By Christopher Tan & Alexander Watts
On May 12, 2025, the Federal Court allowed Alexion’s action under the Patented Medicines (Notice of Compliance) Regulations in relation to the drug eculizumab (Alexion’s SOLIRIS®). Alexion had alleged that Amgen infringed Claims 1 and 2 (the “Asserted Claims”) of Canadian Patent No. 2,645,810 (the “810 patent”), entitled “Treatment of Paroxysmal Nocturnal Hemoglobinuria Patients by an Inhibitor of Complement”. Amgen admitted infringement of the Asserted Claims, but in defence, alleged that the 810 Patent was invalid for anticipation and/or obviousness. Justice Furlanetto found that Amgen did not establish that the Asserted Claims are invalid for either anticipation or obviousness: Alexion Pharmaceuticals, Inc v Amgen Canada Inc, 2025 FC 754.
Practice highlights from this case
- Strict Limits on Incorporation by Reference Reinforce the Single-Document Rule for Anticipation
The Court reaffirmed that for anticipation to be established, a single prior art reference must disclose the claimed invention clearly and completely, unless a secondary source is expressly incorporated with specific direction. The burden to show that information from a second source would actually be consulted by the skilled person is on the party seeking to use the second source. - An intention to disclose before filing is not equivalent to an actual invalidating disclosure
Alexion’s submission and disclosure of an eculizumab sequence did not amount to an enabling public disclosure, as the deposited sequence contained significant errors and there was no evidence that further inquiries by a skilled person would have been routine practice.
A party seeking to rely on prior art that was intended for disclosure but never actually disclosed, must show that the skilled person, using the common general knowledge, could derive the error from the prior art document and would attempt to make further inquiries into correcting the error.
The reverse scenario — where an enabling disclosure is made unintentionally or by mistake — is still invalidating. This includes situations where disclosures are made to third parties without any restrictions that would prevent the information from entering the public domain, such as those typically imposed by a formal confidentiality agreement or joint venture arrangement (see g., Wenzel Downhole Tools Ltd v National-Oilwell Canada Ltd, 2011 FC 1323 at paras 138, 142).
Background
SOLIRIS is an intravenously administered biologic drug containing eculizumab as its active ingredient. Eculizumab is a recombinant humanized monoclonal antibody, which is used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder that causes the breakdown of red blood cells. SOLIRIS prevents cleavage and the terminal complement pathway from attacking abnormal red blood cells by binding to complement protein C5, thereby protecting red blood cells from lysing and, as a result, stabilizing hemoglobin levels.
The 810 Patent is listed on the Patent Register against SOLIRIS. As such, Amgen (and any other party seeking to market a biosimilar eculizumab drug product in Canada) is required to address the 810 Patent (and any other patent listed on the Patent Register) by either establishing that the patent(s) will not be infringed and/or that the patent(s) is invalid. The 810 Patent was filed on March 15, 2007, published on September 20, 2007, issued on December 11, 2018 and will expire on March 15, 2027. Although the 810 Patent has a priority claim, Alexion did not seek to assert the priority date. As such, the Court considered whether the 810 patent was anticipated or obvious as of March 15, 2007.
The 810 Patent states that in certain embodiments, the antibody that binds C5 has a heavy chain that consists of SEQ ID NO:2 and a light chain that consists of SEQ ID NO:4 (the full amino acid sequence is provided for both heavy and light chains). Together, these defined sequences correspond to the structure of eculizumab.
Asserted Claims
The 810 Patent includes 16 claims, only two of which were at issue; Claims 1 and 2 of the 810 Patent read as follows:
- An antibody that binds C5 comprising a heavy chain consisting of SEQ ID NO:2 (“Heavy Chain Sequence”) and a light chain consisting of SEQ ID NO:4 (“Light Chain Sequence”).
- A pharmaceutical composition comprising the antibody of claim 1 and a carrier.
Anticipation
Amgen asserted that Claims 1 and 2 are anticipated by United States Patent Application Publication No. 2003-0232972 (“US972”), which claims the use of antibodies as a structural framework to provide mimetic peptides with enhanced stability. US972 discloses both a light chain and heavy chain sequence which is the same as the Light Chain Sequence and Heavy Chain Sequence of eculizumab, respectively, except that the native complementarity determining region (“CDR3”) of the heavy chain was substituted for a thrombopoietin mimetic peptide.
While it was not disputed that US972 does not disclose the full sequence of eculizumab, Amgen argued that the skilled person would look to US Patent No. 6,355,245 (“US245”) — which is cited in both the 810 Patent and US972 — as teaching the humanized constructs of the native CDR3 region for binding C5. According to Amgen, transplanting the CDR3 sequence from US245 into the antibody scaffold disclosed in US972 would result in eculizumab. Alexion disagreed, maintaining that US972 does not direct the skilled person to reconstruct eculizumab and that its preparation is not a necessary outcome of following US972’s teachings.
Alexion also took issue with Amgen’s reliance on US245 as part of the teaching of US972 and argued that eculizumab is not necessarily made in the preparation of the US972 antibody product. The Court noted that the critical factor for anticipation is whether the prior reference provides clear direction, such that the skilled person would arrive inevitably at the claimed invention. Where an incorporation by reference is used, it will depend on what directions the primary source provides as to how the incorporated reference is to be used. It is only where the incorporation is explicit and directs the skilled person to specific teachings that are necessary to complete the disclosure that more than one publication may be deemed a single prior publication. This reinforces the long-standing prohibition against ‘mosaicking’ prior art in anticipation analyses and clarifies that incorporation by reference depends “on what directions are provided in the primary source as to how the incorporated reference is to be used.” The Court held that Amgen’s approach was akin to using incorporation by reference to mosaic information from US245 with teachings from US972 due to the lack of clear direction.
Amgen’s reliance on US245 was inconsistent with the requirement that anticipation be based on a single disclosure, as US972 alone did not meet the standard for enabling disclosure. The Court emphasized that US972 did not instruct the skilled person to use a “reverse cloning” approach to recreate eculizumab and agreed that, while it might be possible to produce eculizumab using the patent’s teachings, “this approach would only arise as a matter of hindsight” in the mind of the skilled person. Accordingly, US972 did not provide the clear and unambiguous disclosure required to anticipate the claims of the 810 Patent.
Obviousness
As eculizumab was known by the claim date to selectively bind C5, the Court accepted that the inventive concept of Claim 1 was the identification of eculizumab’s specific Heavy Chain Sequence and Light Chain Sequence. The inventive concept of Claim 2 is the formulation of the antibody of Claim 1 into a pharmaceutical composition so that it can be delivered to a patient to provide the intended therapeutic effect.
As part of the state of the art, numerous publications and disclosures were reviewed by the Court, including Alexion’s depositing — without any obligation of confidentiality — of what it thought was the correct amino acid sequence for eculizumab with the Chemical Abstract Service (“CAS”). However, this CAS sequence included significant errors. As a result, while the Court agreed that the evidence indicates that Alexion wanted to disclose the sequence of eculizumab to the public as early as 1999, by depositing a sequence that had errors, it did not do so. Expert evidence about whether the skilled person would have inquired with CAS or Alexion about the sequences was not before the Court, though it was apparent the skilled person could have done so. Alexion’s intention to disclose was therefore found to be distinct from actual disclosure.
The Court concluded that from the state of the art, the skilled person would have known that Alexion had a drug named eculizumab, which was associated with the humanized murine monoclonal antibody 5G1.1, selective for C5, and being used to treat patients with PNH. The Court concluded however, that none of the prior art disclosed both the Heavy Chain Sequence and Light Chain Sequence.
The Court therefore held that, although the prior art described components of similar antibodies, the prior art did not demonstrate a clear and obvious path to the claimed invention. Justice Furlanetto concluded that the PSA would not have been led, without hindsight, to select and combine the prior art references to reconstruct eculizumab’s precise structure. In particular, the Court noted the absence of disclosure or suggestion in the prior art connecting the specific sequences of Claim 1 with therapeutic success. As such, the skilled person would not be able to bridge the differences between the state of the art and the claimed invention using only routine skill and the common general knowledge such that the Asserted Claims were found to be non-obvious.
Conclusion
In summary, the Court determined that the Asserted Claims of the 810 Patent were both valid and infringed. Justice Furlanetto dismissed Amgen’s arguments relating to anticipation and obviousness in their entirety.
Amgen has appealed the decision to the Federal Court of Appeal (Court File No. A-207-25).
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