United States: Invalidity Of A Patent Claiming Antibodies Characterized By Their Function In View Of Amgen

Baxalta Inc. and Baxalta GmbH (Baxalta) appealed a district court decision that the claims of U.S. Patent No. 7,033,590 were invalid for lack of enablement. The Federal Circuit (the Court) affirmed the decision.

The '590 patent intended to provide alternative means to treat Hemophilia A in patients who develop Factor VIII inhibitors. Factor VIII plays a key role in the coagulation cascade and formation of blood clots. Activated Factor VIIIa complexes with activated Factor IX (Factor IXa) to activate Factor X. Antibodies in the '590 patent bind to Factor IX/IXa to increase the procoagulant activity of Factor IXa, and to allow Factor IXa to activate Factor X in the absence of Factor VIII/VIIIa. Representative claim 1 reads:

The inventors discovered that only 1.6% of the thousands of screened antibodies increased the procoagulant activity of Factor IXa. The '590 patent discloses the amino acid sequences of eleven antibodies that bind to Factor IX/IXa and increase the procoagulant activity of Factor IXa. The disclosed antibodies are all monospecific (bind to a single antigen) and monoclonal (produced by a single cell line). The'590 patent explains that a skilled artisan may use well-known antibody engineering techniques to transform the resulting antibody into different structural formats. For example, scientists can create "bispecific antibodies" in which, unlike monospecific antibodies, each arm binds to a different antigen, can create "humanized antibodies" in which animal CDRs are inserted into an otherwise human antibody.

Baxalta sued Genentech, Inc. alleging Genentech's Hemlibra® (emicizumab) product infringes the '590 patent. Emicizumab is a humanized bispecific antibody that binds to Factor IXa with one arm and Factor X with the other arm, thereby mimicking the function of Factor VIIIa. Previously, the Court held that the proper construction of "antibody" was an immunoglobulin molecule having a specific amino acid sequence comprising two heavy (H) chains and two light (L) chains, and the proper construction of "antibody fragment" was a portion of an antibody. The Court vacated the judgment of non-infringement and remanded for further proceedings on a prior appeal, because the district court's construction erroneously excluded bispecific antibodies. On remand, Genentech moved for summary judgment of invalidity of claims 1–4, 19, and 20 for lack of enablement. The district court granted summary judgment.

On appeal, Baxalta argued that a skilled artisans could obtain the full scope of claimed antibodies without undue experimentation by making and identifying new claimed antibodies using the routine hybridoma-and-screening process disclosed in the '590 patent and that such routine screening does not amount to undue experimentation. In light of the Supreme Court's decision in Amgen v. Sanofi, 598 U.S. 594 (2023), the Court disagreed.

The Court found that the facts of this case were materially indistinguishable from those in Amgen. Claim 1 of the '590 patent covers all antibodies that bind to Factor IX/IXa and increase the procoagulant activity of Factor IXa. There are millions of potential candidate antibodies, but the written description discloses the amino acid sequences for only eleven antibodies with the two claimed functions. The Court explained that "to obtain the undisclosed but claimed antibodies, the written description directs skilled artisans to: (1) immunize mice with human Factor IX/IXa; (2) form hybridomas from the antibody-secreting spleen cells of those mice; (3) test those antibodies to determine whether they bind to Factor IX/IXa; and (4) test those antibodies that bind to Factor IX/IXa to determine whether any increase procoagulant activity." The Court concluded that "[j]ust like the roadmap rejected by the Supreme Court in Amgen, the '590 patent's roadmap simply directs skilled artisans to engage in the same iterative, trial-and error process the inventors followed to discover the eleven antibodies they elected to disclose." "In both cases, 'nothing in the specification [teaches] how to identify any antibodies complying with the claim limitations other than by repeating the same process the inventors used to identify the . . . examples disclosed in the specification.'"

The Court agreed that the '590 patent contained no disclosures of "a quality common to every functional embodiment" and that there was no disclosure a common structural or other feature "delineating which antibodies will bind to Factor IX/IXa and increase procoagulant activity from those that will not that would allow a skilled artisan to predict which antibodies will perform the claimed functions." The patent does not explain why the eleven disclosed antibodies perform the claimed functions, or why the other screened antibodies do not. The Court noted that "[t]he only guidance the patent provides is 'to create a wide range of candidate antibodies and then screen each to see which happen to bind' to Factor IX/IXa and increase procoagulant activity." Referring again to Amgen, the Court concluded that it was clear "that such an instruction, without more, is not enough to enable the broad functional genus claims at issue here."

Baxalta argued the hybridoma-and-screening process disclosed in the '590 patent did not require trial and error but "instead predictably and reliably generates new claimed antibodies every time it is performed." The Court replied that "this does not take the process out of the realm of the trial-and-error approaches rejected in Amgen." Making candidate antibodies and screen them to determine which ones perform the claimed functions is "the definition of trial and error." The Court referred to Amgen and explained again "such random trial-and-error discovery, without more, constitutes unreasonable experimentation that falls outside the bounds required by § 112(a)." The Court also rejected Baxalta's argument that the district court's enablement determination was inconsistent with In re Wands, 858 F.2d 731 (Fed. Cir. 1988) and pointed out that "[w]e have previously explained the factual distinction between Wands and Amgen." Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080, 1085–86 (Fed. Cir. 2021). The Court held that the '590 patent failed to teach skilled artisans how to make and use the full scope of claimed antibodies without unreasonable experimentation, and affirmed the district court's grant of summary judgment that claims 1–4, 19, and 20 are not enabled.

22-1461.OPINION.9-20-2023_2193254.pdf (uscourts.gov)

Baxalta Inc. v. Genentech, Inc., No. 22-1461, — F.4th — (Fed. Cir. Sept. 20, 2023).

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