For the first time, in Re Immunex Corporation Patent Application No 583,988 (Commissioner's Decision 1302), the commissioner of patents has allowed claims directed to monoclonal antibodies in the absence of a working example in the patent specification demonstrating the preparation of at least one monoclonal antibody within the scope of the claims.

Canadian patent applications filed before October 1 1989 under the old Patent Act are not laid open for public inspection until grant. Application 583,988 was filed on November 24 1988, but the patent was issued only on April 12 2011. Accordingly, neither the application file nor the commissioner's decision, rendered in June 2010, were available to the public until very recently.

In the June 2010 decision the commissioner considered whether the description could provide sufficient support for claims directed to monoclonal antibodies in light of the fact that there was no working example in the specification of any such monoclonal antibody and no supporting biological deposit. The claims at issue in the application were directed to monoclonal antibodies immunoreactive with IL-1R polypeptides and monoclonal antibodies produced by a claimed process.

In addressing the question of sufficient support, the commissioner addressed the questions of whether:

  • the claimed monoclonal antibodies were enabled;
  • such antibodies were adequately described; and
  • such antibodies were useful.

The commissioner accepted that in foreign jurisdictions, monoclonal antibodies are typically described and claimed in terms of immunoreactivity with a defined antigen, and that valid claims may issue even if no working example has been provided to demonstrate actual production of a monoclonal antibody falling within the scope of the claim. Enablement in such jurisdictions has generally been accepted in view of the maturity of monoclonal antibody production technology.

Thus, in Immunex the issue of enablement of a monoclonal antibody defined in terms of immunoreactivity with a particular polypeptide antigen was found by the commissioner to rest on whether the polypeptide itself was enabled by the description. The commissioner concluded that the description disclosed the construction, expression and purification of Type I IL-1R polypeptides, and that a skilled person would appreciate that the Type I IL-1R polypeptides would be immunogenic. Thus, the specification was enabling for monoclonal antibodies immunoreactive with Type I IL-1R polypeptides. When addressing the issue of enablement, the commissioner considered post-filing evidence relating to the routine nature and success of methods of preparing the anti-IL-1R monoclonal antibodies based on techniques described in the specification.

The commissioner in Immunex also looked to the following factors enumerated in a previous decision in Re Central Sydney Area Health Service Patent Application No 605,669 (Commissioner's Decision 1283):

  • whether there is a description of the antigenic polypeptide and knowledge of its real or expected immunogenicity;
  • the scope of the antibody claim;
  • the availability or ease of producing the polypeptide;
  • whether a monoclonal antibody was actually prepared;
  • indications of success or failure of preparing a monoclonal antibody;
  • any indications that suggest undue experimentation is required; and
  • any indications of irreproducibility of an actual or proposed method of preparing a monoclonal antibody.

The commissioner then addressed whether there was adequate "specific description" of the monoclonal antibodies. It was held that where the antigen is a novel polypeptide that has been fully characterised (eg, by sequence), the applicant can claim monoclonal antibodies that are immunoreactive with the polypeptide without having made or deposited a specific embodiment, as with the described novel Type I IL-1R polypeptides. However, the commissioner noted that in cases where the antigenic material is complex or includes known epitopes, or the antibodies are claimed as therapeutic or diagnostic antibodies, preparation and characterisation may be required.

Finally, the commissioner addressed utility of the claimed monoclonal antibodies. In the final rejection, the examiner had raised questions about the lack of support for utility of monoclonal antibodies that had not been made. The commissioner reasoned that if monoclonal antibodies were enabled and could be made without undue experimentation, such antibodies would necessarily be able to bind to the specified antigen. The soundness of prediction of utility would be self-evident: the enabled monoclonal antibodies would have at least utility in assays for, or immunopurification of, the specified antigen.

Thus, Immunex provides that where a monoclonal antibody is described in reference to immunoreaction with a defined, characterised polypeptide, claims to the monoclonal antibody do not require demonstration that such a monoclonal antibody has in fact been made, provided that there are no uncertainties regarding the description of the antigen or the antigenicity of the antigen, and that there are no higher levels of utility required, such as therapeutic or diagnostic utilities.

In Immunex the antigen was a well-defined polypeptide and was therefore accepted as being immunogenic. For antigens that are not well-defined polypeptides or where immunogenicity cannot be assumed, it may be necessary to have further support in the description, for example, to demonstrate immunogenicity of the antigen.

The decision in Immunex reverses the previous position of the Patent Office as set out in Re Institut Pasteur Patent Application (Commissioner's Decision 1206). The decision in Institut Pasteur, rendered on December 11 1995, held that the description in that application did not provide adequate support for claims directed to monoclonal antibodies, since no monoclonal antibodies had in fact been made. There was no 'specific description' of the claimed monoclonal antibodies and no process for the preparation of any such monoclonal antibodies was disclosed. The commissioner in Institut Pasteur held that, as of the January 1986 priority date in that application, techniques for preparing monoclonal antibodies were not routine and were unpredictable. The lack of evidence of even one monoclonal antibody meant that there was no basis for a sound prediction that the claimed antibodies having the desired immunogenicity could be made. Significantly, the decision in Immunex concerns similarly early monoclonal antibody technology, the Canadian application having been filed in 1988.

Thus, Immunex represents a significant step forward in Canadian biotechnology patent law and brings Canadian practice into line with that in other jurisdictions.

The Köhler and Milstein hybridoma methodology for producing monoclonal antibodies was published in 1975 and by the early 1980s was well established and routine. As indicated by the commissioner in Immunex, this state of the art has been acknowledged by patent offices in other jurisdictions, including the United States. However, in view of the 1995 Institut Pasteur decision, until now, Canadian patent applicants have been unable to obtain claims to monoclonal antibodies without a specific working example in the patent specification demonstrating that monoclonal antibodies had been made before the filing of the application.

In Immunex the commissioner has confirmed not only that monoclonal antibodies may be claimed based on the provision of a well-characterised antigen in view of known techniques for making monoclonal antibodies, but also that the state of the art permitted sound prediction of such monoclonal antibodies at least as early as the late 1980s.

For further information on this topic please contact Sally A Hemming at Smart & Biggar/Fetherstonhaugh by telephone (+1 416 593 5514), fax (+1 416 591 1690) or email ().