Source: https://www.ipwatchdog.com/2018/05/18/patenting-antibodies-written-description-considerations-antibody-patents/id=97398/
Timestamp: 2019-04-19 00:25:10+00:00

Document:
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.
“[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.
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.
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.
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.
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.
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.
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.
[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.
I have to admit up front that I am possibly forty years out of date on this issue of structural vs. functional claiming for an antibody treatment or therapy, but from browsing current literature, I have to hypothesize the following.
If I were a researcher in this particular art, merely sequencing would not seem enough to understand how the treatment or the therapy operated in a patient. I would probably try to characterize the structure of the antibody at least in crystalline form.
The data from x-ray crystallography could provide information helpful to identifying a genus of antibodies that could be effective in treatment or in therapy.
Such data might also be helpful in developing alternate methods of production for an embodiment. Such data might also provide enablement for production of the other members of the genus that I might wish to claim.
In addition, software is available for generating (theoretical) structure from amino acid sequences. Such structure can also be helpful for suggesting new syntheses, similar treatments, or alternate treatments.
Today there seems to be much knowledge that should be disclosed if an inventor of a new antibody treatment or therapy is trying to claim a genus in addition to a specific embodiment.
AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1299 (Fed. Cir. 2014) seems to align the art with the current state of technology.
Sorry, I meant that Amgen, Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) seems to align the art with the current state of technology.

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