Interpretational Spotlight: “Epitope”

Claim 1 of the main request before the Board read:

An antibody binding exclusively to a Prp^Sc isoform of the prion protein and recognizing the epitope having the three dimensional conformation provided by the protein sequence

Cys-Ile-Thr-Gln-Tyr-Glu-Arg-Glu-Ser-Gln-Ala-Tyr-Tyr

of the PrP^Sc isoform of the prion protein while not binding to the PrP^C form, obtainable by a method comprising the step of immunising an animal with a peptide consisting of the amino acid sequence

Cys-Ile-Thr-Gln-Tyr-Glu-Arg-Glu-Ser-Gln-Ala-Tyr-Tyr

or

Cys-Ile-Thr-Gln-Tyr-Gln-Arg-Glu-Ser-Gln-Ala-Tyr-Tyr.

When discussing the novelty of this claim, the Board had to face an interpretational problem:

[1] Claim 1 relates to antibodies which are inter alia defined by the feature “and recognizing the epitope having the three dimensional conformation provided by the protein sequence Cys-Ile-Thr-Gln-Tyr-Glu-Arg-Glu-Ser-Gln-Ala-Tyr-Tyr of the PrP^Sc isoform of the protein”. There is disagreement between the parties about the meaning of this feature, i.e. whether or not it is to be interpreted as meaning that the claimed antibodies bind exclusively to this epitope.

[2] Generally the term “epitope” is used to describe a part of a molecule to which the antigen-binding site of an antibody attaches.

[2.1] In the case of a protein, an epitope may be formed by a continuous stretch of amino acids. These epitopes are sometimes referred to as “linear” epitopes. However, although they are denoted as “linear”, these epitopes may also adopt a specific three-dimensional conformation as, for example, the epitope of the PrP^Sc protein recited in claim 1.

[2.2] Epitopes may also be formed by amino acids stemming from different parts of a protein, which are however brought into proximity by the folding of the protein into its three dimensional structure. These epitopes are often referred to as “conformational” epitopes.

[3] In the case of a conformational epitope, a distinction is made between the denomination of the parts of a protein contributing to the epitope and the epitope as a whole. This is for example apparent from documents D1 and D2 (emphasis added):

“whereas three distinct peptide sequences were found to form the 15B3 epitope” (D1 […]); “[t]he polypeptide segments of the 15B3 epitope ...” (D1 […]); “[m]apping of the 15B3 epitope onto the NMR structure of the C-terminal domain of mouse PrP (ref. 12) reveals close proximity of the peptide segments 2 and 3, but a much larger spatial separation of the segment 1 ...” (D1 […]); “recognizes three discontinuous linear polypeptide segments that are hypothesized to form a conformational epitope on the surface of prions” (D2 […]); “it was assumed that the epitope was indeed conformational and that the three polypeptide segments represented partial epitopes thereof” (D2 […]).

Hence, if an epitope is formed by distinct parts of a protein, the parts are usually not denoted as “the” epitope.

[4] It is also clear from the description of the patent that the epitope recognized by the claimed antibodies is a “linear” epitope […] as opposed to a conformational epitope […]. It is, for example, stated in paragraph [0022]:

“The antibodies are directed to the region comprised by amino acids 190 to 214 of PrP^Sc, more preferably to the sequence from about 202 to about 214 of PrP^Sc.”

[5] The board is therefore satisfied that the skilled person would understand the feature in claim 1 “and recognizing the epitope having the three dimensional conformation provided by the protein sequence Cys-Ile-Thr-Gln-Tyr-Glu-Arg-Glu-Ser-Gln-Ala-Tyr-Tyr of the PrPSc isoform of the protein” to mean that the claimed antibodies bind to a protein segment which is built by the indicated linear sequence and only that sequence.

Hence, by virtue of the first part of claim 1 as just quoted, the claimed antibodies are defined as binding exclusively to “the epitope having the three dimensional conformation provided by the protein sequence Cys-Ile-Thr-Gln-Tyr-Glu-Arg-Glu-Ser-Gln-Ala-Tyr-Tyr of the PrPSc isoform of the protein”. In the board’s view the process-feature in claim 1 (see section II above, “obtainable by ....”) provides the same definition.

To download the whole decision (T 30/09), click here.

The file wrapper can be found here.