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District of Delaware Finds Use of Antibody Tech Protected by Safe Harbor

Fish & Richardson

Authors

The U.S. District Court for the District of Delaware recently granted defendant Xencor’s motion to dismiss an infringement suit, holding that the accused use of plaintiff Merus N.V.’s patented antibody technology was protected by the Hatch-Waxman safe harbor.1

Statutory background

The safe harbor provision, 35 U.S.C. § 271(e)(1), was enacted as part of the Hatch-Waxman Act. In relevant part, it provides:

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention . . . solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.2

Factual background

Merus is the holder of three U.S. patents: No. 9,944,965, covering a method of making an antibody using a transgenic mammal; No. 9,358,286, covering a method of making multispecific antibodies, or antibodies that bind to two or more different antigen receptors; and No. 11,926,859, covering a method of making antibodies.3

Merus asserted that its ʼ695 patent covered its Merus Mouse, a mouse that has human genes allowing it to create new, multispecific antibodies targeting tumor cells.4 It alleged that Xencor infringes the ʼ695 patent by:

  • “obtaining [multispecific] antibodies that bind to an antigen”
  • “collaborating with a third-party ‘to obtain and/or use’ a product called the ‘RenLite mouse’ as a ‘platform for bispecific antibody discovery’”
  • “immunizing the ‘RenLite mice with antigens’ to obtain ‘B cells that produce antibodies specific to those antigens’”
  • “incorporating the third party’s process ‘to create and obtain antigen-specific antibodies’” and
  • “making ‘multispecific antibodies that bind to’ cancerous proteins, as disclosed in Xencor’s patent application number U.S. 2023/0383012”5

Merus asserted that the ʼ286 and ʼ859 patents cover its own Zeno and Peto antibodies and their method of manufacture. It alleged that Xencor infringes these patents by:

  • “making ‘stable bispecific antibodies’ by Xencor’s ‘XmAb bispecific platform,’ which is a set of methods to create antibodies with specific properties in a protein structure known as the Fc domain”
  • “changing the charge of two amino acids from neutral to one positive charge and one negative charge to ‘drive preferential pairing’ and ‘create stable bispecific antibodies’” and
  • “generating ‘early discovery,’ ‘preclinical,’ and ‘clinical . . . multispecific antibodies.’”6

Merus asserted that Xencor infringes “long before any antibody is selected as a possible candidate for regulatory review or approval.”7

The district court’s decision

The court noted that § 271(e)(1) has two statutory requirements: “(1) mandatory premarket approval of the accused infringer’s product by a specific regulator and (2) a reasonable relationship between the allegedly infringing use and that regulatory end.”8 The court referred to these requirements as an “ends” and a “means” test.9

The court’s recitation and application of the “ends” test

Judge Campbell Barker, sitting by designation, began his analysis by noting that the “ends” test was derived from the Supreme Court’s decision in Eli Lilly & Co. v. Medtronic.10 There, the Court interpreted § 271(e)(1)’s language of “the development and submission of information under” and “a Federal law which regulates.”11 Judge Campbell Barker noted that these two phrases constrain the “uses [that] are eligible for immunity,” whereas § 271(e)(1)’s “reasonably related to” language, which constrains “the means used, or how those uses objectively relate to obtaining federal regulatory premarket approval.”12 In Eli Lilly, the Supreme Court held that the language “of the development and submission of information under” a federal law means that the law must have a “‘requirement for premarket approval.’”13

Merus disputed that Xencor’s alleged infringing conduct of the ʼ695 patent met the “ends” test for safe harbor immunity.14 In its briefing, Merus argued that Xencor’s “infringing use of the RenLite mouse is akin to use of a research tool like a cell line,” and research tools are not eligible for safe harbor protection.15 The court disagreed.16 All of Merus’s allegations regarding infringement of the ʼ695 patent include producing or obtaining antigen-specific antibodies.17 Those antigen-specific antibodies are subject to premarket Food and Drug Administration (FDA) approval and, therefore, subject to protection under the safe harbor.18 If Xencor’s activity were “mere general research,” however, and the defendant did not obtain an antibody, then Xencor’s activities would be non-infringing.19 To infringe the ʼ695 patent, the court found that Xencor must have used a specific antigen.20 “Such a method to obtain an antigen-specific antibody is not a mere research tool. It is the kind of trial-and-error that falls within the safe harbor.”21

Merus also disputed that Xencor’s alleged infringement of the ʼ286 and ʼ859 patents was protected under the safe harbor.22 For substantially the same reasons, the court found that the allegedly infringing activities met the “ends” test. Either Xencor “must harvest, possess, or create a multispecific antibody to infringe” or, if it does not, “it is not infringing in the first place.”23 Under the court’s ruling, as long as the research is designed to produce a product subject to regulatory approval, the “ends” test is satisfied.24

The court’s recitation and application of the “means” test

The “means test” relates to the safe harbor’s requirement that the use of a patented invention be “reasonably related to” the development and submission of data for premarket approval.25 The district court identified the Federal Circuit tests — first, look objectively at the accused infringer’s use and assess whether that use creates data appropriate for FDA submission.26 If so, the use is “reasonably related” to FDA approval.27 Second, a “patented method can be reasonably related to developing information to gain regulatory approval of a product.”28

The court found that “[j]udging solely from the face of the complaint, the accused infringement meets the means test for § 271(e)(1) infringement immunity” because “[i]t is ‘reasonably related’ as a matter of law to developing data for FDA premarket approval of [the] defendant’s antibodies.”29

As with the “ends” test, in order to infringe the ʼ695 patent, Xencor must have immunized a transgenic mouse to obtain an antigen-specific antibody.30 Relying on the Supreme Court’s decision in Merck, the district court found that Xencor allegedly infringed with “‘the intent to develop a particular drug’ or with ‘a reasonable belief that the compound will cause the physiological effect the researcher intends to induce.’”31 That makes Xencor’s conduct “reasonably related” to FDA approval.32

Merus argued that Xencor’s alleged infringement was actually earlier than the “basic scientific research on a particular [antibody] that [Merck] excludes.”33 But that argument failed when considering that the claims of the ʼ695 patent required development of an antigen-specific antibody.34 Thus, either Xencor used the antibody and was subject to safe harbor protection because its antibody work was “reasonably related” to premarket FDA approval, or Xencor did not use the antibody and therefore did not infringe.35

The court found that Merus’ reliance on two decisions denying a motion to dismiss under the safe harbor, REGENXBIO v. Sareptaxxxvi and BlueAllele Corp. v. Intellia Therapeutics,37 was misplaced. REGENXBIO involved “cultured host cells” that did not require premarket approval; Xencor’s antibodies did.38 In BlueAllele, the defendant used gene editing technology for “basic research,” which distinguished the case from Xencor.39

The court also found Merus’s reliance on Isis Pharmaceuticals, Inc. v. Santaris Pharma A/S Corp.40 was unpersuasive.41 In Isis, the alleged infringement occurred before a “therapeutic target” was identified.42 In contrast, the claims of the asserted patents were antigen-specific and, thus, already identified a therapeutic target.43 Again, the court reiterated that if Xencor were infringing, it would have sought to develop an antibody with a therapeutic target and, thus, would be protected under the safe harbor.44

Like the ʼ695 patent, the court found that to infringe the ʼ286 and ʼ859 patents, Xencor must have created an antigen-specific antibody.45 It continued to discuss the safe harbor implications.46 Quoting the Merck decision again, the court noted, “when an accused infringer ‘has a reasonable basis for believing that a patented compound may work, through a particular biological process, to produce a particular physiological effect, and uses the compound in research that, if successful, would be appropriate to include in a submission to the FDA, that use is reasonably related.”47

Takeaways

While the district court granted Xencor’s motion to dismiss, the court permitted Merus leave to amend the complaint.48 It will be interesting to see what, if any, allegedly infringing conduct Merus can identify that would be outside the scope of the safe harbor given the specificity of its asserted claims.

The court’s ruling on the so-called “ends” test is consistent with earlier decisions. As to the “means” test, however, the court possibly adopts a rather expansive view. Although the exact phase of Xencor’s challenged research is not provided, it would seem that, as long as the accused conduct generates data appropriate for FDA submission, the safe harbor applies. It is possible that such data could be developed early in a research project when numerous potential candidates are being evaluated generally, even during “basic research,” which, of course, is not protected.

  1. Merus N.V. v. Xencor, Inc., No. 1:24-cv-00913, 2025 U.S. Dist. LEXIS 195929, at *1 (D. Del. Sept. 30, 2025). (hereinafter, “Merus”). 

  2. 35 U.S.C. § 271(e)(1) (emphasis added). 

  3. Merus, at *11. 

  4. Id. at *12.

  5. Id. at *13 (citations omitted).

  6. Id. at *15.

  7. Id.

  8. Merus, at *4.

  9. Id. at *4.

  10. 496 U.S. 661, 669-70 (1990).

  11. Merus, at *4-*5.

  12. Id. at *5.

  13. Id. (citing Eli Lilly, 496 U.S. at 674 n.6).

  14. Id. at *17.

  15. Merus N.V. v. Xencor, No. 24-913, D.I. 20 at 20 (D. Del. Oct. 31, 2024) (citing, inter alia, Integra Lifesciences I, Ltd. v. Merck KGaA, 496 F.3d 1334, 1347, n.3 (Fed. Cir. 2007)).

  16. Merus at *18. 

  17. Id.

  18. Id.

  19. Id.

  20. Id.

  21. Id. (citing Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005)).

  22. Id. at *19.

  23. Id.

  24. Id. at *18-*19.

  25. Id. at *8.

  26. Id. at *9.

  27. Id. (citing Abtox, Inc. v. Exitron Corp., 122 F.3d 1019, 1029 (Fed. Cir. 1997)). 

  28. Id. at *9-*10 (citing Amgen v. Hospira, Inc., 944 F.3d 1327, 1338-39 (Fed. Cir. 2019)) (emphasis in original).

  29. Id. at *20.

  30. Id.

  31. Id. at *21 (quoting Merck, 545 U.S. at 205-06) (emphasis in original).

  32. Id. 

  33. Id. 

  34. Id. 

  35. Id. 

  36. No. 1:20-cv-01226, 2022 U.S. Dist. LEXIS 1945 (D. Del. Jan. 4, 2022). For an in-depth discussion of the REGENXBIO decision, please see Kelly Allenspach Del Dotto’s and Brian Coggio’s blog post, “REGENXBIO v. SAREPTA: Make Sure You’re Safely Within the Safe Harbor Before Using a ‘Research Tool,’” available at REGENXBIO v. SAREPTA: Make Sure You're Safely Within the Safe Harbor Before Using a "Research Tool". 

  37. No. 1:24-cv-00791, U.S. Dist. LEXIS 222094 (D. Del. Dec. 9, 2024). For an in-depth discussion of the BlueAllele decision, please see Kelly Allenspach Del Dotto’s and Brian Coggio’s blog post, “The Not-So-Safe Harbor for Research Tools: Lessons Learned From the District of Delaware,” available at The Not-So-Safe Harbor for Research Tools: Lessons From the District of Delaware.

  38. Merus, at *22.

  39. Id.

  40. No. 3:11-cv-02214, 2012 U.S. Dist. LEXIS 134107 (S.D. Cal. Sept. 19, 2012).

  41. Merus, at *26.

  42. Id.

  43. Id.

  44. Id.

  45. Id. at *24.

  46. Id.

  47. Id. (citing Merck, 545 U.S. at 207).

  48. Id. at *27.

The opinions expressed are those of the authors on the date noted above and do not necessarily reflect the views of Fish & Richardson P.C., any other of its lawyers, its clients, or any of its or their respective affiliates. This post is for general information purposes only and is not intended to be and should not be taken as legal advice. No attorney-client relationship is formed.