The patent relates to a method of producing an antibody comprising a human variable region and a rodent constant region, i.e. chimeric antibodies.
Brief outline of the case
The patent was revoked and the proprietor appealed.
For the OD, the new MR and AR 1-11 as well as AR 14 contravened Art 123(2).
The new MR, comprised 4 independent claims, and corresponded in substance to claim 1 as granted with minor amendments.
The amendment to claim 1 of AR 12 lacked clarity.
AR 13 the requirements of Art 84 but contravened Art 123(2).
In appeal the proprietor filed the MR and AR 1-29.
Claim 1 of all the requests contains a proviso or negative feature = a “disclaimer” which reads: “wherein said rodent/mouse or rat/mouse does not produce fully human antibodies“.
The board decided that all requests on file contravened Art 76(1).
The board thus confirmed the revocation, but for another reason.
The decision is interesting in that it deals with negative formulations known as disclaimers.
The OD’s position
The OD considered that “in view of the application as a whole, it is only with a mind unwilling to understand claim 1, that one would interpret the claim -when disregarding the disclaimer- as also embracing ‘fully human’ antibodies. In other words, since even when disregarding the disclaimer, fully-human antibodies are not embraced by the claim, the disclaimer has no technical effect on the claim“.
The proprietor’s position
For the proprietor, there was a clear disclosure that hybrid antibodies and not fully human antibodies were produced in rodents, and there was also an implicit basis for the disclaimer in the technical teaching of the application.
The proprietor argued that a disclaimer not falling within the definitions provided in decisions G 1/03, G 2/03, G 2/10 and G 1/16 could still lead to an allowable claim, relying solely on the “gold-standard” for amendments.
The disclaimer related to an amendment which the skilled person would have directly and unambiguously derived from the teaching of the grandparent application as filed.
In AR18, the claimed method was limited to mice. The disclaimer was an implicit feature of the disclosed method for producing antibodies in a mouse having targeted integration of a human variable region which created hybrid antibodies and not fully human antibodies.
The opponents’ position
The disclaimer was an unallowable disclaimer, as it presented the skilled person with new information.
Furthermore, the disclaimer did have a technical effect on the scope of the claims: each claim now required the essential technical feature that the transgenic animal did not produce any type or any level of fully human antibody.
However, the grandparent application as filed did not rule out the possibility that a fully human antibody could be produced as well as the chimeric antibody. The grandparent application as filed did not include any language that was the same as or came close to that of the disclaimer.
Therefore, between the mice of the prior art that produced fully human antibodies and the mice of the grandparent application that produced hybrid antibodies, the latter were mice that had been subjected to in-situ replacement of some gene segments. This, however, was not the subject-matter of claim 1 of any of the requests. Claim 1 of all the requests contravened Art 76(1).
The board’s position
It was undisputed that the subject-matter which is disclaimed in claim 1 of all the requests, i.e. a rodent/mouse or rat/mouse which produces fully human antibodies, is not disclosed as a (positive) embodiment of the invention in the earlier (“grandparent”) application as filed.
The board concluded that the disclaimer in claim 1 of all the requests is not a “disclaimer disclaiming from [a claim] subject-matter disclosed in the application as filed”, in the sense of decision G 2/10.
It was also undisputed that the disclaimer in claim 1 of all the requests does not fall under the criteria allowing so-called “undisclosed” disclaimers as established in decision G 1/03 or G 1/16.
It was further undisputed that the disclaimer was not explicitly disclosed in the grandparent application as filed, since the wording “fully/entirely/totally human antibody” occurs only in relation to the prior art.
For the board, when dealing with negative technical features = “disclaimers”, there exists a fundamental difference between
- an implicit disclosure in an (earlier) application as filed of the absence of certain features derivable from the comparison of the invention with the prior art, in the present case the (alleged) implicit disclosure that the animals employed in the methods should not produce fully human antibodies, and
- (ii) a claim wording that specifies the mandatory absence of certain features as an explicit negative technical feature from the specific subject-matter defined in the claim under consideration.
For the board, the content of the first, i.e. the implicit disclosure, can be at best vaguely understood from the disclosure actually made in the application as filed, the second, i.e. the disclaimer in a claim, should be, and in a granted patent claim must be, of a precise nature.
In view of the uncertainties caused by the absence of any explicit disclosure of the alleged preferable absence of fully human antibodies, the board considers that the disclaimer concerned is in fact an undisclosed disclaimer.
The findings of decisions G 1/03, G 2/03 and G 1/16 thus apply, and the fact that the disclaimer does not fall into any of the categories established in those decisions means that, for this reason alone, it is not allowable.
Even disregarding G 1/03, G 2/03, G 2/10 and G 1/16, and relying on the “gold-standard”, the board considered that the subject-matter of claim 1 extends beyond the content of the earlier application as filed.
The board examined the subject-matter of claim 1 of AR 18 first, because it is the most restricted request for which the proprietor provided specific arguments. In particular, claim 1 is limited to methods in mice.
The board did not share the OD’s view. Rather, the board considered that subject-matter “comprising” certain features is not limited to having only those features.
In the present case, therefore, the wording of claim 1 without the disclaimer does not exclude the possibility that the mouse contains further genetic modifications such that the mouse produces fully human antibodies by some other mechanism.
This means that the addition of the disclaimer changes the subject-matter of the claim, by excluding all methods in which mice also produce fully human antibodies.
The board held that, what claim 30 of the grandparent application does not disclose, is that “said mouse does not produce fully human antibodies”. On the contrary, because the term “comprising” is used, the claim includes mice having further modifications in their genome, e.g. such that the mice also produce fully human antibodies.
For the board, the passage in the grand parent application relates to prior art methods without indicating that those methods had to be completely avoided or were not compatible with the invention as disclosed.
Rather, the application states that the prior art method “has not resulted in optimal antibodies“, which indicates only that the method was not optimal but not that it failed completely. Thus, the passage does not exclude from the disclosed invention mice which also produce fully human antibodies.
Even if example 3 of the grand-parent was interpreted as implicitly disclosing mice which do not produce fully human antibodies and claim 30 was considered to provide a basis for the subject-matter of claim 1 without the disclaimer, the skilled person had no reason to read any implicit restrictions on the specific method of example 3 into the wording of the much more broadly defined mouse of claim 30 of the grandparent application as filed, and thus to arrive at the subject-matter represented by the method of claim 1.
Introducing the disclaimer “wherein the mouse does not produce fully human antibodies” adds subject-matter under Art 76(1).
The present decision is interesting in that it shows that there could be disclaimers which a priori do not fall under any of G 1/03, G 2/03, G 2/10 and G 1/16, but that those disclaimers have to abide by the “gold-standard”.
Although being highly specialised, the present decision shows that it is not possible to imply from the prior art cited in the original application, some characteristics which could provide the basis for a negative formulation.
There exist a series of decisions which have made clear that the passages relating to background art in the application as filed cannot serve as a basis for an amendment during examination/opposition. See e.g. T 1084/06, T 1652/06 or T 912/08.
The present decision shows that this stance also applies when the prior art does merely allow to imply some “non-disclosed” features from the prior art.
A disclaimer based on such implied features cannot be said to be directly and unambiguously derivable from the application as filed or from a parent application.
On the procedure
The present decision confirmed the revocation by the OD, but for different reasons. It implies thus that the decision of the OD was not correct.