Court dismisses first biologic prohibition application

Amgen brought this prohibition application to prevent the issuance of a Notice of Compliance to Apotex for its proposed filgrastim product. The order would last until the July 31, 2024 expiry of Amgen’s Canadian Patent No. 1,341,537, entitled “Production of Pluripotent Granulocyte Colony-Stimulating Factor” and which is listed on the Patent Register against Amgen’s filgrastim product, NEUPOGEN.

Prior Art

The most relevant piece of prior art was the Welte paper, wherein its authors had partially purified and characterized human G-CSF, from a particular bladder carcinoma cell line. The Welte paper did not disclose the amino acid sequence of GCSF and concludes with the following paragraph:

Constitutive production of pluripotent CSF by the bladder carcinoma cell line 5637 suggests that it is a valuable source for large-scale production and for isolation and cloning of the gene that codes for pluripotent CSF. The availability of purified human pluripotent CSF has important and far-reaching implications in management of clinical diseases involving hematopoietic derangement or failure.

Skilled Person

One area of dispute between the parties was the expertise of the skilled person. While both Amgen and Apotex agreed that the 537 Patent was directed to a team with expertise in biochemistry, molecular biology and hematology, Amgen argued that in the mid 1980s almost all molecular cloning was accomplished in highly sophisticated labs and that Amgen attempted to raise the skilled person to the level of skill of the inventors. Justice Hughes held that Amgen had “pitched it too high” when it urged that the skilled team must be persons in highly expert laboratories.

Construction

The only claim at issue, claim 43, is directed to a polypeptide defined by a specific amino acid sequence. Justice Hughes later again construed Claim 43 to be “directed to a polypeptide having an amino acid sequence beginning with methionine with the remainder of the sequence having some or all of the sequence and some or all of the biological properties of the natural factor identified by Welte.”

Anticipation

The presence of a methionine at position 1 of the claimed amino acid sequence made it sufficiently different from endogenous protein to rebut Apotex’s allegation of anticipation. On this point, Justice Hughes reasoned:

[80] I am satisfied, on the evidence before me, that the product of Claim 43 is not identical to the “natural” product of Welte because of the inclusion of the “Met” at the beginning of the amino acid sequence, and because the amino acid sequence of Claim 43 following the “Met” is quite possibly but not certainly the sequence of the natural product. Therefore, I am satisfied that Amgen has shown that Apotex’s allegations in respect of anticipation (lack of novelty) are not justified.

Obviousness

Justice Hughes construed the inventive concept of Claim 43 to be “a recombinantly produced polypeptide having an amino acid sequence beginning with a Met followed by some or all of the amino acid sequence of the Welte protein possessing some or all of its biological properties.”

Justice Hughes noted that Welte laid the groundwork for the PSA to find the claimed invention by routine experimentation using established methods:

[93] The Welte article is the most relevant piece of prior art. Techniques for taking the various steps undertaken by Amgen were known. There were a variety of choices to be made at each step and each step had to be carefully undertaken. A wrong choice or improperly conducted step could lead to failure. However, Amgen did not utilize any hitherto unknown step or technique.

Justice Hughes then went on to find that in light of Welte, Amgen’s work amounted to “skilled work” but not “creative work” necessary to deserve patent protection:

[106] In this case, Welte found the protein and said to the readers of his paper to go out and make it in quantity. Amgen did that. Perhaps Amgen did so using an inventive process, and perhaps it is entitled to a patent claiming such a process or processes. I note that there are several claims in the ‘537 patent directed to processes. The end product, which is simply the protein made by whatever process, was not itself inventive. Welte clearly and unambiguously pointed to that protein, leaving to others to devise new processes, or use old processes, to get that product in quantity. Amgen did that and obtained a product having an amino acid sequence beginning with a Met. The addition of the methionine, as pointed out in paragraph 78, was simply part of the process necessary in order to create the recombinant protein that Welte said should be made.

Sound Prediction

Justice Hughes rejected Apotex’s arguments that the 537 Patent promised that the subject matter of claim 33 had therapeutic utility, noting that the statement in the 537 Patent upon which Apotex relied starts with the word “also”. While the promise of therapeutic utility may apply to claim 33, it did not apply to claim 43.

Costs

Both parties narrowed their cases gradually leading up to trial. At a prehearing conference a few weeks before the hearing, Apotex confirmed that it would be pursuing all of the allegations in its NOA. On the eve of the hearing, however, Apotex dropped its allegation of non-infringement and reduced its allegations of invalidity to four, one of which was subsequently dropped at the hearing. Given this constantly changing scenario, Justice Hughes Ordered the parties shall each bear their own costs.

Justice Hughes’ decision is available here.