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Patenting antibodies in the US and Europe

May 2022

Is the USPTO now stricter than the EPO on antibody claims? A consideration of recent developments from both sides of the pond.

Patent protection for monoclonal antibodies, bispecific antibodies and nanobodies, as well as CAR-T and CAR-NK cells may represent an important aspect for a company’s intellectual property position. Companies seeking protection in the United States should consider the different criteria for obtaining patent protection, and especially how this differs from the position in Europe. In the US, a patentable biologic must meet the written description and enablement requirements, among other things. These requirements are similar in many ways to the sufficiency and support requirements in Europe, essentially defining that an invention must have been adequately described in the application as filed, but also that it has been exemplified and shown to work. Whilst these requirements have always been in place, a recent line of case law in the US has rendered them more stringent, and potentially more stringent than in Europe.

In 2017, the written description criterion for obtaining patent protection for antibodies in the US was definitively changed by Amgen Inc. v. Sanofi (2017)[1]. The Court rejected the “newly characterized antigen” test, which had allowed claims directed to the antibody by describing, as the name suggests, a newly characterized antigen to which it binds. Instead, the Court required adequate written description of the antibody itself. Since this key decision, additional case law has continued to develop in the antibody-related space.

Moving forward several years, Juno Therapeutics, Inv. v. Kite Pharma, Inc. (2021) took the written description standard and applied it to the nearby field of CAR-T cell technology, and added doubts as to the use of functional claim limitations. The claims were directed to nucleic acid encoding a chimeric T cell receptor that has a “binding element that specifically interacts with a selected target,” the binding element being a single chain antibody variable fragment (scFV). However, the application merely disclosed two examples of scFVs. The claims were deemed to have insufficient written description for the full scope of possible binding elements encompassed by the claims, in part because the application did not disclose common structural features to identify which binding element would function as claimed.

Even more recently, Amgen Inc. v. Sanofi (2021)[2] created an additional hurdle with respect to the enablement doctrine and functional limitations. At issue was a genus claim with a functional limitation: “An isolated monoclonal antibody [that] binds to at least one [listed residue of PCSK9] and … blocks binding of PCSK9 to LDRL.” The Court found that the functional limitation – blocks binding of PCSK9 to LDRL – provided a genus that is too vast in number where all or nearly all the embodiments cannot be made without undue experimentation and thus, is not enabled.

In stark contrast to these cases in the US, an EPO Board of Appeal decision has recently maintained an antibody claim based only on an epitope and a functional definition. In T1964/18 the genus claim was as follows ‘a monoclonal antibody or fragment thereof that a) specifically blocks NKG2A but not the related receptors NKG2C and E, and b) binds the same epitope on NKG2A as a deposited antibody, such that binding of the antibody to its target on a NK cell activates NK-cell killing’. Whilst sufficiency was not considered, it is notable that the Board accepted this claim format. In the equivalent US case, however, following Amgen Inc. v. Sanofi (2021) the examiner did not allow such a claim for the reason that there was insufficient written description to demonstrate that applicant was in possession of the claimed genus of monoclonal antibodies that specifically bind NKG2A and do not specifically bind to NKG2C. Similar broad claims have survived opposition in Europe, such as claims to an antibody that binds to a specific epitope within human alpha-synuclein for use in therapy[4], and claims to an antibody that binds a specific epitope on the antigen CD47, and thereby inhibits the function of CD47[5].

These US decisions beg the question, “How does an applicant successfully obtain valuable patent protection in the US for antibodies or antibody related products such as CAR-T cells, if the use of broad target based definitions or function based definitions are severely limited?”

In our view, the ability to disclose structural features of the antibodies and antibody-related biologics will be key to obtaining US patent protection. Applicants can still strive for useful patent protection in both the US and Europe by keeping the following in mind.

For a sequenced antibody, the amino acid sequences of the complementarity-determining regions (CDRs) should be disclosed and claimed. Further, disclosures relating to acceptable substitutions, additions or deletions of amino acids in the CDRs may help broaden the scope of protection. These disclosures serving as representative number of species, along with common structural features of the applicable amino acid sequence among the members of the genus can assist in pursuing a genus of antibodies, scFVs and the like. Similarly in Europe, whilst broad non-structural definitions are possible, examiners will often want to see the antibody defined by its CDRs, and the description should certainly provide the variable region sequences if not the full antibody sequence.

While Amgen Inv. v. Sanofi (2021)[3] currently places a damper on utilizing functional features in US claims, the case may be reviewed by the Supreme Court of the United States, and thus a possibility exists that it may be overturned. Amgen Inv. v. Sanofi (2021) was also decided based on a claim that relied on a functional feature and lacked any structural features of the antibody itself. In instances wherein functional features, such as binding affinity, are tied to common structural features of the antibody itself (and not the target), such as conservations of certain amino acids, there can still be room to obtain meaningful claims based on combinations of these features much like Europe. Conversely, one should consider if the claims can satisfy written description and enablement requirements without the need of functional features and only recite structural features. If so, the application should include embodiments where functional features are not required by the claims.

In instances where the antibody has not been sequenced, a biological deposit of hybridomas secreting the antibodies can be made at any time before allowance in the US, and remains a viable option in many instances to satisfy the written description requirement. The claims would be directed to the hybridoma and antibodies produced by the hybridoma, which can be narrow protection. That said, if the protection covers the commercial product, it can still be very useful, particularly for pending patent applications that were drafted prior to the changes in the law. For Europe, an antibody may also be defined by reference to a hybridoma, however, applicants should ensure that hybridomas are deposited on or before the effective filing date of the application for the invention to be considered sufficiently disclosed as of the effective filing date. Furthermore, the applicant should strongly consider including some sequences to define the antibody in the application. A recent EPO Board of Appeal decision, T0032/17, clarified that mere reference to a hybridoma does not limit an antibody claim to a particular structure, and applicants may end up limited to the hybridoma per se, making this claim format less desirable in Europe.

Another point to bear in mind is that there is still room for methods of using these types of biologics, and the threshold for satisfying written description for such claims may be different to that of the product claims. The same can be said for Europe with regard to medical use claims. As an example, a claim may be directed to a method of using “antibodies that inhibit X” to treat cancer based on applicant’s discovery that inhibiting X inhibits cancer growth. Assuming there are well-known antibodies that inhibit X, disclosure of the actual structures of these antibodies may not be necessary. In this instance, providing the names of known antibodies that inhibit X as examples may be sufficient for written description of “antibodies that inhibit X.” That said, the application should still include representative data showing that the antibodies indeed treat cancer so as to satisfy the written description requirement with respect to the treatment claimed. This is also key in Europe where examiners can be strict as to the level of data required to show that a novel therapeutic effect was indeed obtained with the known agent, especially if a medical use is claimed which relies on a more nuanced effect, such as the way in which a treatment is applied. On the enablement side of the coin, details that would lessen the experimental burden to determine which antibodies can inhibit X and inhibit cancer growth will also be beneficial to include in the application for US and European purposes.

Recent US case law has therefore slighted the ability to obtain broad protection of antibodies and related biologics, even though it remains to be seen if Amgen Inv. v. Sanofi (2021) will be overturned. In contrast, the position is more permissive in Europe, where the EPO guidelines issued on antibody claims[6] explicitly mention that claims defined by only function or epitope are allowed, and the Boards of Appeal have upheld such broad claims.

Despite the challenges, we believe there is still room for obtaining meaningful patent protection in the US, particularly when the above points are considered during the invention development and application drafting process. Furthermore, each invention’s patentability is still considered on a case-by-case basis. It is possible that common ground using the same strategies for claim drafting as identified above can be implemented across both the US and Europe, such as by combining structural and functional features or medical treatments. However, applicants wishing to rely on broad function or target alone may now experience differences across portfolios, with a divergent claim scope being allowed in their equivalent US and European applications.

This article was prepared by Linda Huber, Partner at Nixon Peabody LLP & HGF’s Patent Director Ellie Purnell.

Linda Huber is a US patent attorney and intellectual property partner in the Los Angeles office of Nixon Peabody LLP. As an attorney, Linda leverages her biochemistry background and patent experience to represent universities, academic medical centers, biotechnology companies, and medical device companies. She focuses her practice on prosecuting patents, counseling clients on their patent portfolios and prosecution strategies, advising clients on patent-related license provisions, and conducting due diligence on patent portfolios in corporate transactions and patent license agreements. Some representative areas of experience include biologics, cancer therapeutics, vaccines, diagnostics, microbiome, stem cells, and nutritional products.

[1] Amgen Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017)

[2] Amgen Inc. v. Sanofi, 987 F.3d 1080 (Fed. Cir. 2021). A petition for a writ of certiorari was filed with the Supreme Court of the United States in November 2021.

[3] A petition for a writ of certiorari was filed with the Supreme Court of the United States in November 2021.

[4] https://register.epo.org/application?number=EP05783732&lng=en&tab=doclist

[5] https://register.epo.org/application?number=EP13746964&lng=en&tab=doclist

[6] https://www.hgf.com/healthcare-scanner/the-epo-how-to-guide-for-antibody-applications-in-europe/

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