow construction limited to a specific humanized version of 2H10, potentially the one described in the patent's own examples. The patent refers to the deposited hybridoma (ATCC No. PTA-6889), which provides a definitive reference point for the source antibody (’524 Patent, Claim 3).

VI. Other Allegations

  • Willful Infringement: The complaint alleges that Defendants' infringement has been and continues to be willful for all five asserted patents (Compl. ¶¶ 116, 121, 126, 131, 136). The basis for this allegation appears to be the theory that Defendants intentionally copied Plaintiff's technology, described as using "pirated" information from CSL's patent disclosures to manufacture "knock-off" products (Compl. ¶1, ¶35, ¶49).

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

  • A core issue will be one of evidentiary sufficiency: Can infringement be proven for antibodies that have not been physically tested by the Plaintiff, based on allegations that the Defendant marketed them using the Plaintiff's own internal product codes and copied technical descriptions? This raises the question of whether a defendant's representations about a product can serve as an admission that it meets the technical limitations of a patent claim.
  • A key legal and technical question will be one of product identity: The dispute may turn on whether research-use antibodies, sold as laboratory reagents, meet the specific structural and functional requirements of claims directed to therapeutic antibodies. This involves determining not only if the accused products share key amino acid sequences, but also whether they perform the claimed biological functions (e.g., "neutralizes signaling") in the manner and to the extent required by the patent claims.