United States: Baxalta's Antibody Patent Held Invalid Under Amgen's Enablement Standard By The Federal Circuit

In Baxalta, Inc. v. Genentech, Inc., the Court of Appeals for the Federal Circuit upheld a summary judgment finding from the District of Delaware (Judge Timothy B. Dyk) that claims 1-4, 19 and 20 of Baxalta's patent directed to Factor IX were invalid for lack of enablement based on the Supreme Court's finding in Amgen v Sanofi.¹ Further the Federal Circuit noted the Wands Factors, which the Supreme Court did not specifically address in its Amgen opinion, should still be considered for enablement: "We do not interpret Amgen to have disturbed our prior enablement case law, including Wands and its factors."²

BACKGROUND

Earlier this year, the Supreme Court of the United States ("SCOTUS") held that several claims in Amgen's patents directed to a class of antibodies were invalid for lack of enablement.³ SCOTUS explained that Amgen's claims sweep much broader than the 26 exemplary antibodies it identified by their amino acid sequences, and determined that Amgen failed to enable the millions of antibodies claimed having a particular function.

In Amgen, the patents claimed all antibodies that (1) bind to specific amino acid residues on a protein known as PCSK9, and (2) prevent PCSK9 from binding to low density lipopolysaccharide ("LDL") receptors.⁴ To make and use the claimed antibodies, Amgen's patents provided two roadmaps that parallel Amgen's discovery of the 26 exemplified antibodies. This roadmap was characterized by SCOTUS as "'painstaking experimentation' to see what works."⁵ SCOTUS further elaborated that "this is not enablement."⁶

However, SCOTUS acknowledged that a roadmap might be sufficient to enable the claims if the patent disclosed "a quality common to every functional embodiment."⁷ In other words, if the specification provides example(s) of "some general quality . . . running through" the class that gives the class a "peculiar fitness for the particular purpose."⁸ One interpretation is if the specification taught that an antibody's function can be activated, in all instances, by replacing a specific amino acid with another specific amino acid, then the identification of those amino acids could satisfy the enablement requirement.

In Baxalta, the Federal Circuit held Baxalta's patent invalid for similar reasons as in Amgen. Baxalta is the assignee⁹ of U.S. Patent No. 7,033,590 ("the '590 patent"), which is directed to an isolated antibody, or fragment thereof, which binds Factor IX or IXa and increases procoagulation activity of Factor IXa.¹⁰ Claim 1 is representative and reads:

1. An isolated antibody or antibody fragment thereof that binds Factor IX or Factor IXa and increases the procoagulation of activity of Factor IXa.

Baxalta sued Genentech alleging that Genentech's Hemlibra® (emicizumab) product infringes the '580 patent.¹¹ Emicizumab is a bispecific antibody meaning that each of the two antibody arms bind to a different antigen.

Originally, Judge Dyk narrowly construed the genera of "antibody"¹² and "antibody fragment"¹³ of claim 1 to exclude the species of bispecific antibodies that are listed in claim 4, which is dependent on claim 1. Based on this claim construction and the parties' stipulation to non-infringement.¹⁴ Baxalta appealed the claim construction ruling and the Federal Circuit construed the terms for "antibody" and "antibody fragment" sufficiently broad such that the court vacated the judgment of non-infringement and remanded to the district court for further proceedings.¹⁵

On remand, Genentech moved for summary judgment of, inter alia, invalidity of claims 1-4, 19, and 20 for lack of enablement, and the district court granted summary judgment.¹⁶

FEDERAL CIRCUIT OPINION

Baxalta appealed the district court's summary judgment decision on grounds that a person of ordinary skill on the art ("POSA") can obtain the full scope of the claimed antibodies without undue experimentation.¹⁷ Specifically, Baxalta argued a POSA can make and identify the 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.¹⁸

Regarding undue experimentation, the Court stated they did not interpret Amgen to have disturbed the prior enablement case law, including Wands¹⁹ and its factors.²⁰

Regardless, the Court stated that the facts in Baxalta are "materially indistinguishable" from those in Amgen.²¹ Claim 1 of the '590 patent covers millions of antibodies that (1) bind to Factor IX/IXa, and (2) increase the procoagulation activity of Factor IXa, but the specification discloses only eleven antibodies that perform the recited functions.²² The roadmap provided in Baxalta to identify the antibodies is similar to the roadmap in Amgen, which was rejected by the SCOTUS.²³ According to the Court, the '590 patent roadmap "simply directs skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the eleven antibodies."²⁴

Moreover, the Court examined whether there were any structural features in common with the disclosed antibodies that could allow a POSA to predict which antibodies will perform the claimed functions. But the '590 patent specification did not distinguish which antibodies would bind, or even why the eleven antibodies did bind to Factor IX/IXa and why they increased procoagulation activity.²⁵

Although Baxalta argued one of the roadmaps, called the hybridoma-and-screening processes, disclosed in the '590 patent generates the claimed antibodies each time the process is performed, the Court determined that the roadmap results in trial-and-error because it "leaves the public no better equipped to make and use the claimed antibodies than the inventors were when they set out to discover the antibodies over which they now have an exclusive right."²⁶

Guided by Amgen, such random trial-and-error discovery, without more, "constitutes unreasonable experimentation that falls outside the bounds required by § 112(a)."²⁷

CONCLUSION

Amgen supports the proposition that claims covering millions of antibodies that perform a specific function require the specification to enable a POSA to make and use the entire class without "painstaking experimentation." Even when a roadmap is provided, if it requires experimental testing, the Court could view the experimentation as random trial-and-error that constitutes unreasonable experimentation. Baxalta's claims suffered from covering millions of antibodies but only disclosing eleven antibodies with a general roadmap of how to make them.

Importantly, Amgen did not disturb the courts enablement case law and its reliance on the Wands factors for determining undue experimentation. The Federal Circuit explained "We see no meaningful difference between Wands' 'undue experimentation' and Amgen's '[un]reasonable experimentation' standards."

The Federal Circuit recognized that Amgen also provided guidance that roadmaps might be sufficient to enable large genus claims wherein the patent discloses "a quality common to every functional embodiment." In other words, providing a sufficiently robust specification that discloses the amino acids of the antibody that are responsible for binding to PCSK9, and making sure that all the claimed antibodies contain those specific amino acids, may have aided with the enablement requirement.

Another option is to draft antibody claims without the functional language, and focus on the composition of matter. This approach could be helpful in the pharmaceutical arts where the function of compounds/biologics are known to be unpredictable.

Footnotes

1. Baxalta Inc. v. Genentech, Inc., 2023 WL 6135930, at *1 (Fed. Cir. Sept. 20, 2023).

2. Id. at *5.

3. Amgen Inc. v. Sanofi, 598 U.S. 594, 616 (2023).

4. Id.

5. Id. at 614.

6. Id.

7. Id.

8. Id.

9. The original assignee was Baxter AG, which underwent several name changes to became Baxalta Innovations GmbH, and is now a subsidiary of Takeda Pharmaceutical Company.

10. See U.S. Patent No. 7,033,590, claim 1.

11. Baxalta Inc. v. Genentech, Inc., 2018 WL 6304351, at *12 (D. Del. Dec. 3, 2018), vacated and remanded, 972 F.3d 1341 (Fed. Cir. 2020).

12. Id. ("[T]he term antibody means an immunoglobulin molecule, having a specific amino acid sequence that only binds to the antigen that induced its synthesis or very similar antigens, consisting of two identical heavy chains (H chains) and two identical light chains (L chains).").

13. Id. ("[W]e construe 'antibody fragment' to mean 'a portion of an antibody' as we have defined above, that is: 'a portion of an immunoglobulin molecule having a specific amino acid sequence comprising two heavy chains (H chains) and two light chains (L chains).'").

14. Baxalta, 972 F.3d at 1343.

15. Id. at 1349.

16. Baxalta Inc. v. Genentech, Inc. , 579 F. Supp. 3d 595, 625 (D. Del. 2022), aff'd, 2023 WL 6135930 (Fed. Cir. Sept. 20, 2023).

17. Baxalta, 2023 WL 6135930, at *3.

18. Id.

19. Under Wands, "whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988). The factual considerations, known as the "Wands factors," are: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.

20. Id. at *5.

21. Id.

22. Id.

23. Id. at *4.

24. Id.

25. Id.

26. Id.

27. Id., citing Amgen 598 U.S. at 613-15.

28. Baxalta, 2023 WL 6135930, at *5 n. 4.

29. Id. at *3.

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