17.08
Special topics - January 2009
This section concerns areas of biotechnology for which particular practices exist and which practices merit particular attention, elaboration or clarification.
17.08.01
Antibodies
Antibodies, as a class of chemical compounds, have been structurally and functionally well-characterized and it is known that, in general, immunization of a mammal with an antigen results in the production of antiserum containing antibodies reactive with the antigen. Antiserum contains a generic family, genus or polyclonal mixture of antibodies where each individual antibody binds to an antigenic determinant or epitope carried on the immunizing antigen. The antiserum is representative of the entire family of antibodies capable of binding to the antigen.
As is the case with claims to any product or process, a claim to an antibody must be supported by a specification which (a) provides a written description of the antibody, and (b) would enable a person of skill in the art to produce the antibody.
17.08.01a
“Generic” and polyclonal antibodies
Methods for preparing polyclonal sera are well known in the art and a specification need not describe in detail any of these methods to be enabling.
With respect to written description, an antibody, like any other chemical compound, can be described in terms of its chemical structure (polypeptide sequence). However, antibodies are rarely described this way. Indeed, it has become accepted practice to describe antibodies in terms of the antigen to which they bind and claims to antibodies often include functional language such as “capable of binding to”. Therefore, a written description of an antibody can be provided by a written description of its antigen binding partner. Since antigens are chemical compounds, the best way to describe an antigen is in terms of its chemical structure. A description in terms of physical or chemical properties may be adequate provided that whatever properties are recited are sufficient to distinguish the antigen from other chemical compounds.
Since an antigen is implicitly understood to carry many epitopes, a written description of the antigen is akin to a written description of the collective of epitopes carried on the antigen and therefore provides a description of the corresponding generic or polyclonal binding partners.
If an application includes a claim to an antigen and a claim to an antibody reactive with the antigen, both claims should be commensurate in scope with respect to the antigen.
If the prior art teaches that antigen X is old, obvious or lacks utility, then antibodies reactive with that antigen would generally be considered obvious or lacking utility. Where the prior art discloses antibodies reactive with a close structural relative of antigen X, then a claim to “an antibody capable of binding to antigen X” may read on the old and known antibody by virtue of cross-reactivity and the claim may therefore be considered to be anticipated.
A claim to “an antibody capable of binding to antigen X” or “a polyclonal antibody capable of binding to antigen X” will generally be considered to be supported by a specification provided:
- antigen X itself has been adequately described; and
- either antiserum has been prepared, or where antiserum has not been prepared, there is neither anything peculiar about the antigen nor any indications that would lead a person of skill in the art to question the likelihood of success if that person desired to produce an antibody to the antigen.
Examples:
- The specification discloses a novel protein isolated from a bacterial pathogen, that has utility as a diagnostic target for detecting disease caused by the bacterium. Further, the specification provides the amino acid sequence (SEQ ID NO: 1) of the protein, methods of purifying it using recombinant techniques, and methods of preparing antibodies to the protein by immunizing a suitable mammalian host. No working examples of an antibody are provided. The protein appears to be a member of a new class of bacterial proteins and a sequence search reveals that the closest structural relative is 20% identical with no common domains of any significance.
Claim:
- An antibody capable of binding to the protein defined by SEQ ID NO: 1.
Analysis: The claim is acceptable. Since the protein is new, useful as a diagnostic target, and exhibits little structural similarity to known proteins, antibodies prepared against it are likewise, new, useful and unobvious. The specification is both enabling with respect to preparing antibodies and includes a written description (amino acid sequence) of the antigen. The claim is therefore fully supported by the specification.
- The specification discloses a novel protein isolated from a bacterial pathogen, that has utility as a diagnostic target for detecting disease caused by the bacterium. Further, the specification provides the amino acid sequence (SEQ ID NO: 1) of the protein, methods of purifying it using recombinant techniques, and methods of preparing antibodies to the protein by immunizing a suitable mammalian host. No working examples of a novel antibody are provided. The gene encoding the protein was cloned by immunoscreening a phage library with an old and known antibody reactive with a close homologue of the protein.
Claim:
- An antibody capable of binding to the protein defined by SEQ ID NO: 1.
Analysis: The claim is objectionable. Despite the fact that the protein defined by SEQ ID NO: 1 itself appears to be novel, the claimed antibody is anticipated since the claim reads on the old and known antibody that has the requisite binding capability, i.e., the antibody used for immunoscreening.
- The specification discloses a correlation, identified by chromatographic analysis, between a novel hydrophobic peptide and a disease. The amino acid sequence of the peptide is provided and reveals that it is a low-molecular-weight member of a class of peptides to which no known antibodies have ever been prepared despite several attempts. The specification asserts that antibodies to the peptide may be prepared for eventual use in an immunoassay for the disease. The specification does not provide any working examples of an antibody reactive with the peptide.
Claim:
- An antibody capable of binding to the peptide defined by SEQ ID NO: 1.
Analysis: The claim is objectionable. No antibodies were raised against the novel peptide and the specification teaches that, despite several attempts, antibodies have never been raised against peptides of similar type. A person skilled in the art would not regard the specification as enabling the production of the claimed antibody.
17.08.01b
Monoclonal antibodies
A monoclonal antibody binds to a specific antigenic determinant or epitope carried on an immunizing antigen. A monoclonal antibody can be viewed as one member of the family of polyclonal antibodies contained in antiserum produced by an immunizing antigen.
As with claims to polyclonal antibodies, a claim to a monoclonal must be supported by a specification that is both enabling and includes an adequate written description of the antibody.
The core steps for preparing monoclonal antibodies are now well-known and established. Thus, for a specification to be enabling, the polypeptide antigen against which the monoclonal is raised must be described but an applicant need not set out a detailed procedure for producing the antibody. A detailed step-by-step protocol would only be necessary if the invention resides, at least in part, in an applicant having adapted known procedures to overcome some difficulty in making a monoclonal to a particular antigen.
An examiner will consider the following when determining whether a specification is enabling with respect to monoclonal antibodies:
- whether the applicant actually prepared a monoclonal antibody;
- where a monoclonal antibody has not been prepared,
- whether the antigen and core steps for preparing the monoclonal are described,
- the availability and/or ease of production of the antigen,
- whether there are indications that the applicant was unable to produce a monoclonal antibody or to suggest that one of skill in the art would not be able to reproducibly make a monoclonal to the subject antigen,
- whether there are indications which suggest that undue experimentation or undue adaption of known core steps would be necessary for preparing a monoclonal.
The foregoing list is non-exhaustive and non-cumulative and is intended as a guide only. Each application will be considered on its own merits.
A specification must not only be enabling with respect to a claimed monoclonal antibody but also must provide a written description of the antibody. The written description requirement is satisfied where a specification describes at least one monoclonal and it is evident that the applicant was in possession of the antibody at the time the patent application was filed. Reference to a biological deposit of either a hybridoma or a monoclonal antibody is the best way to demonstrate possession.
Applicants should note however, that a deposit for patent purposes, i.e., for consideration in determining whether or not subsection 27(3) of the Patent Act has been complied, must be in accordance with sections 104 to 106 of the Patent Rules.
An adequate written description of a monoclonal antibody can also be provided by an explicit description of the epitope to which it binds in the same way as a written description of a generic antibody or polyclonal can be provided by a general description of an antigen. As discussed in section 17.08.01a, a written description of the antigen amounts to a written description of the collective of epitopes carried on the antigen and therefore provides a description of the family of polyclonal binding partners. Since a monoclonal is one member of the family which binds to a specific epitope, if it is to be described in terms of its binding partner, the specification must include a structural description of the epitope.
An epitope on a protein can be described in terms of a specific amino acid sequence which is a subset of the complete polypeptide sequence of the protein, or as a binding pocket defined by specific non-contiguous amino acids.
Where existence of an epitope has not been demonstrated but rather is predicted, for example by computer modelling, a specification must disclose not only a structural description of the epitope, but also a factual basis and sound line of reasoning to support the prediction of a putative antibody binding site.
An examiner will consider the following when determining whether a specification provides a written description with respect to monoclonal antibodies:
- whether the applicant was in physical possession of a monoclonal antibody at the time of filing;
- whether the applicant had made a deposit of a hybridoma or monoclonal antibody for patent purposes or was in a position to do so at the time of filing;
- whether there is specific structural description of an epitope or epitopes carried on the antigen to which the monoclonal will bind.
The foregoing list is non-exhaustive and non-cumulative and is intended as a guide only. Each application will be considered on its own merits.
Where the prior art discloses a monoclonal antibody specific for antigen X, a broad claim would not be acceptable as it would read on the prior art.
A prior art document which merely describes how a monoclonal antibody to an antigen might be prepared yet does not specifically describe such a monoclonal antibody, is not considered an anticipatory document against an application that claims and specifically describes a monoclonal antibody.
Example:
- The specification discloses a novel isolated protein from a bacterial pathogen that has utility as a diagnostic target for detecting disease caused by the bacterium. Further, the specification provides the amino acid sequence (SEQ ID NO: 1) of the protein, methods of purifying it using recombinant techniques as well as methods of preparing monoclonal antibodies to the protein by using traditional techniques. The specification describes neither an actual monoclonal antibody, nor a paratope thereof, nor a specific epitope of the protein.
Claim:
- A monoclonal antibody capable of binding to the peptide defined by SEQ ID NO: 1.
Analysis: The claim is objectionable. Although the specification is enabling with respect to preparing a monoclonal antibody capable of binding to the antigen, there is no written description of such a monoclonal. The specification does not disclose that the applicant was in possession of a monoclonal antibody nor does it disclose a structural description of a specific epitope where a putative monoclonal antibody would bind.
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