The High Court has ruled that Janssen Alzheimer Immunotherapy’s patent EP 1994937, claiming the use of a class of antibodies for treating Alzheimer’s disease, is invalid on grounds of insufficiency. The case is principally of note in relation to the relevance of post-patent publications when considering insufficiency.
Eli Lilly had sought revocation of Janssen’s patent on the grounds of added matter, lack of novelty, obviousness and insufficiency, and had also applied to the Court for a declaration that solanezumab, a medicinal antibody in development, would not infringe the patent.
In Alzheimer's disease the beta-amyloid peptide (‘β-amyloid’) collects to form deposits in the brain, known as plaques, which disrupt neurological function. There are several β-amyloid peptides of different lengths created when a precursor protein (the β-amyloid precursor protein 'APP') is cleaved by different enzymes. The disputed patent claimed a pharmaceutical composition comprising a human IgG1 antibody to β-amyloid for use in preventing or treating a disease characterised by β-amyloid deposits.
The two principal issues before the Court were added matter and insufficiency. Eli Lilly argued that added matter had resulted in Janssen’s patent not being limited to antibodies which induced an immune response. Arnold J held that the administration of the claimed therapeutic antibody would produce an immune response, and that even if the claim did cover antibodies that did not produce an immune response, it did not disclose such antibodies. Arnold J also held that the limitation in the granted claims to antibodies of the human IgG type served merely to restrict the scope of the claims, and did not constitute added matter.
The evolving law on insufficiency
Section 72(1)(c) of the Patents Act 1977 requires that for a patent to be valid, it must specify the invention ‘clearly enough and completely enough’ for it to be performed by a person skilled in the art. Failure to enable the invention to be performed without undue burden is often referred to as ‘classical insufficiency’. Failure to enable the invention to be performed over the whole scope of the claim is often termed ‘Biogen insufficiency’, following the ruling in Biogen v Medeva which established that a claim will be invalid for sufficiency if the scope of the claim exceeds the technical contribution to the art made by the invention.
In the assessment of the principle of undue burden, the Court of Appeal has recently held in Regeneron v Genentech that a valid patent must show that a medicinal product has an effect on the disease process so as to make the claimed therapeutic effect plausible. The law on the excessive scope of claims was recently reviewed in MedImmune v Novartis as well as in Regeneron v Genentech where Kitchin LJ stated that the scope of a claim would exceed the technical contribution if it was not possible to make a reasonable prediction that the invention could be performed with substantially everything falling within the scope of the claim.
In assessing the scope of the claim, Arnold J had to consider the admissibility of evidence not available at the patent publication date. Previously, in Generics v Yeda there were restrictions placed on the degree to which information, published after the disputed patent, can be relied on in relation to obviousness, and in particular restrictions on the use of post-patent literature to establish or rebut a claimed technical effect.
In assessing the recent case law, Arnold J rejected Janssen’s submission that there should be restrictions on the use of information published after the disputed patent in regard to sufficiency. The decision in Regeneron v Genentech related to obviousness and not sufficiency, and it is well established that post-dated evidence was generally permissible in a dispute concerning the validity of a patent. Instead, Arnold J set out a two stage process. First, it is necessary to determine whether the disclosure of the patent (read in light of the general knowledge of the skilled man) makes it plausible that the invention will work across the scope of the claim. If the disclosure does make it plausible, then it is necessary to consider whether the later evidence establishes that in fact the invention cannot be performed across the scope of the claim without undue burden, or is of excessive breadth.
Arnold J held that Janssen’s patent was invalid on grounds of insufficiency. First, although Janssen’s patent did make it plausible that a suitable antibody to β-amyloid will be effective to treat Alzheimer’s disease, the teaching of the specification suggested selecting an N-terminal antibody and did not make it plausible that all antibodies to β-amyloid will be effective to prevent the disease.
In case he was wrong about this, the judge went on to analyse both classical and Biogen insufficiency in greater depth. Since a later Phase 3 clinical trial had demonstrated that despite a decade of work, the patentee had not succeeded in making a suitable therapeutic antibody, the patent was ‘classically insufficient’. Further, and again by reference to post-patent publications, it was held that it was not possible for a person skilled in the art to perform the invention across the whole breadth of the claim without undue burden, as in the words of Arnold J, ‘the patent did no more than invite the skilled team to perform a very significant research project with a high prospect of failure’.
This decision demonstrates the challenges in obtaining strong patent protection for medicinal products used to treat medical conditions with uncertain pathologies and that are difficult to diagnose, such as Alzheimer’s disease where various isoforms of β-amyloid are implicated. This case highlights the perennial question of when lifescience inventors should prosecute their inventions, torn between obtaining an early filing date and in generating more significant clinical data to substantiate their claims. In the competitive arena of lifescience research, the high cost of lengthy R&D programs often prompts companies to file for patent protection at the earliest possible opportunity in order to protect the investment made in their clinical assets. Should inventors wait for the results of extensive and time-consuming clinical trials, in doing so they risk a competitor filing before them. However, in rushing to file too early on in the developmental process to secure an early filing date, they run the risk of potential revocation of their patent on grounds of insufficiency.
For the full judgment, please click here.