Written description under 35 U.S.C. §112 is a primary battleground for antibody patent disputes. Small molecule compounds with a small change in structure may possess very different properties, while antibodies with varying amino acid sequences may possess similar binding properties. Claims to a genus of amino acid sequences may not fully cover the essence of the invention, but claims to their functional properties may. So, patent applicants often employ functional claims to cover antibody inventions. This article will discuss several cases relating to antibody claims, in particular, functional antibody claims.
The “Newly Characterized Antigen” Test
“[T]he written description requirement with respect to particularly claimed subject matter is met if the specification shows that the stated inventor has in fact invented what is claimed, that he had possession of it.” AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1299 (Fed. Cir. 2014); see also Manual of Patent Examining Procedure (MPEP) §2163 (I) ¶ 2 (9th ed., rev. 08.2017). The specification must fully set forth the claimed invention through words, structures, figures, diagrams, or formulas. MPEP §2163 (I) ¶ 3. The USPTO, however, previously provided an exception to this general rule for antibody claims with the so-called “newly characterized antigen” test. MPEP §2163 (II)(A)(3)(a) appearing in the “Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1, ‘Written Description’ Requirement,” 66 Fed. Reg. 1099 (Jan. 5, 2001) and later in the March 2008 USPTO Written Description Training Materials Revision 1. This test allowed written description support for a claim to a genus of antibodies through the disclosure of a newly characterized antigen if the production of such antibodies was conventional or routine. This test was a powerful tool allowing patent owners to obtain claims covering any potential competing products that bind to the same epitope or antigen.
The “newly characterized antigen” test was recently eviscerated by the Federal Circuit in Amgen, Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). In Amgen, a representative claim of the asserted patents reads:
Claim 1. An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDL[-]R.
Sanofi contended that the asserted claims did not meet the written description requirement. At trial in the lower court, an instruction to jury regarding the written description stated:
In the case of a claim to antibodies, the correlation between structure and function may also be satisfied by the disclosure of a newly characterized antigen by its structure, formula, chemical name, or physical properties if you find that the level of skill and knowledge in the art of antibodies at the time of filing was such that production of antibodies against such an antigen was conventional or routine.
Id. at 1376. According to Amgen, that jury instruction was correct because it merely restated the law as set forth in previous Federal Circuit cases. Sanofi argued that disclosure of an antigen could not satisfy the written description requirement for a claim to an antibody. Id.
The Federal Circuit disagreed with Amgen, holding that the jury instruction was improper because it permitted “a finding of adequate written description merely from a finding of ability to make and use[.]” Id. at 1378. The Federal Circuit disparaged the “newly characterized antigen” test as not based on “generally known” or “accurately and readily” ascertainable scientific principles, and “flout[ing] basic legal principles of the written description requirement.” Id. “[T]his test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen.” Id. The Federal Circuit remanded the case for a new trial with a direction to amend the jury instructions.
After the Amgen v. Sanofi decision, the PTO issued a memorandum on Feb. 22, 2018, with the subject line: “Clarification of Written Description Guidance For Claims Drawn to Antibodies and Status of 2008 Training Materials” to patent examiners to conform to patent examination with the Federal Circuit case law. The memo acknowledged the court’s decision on the “newly characterized antigen test”:
The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. §112(a) for a claim drawn to an antibody.
Therefore, the memorandum instructs examiners that adequate written description of a newly characterized antigen alone should not be considered an adequate written description of a claimed antibody to that newly characterized antigen, even when the preparation of such an antibody is routine and conventional. According to the USPTO, “personnel should continue to follow the guidance in the MPEP regarding written description (see, e.g., MPEP 2161.01 and 2163), except insofar as MPEP 2163 indicates that disclosure of a fully characterized antigen may provide written descriptive support of an antibody to that antigen.”
Possession of Invention
As with other subject matter, in order to meet the written description requirement, a patent application claiming antibodies must disclose the invention in such detail that a person of ordinary skill in the art would understand that the inventors had possession of the claimed invention at the time of filing the patent application. See Ariad Pharms., Inc. v. Eli Lilly and Co., 598 F.3d 1336 (Fed. Cir. 2010). One approach to show possession of an antibody genus involves drafting patents that disclose either a representative number of species or common structural features of antibodies. See Id. at 1350 (stating “functional claim language can meet the written description requirement when the art has established a correlation between structure and function.” emphasis added). But, when the claims are challenged, the courts will look closely to the species disclosed in the specification, as well as the relationship between the disclosed structures and the claimed functionality, if any. There is no hard and fast rule for how much data is sufficient to support an antibody genus claim. But if an accused infringer can identify an antibody that is covered by the patent claims but has significantly different properties from the disclosed species, or if the disclosed species is found not representative of the claimed antibody genus, the patent will likely be declared invalid for lack of written description.
Such was the case in Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341 (Fed. Cir. 2011). There, Centocor sued Abbot for infringement of U.S. Patent No. 7,070,775, claiming a humanized antibody with the ability to bind to a specific epitope:
- An isolated recombinant anti-TNF-? anti-body or antigen-binding fragment thereof, said antibody or antigen-binding fragment comprising a human constant region, wherein said antibody or antigen binding fragment (i) competitively inhibits binding of A2 (ATCC Accession No. PTA–7045) to human TNF-?, and (ii) binds to a neutralizing epitope of human TNF-? in vivo with an affinity of at least 1×10 8 liter/mole, measured as an association constant (Ka), as determined by Scatchard analysis.
- The antibody or antigen-binding fragment of claim1, wherein the antibody or antigen binding fragment comprises a human constant region and a human variable region.
The Federal Circuit conducted an objective inquiry into the “4 corners of the specification,” noting that a “mere wish or plan” for an invention was not enough to satisfy written description. Id. at 1348. The specification must describe an invention understandable to a person of ordinary skill that shows the inventor actually invented it. Id. Abbott argued that Centocor was not in possession of the claimed antibody at the time of application because the specification did not disclose “any fully-human, high affinity, neutralizing, A2 specific antibody,” and therefore did not satisfy written description. Id. In Centocor, the Federal Circuit did not reject the “newly characterized antigen test;” rather, the court distinguished the case from the scenarios described in the USPTO guidelines concerning the “newly characterized antigen test.”
Abbott showed that Centocor’s specification described a single mouse variable region, but that could not serve as written description support for a human variable region, which was “’very different’ from the sequence of a human variable region[.]” Id. at 1350. The Federal Circuit agreed with Abbott:
while the patent broadly claims a class of antibodies that contain human variable regions, the specification does not describe a single antibody that satisfies the claim limitations. … There is nothing in the specification that conveys to one of skill in the art that Centocor possessed fully-human antibodies or human variable regions that fall within the boundaries of the asserted claims.
Id. at 1350-51.
Like functional composition claims, patents must also take care to provide written description support for any claimed antibody genus recited in the method of treatment claims. As the variation in the genus grows, each particular species becomes less representative. One example of this principle, In re Alonso, 545 F.3d 1015 (Fed. Cir. 2008), involved patent claims to a method of treating neurofibrosarcoma reciting a broad antibody genus. The specification at issue disclosed a single antibody, but the patent claimed a method of treatment reciting a large genus of antibodies, essentially any monoclonal antibody that binds to a neurofibrosarcoma:
[a] method of treating neurofibrosarcoma in a human by administering an effective amount of a monoclonal antibody idiotypic to the neurofibrosarcoma of said human, wherein said monoclonal antibody is secreted from a human-human hybridoma derived from the neurofibrosarcoma cells.
The court held that the specification lacked written description for the broad, heterogeneous genus of all monoclonal antibodies against patient-derived neurofibrosarcomas. Even though the applicant had reduced the invention to practice, i.e., they had synthesized at least one representative species and used it in treatment, the Federal Circuit held the specification lacked an adequate description of the antibodies and did not satisfy written description requirements, because just “one compound disclosed by Alonso cannot be said to be representative of a densely populated genus.” Id. at 1021.
The Amgen v. Sanofi decision put most functional antibody claims into question, including epitope and competitive binding claims, as well as antibody claims based on a newly characterized antigen. After Amgen v. Sanofi, non-sequence based antibody claims may become more difficult to obtain before the USPTO from a written description standpoint. Yet, to fully protect the essence of the invention and avoid design-arounds, such claims are extremely valuable to patent owners. To obtain antibody genus claims beyond those defined by sequences, the patent applicant will need to make and test a sufficient number of representative antibodies across the claimed genus, or establish a clear structure/function relationship among the members of the genus. Patent applicants should carefully assess the amount of data they have acquired, in comparison to the scope of claims that they wish to obtain, before rushing to the Patent Office.