Supreme Court Holds Invalid Cholesterol Drug Patent That Covered Millions of Undisclosed Antibodies | Manatt, Phelps & Phillips, LLP
In Amgen Inc. v. Sanofi,1 the Supreme Court unanimously held that “[i]f a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent specification must enable a person skilled in the art to make and use the entire class.”2 That is, “the specification must enable the full scope of the invention as defined by its claims.”3 The Court held that Amgen’s patents on the cholesterol drug Repatha were invalid because they encompassed any antibody that could bind to a specific protein and Amgen’s specification did not include a sufficient description to enable a skilled person to make and use Amgen’s claimed invention, which covered potentially millions of undisclosed antibodies that performed these same functions.
Amgen’s patents related to antibodies that decreased amounts of low-density lipoprotein cholesterol (LDL cholesterol), or bad cholesterol, because it could cause cardiovascular disease, heart attacks and strokes.
Amgen’s patents claimed all antibodies that (1) bind to particular amino acids on a protein called PCSK9 and (2) block PCSK9 from harming the body’s system for eliminating LDL cholesterol from the bloodstream. Amgen sued Sanofi for infringement, and Sanofi countered that the patents were invalid under 35 U.S.C. § 112 as not enabled. Sanofi argued that Amgen’s patents did not enable the invention because they covered potentially millions more antibodies than the company had disclosed in the patent specification. Both the district court and the U.S. Court of Appeals, Federal Circuit, agreed with Sanofi that Amgen’s claims were invalid as not enabled.4 Amgen appealed, and the Court affirmed.
On appeal, the Court explained that antibodies are made up of amino acids and a specific antibody is typically identified by its sequence of amino acids. The antibody structure influences its function, including its ability to bind to an antigen and to prevent other molecules from doing the same. Scientists design antibodies to aid in treating illnesses. Certain of these lab-made antibodies target the body’s proteins, receptors and ligands, such as a PCSK9 inhibitor used to treat patients with high LDL cholesterol.5 PCSK9 is a naturally occurring protein that binds to and weakens LDL receptors. Researchers attempted to produce antibodies that could bind to a specific region of PCSK9 termed the “sweet spot,” which was 15 amino acids out of PCSK9’s 692 total amino acids. By binding to the sweet spot, an antibody could block PCSK9 from binding to and weakening LDL receptors. Amgen advanced a PCSK9-inhibiting drug that it sold under the name Repatha, and Sanofi developed its own PCSK9-inhibiting drug called Praluent. Each drug used a distinct antibody with its own distinct amino acid sequence.6
Amgen obtained two patents, U.S. Patent No. 8,829,165 (’165 patent) and U.S. Patent No. 8,859,741 (’741 patent). Claims 19 and 29 of the ’165 patent and claim 7 of the ’741 patent claim the entire genus of antibodies that (1) bind to particular amino acid excesses on PCSK9 and (2) prevent PCSK9 from binding to LDL receptors.
The specification described the amino acid sequences of 26 antibodies that executed these two functions, and it showed the three-dimensional compositions of two of the 26 antibodies. Amgen only presented two methods to make other antibodies that executed the binding and blocking functions. The first method Amgen called the “roadmap,” which instructed to (1) produce a range of antibodies, (2) test those antibodies to decide whether any bind to PCSK9, (3) test those antibodies that bind to PCSK9 to decide whether any bind to the sweet spot as recited in the claims, and (4) test those antibodies that bind to the sweet spot to decide whether any block PCSK9 from binding to LDL receptors. The second method was “conservative substitution” thatinstructed to (1) begin with an antibody known to perform specific functions, (2) substitute specific amino acids in the antibody with other amino acids recognized to have comparable characteristics, and (3) test the ensuing antibody to see whether it also executed the specific functions.7
Sanofi argued that Amgen’s claims encompassed possibly millions of undisclosed antibodies that executed these same functions. Sanofi asserted that neither of the two methods Amgen disclosed to produce further antibodies with the same functions reliably enabled a person skilled in the art to make the potentially millions of antibodies. The district court agreed and awarded Sanofi judgment as a matter of law, determining that the claims at issue were not enabled, and the Federal Circuit affirmed.8
On appeal, the Court affirmed, observing that the Constitution empowers Congress to “promote the Progress of Science and useful Arts, by securing for limited Times to Authors and Inventors the exclusive Right to their respective Writings and Discoveries.”9
The Patent Act of 1790 provided up to a 14-year patent term to any individual who “invented or discovered any useful art, manufacture, … or device, or any improvement therein not before known or used.”10 The statute necessitated the applicant to submit a “specification … so particular … as not only to distinguish the invention or discovery from other things before known and used, but also to enable a workman or other person skilled in the art or manufacture … to make, construct, or use the same.”11
Current 35 U.S.C. Section 112 requires a patent specification with “a written description of the invention, and of 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 make and use the same.”12
The Court noted that prior decisions reiterated this plain statutory language:
If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. …
That is not to say a specification always must describe with particularity how to make and use every single embodiment within a claimed class. For instance, it 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.13
The Court acknowledged, however, that a specification is not automatically deficient even when one of ordinary skill must employ some amount of adaptation or testing to enable the invention to be used or made. That is, a specification may need a reasonable amount of experimentation to make and use the claimed invention and still be considered to be enabled. The Court conceded that what is considered reasonable experimentation depends on the nature of the invention and the prior art.14
With respect to claims 19 and 29 of the ’165 patent and claim 7 of the ’741 patent, the Court explained:
[W]e do not doubt that Amgen’s specification enables the 26 exemplary antibodies it identifies by their amino acid sequences. Even Sanofi concedes that description is enough to allow a person skilled in the art to make and use those embodiments. … But the claims before us sweep much broader than those 26 antibodies. And we agree with the lower courts that Amgen has failed to enable all that it has claimed, even allowing for a reasonable degree of experimentation. … Amgen seeks to monopolize an entire class of things defined by their function—every antibody that both binds to particular areas of the sweet spot of PCSK9 and blocks PCSK9 from binding to LDL receptors. The record reflects that this class of antibodies does not include just the 26 that Amgen has described by their amino acid sequences, but a “vast” number of additional antibodies that it has not.15
The Court reasoned that the more a party claims, the more the specification must enable the claimed invention. The Court noted that Amgen admitted it was attempting to claim “an entire universe of antibodies,” but argued its broad claims were enabled because scientists could make and use all functional antibodies if its roadmap or conservative substitution methods were followed. The Court rejected Amgen’s argument and held the following:
We cannot agree. These two approaches amount to little more than two research assignments. The first 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 happen to bind to PCSK9 in the right place and block it from binding to LDL receptors. … The second isn’t much different. It 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 license.”16
The Court explained that there is only one enablement standard; however, “the more a party claims for itself the more it must enable.”17 The Court reasoned as follows:
Section 112 of the Patent Act reflects Congress’s judgment that if an inventor claims a lot, but enables only a little, the public does not receive its benefit of the bargain. For more than 150 years, this Court has enforced the statutory enablement requirement according to its terms. … Today’s case may involve a new technology, but the legal principle is the same.18
Practical Considerations
The Court’s decision makes it more difficult for patent owners to obtain protection for an entire genus of antibodies defined by their function. The decision would appear to encourage patent practitioners to draft more detailed specifications with more examples than perhaps was the previous practice, which might delay the filing of the patent application until additional experiments are conducted. Such specifications might include more structural descriptions of an antibody according to its specific sequence of amino acids instead of the function, to the extent possible.
The decision also emphasizes that the same standard for enablement applies to all inventions. Going forward, patent practitioners will also have to consider whether more detailed claims should be included as a fail-safe should the broader claims be considered not enabled.
The decision affects litigation, licensing and how patents are drafted and prosecuted. For example, patent portfolios should be reviewed to determine whether key patent assets with broad claims should have continuation, reissue or reexamination applications filed with complementary claims to improve/expand patent protection. Litigators might consider enforcing narrower claims while employing the doctrine of equivalents for similar inventions. In addition, the Court’s decision should deter lawsuits for patents having overly broad functional claims, arguably allowing companies to focus capital on the development of new inventions.
1 Amgen Inc. v. Sanofi, 143 S.Ct. 1243, 2023 USPQ2d 602 (2023).
2 Id., 143 S.Ct. at 1254–55.
3 Id., 143 S.Ct. at 1254–55.
4 Id., 143 S.Ct. at 1248.
5 Id., 143 S.Ct. at 1248–49.
6 Id., 143 S.Ct. at 1250.
7 Id., 143 S.Ct. at 1250.
8 Id., 143 S.Ct. at 1250–51.
9 Id., 143 S.Ct. at 1251 (quoting Art. I, § 8, cl. 8).
10 Id., 143 S.Ct. at 1251 (quoting the Patent Act, Apr. 10, 1790, § 1, 1 Stat. 110).
11 Id., 143 S.Ct. at 1251 (quoting the Patent Act, Apr. 10, 1790, § 2, 1 Stat. 110).
12 Id., 143 S.Ct. at 1251 (quoting 35 U.S.C. § 112(a)).
13 Id., 143 S.Ct. at 1254–55.
14 Id., 143 S.Ct. at 1255.
15 Id., 143 S.Ct. at 1256.
16 Id., 143 S.Ct. at 1256.
17 Id., 143 S.Ct. at 1257.
18 Id., 143 S.Ct. at 1258.
