The Future of Genus Patenting Strategies for Antibodies Post-Amgen

In 2023, the Supreme Court issued a decisive opinion that undermined the validity of broad functional genus claims for patents directed to biological antibodies. The case itself, in which Amgen sued Sanofi and Regeneron for infringing two antibody patents related to PCSK9 inhibitors, exemplified how powerful functional genus patents could be used to corner the market on nearly all antibodies inhibiting a particular binding region of an antigen. Amgen’s patents covered potentially billions of different antibodies that bind to specific residues on PCSK9, even though the patents themselves only reduced to practice 26 example antibodies that performed that function. The Supreme Court held that Amgen’s patents failed to enable anything close to the scope of antibodies actually claimed.

Broad functional genus claiming was previously a standard strategy for innovators seeking IP protection for antibodies. Prior guidance from the USPTO, including the “newly characterized antigen” test, encouraged broad claiming of antibodies based upon their function alone. For decades, that effectively allowed innovators to claim much more than they in fact discovered in practice.

In the wake of the Supreme Court’s Amgen decision, courts have adopted the reasoning articulated in Amgen to strike down functional genus antibody claims for lacking either enablement or written description. For instance, in Baxalta Inc. v. Genentech, Inc., 81 F.4th 1362 (Fed. Cir. 2023), the court found a patent claim directed to “An isolated antibody or antibody fragment thereof that binds Factor IX or Factor IXa and increases the procoagulant activity of Factor IXa” was not enabled for the same reasons articulated in Amgen.

Strategies for a New Era

The era of broad functional claiming pre-Amgen is decidedly over. Regrettably or not, depending on where you sit, patents can no longer be used to acquire the same breadth of coverage previously available through functional claiming. Nevertheless, numerous alternate strategies are emerging that themselves can sustain a healthy breadth of coverage. The currently available strategies each include tradeoffs, which means prudence likely dictates pursuing a mix of tactics to acquire the broadest coverage possibly.

Parental Sequence Claims

For instance, a first strategy includes pursuing parental sequence claims. This would include claims directed to the amino acid sequence for a particular antibody. Parental sequence claims are likely ineffective against brand-name competitor drugs. For instance, in the Amgen case, both Amgen and Regeneron sold PCSK9-inhibitors, even though Regeneron’s antibody sequence bore no resemblance to Amgen’s. (Indeed, the case involved an evidentiary dispute where Regeneron wished to show the jury how different its antibody was from Amgen’s for the purpose of demonstrating how Amgen’s patents came nowhere close to reducing Regeneron’s antibody to practice). That said, parental sequence claims can be important for protection against prospective biosimilars.

Percentage Sequence

Another available strategy includes percentage sequence claims. These patents are directed to claiming an antibody that is identical to a reference antibody by an enumerated percentage. The enumerated percentages can be very high—on the order of 90% or 95%. On its face, that suggests that percentage sequence claims would likely pass muster under Amgen.

In reality, however, even percentage sequence patents can run up against the same enablement and written description problems that doomed the patents at issue in Amgen. An interesting example includes a series of Post-Grant Review petitions filed by Merck. (See e.g., Merck, Sharp & Dohme, LLC v. Halozyme, Inc., PGR2025-0003 and other PGR’s (June 2025)). The PGRs were instituted on written description and enablement challenges against patents claiming modified PH20 polypeptides with at least 95% sequence identity to reference PH20 proteins. (As of May and June 2026, many of the patents have been successfully invalidated). Despite claiming upwards of 95% sequence identity, given the way the math works out with available amino acid substitutions, Merck was still able to argue that if all antibodies encompassed within the claims were reduced to practice, their aggregate weight would exceed that of the planet earth.

Interestingly, the patent owner in the Merck PGR’s attempted to circumvent the enablement and written description challenges by arguing that the patented claims did not require any function. In other words, the patent owner argued the claimed antibodies were claimed for themselves, not because they were efficacious in inhibiting any particular antigen or for any other purpose. Indeed, structure is often claimed, including for pharmaceutical patents, that does not also claim any function. If successful, this would be a clever workaround Amgen’s prohibition against broad functional claiming—if there is no function to be satisfied, there can be no argument the patent specification fails to enable all claimed antibodies to perform that function. Yet, doing so would likely violate the utility requirement for all patents, and thus, this strategy, in the long term, likely has no legs.

Means-Plus-Function

Another available strategy for claiming antibodies includes recourse to means-plus-function claiming. On the one hand, means-plus-function claims would be limited to the disclosed structure, thus suggesting they could not protect more than any amino-acid sequences disclosed in the specification. On the other hand, means-plus-function claims also encompass statutory equivalents, which would presumably broaden the scope of covered antibodies beyond those actually disclosed in the specification. Indeed, at least one court has already confirmed that for antibody patents, structural equivalents need not be disclosed in the specification. See Ex parte Chamberlain, No. 2022-001944 (PTAB May 21, 2024).

Statutory equivalents, however, must typically be known and exist prior to patent issuance. See Al-Site Corp. v. VSI Int’l, Inc., 174 F.3d 1308, 1320 (Fed. Cir. 1999). That means an innovator could not rely upon equivalents to assert a patent against a competitor that developed an infringing antibody after the patent’s issuance. Indeed, the opposite may be even worse. If a statutory equivalent, such as that used by a competitor, must be known prior to patent issuance, that raises the prospect that your competitor’s “equivalent” antibody may be prior art to your patent.

Experimental Data

Another viable approach is to rely on experimental data rather than patent drafting alone. For example, paratope mapping with CDR-scanning technology substitutes every amino acid across an antibody’s complementarity-determining regions (CDRs)—typically generating approximately 1,000 variants—to determine which residues are critical for antigen binding and which substitutions are tolerated. The resulting dataset experimentally defines a genus of antibodies that share the common structural feature of the paratope, i.e. the region of the antibody responsible for binding the antigen. These data provide a strong foundation for the enablement and written description requirements of a patent application. Data that supports enablement and written description for thousands of antibody variants is superior to older patents, such as those at issue in the Amgen case that included testing for only 26 embodiments.

This approach does not test the millions or billions of potential antibody variants that were previously permitted under the pre-Amgen functional claiming regime. Competitors can thus still develop a new parental antibody that does not fall within patent claims enabled by paratope mapping using CDR scanning. However, it bears remembering that the Supreme Court eviscerated broad functional genus claims arguably because they allowed one company to corner the market on a given inhibitor, to the public’s detriment, by claiming more than they actually invented.

Paratope mapping using CDR scanning adds an additional cost to a company’s IP spend for protecting developing antibodies. While the cost may not be prohibitive for a given antibody (i.e., comparable to the cost of 50 to 100 hours of attorney time), the aggregate cost may rise for companies with numerous potential antibodies in their pipeline, without knowing which candidates are likely to clear Phase III trials. On the other hand, the results of paratope mapping using CDR scanning are not just for in-house patent attorneys, but yield potentially critical data for the research arm developing a particular parental sequence. Similarly, for biotech startups focused only on a single antibody, paratope mapping using CDR scanning may bolster IP protection important to future investors. Indeed, savvy investors may soon require it because CDR scanning provides broader protection that is less susceptible to enablement or written description challenges.

Additional limitations on the feasibility of paratope mapping using CDR scanning for antibody patents exist, but they are likely to be ironed out in the near future, as the technology develops. For instance, the paratope mapping technology disclosed in the Nature Biotechnology article above is limited to mutating only a single CDR residue to the other 19 amino acids. Mapping for multiple mutations would dramatically increase the breadth of patentable proteins. In addition, Section 112 issues may arise if a patent is asserted against a protein that mirrors the claimed antibody except for additions or deletions in the amino acid sequence that were not technically mapped. Whether the technology will develop to accommodate these limitations is likely to be known in the short term.

At least one patent, namely, U.S. Patent No. 12,545,726, has been granted based upon paratope mapping using CDR scanning. The patent’s claims cover single mutations supported by CDR scanning data, but also combinations of mutations. Whether those combination claims will survive Section 112 challenges is likely to be determined by the courts in the future.

That said, the technology is likely to get there before the courts. The technology to test a combination of mutations for a given parental antibody does currently exist, and it is likely to be commercially-available very soon, if not already. Paratope mapping using CDR scanning defines a common structural feature and helps identify those mutations that are permissible. Enabling combinations of mutations could therefore exponentially increase the scope of patentable antibodies, even within a post-Amgen era. This technology, including an identification of the paratope that cannot change, will also soon be coupled with machine-learning to identify “smart” combinations that are likely to meet certain antibody metrics such as affinity, species cross reactivity and fold improvements. Thus, patenting billions of potential antibodies based upon function alone may no longer be required given that existing CDR scanning technology can allocate resources to testing only worthwhile combinations.

There is Hope Post-Amgen

The Amgen decision generated a debate about whether discarding broad functional genus claiming for antibody patents would encourage or discourage biotech innovation and investment. On balance, while IP coverage shrank after Amgen, biotech innovation is likely to blossom in its wake. Paratope mapping along with other patenting strategies will hopefully provide a healthy balance of patent protection to foster the best medicine for the public.

Image Source: Deposit PHotos
Image ID: 32690747
Image Author: Authoralexmillos