T 1328/20 - Endoxifen - Protocols for testing without actual results

Key points

Claim 1 of the main request reads: "Claim 1 of the main request defined: "A composition comprising an effective amount of a complex comprising synthetic endoxifen, wherein said endoxifen is a free base or is in the form of a salt for use in the treatment or prevention of cancer by the oral mode of administration."
"Document E1 reports results of in vitro assays for estrogen receptor binding, inhibition of estrogen stimulated breast cancer cell proliferation and regulation of estrogen responsive genes indicating that endoxifen has equivalent activity to 4-OH-Tam, which is known as a potent active tamoxifen metabolite [i.e. is a metabolite of tamoxifen, and is potent and active]."

The abstract of E1, from 2004, can be found here; the authors are not the inventors of the patent: https://link.springer.com/article/10.1023/B:BREA.0000025406.31193.e8.
The abstract includes: "We demonstrate that endoxifen has essentially equivalent activity to the potent metabolite 4-hydroxy tamoxifen (4-OH-tam) often described as the active metabolite of this drug [tamoxifen]. "
"Tamoxifen is a nonsteroidal antiestrogen that has found successful applications for each stage of breast cancer in the treatment of selected patients. " (link, from 1992)

The Board: "Document E1 does not describe a composition for use in the treatment or prevention of cancer by the oral mode of administration as defined in claim 1 of the main request."

As a comment, it is unclear to me if the Board considers that E1 does not describe endoxifen for use in the treatment or prevention of cancer, or only fails to teach the oral administration.

" the patent presents in example 10 results of in vitro experiments which are in line with the results from the experiments already described in document E1. In example 9 the patent further reports that mice can survive exposure to certain doses of intravenously administered endoxifen, whilst examples 11-15 relate to protocols for testing the effects of endoxifen following oral administration without presentation of any actual results."

"In view of document E1 and having regard to the teaching in the patent the Board considers the objective technical problem as the provision of an effective and convenient administration form for endoxifen in the treatment of cancer."

Note, the formulated problem does not refer to safety, so the additional example 9 regarding mice safety is not apparently considered. Hence, possibly, providing in vitro results that are "in line" with the in vitro results of E1, is seen as solving the problem of "the provision of an effective ... administration form", or the protocols that are presented without results, or some information added in the general part of the description (which uses claim-like language instead of the language used in the scientific paper E1).
Note, apparently, the presented in vitro results are considered to be sufficient proof that an effective administration form for endoxifen in the treatment of cancer is provided (together with any other technical information in the patent); though it must be borne in mind that the Board found the claimed subject-matter not inventive even when seen as solving this problem..

The Board: " In view of the pharmacological activity of endoxifen as known from document E1 and taking account of the well known convenience of oral administration the Board considers that the skilled person would, in the absence of any prejudice against oral administration of endoxifen, regard the claimed subject-matter an obvious solution for providing a convenient and effective mode of administration for endoxifen in the treatment of cancer."
A detailed discussion follows whether there was a technical prejudice "against effective oral administration of endoxifen." The Board considers such prejudice not proven after a detailed review of the (technical) evidence.
The appeal of the proprietor is dismissed, and the patent remains revoked.
As it stands, the Board does not need to comment on the holding of G 2/21 (which was issued a few days before the present decision was taken) that for second medical use claims, "it is necessary that the patent at the date of its filing renders it credible that the known therapeutic agent, i.e. the product, is suitable for the claimed therapeutic application".
Of course, whether the in vitro assay results are sufficient for meeting that requirement of G 2/21 can be a matter of debate requiring great expertise in the technical field at issue.

EPO

The link to the decision is provided after the jump, as well as (an extract of) the text of the decision.

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