The Federal Court (FC) has upheld the validity of a patent concerning a biologic drug used to treat patients with paroxysmal nocturnal hemoglobinuria (PNH), a rare blood disorder, in an infringement action under section 6 of the Patented Medicines (Notice of Compliance) Regulations (the Regulations). In reaching its decision, the FC dismissed allegations that the patent was invalid for anticipation or obviousness. The FC granted an injunction and other relief in respect of the proposed biosimilar.
Background
Alexion Pharmaceuticals, Inc. and Alexion Pharma International Operations Limited (together, Alexion) market SOLIRIS® (eculizumab), a biologic drug used to treat PNH. Eculizumab works by binding to protein C5 of the body’s complement system, thereby “preventing its cleavage and the terminal complement pathway from attacking abnormal red blood cells”. (Decision, para. 11) This protects the red blood cells from lysing and stabilizes hemoglobin levels.
Amgen Canada Inc. (Amgen) sought to market a biosimilar eculizumab product, BEKEMV®. It served Alexion with two notices of allegation and in response, Alexion commenced two actions under section 6 of the Regulations claiming that BEKEMV® would infringe claims 1 and 2 of Canadian Patent No. 2,645,810 (the 810 Patent). Claim 1 claimed an antibody that binds to C5 consisting of a specific amino acid sequence for the heavy and light chains of the antibody (i.e., eculizumab). Claim 2 claimed a pharmaceutical composition comprising eculizumab and a carrier.
Amgen admitted infringement; at trial, the only issue was whether the asserted claims were invalid for anticipation or obviousness.
The asserted claims are novel
Amgen’s anticipation argument centred on US Patent Application Publication No. 2003/023972 (US972). This reference disclosed the sequences of the heavy and light chains of eculizumab, but for one difference: instead of the CDR3 portion of the eculizumab heavy chain, US972 taught an antibody that included a “TPO mimetic peptide”. US972 also contained a reference to an earlier patent (US245), which disclosed the heavy chain CDR3 sequence of eculizumab. Amgen argued that the skilled person to whom the patent is addressed (the PSA) could combine US972 and US245 to make the full amino acid sequences of eculizumab.
Anticipation can only be established by a single disclosure (i.e., no mosaicking); as a result, the question became whether the incorporation-by-reference of US245 into US972 amounted to a single disclosure that anticipated the asserted claims.
The FC recognized that, in some circumstances, a primary document may incorporate a secondary document by reference, such that the teachings of the secondary document are considered part of the disclosure. However, quoting from the Manual of Patent Office Practice (MOPOP), the FC emphasized that this is only permissible where the primary document gives “explicit reference to specific teachings in a secondary source, thereby making clear to the skilled reader that the teachings of the secondary source are to be relied on in order to understand or complete the disclosure of the invention in the primary source.” (Decision, para. 76) As the FC put it:
…the sole fact that Example 4 of US 972 uses an incorporation by reference is not enough, on its own, to conclude on anticipation. The critical question is what is disclosed to the PSA by reading Example 4 of US972 and the reference in paragraph [0191] to [US245]. (Decision, para. 80)
Here, the reference to US245 did not reach the level of specificity required to complete the disclosure of US972. The Trial Judge found that US972 did not contain a clear direction to make eculizumab using specific information from US245; rather, the PSA would have had to “reverse engineer” eculizumab. Even if US245 could be incorporated by reference more broadly, the evidence did not establish that Example 4 of US972 would have led the PSA to eculizumab, inevitably and without hindsight. As a result, the FC found the asserted claims of the 810 Patent to be novel.
The asserted claims are inventive
The FC’s obviousness analysis centred on the fourth step of the well-established Sanofi test: would the differences between the prior art and the claimed invention have been bridged by the PSA without inventiveness? The FC agreed with Amgen’s formulation of the question: “whether a PSA specifically looking for the sequence of eculizumab” — the existence of which was known — “would have been led to the claimed sequences.” (Decision, para. 152)
Amgen argued that it would have been obvious for the PSA to bridge the gap between the prior art and the inventive concept by combining (i) US245 with US972 or (ii) US245 with WO 97/11971 (WO971). In support of its argument, Amgen also pointed to a range of other prior art publications as context.
The FC agreed that “while it is possible to mosaic or combine prior art references that are not part of the CGK,” (Decision, para. 163) mosaicking is not automatic. Rather:
As highlighted by Alexion, the obviousness analysis concerns what the PSA would have done in light of the state of the art and their CGK. It is not sufficient to establish what the PSA could have done: Usinage at para 33. (Decision, para. 184)
The FC found that the PSA would not have been led to combine the prior art in the manner argued by Amgen, as there was no clear direction to do so.
For example: the Trial Judge was not “satisfied the PSA would have considered US972 to be a reference of particular interest to pursue” because US972 did not disclose anti-C5 activity studies or a direct connection to eculizumab in the relevant example. (Decision, para. 170) Similarly, the FC found that in order to arrive at the claimed sequence of eculizumab via US245 and WO971, it would have been necessary for the PSA to make a connection between them through the use of certain notation that, while common to both references, would not have been striking or meaningful to the PSA without the benefit of hindsight. The FC concluded:
Admittedly, Amgen’s case is based on a paper record. However, there are too many connections to be made and gaps to fill to establish a clear path to the claimed invention. (Decision, para. 201)
Ultimately, the FC rejected Amgen’s obviousness allegations.
Injunction granted
The FC granted an injunction against Amgen’s proposed biosimilar until the expiry of Alexion’s 810 Patent on March 15, 2027. The FC also ordered Amgen to deliver up to Alexion, or destroy under oath, “all eculizumab product, including, but not limited to, any intermediates, bulk product, and finished product thereof, in Amgen’s power, possession or control that is not otherwise exempted from infringement under the Patent Act that would offend the injunction” granted by the Court. (Judgment, para. 4)
Link to decision
Alexion Pharmaceuticals, Inc. v. Amgen Canada Inc., 2025 FC 754