United States Court of Appeals 

for the Federal Circuit ______________________ 

BAXALTA INCORPORATED, BAXALTA GMBH,

Plaintiffs-Appellants

v.

GENENTECH, INC.,

Defendant-Appellee

______________________ 

2022-1461

______________________ 

Appeal from the United States District Court for the 

District of Delaware in No. 1:17-cv-00509-TBD, Circuit 

Judge Timothy B. Dyk.

______________________ 

Decided: September 20, 2023

______________________ 

WILLIAM R. PETERSON, Morgan, Lewis & Bockius LLP, 

Houston, TX, argued for plaintiffs-appellants. Also represented by MICHAEL J. ABERNATHY, CHRISTOPHER JOHN 

BETTI, MARIA DOUKAS, KARON NICOLE FOWLER, Chicago, 

IL; JULIE S. GOLDEMBERG, Philadelphia, PA.

 ERIC ALAN STONE, Groombridge, Wu, Baughman & 

Stone LLP, New York, NY, argued for defendant-appellee. 

Also represented by NICHOLAS P. GROOMBRIDGE, NAZ 

WEHRLI, JOSEPHINE YOUNG. 

______________________ 

Case: 22-1461 Document: 53 Page: 1 Filed: 09/20/2023
2 BAXALTA INCORPORATED v. GENENTECH, INC. 

Before MOORE, Chief Judge, CLEVENGER and CHEN,

Circuit Judges.

MOORE, Chief Judge. 

Baxalta Inc. and Baxalta GmbH (collectively, Baxalta) 

appeal the United States District Court for the District of 

Delaware’s grant of summary judgment that claims 1–4, 

19, and 20 of U.S. Patent No. 7,033,590 are invalid for lack 

of enablement. For the following reasons, we affirm.

BACKGROUND

A 

Blood clots are formed through a series of enzymatic 

activations known as the coagulation cascade. ’590 patent 

at 1:6–10. In a “key step” of the cascade, an enzyme known 

as activated Factor VIII (Factor VIIIa) complexes with another enzyme known as activated Factor IX (Factor IXa) to 

activate Factor X. Id. at 1:17–19. Hemophilia A is a blood 

clotting disorder where the activity of Factor VIII is functionally absent, thereby impeding the coagulation cascade

and the body’s ability to effectively form blood clots. Id. at 

1:19–27. Historically, Hemophilia A has been treated by

intravenously administering Factor VIII. Id. at 1:28–30. 

However, approximately 20–30% of Hemophilia A patients 

cannot benefit from this traditional treatment because 

their bodies develop Factor VIII inhibitors (i.e., antibodies 

against Factor VIII). Id. at 1:30–35.

Recognizing these drawbacks, the ’590 patent sought to 

provide alternative means to treat Hemophilia A, particularly in patients who develop Factor VIII inhibitors. Id. at 

2:22–28. Such preparations comprise antibodies or antibody derivatives that bind to Factor IX/IXa to increase the 

procoagulant activity of Factor IXa. Id. at 2:29–38. These 

antibodies allow Factor IXa to activate Factor X in the absence of Factor VIII/VIIIa. Id. at 1:61–67, 2:39–44. Independent claim 1 is representative and recites:

Case: 22-1461 Document: 53 Page: 2 Filed: 09/20/2023
BAXALTA INCORPORATED v. GENENTECH, INC. 3

1. An isolated antibody or antibody fragment 

thereof that binds Factor IX or Factor IXa and increases the procoagulant activity of Factor IXa.

Id. at claim 1.

Antibodies are proteins that bind to antigens (foreign 

molecules in the body). More specifically, an antibody is a 

Y-shaped immunoglobulin molecule having a specific 

amino acid sequence comprising two heavy chains and two 

light chains. Each chain includes two regions: a variable 

region and a constant region. The variable region—the 

amino acid sequence at the tips of the “Y”—is the portion 

of the chain that varies between antibodies of the same isotype.1 The variable region contains complementarity-determining regions (CDRs), which are the amino acid 

sequences primarily responsible for the antibody’s binding 

and functional properties. The remaining constant region 

is identical across antibodies of the same isotype. 

The inventors generated the antibodies claimed in the 

’590 patent using a prior art method known as the hybridoma technique. Id. at 9:62–10:37. This process involves 

first immunizing mice with human Factor IX/IXa to generate anti-Factor IX/IXa antibody-secreting B-cells. Id. The 

antibody-secreting B-cells are then removed and fused to 

myeloma cells to create hybridomas that secrete anti-Factor IX/IXa antibodies.

The inventors performed four such hybridoma fusion 

experiments. Id. at 10:11–13. Using routine techniques, 

the inventors screened the candidate antibodies from the 

four fusion experiments to determine whether the antibodies bind to Factor IX/IXa and increase procoagulant activity, as claimed. Id. at 10:39–12:56. The inventors 

1 Antibodies are grouped into five classes known as 

“isotypes”: IgA, IgD, IgE, IgG, and IgM. “Ig” stands for immunoglobulin, and the following letter specifies the class.

Case: 22-1461 Document: 53 Page: 3 Filed: 09/20/2023
4 BAXALTA INCORPORATED v. GENENTECH, INC. 

discovered that only 1.6% of the thousands of screened antibodies increased the procoagulant activity of Factor IXa. 

J.A. 17684. 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. See ’590 

patent at 12:36–49. These disclosed antibodies are all monospecific (i.e., bind to a single antigen) and monoclonal (i.e., 

produced by a single cell line). The written description of 

the ’590 patent explains that a skilled artisan may use 

well-known antibody engineering techniques to transform 

the resulting antibody into different structural formats. 

See id. at 6:15–7:50 (discussing “technically modified antibodies”). For example, scientists can create “bispecific antibodies” by combining a heavy and light chain of one 

antibody with a heavy and light chain of a different antibody. In bispecific antibodies, unlike monospecific antibodies, each arm binds to a different antigen. Id. at 7:32–34. 

As another example, scientists can create “humanized antibodies” in which animal CDRs are inserted into an otherwise human antibody. Id. at 6:49–57.

B 

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. Following the district court’s construction of the claim terms 

“antibody” and “antibody fragment” to exclude bispecific 

antibodies, the parties stipulated to non-infringement subject to appeal. 

On a prior appeal, we held the proper construction of 

“antibody” was “an immunoglobulin molecule having a specific amino acid sequence comprising two heavy chains (H 

chains) and two light chains (L chains),” and the proper 

construction of “antibody fragment” was “a portion of an 

antibody.” Baxalta Inc. v. Genentech, Inc., 972 F.3d 1341, 

Case: 22-1461 Document: 53 Page: 4 Filed: 09/20/2023
BAXALTA INCORPORATED v. GENENTECH, INC. 5

1345–49 (Fed. Cir. 2020). Because the district court’s construction erroneously excluded bispecific antibodies, we vacated the judgment of non-infringement and remanded for 

further proceedings. Id. at 1349. On remand, Genentech 

moved for summary judgment of, inter alia, invalidity of 

claims 1–4, 19, and 20 for lack of enablement. The district 

court granted summary judgment. Baxalta Inc. v. Genentech, Inc., 579 F. Supp. 3d 595 (D. Del. 2022). Baxalta appeals. We have jurisdiction under 28 U.S.C. § 1295(a)(1).

DISCUSSION

We review summary judgment rulings under the law of 

the regional circuit, here the Third Circuit. Junker v. Med. 

Components, Inc., 25 F.4th 1027, 1032 (Fed. Cir. 2022). 

The Third Circuit reviews the grant of summary judgment 

de novo. Melrose, Inc. v. City of Pittsburgh, 613 F.3d 380, 

387 (3d Cir. 2010). Summary judgment is appropriate 

when, drawing all reasonable inferences in the nonmovant’s favor, there is no genuine issue of material fact 

and the movant is entitled to judgment as a matter of law. 

Fed. R. Civ. P. 56(a); Anderson v. Liberty Lobby, Inc., 477 

U.S. 242, 255 (1986).

A patent’s specification must describe the invention 

and “the manner and process of making and using it, in 

such full, clear, concise, and exact terms as to enable any 

person skilled in the art to which it pertains . . . to make 

and use the same.” 35 U.S.C. § 112(a). As the Supreme 

Court recently reaffirmed in Amgen Inc. v. Sanofi, “the 

specification must enable the full scope of the invention as 

defined by its claims,” allowing for “a reasonable amount of 

experimentation.” 598 U.S. 594, 610–12 (2023). In other 

words, “the specification of a patent must teach those 

skilled in the art how to make and use the full scope of the 

claimed invention without undue experimentation.” MagSil Corp. v. Hitachi Glob. Storage Techs., Inc., 687 F.3d 

1377, 1380 (Fed. Cir. 2012) (internal quotation marks and 

citation omitted). Enablement is a question of law based 

Case: 22-1461 Document: 53 Page: 5 Filed: 09/20/2023
6 BAXALTA INCORPORATED v. GENENTECH, INC. 

on underlying factual findings. Id. “Because patents are 

presumed valid, lack of enablement must be proven by 

clear and convincing evidence.” ALZA Corp. v. Andrx 

Pharms., LLC, 603 F.3d 935, 940 (Fed. Cir. 2010).

Baxalta argues summary judgment of invalidity for 

lack of enablement was improper because, when viewing 

the evidence in the light most favorable to Baxalta, skilled 

artisans can obtain the full scope of claimed antibodies 

without undue experimentation. Specifically, Baxalta argues skilled artisans can make and identify new claimed 

antibodies (with new variable regions) 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 

recent decision in Amgen, we cannot agree.

In Amgen, the patents claimed all antibodies that (1) 

bind to specific amino acid residues on a protein known as 

PCSK9; and (2) block PCSK9 from binding to LDL receptors. 598 U.S. at 602. The full scope of the claims covered 

potentially millions of antibodies, but the specification only 

disclosed the amino acid sequences of twenty-six antibodies 

that performed the two claimed functions. Id. at 612–13. 

To make and use the undisclosed claimed antibodies, 

skilled artisans could either follow the “roadmap” disclosed 

in the patent or employ a technique known as “conservative 

substitution.” Id. at 603. The roadmap directed skilled artisans to: 

(1) generate a range of antibodies in the lab; (2) test 

those antibodies to determine whether any bind to 

PCSK9; (3) test those antibodies that bind to 

PCSK9 to determine whether any bind to the sweet 

spot as described in the claims; and (4) test those 

antibodies that bind to the sweet spot as described 

in the claims to determine whether any block 

PCSK9 from binding to LDL receptors. 

Case: 22-1461 Document: 53 Page: 6 Filed: 09/20/2023
BAXALTA INCORPORATED v. GENENTECH, INC. 7

Id. The conservative substitution technique directed 

skilled artisans to: “(1) start with an antibody known to 

perform the described functions; (2) replace select amino 

acids in the antibody with other amino acids known to have 

similar properties; and (3) test the resulting antibody to see 

if it also performs the described functions.” Id. 

The Supreme Court held these methods “amount to little more than two research assignments” and fail to enable 

the full scope of the claims. Id. at 612–15. The Court reasoned Amgen’s roadmap “merely describes step-by-step

Amgen’s own trial-and-error method for finding functional

antibodies—calling on scientists to create a wide range of 

candidate antibodies and then screen each to see” which

practice the claims. Id. at 614. Similarly, the conservative

substitution technique simply “requires scientists to make

substitutions to the amino acid sequences of antibodies 

known to work and then test the resulting antibodies to see

if they do too—an uncertain prospect given the state of the

art.” Id. Such approaches leave skilled artisans to “engage 

in ‘painstaking experimentation’ to see what works,” which

“is not enablement.” Id. (quoting Consol. Elec. Light Co. v. 

McKeesport Light Co., 159 U.S. 465, 475 (1895)). The Supreme Court acknowledged, however, that methods like a 

roadmap or conservative substitution might be sufficient to 

enable other claims under different circumstances, such as 

where the patent discloses “a quality common to every 

functional embodiment.” Id.; see also id. at 611 (“[I]t may 

suffice to give an example (or a few examples) if the specification also discloses ‘some general quality . . . running 

through’ the class that gives it ‘a peculiar fitness for the 

particular purpose.’ In some cases, disclosing that general 

quality may reliably enable a person skilled in the art to 

make and use all of what is claimed, not merely a subset.” 

(quoting Consol. Elec. Light Co., 159 U.S. at 475)).

The facts of this case are materially indistinguishable 

from those in Amgen. Claim 1 of the ’590 patent covers all

antibodies that (1) bind to Factor IX/IXa; and (2) increase 

Case: 22-1461 Document: 53 Page: 7 Filed: 09/20/2023
8 BAXALTA INCORPORATED v. GENENTECH, INC. 

the procoagulant activity of Factor IXa.2 There are millions of potential candidate antibodies, J.A. 18754–55 ¶ 22, 

but the written description discloses the amino acid sequences for only eleven antibodies with the two claimed 

functions. See ’590 patent at 12:36–49. 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. Id. at 

9:62–12:56. Just 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-anderror process the inventors followed to discover the eleven 

antibodies they elected to disclose. See Amgen, 598 U.S. at 

613–14. 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.” Baxalta, 579 F. Supp. 3d at 619.

Moreover, it is undisputed the ’590 patent contains no 

disclosures—such as “a quality common to every functional 

2 The parties do not raise distinct arguments with 

respect to dependent claims 2–4, 19, and 20. Rather, the 

parties agree that practicing the challenged claims requires two steps: (1) obtaining new antibodies with new 

variable regions that bind to Factor IX/IXa and increase 

procoagulant activity; and (2) engineering these variable 

regions into the isotypes and formats recited in the dependent claims. Because, as discussed infra, we hold it requires 

unreasonable experimentation to practice the first step, we 

need not consider whether it would require unreasonable

experimentation to practice the second step. 

Case: 22-1461 Document: 53 Page: 8 Filed: 09/20/2023
BAXALTA INCORPORATED v. GENENTECH, INC. 9

embodiment,” Amgen, 598 U.S. at 614—that would allow a 

skilled artisan to predict which antibodies will perform the 

claimed functions. The patent does not disclose any common structural (or other) feature delineating which antibodies will bind to Factor IX/IXa and increase procoagulant 

activity from those that will not. Nor does the patent describe why the eleven disclosed antibodies perform the 

claimed functions, or why the other screened antibodies do 

not. The 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. Id. Amgen makes clear that such 

an instruction, without more, is not enough to enable the 

broad functional genus claims at issue here. Id. at 614–15

(“[T]he . . . problem we see [is that] Amgen offers persons 

skilled in the art little more than advice to engage in ‘trial 

and error.’”).

In an attempt to distinguish Amgen, Baxalta argues 

the hybridoma-and-screening process disclosed in the ’590 

patent does not require trial and error but instead predictably and reliably generates new claimed antibodies every

time it is performed. Even accepting as true that skilled 

artisans will generate at least one claimed antibody each 

time they follow the disclosed process, this does not take 

the process out of the realm of the trial-and-error approaches rejected in Amgen.3 Amgen made clear 

that § 112(a) requires inventors to enable the “full scope” 

of the claimed invention without unreasonable

3 Indeed, the same was apparently true in Amgen. 

See Brief for Petitioners at 49, Amgen, 598 U.S. 594 (No. 

21-757) (“It was undisputed that, by following the patents’ 

roadmap, skilled artisans can generate other claimed antibodies every time.”). Yet, the Supreme Court still held 

Amgen’s roadmap required trial and error. See Amgen, 598 

U.S. at 614–15.

Case: 22-1461 Document: 53 Page: 9 Filed: 09/20/2023
10 BAXALTA INCORPORATED v. GENENTECH, INC. 

experimentation. Id. at 610–12. Here, it is undisputed 

that to practice the full scope of the claimed invention, 

skilled artisans must make candidate antibodies and 

screen them to determine which ones perform the claimed 

functions. See J.A. 16451, 17340–41 (Baxalta’s experts testifying the only way for skilled artisans to identify a new 

embodiment of the genus “is to make antibodies and test 

them”). This is the definition of trial and error and 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. Under Amgen, such random trial-and-error discovery, without more, constitutes unreasonable 

experimentation that falls outside the bounds required by 

§ 112(a). 598 U.S. at 613–15.

Finally, Baxalta argues the district court’s enablement 

determination is inconsistent with In re Wands, 858 F.2d 

731 (Fed. Cir. 1988). We do not agree. We 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 facts of this case are 

more analogous to—and are, in fact, indistinguishable 

from—those in Amgen. We do not interpret Amgen to have 

disturbed our prior enablement case law, including Wands

and its factors.4

In light of the foregoing, we hold the ’590 patent fails 

to teach skilled artisans how to make and use the full scope 

of claimed antibodies without unreasonable 

4 At oral argument, both parties agreed the Supreme 

Court did not disturb the Wands factors. Oral Arg. at 

00:40–1:16, 30:31–31:15, available at https://cafc.uscourts. 

gov/home/oral-argument/listen-to-oral-arguments. We see 

no meaningful difference between Wands’ “undue experimentation” and Amgen’s “[un]reasonable experimentation” 

standards.

Case: 22-1461 Document: 53 Page: 10 Filed: 09/20/2023
BAXALTA INCORPORATED v. GENENTECH, INC. 11

experimentation. We therefore affirm the district court’s 

grant of summary judgment that claims 1–4, 19, and 20 are 

not enabled. 

CONCLUSION

We have considered the parties’ remaining arguments 

and find them unpersuasive. For the reasons given above, 

we affirm the district court’s grant of summary judgment.

AFFIRMED 

Case: 22-1461 Document: 53 Page: 11 Filed: 09/20/2023