T 1919/11 – Taxus Chinensis

In this case Board 3.3.02 had to deal with an appeal against the refusal of a divisional application on the ground that it extended beyond the content of the earlier application

[2.1] The subject-matter of claim 1 of the main request relates to

a method for producing taxanes …

• in cell culture of Taxus chinensis comprising:
• (a) cultivating in suspension culture …
• (b) recovering one or more taxanes from said cells or said medium of said cell culture, or both, wherein the nutrient media contain
• (i) silver at a concentration of at least 1 µM to less than 200 µM in the form of a silver-containing compound, or a silver complex, or a silver ion, and
• (ii) an enhancement agent selected from:a) ... …; and
  b) an auxin.

Subject-matter [underlined] characterises issues particularly discussed during the oral proceedings under A 76(1) EPC 1973.

[2.2] The question is whether these three features in the context of the whole subject-matter of claim 1 of the main request represent added subject-matter with respect to the parent application as originally filed.

[2.2.1] The subject-matter of claim 1 of the main request relates to Taxus chinensis only.

In contrast, under the heading “Summary of the invention”, […] of the description as originally filed for the parent application (synonymously used for “earlier application”; references relate to WO 1997/044476), it is set out that

“the inventors have discovered that taxol, baccatin III, and other taxol-like compounds, or taxanes, can be produced in very high yield from all known Taxus species, e.g., brevifolia, canadensis, cuspidata, baccata, globosa, floridana, wallichiana, media and chinensis. Further, by the methods of this invention it is possible to obtain taxol, baccatin III, and other taxanes in a much shorter time frame than previously reported.”

This subject-matter is described in the text of the parent application as comprising “one embodiment” […] and “another embodiment” […], the latter being selected as the subject-matter of the current divisional application […]:

“In another embodiment, this invention provides a method for producing taxanes in high yields in cell culture of a Taxus species by cultivating cells of a Taxus species in suspension culture … the nutrient media containing silver … along with at least one enhancement agent …”.

Page 8, lines 3 to 11, states:

“Preferably, cells cultured according to the method of this invention are cells of Taxus species, and the species may be T. brevifolia, T. canadensis, T. chinensis, T. cuspidata, T. baccata, T. globosa, T. floridana, T. wallichiana, or T. media.

Preferably, the cells of a Taxus species used in the method of this invention are cells which produce taxol above background by ELISA in callus culture or suspension culture in medium that contains no enhancement agents. More preferably, the cells of a Taxus species used in the method of this invention are cells which produce taxanes in suspension culture at an average volumetric productivity of 10mg/L in a medium containing silver thiosulfate, methyl jasmonate and auxin.”

In addition to this summarising text relating to a plurality of Taxus species, any particular mention of Taxus chinensis is followed by an endorsement that Taxus chinensis may be the best in many issues, but that the important subject-matter of the application equally is the teaching to use any member of the list of Taxus species for producing taxanes:

So, the text […] reading 

“In particular, the inventors found that the species, Taxus chinensis, is capable of rapid growth and of producing extremely high levels of taxol, baccatin III, and taxanes within a short period of time. With the species Taxus chinensis, the inventors have been able to manipulate cells to yield taxol, baccatin III, and taxanes in amounts far in excess of the amounts obtained from tissue cultures of the other Taxus species.”

is followed by

“Particular modifications of culture conditions (i.e., media composition and operating modes) have been discovered to enhance the yield of various taxanes from cell culture of all species of Taxus.” […].

On page 5, line 30 to page 6, line 2,

“While the yield of taxanes from plant cell culture of T. chinensis is particularly enhanced by use of one or more of these conditions,”

is followed by

“yield of taxanes for all Taxus species has been found to benefit from use of these conditions.” […].

Finally, […]

“In particular, the inventors have identified the species Taxus chinensis as capable of producing significant quantities of taxol, baccatin III, and taxanes at high volumetric productivities.”

is followed by the generalising text

“It has been found by the inventors that specific taxane content varies with plant species, and within plant species from tissue source and specific trees. Selecting a high yielding source and culture for taxane production is an important first step towards providing sufficient quantities of taxanes for therapeutic use.” […].

Consequently, some of the examples relate to different Taxus species and some use Taxus chinensis as a model substance to show particular effects of the cultivation conditions.

On this basis, there is no direct and unambiguous disclosure that the subject-matter of the overall content of the application relates to nothing else than a method using Taxus chinensis.

[2.2.2] The subject-matter of claim 1 of the main request relates to silver at a concentration of at least 1µM to less than 200µM.

Original claim 9 of the parent application contains the feature of silver content at a concentration of 900µM or less.

In the description [...] it is stated in two separate consecutive sentences that

“When silver is incorporated in the medium, it will be added at a concentration of less than 900 µM, preferably less than 500 µM, and more preferably less than 200 µM.” and

“When silver is incorporated in the medium, it will be added at a concentration of at least 10 nM, preferably 100 nM, more preferably 1 µM, and typically at 10 µM.”

This present situation is not comparable with that in T 1107/06 [48] and dealt with in the settled jurisprudence of the boards of appeal, where – starting from a general and a preferred range – “a combination of the preferred disclosed narrower range and one of the part-ranges lying within the disclosed overall range on either side of the narrower range” is considered to be originally disclosed.

A general range, which means a lower limit which is unequivocally combined with an upper limit and a preferred disclosed narrower range – equally consisting of a lower limit which is unequivocally combined with an upper limit – are simply missing. Even a kind of parallel structure in indicating the upper and lower limits (less/at least, preferred or more preferred) implies no unequivocal correlation between a particular upper limit and a particular lower limit because there is no teaching that such an arrangement was intended.

Therefore, in the present case, one of the upper limits mentioned in the first sentence in the description of the parent application as originally filed (as cited above) and one of the lower limits mentioned in the second sentence are arbitrarily combined, which does not represent a direct and unambiguous disclosure.

[2.2.3] The subject-matter of claim 1 of the main request relates to an enhancement agent selected from: ... and b) an auxin.

Since the auxin-related growth regulator mentioned in claim 9 of the parent application as originally filed as

“an enhancement agent selected from:

a) jasmonic acid or an ester of jasmonic acid; and

b) an auxin-related growth regulator”

is defined in the corresponding part of the description as including “auxins, compounds with auxin-like activity, and auxin antagonists” [...], the selection of auxin only under component b) is arbitrary.

2.2.4 Regarding the three particularly discussed features

• restriction to a method using Taxus chinensis together with the
• application of silver at a particular concentration of at least 1µM to less than 200µM and the
• restriction of auxin-related growth regulators to auxin,

the board comes to the conclusion that the skilled person was not in a position to derive in a direct and unambiguous way, from the parent application as originally filed, that these features were present in the particular combination now claimed. The selections are arbitrary and thus their present combination represents information not originally disclosed and, as such, added subject-matter.

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