A recently published decision of the Commissioner of Patents in Re Immunex Corporation Patent Application No. 583,988 1 has provided prospective Canadian patentees of inventions relating to monoclonal antibodies with some long-sought clarity in this rapidly evolving practice area.
The Immunex application was filed on November 28, 1988 and related to interleukin-1 receptors (IL-1R). Claim 29 was directed to “A monoclonal antibody immunoreactive with IL-1R polypeptide.” Claim 54 was added during prosecution to specifically cover an antibody directed to polypeptides defined by sequence, while claim 58 was a parallel product-by-process claim. The Examiner objected to these claims in a Final Action for being insufficiently supported by the description, citing a lack of a specific example of such an antibody, and no supporting biological deposit.
The Applicant argued that the subject matter of the claims, though not specifically exemplified, was supported by a full, enabling disclosure of how to make and use the claimed monoclonal antibodies; the IL-1R protein had been fully described, and detailed protocols for making antibodies had been included. These methods were routine at filing, according to the Applicant.
In its decision, the Patent Appeal Board noted that U.S. and U.K. courts have recently recognized that no undue experimental burden is required to raise monoclonal antibodies targeted to a defined polypeptide. Broad claims to such antibodies have been allowed in these jurisdictions in view of the maturity of antibody production technologies.
Turning to the case at hand, the Board noted that two types of IL-1R polypeptides exist: Type I and Type II. The specification disclosed the construction, expression, and purification of an extracellular domain of a Type I IL-1R. Thus, the Board concluded that the specification only described and enabled antibodies directed to Type I polypeptides, while the claims in question encompassed both types. However, the Board was willing to allow the claims if the scope of the antibody target was limited to Type I IL-1R polypeptides, and invited the Applicant to effect the necessary amendments.
In arriving at its decision, the Board noted that the description taught the cloning and protein expression techniques required to prepare the immunogen. It also considered a 1989 (i.e. post- filing) publication from a third party, as well as an affidavit signed by one of the inventors, to support its conclusions that generation of monoclonal antibodies was sufficiently supported. Once the antigen was in hand, the work which followed did not, in the Board’s view, involve undue experimental burden. The actual techniques used post-filing closely mirrored the general protocol taught in the description.
The Board also stated
… the skilled person would appreciate that monoclonal antibodies can be adequately described based on a combination of a structural description of the antigen, functional identity [i.e. specific immunoreactivity] between the antibody and antigen, and knowledge of predictable production methods.
Of particular note, the Board indicated that a target polypeptide could be “fully characterized” by providing a complete amino acid sequence.
However, the Board cautioned that claims to antibodies having special functional attributes, such as diagnostic or therapeutic antibodies, may require “correspondingly detailed support”.
WHAT DOES IT MEAN FOR PROSPECTIVE PATENTEES?
Publication of this decision mirrors a recent – though, until now, unexplained – trend for Canadian Patent Examiners to allow broader claims to monoclonal antibodies in some applications. This decision sheds light on the underlying reasons for this change, and supports the argument that claims to monoclonal antibodies can be routinely generated without undue experimentation when a well defined target protein is disclosed, for example, by sequence and/or structure. It also highlights the importance of providing general protocols and prophetic examples in patent specifications for the purposes of support.
WHAT ABOUT OTHER TYPES OF ANTIBODIES?
While claims to monoclonal and chimeric antibodies are now being entertained, claims to humanized antibodies are still being routinely objected to unless they have been specifically exemplified in the description. A basis for this Patent Office policy may lie in the 2009 Commissioner’s Decision in Re Sloan-Kettering Institute for Cancer Research Patent Application No. 2,072,017 2 in which the Board considered a claim encompassing humanized antibodies to be neither supported nor enabled because (amongst other considerations) few laboratories (“in the neighbourhood of ten”) were active in the field of antibody humanization at the filing date (December 14, 1990), and because the steps to a humanized antibody were “considerably more involved” than those involved in constructing a chimeric antibody.
The recent decision in Re Immunex Corporation should embolden prospective patentees to argue that the standards set forth in this decision should equally apply to other sub-types of antibodies, particularly in view of technological advancements since 1990.