Anticipation Through Incorporation by Reference Legally Permissible

In a recent Federal Court decision dated May 12, 2025 (Alexion Pharmaceuticals, Inc v Amgen Canada Inc, 2025 FC 754), Alexion successfully defended its Canadian Patent No. 2,645,810 (CA810) against allegations of anticipation and obviousness and succeeded in preventing Amgen from entering into the market with its eculizumab biosimilar.

In one interesting aspect of the decision, the Court ruled that an allegedly anticipating prior art document could in principle be combined with another document that was “incorporated by reference”.

Context: The usual rule in anticipation under Canadian law is that all of the essential claim elements must be found in a “prior, single publication”. (Free World Trust, 2000 SCC 66 at para 26.)

However, the prior art reference at issue in Alexion was a prior US patent (US972) which referred to another prior art document (US245) using the common patent drafting practice of “incorporation by reference”. In many jurisdictions (but not in Canada) patent specifications are often drafted to refer to other documents and include its teachings using a phrase such as “the contents of which are herein incorporated by reference”. This is often employed as a quick way to add support in a patent specification for various teachings without reproducing passages from another document.

Amgen argued that the Court should look not only at US972, but also to US245 for anticipatory disclosure. This was necessary because US972 did not disclose the full sequence of eculizumab and the asserted Example 4 within US972 would not necessarily lead to the preparation of eculizumab – it only disclosed an antibody framework for production of a recombinant antibody product but not to a specific antibody or fragment.

US245, by contrast, disclosed a murine monoclonal antibody and other antibody fragments including humanized fragments (notably, one of the CDR heavy chains that form part of eculizumab), although US245 did not disclose any full-length humanized antibodies. To arrive at eculizumab (a humanized monoclonal antibody that had heavy chains which specifically bind to C5), a skilled person would have had to start with the example from US972 as a “scaffold” and then select a relevant humanized fragment (in particular, a CDR3 fragment) from US245 that corresponded to eculizumab.

Incorporation by reference legally permissible: The Court rejected the patentee Alexion’s argument that reading two prior art references was impermissible for anticipation. Instead, the Court held, relying in part on the Manual of Patent Office Practice (a collection of practice guidelines for Canadian patent prosecution which is not legally binding), that if the primary source “makes explicit reference to specific teachings in a secondary source” with sufficient precision, then “incorporated reference is not being used to add new teachings to the primary document to create a cumulative effect where the PSA [person of skill in the art] is left to look to multiple sources to determine what information to combine. Rather, the primary source leads the PSA directly to the information that completes the disclosure.”

In other words, the Court held that where the anticipating reference makes an explicit and precise reference to another document, those two references together, could at law anticipate a later invention.

US972 and its reference to US245 did not anticipate eculizumab. Although the Court held that incorporation by reference was legally permissible, it did not find in Amgen’s favour on the facts. For one, the Court noted that the asserted portion of the primary reference, US972, did not refer generally to US245 but only to a specific construct.

Moreover, US972 did not specifically direct a skilled person to the particular sequence or CDR3 fragment that would have corresponded to eculizumab (there were 12 heavy chain sequences disclosed in US245). Thus, in the Court’s view the attempt to reconstruct eculizumab would require “reverse engineering” in combining the scaffold with the relevant heavy chain.

The Court opined that this would require a “mosaic” of information from the two references that went beyond incorporation of specific information by reference. In the Court’s words, these steps “necessitate the PSA choosing specific bits and pieces from US245 and assembling this with other information from US972. This amounts to more than mere direction from US972 to specific information in US245.”

The Court also held in the alternative that even if the full disclosure of US245 were to be incorporated by reference into US972, it would not have been sufficient to anticipate Alexion’s eculizumab patent because the asserted example of US972, even combined with all of US245, would not “inevitably” lead the skilled person to eculizumab.

Eculizumab patent also not obvious. In a separate analysis, the Court also found that Alexion’s patent was not obvious. Notably, with respect to US972, the Court noted that it did not disclose whether the asserted examples had any immunologic effects, and did not disclose any anti-C5 activity studies. Since the inventive concept was found to include C5 binding and the identification of the specific heavy chains that led to this binding, the Court found that the skilled person would not have considered US972 “to be a reference of particular interest to pursue”.

In the result, Alexion’s patent infringement claim was allowed and Amgen was enjoined from entering into the market with its eculizumab biosimilar (BEKEMV) until expiry of Alexion’s CA810 patent.

Amgen has appealed the decision to the Federal Court of Appeal.