Immunogen, Inc. v. Stewart, decided March 6, 2025

Case Name and Citation: IMMUNOGEN, INC. v. COKE MORGAN STEWART, ACTING UNDER SECRETARY OF COMMERCE FOR INTELLECTUAL PROPERTY AND ACTING DIRECTOR OF THE UNITED STATES PATENT AND TRADEMARK OFFICE, No. 2023-1762 (Fed. Cir. March 6, 2025)

Court: United States Court of Appeals for the Federal Circuit

Lower Court: United States District Court for the Eastern District of Virginia (No. 1:20-cv-00274-TSE-LRV)

Judges: LOURIE, DYK, and PROST (Opinion by LOURIE, Circuit Judge)

Issue: Did the district court err in finding that the claims of U.S. Patent Application 14/509,809 ("the '809 application") directed to a dosing regimen for administering IMGN853 are unpatentable for indefiniteness and obviousness?

Holding: The Federal Circuit affirmed the district court's judgment denying ImmunoGen's claim for entitlement to a patent, finding that the claims are unpatentable based on obviousness. The court did not address the issue of indefiniteness.

Background:

• The '809 application, with a priority date of October 8, 2013, claims a method for treating FOLR1-expressing ovarian or peritoneal cancer by administering an immunoconjugate (IMGN853 or mirvetuximab soravtansine) at a dose of 6 milligrams (mg) per kilogram (kg) of adjusted ideal body weight (AIBW) of the patient.

• IMGN853 is an antibody-drug conjugate (ADC) consisting of the antibody "huMov19," the toxic maytansinoid payload "DM4," and a "charged sulfo-SPDB linker."

• The application acknowledged that while IMGN853 showed promise, it could cause ocular toxicity in humans. The claimed invention aimed to develop "a therapeutically effective dosing regimen [of IMGN853] that results in minimal adverse effects." ('809 application, J.A. 209).

• Claim 1 is representative and specifies the antibody components and the "dosing limitation" of 6 mg/kg of AIBW.

• It was undisputed that "a method of using IMGN853 to treat FOLR1-expressing ovarian cancer or peritoneum cancer was known in the art" at the time of the invention (J.A. 12176, ¶ 34). Thus, patentability hinged on the dosing limitation.

• The Patent Examiner and the Patent Trial and Appeal Board (PTAB) rejected the claims. ImmunoGen then sued in district court under 35 U.S.C. § 145.

• The district court initially granted summary judgment for the government, finding the claims indefinite, obvious, and unpatentable for obviousness-type double patenting. The Federal Circuit vacated and remanded ("ImmunoGen II") due to the district court resolving factual disputes against ImmunoGen.

• Following a bench trial, the district court again ruled in favor of the government, finding the claims "fatally indefinite and obvious" and unpatentable for obviousness-type double patenting. The indefiniteness finding was based on the '809 application's failure to define AIBW in the claims, while the intrinsic and extrinsic evidence showed various formulas for AIBW. The obviousness finding was based on ImmunoGen's prior art disclosing IMGN853 treatment using total body weight (TBW) dosing and other art disclosing AIBW dosing for other compounds.

• The parties agreed on appeal that the obviousness-type double patenting issue rises and falls with the issue of obviousness.
  

Federal Circuit Analysis:

The Federal Circuit reviewed the district court's obviousness determination, treating it as a question of law reviewed de novo, with underlying factual findings reviewed for clear error.

I. Motivation to Combine:

• ImmunoGen argued that the district court erred in its motivation-to-combine analysis because it was undisputed that at the time of invention, the ocular toxicity of IMGN853 in humans was unknown. Therefore, there was no motivation to solve this problem with the claimed dosing limitation.

• The Federal Circuit disagreed, citing KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 419 (2007), which established that "neither the particular motivation nor the avowed purpose of the patentee controls. What matters is the objective reach of the claim."

• The court emphasized that "any need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed." (KSR, 550 U.S. at 420).

• Even though the specific ocular toxicity of IMGN853 was unknown, the district court found, with no clear error, that "ocular toxicity was 'a well-known adverse event in the administration of immunoconjugates that contain as a toxic payload the maytansinoid known as DM4,'" (Decision, 653 F. Supp. 3d at 268), which IMGN853 includes. Thus, a person of ordinary skill in the art would have been motivated to monitor for and address potential ocular toxicity.

• The district court also found it obvious "to experiment with changing the dosing methodology to reduce toxicity while preserving the therapeutic effects" (Decision, 653 F. Supp. 3d at 278) because drug toxicities are often dose-related. The prior art also disclosed AIBW as a known dosing methodology for both large and small anticancer drugs and its use in reducing ocular toxicity for other drugs. The court concluded that a skilled artisan would have understood AIBW as a "potential solution for ocular toxicity" (Decision, 653 F. Supp. 3d at 294).
  

II. Reasonable Expectation of Success:

• ImmunoGen argued that it would not have been obvious to try AIBW dosing because no ADC had been dosed using AIBW before, and the district court failed to explain the motivation for selecting this particular methodology.

• The Federal Circuit rejected this, stating that the district court's findings reasonably supported the conclusion that AIBW dosing would have been within the knowledge of a skilled artisan when faced with dosing-induced toxicities, especially ocular toxicity.

• The court highlighted ImmunoGen's own prior art publication, U.S. Patent Application Publication 2012/0282282 ("Lutz '282"), which disclosed IMGN853 and the link between the DM4 payload and ocular toxicity. Lutz '282 also stated that "[t]he dosing regimen and dosages of [the disclosed ADCs] will depend on the particular cancer being treated... and can be determined by the physician" (Lutz '282, ¶ 252).

• ImmunoGen further argued that the district court did not find a reasonable expectation of success that a 6 mg/kg AIBW dose would solve ocular toxicity, which they claimed was unpredictable.

• The Federal Circuit clarified that the reasonable expectation of success must be tied to the scope of the claimed invention, which is the effective treatment of ovarian and peritoneal cancers. The obviousness inquiry is generally agnostic to the inventor's specific motivation (solving ocular toxicity in this case).

• The district court found that Lutz '282 disclosed dosing IMGN853 at around 6 mg/kg of TBW, and a 2013 abstract disclosed testing at 5 mg/kg TBW. Given the known AIBW dosing, the district court concluded a skilled artisan "would start with doses of around 5 mg/kg or 6 mg/kg AIBW and then determine the precise dose based on routine optimization" (Decision, 653 F. Supp. 3d at 297).

• Crucially, the court noted that "for patients who weigh exactly their ideal body weight, a dose of 6 mg/kg AIBW is identical to a dose of 6 mg/kg TBW," which was expressly disclosed as suitable in Lutz '282 (Decision, 653 F. Supp. 3d at 297). Thus, the '809 application "in effect seeks to cover a dose that was already disclosed in the prior art" (Decision, 653 F. Supp. 3d at 297).

• The Federal Circuit agreed with the district court that preventing the patent would not hinder doctors from practicing what was already disclosed in the prior art for patients at their ideal body weight. "A doctor dosing a patient at his or her IBW with IMGN853 at a dose of 6 mg/kg TBW would necessarily be dosing that patient at 6 mg/kg AIBW, as claimed" (emphasis added).

• Furthermore, Lutz '282 taught "method[s] to overcome ocular toxicity of DM4-containing antibody drug conjugates at a range of dosages," including 6 mg/kg TBW (Lutz '282, ¶ 272), further supporting a reasonable expectation of success in dosing IMGN853 at 6 mg/kg AIBW, at least for patients at their IBW.
  

Conclusion:

The Federal Circuit found no clear error in the district court's determination that the claims of the '809 application would have been obvious. The prior art disclosed the use of IMGN853 for the claimed cancers at similar TBW dosages, and AIBW was a known dosing methodology. For patients at their ideal body weight, the claimed AIBW dose was equivalent to a disclosed TBW dose. Therefore, the claims were deemed unpatentable due to obviousness. The court did not need to address the indefiniteness argument.