Tocilizumab – UK/USA

On Aug 24, 2018, England and Wales High Court (Patents Court) found Chugai’s product not infringing UCB’s patent & denied royalty.

This case is about United States patent 7,566,771 (expires in 2026); entitled “Humanized Antibodies”. The patent is licensed to the Chugai under a patent licence agreement between Chugai and UCB. This worldwide licence was entered into on 10^th December 2007. Royalties are due on sales of a relevant product in a territory if that product falls within the scope of one of the claims of a patent which is in force in that territory, unless and until that patent expires or is finally held invalid.

Chugai has a pharmaceutical product called tocilizumab. Tocilizumab is an immunosuppressive drug mainly used in the treatment of rheumatoid arthritis. It is a humanised antibody to the interleukin-6 (IL-6) receptor. The brand name for Chugai’s tocilizumab in the USA is Actemra. Chugai has been paying royalties under the licence in relation to sales of tocilizumab. In this particular action, Chugai contends that tocilizumab does not “infringe a Valid Claim of the 771 patent and therefore does not attract royalties to the extent the product is manufactured after 13^th January 2016 (when other remaining patents expire). Accordingly Chugai contends that once the 771 patent is the only remaining patent in force, no royalties are due under the licence for such products. Chugai seeks an appropriate declaration to that effect from the English court.

By the trial the issues had narrowed down to the single question of whether tocilizumab falls within the scope of claim 2 of the 771 patent. Claim 2 is provided herein below:

2. A humanised antibody molecule having affinity for a predetermined antigen and comprising a composite heavy chain and a complementary light chain, said composite heavy chain having a variable domain including complementarity determining regions (CDRs) and framework regions, wherein, according to the Kabat numbering system, in said composite heavy chain: said CDRs are non-human donor at residues 31 to 35, 50 to 58, and 95 to 102; and said framework regions are non-human donor at:

a) residue 6;

b) one or more of residues 23 and 24;

c) one or more of residues 48 and 49;

d) one or more of residues 71 and 73;

e) one or more of residues 75, 76, and 78; and

f) one or more of residues 88 and 91;

provided that said heavy chain is not a chimeric antibody heavy chain having a donor variable domain and a human constant region.

Chugai contends that on UCB’s construction of the claim, the claim would be invalid because it would cover a prior art antibody called anti-Tac described in a reference called Queen. UCB admits that on its case on claim construction the antibody in Queen would indeed fall within the relevant claim and also admits, for the purposes of these proceedings only, that that would make the claim invalid. However, UCB’s submission is that subject to one point, this consequence is irrelevant to the issues the English court has to decide. UCB maintains its case on construction and argues that Chugai’s true remedy is and has always been to bring proceedings in the US court to invalidate the relevant claims. If those proceedings were to be commenced, one of the things UCB has made clear is that it would defend such an invalidity attack on the basis that it can “swear behind” Queen. 

Court after hearing both the parties said that the claims alone could be read either way. The specification, which is the single best guide and primary basis for construing the claims, is hard to interpret and contains some material which positively supports one side and some material which positively supports the other side. The prosecution file is similar, containing statements which support each side’s case. The extrinsic evidence, albeit the least powerful source of evidence, is different. It firmly supports Chugai construction of “donor” residue. Court said that claim 2 can be seen that for an antibody to fall within the claim requires that certain specified residues in the framework region “are non-human donor”. UCB’s case is that “donor” includes conserved residues. Chugai’s case is that the term “donor” is used to describe source and so, since the source of the acceptor framework region is human, only framework residues which have been changed into a different mouse residue count as donor. An unchanged framework residue is an acceptor residue. Thus for the numbered framework residues set out in the claims, any framework residues which are conserved as between the murine and human sequences are not “donor”. Court held that on UCB’s case the claim would cover an antibody for which no changes were made at all but, despite the breadth of the description, and the suggestion that one way to go is to go for high homology, the idea of no changes at all is not suggested anywhere and in court’s judgment the person of ordinary skill in the art would not understand the specification to go that far.

Thus, Court held that Chugai’s tocilizumab product does not infringe a valid claim of US patent 7,566,771. No royalties are due for tocilizumab under the patent licence between Chugai and UCB for product manufactured after 13^th January 2016.